Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
3.7
4.7
Journals
Biomedicines
Special Issues
10th Anniversary of Biomedicines—Sepsis: Diagnostics and Therapeutics
share announcement

10th Anniversary of Biomedicines—Sepsis: Diagnostics and Therapeutics

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

Deadline for manuscript submissions: closed (15 November 2022) | Viewed by 25218

Special Issue Editors

Dr. Tsukasa Nakamura

E-Mail Website
Guest Editor
Division of Nephrology, Department of Internal Medicine, Kashiwa Forest Clinic, Kashiwa, Chiba, Japan
Interests: sepsis; critical care medicine; renal replacement therapy; LDL-apheresis; diabetic nephropathy
Special Issues, Collections and Topics in MDPI journals
Dr. Eiichi Sato

E-Mail Website
Guest Editor
Division of Nephrology, Department of Internal Medicine, Shinmatsudo Central General Hospital, Matsudo, Chiba, Japan
Interests: sepsis; acute kidney injury; chronic kidney disease; hemodialysis therapy; diabetic nephropathy; aquaporin 2
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The year 2023 marks the 10th anniversary of Biomedicines, a peer-reviewed open access journal in the biomedical field. So far, Biomedicines has published more than 2700 papers from more than 17,000 authors. We appreciate each author, reviewer, and academic editor whose support has brought us to where we are today.

To celebrate this significant milestone, we aim to publish a Special Issue entitled 10th Anniversary of Biomedicines—Sepsis: Diagnostics and Therapeutics.

The recently-modified Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) defines sepsis as a “life-threatening organ dysfunction caused by a dysregulated host response to infection” and septic shock as “a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone”. Sepsis-3 guidelines still prompt debate and discussion, such as the requirement for a serum lactate level to diagnose septic shock, or use of the quick sepsis-related organ failure assessment (SOFA) score in the diagnosis of sepsis. Further detailed verification is required for reevaluation and future revision of Sepsis-3.

This Special Issue of the Biomedicines will focus on sepsis, and report new insights into epidemiology, pathophysiology, diagnosis, biomarkers, and treatment. In addition, other morbidities and renal replacement therapy, including acute kidney injury and hemodiafiltration, are associated with sepsis, and submissions dealing with these conditions are welcome.

Dr. Tsukasa Nakamura
Dr. Eiichi Sato
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-3
  • infection
  • septic shock
  • SOFA
  • organ dysfunction
  • acute kidney injury
  • renal replacement therapy
  • hemodiafiltration
  • biomarkers
  • therapeutics

Related Special Issues

Published Papers (13 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Review, Other

20 pages, 2473 KiB  
Article
Parallel Dysregulated Immune Response in Severe Forms of COVID-19 and Bacterial Sepsis via Single-Cell Transcriptome Sequencing
by Alexis Garduno, Gustavo Sganzerla Martinez, Ali Toloue Ostadgavahi, David Kelvin, Rachael Cusack and Ignacio Martin-Loeches
Biomedicines 2023, 11(3), 778; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines11030778 - 03 Mar 2023
Cited by 3 | Viewed by 2461
Abstract
Critically ill COVID-19 patients start developing single respiratory organ failure that often evolves into multiorgan failure. Understanding the immune mechanisms in severe forms of an infectious disease (either critical COVID-19 or bacterial septic shock) would help to achieve a better understanding of the [...] Read more.
Critically ill COVID-19 patients start developing single respiratory organ failure that often evolves into multiorgan failure. Understanding the immune mechanisms in severe forms of an infectious disease (either critical COVID-19 or bacterial septic shock) would help to achieve a better understanding of the patient’s clinical trajectories and the success of potential therapies. We hypothesized that a dysregulated immune response manifested by the abnormal activation of innate and adaptive immunity might be present depending on the severity of the clinical presentation in both COVID-19 and bacterial sepsis. We found that critically ill COVID-19 patients demonstrated a different clinical endotype that resulted in an inflammatory dysregulation in mild forms of the disease. Mild cases (COVID-19 and bacterial non severe sepsis) showed significant differences in the expression levels of CD8 naïve T cells, CD4 naïve T cells, and CD4 memory T cells. On the other hand, in the severe forms of infection (critical COVID-19 and bacterial septic shock), patients shared immune patterns with upregulated single-cell transcriptome sequencing at the following levels: B cells, monocyte classical, CD4 and CD8 naïve T cells, and natural killers. In conclusion, we identified significant gene expression differences according to the etiology of the infection (COVID-19 or bacterial sepsis) in the mild forms; however, in the severe forms (critical COVID-19 and bacterial septic shock), patients tended to share some of the same immune profiles related to adaptive and innate immune response. Severe forms of the infections were similar independent of the etiology. Our findings might promote the implementation of co-adjuvant therapies and interventions to avoid the development of severe forms of disease that are associated with high mortality rates worldwide. Full article
(This article belongs to the Special Issue 10th Anniversary of Biomedicines—Sepsis: Diagnostics and Therapeutics)
►▼ Show Figures

Figure 1

9 pages, 1184 KiB  
Article
Levosimendan Increases Survival in a D-Galactosamine and Lipopolysaccharide Rat Model
by Tatsuma Sakaguchi, Fusao Sumiyama, Masaya Kotsuka, Masahiko Hatta, Terufumi Yoshida, Mikio Hayashi, Masaki Kaibori and Mitsugu Sekimoto
Biomedicines 2022, 10(12), 3161; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10123161 - 07 Dec 2022
Viewed by 1235
Abstract
Levosimendan, a calcium sensitizer, has an organ protective profile through the inhibition of inflammatory mediators and cytokines in critical conditions, such as heart failure, ischemia-reperfusion injury, and sepsis. The survival effect of levosimendan for acute liver failure has not been examined yet. Male [...] Read more.
Levosimendan, a calcium sensitizer, has an organ protective profile through the inhibition of inflammatory mediators and cytokines in critical conditions, such as heart failure, ischemia-reperfusion injury, and sepsis. The survival effect of levosimendan for acute liver failure has not been examined yet. Male Sprague-Dawley rats were examined in the D-galactosamine hydrochloride and lipopolysaccharide (GalN/LPS) model. Levosimendan was injected intraperitoneally before GalN/LPS treatment. Survival was monitored for 7 days. For biochemical analyses, liver and blood samples were collected from the rats at 1 and 8 h after GaIN/LPS treatment. The pretreatment of levosimendan at 4 mg/kg significantly increased survival in GalN/LPS rats. In the liver specimen, levosimendan significantly inhibited the activation of nuclear factor-κB (NF-κB) at 1 h, and significantly decreased the mRNA expression of inflammatory mediators, including inducible nitric oxide synthase and tumor necrosis factor-α (TNF-α), at 8 h. In serum, levosimendan decreased the levels of nitrite, a metabolite of nitric oxide, and TNF-α protein, as well as aspartate aminotransferase and alanine aminotransferase. These results indicated that Levosimendan ameliorated liver dysfunction and survival in acute liver failure model rats through the suppression of NF-κB activation. Full article
(This article belongs to the Special Issue 10th Anniversary of Biomedicines—Sepsis: Diagnostics and Therapeutics)
►▼ Show Figures

Figure 1

13 pages, 1022 KiB  
Article
Black Garlic and Thiosulfinate-Enriched Extracts as Adjuvants to Ceftriaxone Treatment in a Rat Peritonitis Model of Sepsis
by Francisco Javier Redondo-Calvo, Natalia Bejarano-Ramírez, Víctor Baladrón, Omar Montenegro, Luis Antonio Gómez, Rubén Velasco, Natalia Villasanti, Soledad Illescas, María Teresa Franco-Sereno, Ignacio Gracia, Juan Francisco Rodríguez, José Ramón Muñoz-Rodríguez and José Manuel Pérez-Ortiz
Biomedicines 2022, 10(12), 3095; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10123095 - 01 Dec 2022
Cited by 1 | Viewed by 1486
Abstract
To date, there have been no new drugs or adjuvants able to decrease both morbidity and mortality in the context of sepsis and septic shock. Our objective was to evaluate the use of thiosulfinate-enriched Allium sativum and black garlic extracts as adjuvants in [...] Read more.
To date, there have been no new drugs or adjuvants able to decrease both morbidity and mortality in the context of sepsis and septic shock. Our objective was to evaluate the use of thiosulfinate-enriched Allium sativum and black garlic extracts as adjuvants in the management of sepsis. An experimental in vivo study was carried out with male Sprague–Dawley® rats. Animals were randomized in four treatment groups: antibiotic (ceftriaxone) treatment (group I), ceftriaxone plus thiosulfinate-enriched extract (TASE, group II), ceftriaxone plus thiosulfinate-enriched extract and black garlic extracts (TASE + BGE, group III), and ceftriaxone plus black garlic extract (BGE, group IV). All animals were housed and inoculated with 1 × 1010 CFU/15 mL of intraperitoneal Escherichia coli ATCC 25922. Subsequently, they received a daily treatment according to each group for 7 days. Clinical, analytical, microbiological, and histopathological parameters were evaluated. Statistically significant clinical improvement was observed in rats receiving garlic extracts in weight (groups II and III), ocular secretions, and piloerection (group IV). Moreover, less liver edema, vacuolization, and inflammation were observed in groups receiving adjuvant support (groups II, III, and IV). When comparing interleukins 24 h after bacteria inoculum, we found statistically significant differences in TNF-alpha levels in groups receiving BGE (groups III and IV, p ≤ 0.05). Blood and peritoneal liquid cultures were also analyzed, and we detected a certain level of Enterococcus faecalis in peritoneal cultures from all treatment groups and less bacteria presence in blood cultures in rats receiving garlic extracts (groups II, III, and IV). In conclusion, TASE and BGE could be promising nutraceutical or medicinal agents as coadjuvants in the treatment of sepsis because of its effects in modulating the inflammatory response. Full article
(This article belongs to the Special Issue 10th Anniversary of Biomedicines—Sepsis: Diagnostics and Therapeutics)
►▼ Show Figures

Figure 1

9 pages, 2035 KiB  
Article
Plasma Mitochondrial DNA and Necroptosis as Prognostic Indicators in Critically Ill Patients with Sepsis
by Hayoung Choi, Hongseok Yoo, Jin Young Lee, Junseon Park and Kyeongman Jeon
Biomedicines 2022, 10(10), 2386; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10102386 - 25 Sep 2022
Cited by 4 | Viewed by 1742
Abstract
Mitochondrial DNA (mtDNA) has been identified as a biomarker for predicting sepsis mortality. Although preclinical studies suggested that necroptosis could explain the mechanistic link of mtDNA in sepsis, this is not yet evident in patients with sepsis. This study evaluated the association between [...] Read more.
Mitochondrial DNA (mtDNA) has been identified as a biomarker for predicting sepsis mortality. Although preclinical studies suggested that necroptosis could explain the mechanistic link of mtDNA in sepsis, this is not yet evident in patients with sepsis. This study evaluated the association between mtDNA and essential necroptosis mediators in prospectively enrolled patients with sepsis. Plasma mtDNA copy number was measured using quantitative PCR assay and necroptosis mediators, including receptor-interacting protein kinase-3 (RIPK3), mixed lineage domain-like pseudokinase (MLKL), and high-mobility group box 1 (HMGB1), were measured by ELISA. Receiver operating characteristic (ROC) analysis was conducted to evaluate the predictive ability of mtDNA copy number as a predictor of hospital mortality. Among the 142 patients with sepsis, the mtDNA copy number was significantly higher in non-survivors than in survivors (median, 4040 copies/µL vs. 2585 copies/µL; p < 0.001), and the area under the ROC curve was 0.73 (95% CI, 0.64–0.82) for the relationship between mtDNA and hospital mortality. Furthermore, the correlation between mtDNA copy number and each necroptosis mediator was excellent (p < 0.001 for all): RIPK3 (r = 0.803), MLKL (r = 0.897), and HMGB1 (r = 0.603). The plasma mtDNA copy number was highly correlated with essential necroptosis mediators, suggesting that mtDNA propagates necroptosis and increases sepsis mortality. Full article
(This article belongs to the Special Issue 10th Anniversary of Biomedicines—Sepsis: Diagnostics and Therapeutics)
►▼ Show Figures

Figure 1

14 pages, 1129 KiB  
Article
Association of Hypernatremia with Immune Profiles and Clinical Outcomes in Adult Intensive Care Unit Patients with Sepsis
by Chiung-Yu Lin, Yu-Mu Chen, Yi-Hsuan Tsai, Kai-Yin Hung, Ying-Tang Fang, Yu-Ping Chang, Meng-Yun Tsai, Hsuan-Feng Wu, Meng-Chih Lin and Wen-Feng Fang
Biomedicines 2022, 10(9), 2285; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10092285 - 14 Sep 2022
Cited by 2 | Viewed by 2488
Abstract
Both hypernatremia and an abnormal immune response may increase hospital mortality in patients with sepsis. This study examined the association of hypernatremia with abnormal immune response and mortality in 520 adult patients with sepsis in an intensive care unit (ICU). We compared the [...] Read more.
Both hypernatremia and an abnormal immune response may increase hospital mortality in patients with sepsis. This study examined the association of hypernatremia with abnormal immune response and mortality in 520 adult patients with sepsis in an intensive care unit (ICU). We compared the mortality and ex vivo lipopolysaccharide (LPS)-induced inflammatory response differences among patients with hyponatremia, eunatremia, and hypernatremia, as well as between patients with acquired hypernatremia on ICU day 3 and those with sustained eunatremia over first three ICU days. Compared with eunatremia or hyponatremia, hypernatremia led to higher 7 day, 14 day, 28 day, and hospital mortality rates (p = 0.030, 0.009, 0.010, and 0.033, respectively). Compared with sustained eunatremia, acquired hypernatremia led to higher 7, 14, and 28 day mortality rates (p = 0.019, 0.042, and 0.028, respectively). The acquired hypernatremia group nonsignificantly trended toward increased hospital mortality (p = 0.056). Day 1 granulocyte colony-stimulating factor (G-CSF) and tumor necrosis factor (TNF) α levels were relatively low in patients with hypernatremia (p = 0.020 and 0.010, respectively) but relatively high in patients with acquired hypernatremia (p = 0.049 and 0.009, respectively). Thus, in ICU-admitted septic patients, hypernatremia on admission and in ICU-acquired hypernatremia were both associated with higher mortality. The higher mortality in patients with hypernatremia on admission was possibly related to the downregulation of G-CSF and TNF-α secretion after endotoxin stimulation. Compared to sustained eunatremia, acquired hypernatremia showed immunoparalysis at first and then hyperinflammation on day 3. Full article
(This article belongs to the Special Issue 10th Anniversary of Biomedicines—Sepsis: Diagnostics and Therapeutics)
►▼ Show Figures

Figure 1

11 pages, 842 KiB  
Article
Association between Vitamin C Deficiency and Mortality in Patients with Septic Shock
by Jong Eun Park, Tae Gun Shin, Daun Jeong, Gun Tak Lee, Seung Mok Ryoo, Won Young Kim, You Hwan Jo, Gil Joon Suh and Sung Yeon Hwang
Biomedicines 2022, 10(9), 2090; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10092090 - 26 Aug 2022
Cited by 2 | Viewed by 1696
Abstract
The prognostic value of low vitamin C levels has not been well investigated in patients with septic shock. We aimed to evaluate the association of vitamin C deficiency with mortality in patients with septic shock. We conducted a retrospective analysis of 165 patients [...] Read more.
The prognostic value of low vitamin C levels has not been well investigated in patients with septic shock. We aimed to evaluate the association of vitamin C deficiency with mortality in patients with septic shock. We conducted a retrospective analysis of 165 patients with septic shock from a prospective multicenter trial and institutional sepsis registry between April 2018 and January 2020. The primary outcome was 28-day mortality. The patients were categorized into vitamin C deficiency and normal groups based on a vitamin C cutoff level of 11.4 mmol/L. Multivariable Cox regression analysis was performed to examine the association between vitamin C levels and 28-day mortality. A total of 165 patients was included for analysis and 77 (46.7%) had vitamin C deficiency. There was no significant difference in the 28-day mortality rate between the vitamin C deficiency group and the normal group (23.4% (n = 18/77) vs. 13.6% (n = 12/88), p = 0.083). Multivariable Cox proportional hazard analysis showed vitamin C deficiency to be associated with increased risk of 28-day mortality (adjusted hazard ratio, 2.65, 95% confidence interval (CI), 1.08–6.45; p = 0.032). Initial vitamin C deficiency was associated with a higher risk of 28-day mortality in patients with septic shock after adjusting for intravenous administration of vitamin C and thiamine, baseline characteristics, laboratory findings, and severity of illness. Full article
(This article belongs to the Special Issue 10th Anniversary of Biomedicines—Sepsis: Diagnostics and Therapeutics)
►▼ Show Figures

Figure 1

11 pages, 1772 KiB  
Article
Percutaneous Endoscopic Interbody Debridement and Fusion (PEIDF) Decreases Risk of Sepsis and Mortality in Treating Infectious Spondylodiscitis for Patients with Poor Physical Status, a Retrospective Cohort Study
by Sheng-Fen Wang, Tsung-Ting Tsai, Yun-Da Li, Ping-Yeh Chiu, Ming-Kai Hsieh, Jen-Chung Liao, Po-Liang Lai and Fu-Cheng Kao
Biomedicines 2022, 10(7), 1659; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10071659 - 10 Jul 2022
Cited by 1 | Viewed by 1336
Abstract
Background: Postoperative immunosuppression is associated with blood loss and surgical trauma during surgery and subsequently predisposes patients to increased morbidity. Spine endoscopic surgery has been accepted as an effective surgical technique with less surgical trauma and less blood loss for the complication of [...] Read more.
Background: Postoperative immunosuppression is associated with blood loss and surgical trauma during surgery and subsequently predisposes patients to increased morbidity. Spine endoscopic surgery has been accepted as an effective surgical technique with less surgical trauma and less blood loss for the complication of infectious spondylodiscitis. Therefore, the aim of this study was to investigate whether PEIDF could reduce the morbidity rates for patients with infectious spondylodiscitis. Methods: We launched a retrospective cohort study on the comparison of the perioperative prognosis between PEIDF and conventional open surgery for single-level lumbar infectious spondylodiscitis in patients with poor physical health (ASA ≥ 4) from 2014 to 2019. Results: Forty-four patients were included in this study. Fifteen of them underwent PEIDF, and the rest of the 29 patients were treated with open surgery. Less surgical blood loss (p < 0.001) and intraoperative transfusions (p < 0.001) with a better decline of CRP (p = 0.017) were statistically significant in patients receiving PEIDF. Patients undergoing conventional open surgery encountered more postoperative sepsis (p = 0.030), a higher qSOFA score (p = 0.044), and prolonged-time for CRP normalization (p = 0.001). Conclusions: PEIDF minimizes a poor postoperative outcome due to less surgical trauma, intraoperative blood loss, and the need for a blood transfusion. Full article
(This article belongs to the Special Issue 10th Anniversary of Biomedicines—Sepsis: Diagnostics and Therapeutics)
►▼ Show Figures

Figure 1

12 pages, 926 KiB  
Article
Using Machine Learning to Develop and Validate an In-Hospital Mortality Prediction Model for Patients with Suspected Sepsis
by Hsiao-Yun Chao, Chin-Chieh Wu, Avichandra Singh, Andrew Shedd, Jon Wolfshohl, Eric H. Chou, Yhu-Chering Huang and Kuan-Fu Chen
Biomedicines 2022, 10(4), 802; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10040802 - 29 Mar 2022
Cited by 4 | Viewed by 2092
Abstract
Background: Early recognition of sepsis and the prediction of mortality in patients with infection are important. This multi-center, ED-based study aimed to develop and validate a 28-day mortality prediction model for patients with infection using various machine learning (ML) algorithms. Methods: Patients with [...] Read more.
Background: Early recognition of sepsis and the prediction of mortality in patients with infection are important. This multi-center, ED-based study aimed to develop and validate a 28-day mortality prediction model for patients with infection using various machine learning (ML) algorithms. Methods: Patients with acute infection requiring intravenous antibiotic treatment during the first 24 h of admission were prospectively recruited. Patient demographics, comorbidities, clinical signs and symptoms, laboratory test data, selected sepsis-related novel biomarkers, and 28-day mortality were collected and divided into training (70%) and testing (30%) datasets. Logistic regression and seven ML algorithms were used to develop the prediction models. The area under the receiver operating characteristic curve (AUROC) was used to compare different models. Results: A total of 555 patients were recruited with a full panel of biomarker tests. Among them, 18% fulfilled Sepsis-3 criteria, with a 28-day mortality rate of 8%. The wrapper algorithm selected 30 features, including disease severity scores, biochemical parameters, and conventional and few sepsis-related biomarkers. Random forest outperformed other ML models (AUROC: 0.96; 95% confidence interval: 0.93–0.98) and SOFA and early warning scores (AUROC: 0.64–0.84) in the prediction of 28-day mortality in patients with infection. Additionally, random forest remained the best-performing model, with an AUROC of 0.95 (95% CI: 0.91–0.98, p = 0.725) after removing five sepsis-related novel biomarkers. Conclusions: Our results demonstrated that ML models provide a more accurate prediction of 28-day mortality with an enhanced ability in dealing with multi-dimensional data than the logistic regression model. Full article
(This article belongs to the Special Issue 10th Anniversary of Biomedicines—Sepsis: Diagnostics and Therapeutics)
►▼ Show Figures

Figure 1

Review

Jump to: Research, Other

16 pages, 1325 KiB  
Review
Changes in Cortisol Secretion and Corticosteroid Receptors in COVID-19 and Non COVID-19 Critically Ill Patients with Sepsis/Septic Shock and Scope for Treatment
by Ioannis Ilias, Alice G. Vassiliou, Chrysi Keskinidou, Charikleia S. Vrettou, Stylianos Orfanos, Anastasia Kotanidou and Ioanna Dimopoulou
Biomedicines 2023, 11(7), 1801; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines11071801 - 23 Jun 2023
Cited by 3 | Viewed by 2087
Abstract
Sepsis is associated with dysregulated cortisol secretion, leading to abnormal levels of cortisol in the blood. In the early stages of the condition, cortisol levels are typically elevated due to increased secretion from the adrenal glands. However, as the disease progresses, cortisol levels [...] Read more.
Sepsis is associated with dysregulated cortisol secretion, leading to abnormal levels of cortisol in the blood. In the early stages of the condition, cortisol levels are typically elevated due to increased secretion from the adrenal glands. However, as the disease progresses, cortisol levels may decline due to impaired adrenal function, leading to relative adrenal insufficiency. The latter is thought to be caused by a combination of factors, including impaired adrenal function, decreased production of corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH) by the hypothalamus and pituitary gland, and increased breakdown of cortisol. The dysregulation of cortisol secretion in sepsis is thought to contribute to the pathophysiology of the disease by impairing the body’s ability to mount an appropriate inflammatory response. Given the dysregulation of cortisol secretion and corticosteroid receptors in sepsis, there has been considerable interest in the use of steroids as a treatment. However, clinical trials have yielded mixed results and corticosteroid use in sepsis remains controversial. In this review, we will discuss the changes in cortisol secretion and corticosteroid receptors in critically ill patients with sepsis/septic shock. We will also make special note of COVID-19 patients, who presented a recent challenge for ICU management, and explore the scope for corticosteroid administration in both COVID-19 and non-COVID-19 septic patients. Full article
(This article belongs to the Special Issue 10th Anniversary of Biomedicines—Sepsis: Diagnostics and Therapeutics)
►▼ Show Figures

Figure 1

13 pages, 1068 KiB  
Review
High-Dose Intravenous Ascorbate in Sepsis, a Pro-Oxidant Enhanced Microbicidal Activity and the Effect on Neutrophil Functions
by Kritsanawan Sae-khow, Awirut Charoensappakit, Direkrit Chiewchengchol and Asada Leelahavanichkul
Biomedicines 2023, 11(1), 51; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines11010051 - 25 Dec 2022
Cited by 8 | Viewed by 1689
Abstract
Vitamin C (ascorbic acid), a water-soluble essential vitamin, is well-known as an antioxidant and an essential substrate for several neutrophil functions. Because of (i) the importance of neutrophils in microbial control and (ii) the relatively low vitamin C level in neutrophils and in [...] Read more.
Vitamin C (ascorbic acid), a water-soluble essential vitamin, is well-known as an antioxidant and an essential substrate for several neutrophil functions. Because of (i) the importance of neutrophils in microbial control and (ii) the relatively low vitamin C level in neutrophils and in plasma during stress, vitamin C has been studied in sepsis (a life-threatening organ dysfunction from severe infection). Surprisingly, the supraphysiologic blood level of vitamin C (higher than 5 mM) after the high-dose intravenous vitamin C (HDIVC) for 4 days possibly induces the pro-oxidant effect in the extracellular space. As such, HDIVC demonstrates beneficial effects in sepsis which might be due to the impacts on an enhanced microbicidal activity through the improved activity indirectly via enhanced neutrophil functions and directly from the extracellular pro-oxidant effect on the organismal membrane. The concentration-related vitamin C properties are also observed in the neutrophil extracellular traps (NETs) formation as ascorbate inhibits NETs at 1 mM (or less) but facilitates NETs at 5 mM (or higher) concentration. The longer duration of HDIVC administration might be harmful in sepsis because NETs and pro-oxidants are partly responsible for sepsis-induced injuries, despite the possible microbicidal benefit. Despite the negative results in several randomized control trials, the short course HDIVC might be interesting to use in some selected groups, such as against anti-biotic resistant organisms. More studies on the proper use of vitamin C, a low-cost and widely available drug, in sepsis are warranted. Full article
(This article belongs to the Special Issue 10th Anniversary of Biomedicines—Sepsis: Diagnostics and Therapeutics)
►▼ Show Figures

Figure 1

20 pages, 2494 KiB  
Review
Endothelial Damage and the Microcirculation in Critical Illness
by Rachael Cusack, Marc Leone, Alejandro H. Rodriguez and Ignacio Martin-Loeches
Biomedicines 2022, 10(12), 3150; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10123150 - 06 Dec 2022
Cited by 8 | Viewed by 2466
Abstract
Endothelial integrity maintains microcirculatory flow and tissue oxygen delivery. The endothelial glycocalyx is involved in cell signalling, coagulation and inflammation. Our ability to treat critically ill and septic patients effectively is determined by understanding the underpinning biological mechanisms. Many mechanisms govern the development [...] Read more.
Endothelial integrity maintains microcirculatory flow and tissue oxygen delivery. The endothelial glycocalyx is involved in cell signalling, coagulation and inflammation. Our ability to treat critically ill and septic patients effectively is determined by understanding the underpinning biological mechanisms. Many mechanisms govern the development of sepsis and many large trials for new treatments have failed to show a benefit. Endothelial dysfunction is possibly one of these biological mechanisms. Glycocalyx damage is measured biochemically. Novel microscopy techniques now mean the glycocalyx can be indirectly visualised, using sidestream dark field imaging. How the clinical visualisation of microcirculation changes relate to biochemical laboratory measurements of glycocalyx damage is not clear. This article reviews the evidence for a relationship between clinically evaluable microcirculation and biological signal of glycocalyx disruption in various diseases in ICU. Microcirculation changes relate to biochemical evidence of glycocalyx damage in some disease states, but results are highly variable. Better understanding and larger studies of this relationship could improve phenotyping and personalised medicine in the future. Damage to the glycocalyx could underpin many critical illness pathologies and having real-time information on the glycocalyx and microcirculation in the future could improve patient stratification, diagnosis and treatment. Full article
(This article belongs to the Special Issue 10th Anniversary of Biomedicines—Sepsis: Diagnostics and Therapeutics)
►▼ Show Figures

Figure 1

15 pages, 666 KiB  
Review
Oncology Drug Repurposing for Sepsis Treatment
by Izabela Rumienczyk, Maria Kulecka, Małgorzata Statkiewicz, Jerzy Ostrowski and Michal Mikula
Biomedicines 2022, 10(4), 921; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10040921 - 17 Apr 2022
Cited by 5 | Viewed by 2232
Abstract
Sepsis involves life-threatening organ dysfunction caused by a dysregulated host response to infection. Despite three decades of efforts and multiple clinical trials, no treatment, except antibiotics and supportive care, has been approved for this devastating syndrome. Simultaneously, numerous preclinical studies have shown the [...] Read more.
Sepsis involves life-threatening organ dysfunction caused by a dysregulated host response to infection. Despite three decades of efforts and multiple clinical trials, no treatment, except antibiotics and supportive care, has been approved for this devastating syndrome. Simultaneously, numerous preclinical studies have shown the effectiveness of oncology-indicated drugs in ameliorating sepsis. Here we focus on cataloging these efforts with both oncology-approved and under-development drugs that have been repositioned to treat bacterial-induced sepsis models. In this context, we also envision the exciting prospect for further standard and oncology drug combination testing that could ultimately improve clinical outcomes in sepsis. Full article
(This article belongs to the Special Issue 10th Anniversary of Biomedicines—Sepsis: Diagnostics and Therapeutics)
►▼ Show Figures

Figure 1

Other

Jump to: Research, Review

14 pages, 2659 KiB  
Systematic Review
A Systematic Review of Gene Expression Studies in Critically Ill Patients with Sepsis and Community-Acquired Pneumonia
by Diego Viasus, Lara Nonell, Carlos Restrepo, Fabian Figueroa, Carla Donado-Mazarrón and Jordi Carratalà
Biomedicines 2023, 11(10), 2755; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines11102755 - 11 Oct 2023
Cited by 1 | Viewed by 1096
Abstract
(1) Background: Sepsis is present in nearly 90% of critically ill patients with community-acquired pneumonia (CAP). This systematic review updates the information on studies that have assessed gene expression profiles in critically ill septic patients with CAP. (2) Methods: We searched for studies [...] Read more.
(1) Background: Sepsis is present in nearly 90% of critically ill patients with community-acquired pneumonia (CAP). This systematic review updates the information on studies that have assessed gene expression profiles in critically ill septic patients with CAP. (2) Methods: We searched for studies that satisfied the following criteria: (a) expression profile in critically ill patients with sepsis due to CAP, (b) presence of a control group, and (c) adult patients. Over-representation analysis was performed with clusterProfiler using the Hallmark and Reactome collections. (3) Results: A total of 4312 differentially expressed genes (DEGs) and sRNAs were included in the enrichment analysis. In the Hallmark collection, genes regulated by nuclear factor kappa B in response to tumor necrosis factor, genes upregulated by signal transducer and activator of transcription 5 in response to interleukin 2 stimulation, genes upregulated in response to interferon-gamma, genes defining the inflammatory response, a subgroup of genes regulated by MYC—version 1 (v1), and genes upregulated during transplant rejection were significantly enriched in critically ill septic patients with CAP. Moreover, 88 pathways were identified in the Reactome database. (4) Conclusions: This study summarizes the reported DEGs in critically ill septic patients with CAP and investigates their functional implications. The results highlight the complexity of immune responses during CAP. Full article
(This article belongs to the Special Issue 10th Anniversary of Biomedicines—Sepsis: Diagnostics and Therapeutics)
►▼ Show Figures

Graphical abstract

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-13
Back to TopTop