Journal of Clinical Medicine

Editorial

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Open AccessEditorial

Sepsis: Current Clinical Practices and New Perspectives: Introduction to the Special Issue

by Andreas Hecker, Winfried Padberg and Matthias Hecker

J. Clin. Med. 2021, 10(3), 443; https://doi.org/10.3390/jcm10030443 - 24 Jan 2021

Cited by 1 | Viewed by 1674

Abstract

Despite modern approaches in intensive care medicine, surgery, and immunology, the mortality of sepsis remains unacceptably high [...] Full article

(This article belongs to the Special Issue Sepsis: Current Clinical Practices and New Perspectives)

Research

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22 pages, 3756 KiB

Open AccessArticle

Who Is Afraid of CRP? Elevated Preoperative CRP Levels Might Attenuate the Increase in Inflammatory Parameters in Response to Lung Cancer Surgery

by Moritz Mecki Meyer, Leon Brandenburg, Helge Hudel, Alisa Agné, Winfried Padberg, Ali Erdogan, Holger Nef, Anca-Laura Amati, Oliver Dörr, Biruta Witte and Veronika Grau

J. Clin. Med. 2020, 9(10), 3340; https://doi.org/10.3390/jcm9103340 - 18 Oct 2020

Cited by 7 | Viewed by 2888

Abstract

During surgery, ATP from damaged cells induces the release of interleukin-1β, a potent pro-inflammatory cytokine that contributes to the development of postoperative systemic inflammation, sepsis and multi-organ damage. We recently demonstrated that C-reactive protein (CRP) inhibits the ATP-induced release of monocytic interleukin-1β, although [...] Read more.

During surgery, ATP from damaged cells induces the release of interleukin-1β, a potent pro-inflammatory cytokine that contributes to the development of postoperative systemic inflammation, sepsis and multi-organ damage. We recently demonstrated that C-reactive protein (CRP) inhibits the ATP-induced release of monocytic interleukin-1β, although high CRP levels are deemed to be a poor prognostic marker. Here, we retrospectively investigated if preoperative CRP levels correlate with postoperative CRP, leukocyte counts and fever in the context of anatomical lung resection and systematic lymph node dissection as first line lung cancer therapy. No correlation was found in the overall results. In men, however, preoperative CRP and leukocyte counts positively correlated on postoperative days one to two, and a negative correlation of CRP and fever was seen in women. These correlations were more pronounced in men taking statins and in statin-naïve women. Accordingly, the inhibitory effect of CRP on the ATP-induced interleukin-1β release was blunted in monocytes from coronary heart disease patients treated with atorvastatin compared to monocytes obtained before medication. Hence, the common notion that elevated CRP levels predict more severe postoperative inflammation should be questioned. We rather hypothesize that in women and statin-naïve patients, high CRP levels attenuate trauma-induced increases in inflammatory markers. Full article

(This article belongs to the Special Issue Sepsis: Current Clinical Practices and New Perspectives)

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13 pages, 2060 KiB

Open AccessArticle

Proteomic Profiles of Exosomes of Septic Patients Presenting to the Emergency Department Compared to Healthy Controls

by Daniel C. Morris, Anja K. Jaehne, Michael Chopp, Zhanggang Zhang, Laila Poisson, Yalei Chen, Indrani Datta and Emanuel P. Rivers

J. Clin. Med. 2020, 9(9), 2930; https://doi.org/10.3390/jcm9092930 - 11 Sep 2020

Cited by 12 | Viewed by 3049

Abstract

Background: Septic Emergency Department (ED) patients provide a unique opportunity to investigate early sepsis. Recent work focuses on exosomes, nanoparticle-sized lipid vesicles (30–130 nm) that are released into the bloodstream to transfer its contents (RNA, miRNA, DNA, protein) to other cells. Little is [...] Read more.

Background: Septic Emergency Department (ED) patients provide a unique opportunity to investigate early sepsis. Recent work focuses on exosomes, nanoparticle-sized lipid vesicles (30–130 nm) that are released into the bloodstream to transfer its contents (RNA, miRNA, DNA, protein) to other cells. Little is known about how early changes related to exosomes may contribute to the dysregulated inflammatory septic response that leads to multi-organ dysfunction. We aimed to evaluate proteomic profiles of plasma derived exosomes obtained from septic ED patients and healthy controls. Methods: This is a prospective observational pilot study evaluating a plasma proteomic exosome profile at an urban tertiary care hospital ED using a single venipuncture blood draw, collecting 40 cc Ethylenediaminetetraacetic acid (EDTA) blood. Measurements: We recruited seven patients in the ED within 6 h of their presentation and five healthy controls. Plasma exosomes were isolated using the Invitrogen Total Exosome Isolation Kit. Exosome proteomic profiles were analyzed using fusion mass spectroscopy and Proteome Discoverer. Principal component analysis (PCA) and differential expression analysis (DEA) for sepsis versus control was performed. Results: PCA of 261 proteins demonstrated septic patients and healthy controls were distributed in two groups. DEA revealed that 62 (23.8%) proteins differed between the exosomes of septic patients and healthy controls, p-value < 0.05. Adjustments using the False Discovery Rate (FDR) showed 23 proteins remained significantly different (FDR < 0.05) between sepsis and controls. Septic patients and controls were classified into two distinct groups by hierarchical clustering using the 62 nominally DE proteins. After adjustment multiple comparisons, three acute phase proteins remained significantly different between patients and controls: Serum amyloid A-1, C-reactive protein and Serum Amyloid A-2. Inflammatory response proteins immunoglobulin heavy constant Δ and Fc-fragment of IgG binding protein were increased. Conclusion: Exosome proteomic profiles of septic ED patients differ from their healthy counterparts with regard to acute phase response and inflammation. Full article

(This article belongs to the Special Issue Sepsis: Current Clinical Practices and New Perspectives)

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18 pages, 2075 KiB

Open AccessArticle

Amyloid Beta Peptide (Aβ_1-42) Reverses the Cholinergic Control of Monocytic IL-1β Release

by Katrin Richter, Raymond Ogiemwonyi-Schaefer, Sigrid Wilker, Anna I. Chaveiro, Alisa Agné, Matthias Hecker, Martin Reichert, Anca-Laura Amati, Klaus-Dieter Schlüter, Ivan Manzini, Günther Schmalzing, J. Michael McIntosh, Winfried Padberg, Veronika Grau and Andreas Hecker

J. Clin. Med. 2020, 9(9), 2887; https://doi.org/10.3390/jcm9092887 - 7 Sep 2020

Cited by 9 | Viewed by 3673

Abstract

Amyloid-β peptide (Aβ_1-42), the cleavage product of the evolutionary highly conserved amyloid precursor protein, presumably plays a pathogenic role in Alzheimer’s disease. Aβ_1-42 can induce the secretion of the pro-inflammatory cytokine intereukin-1β (IL-1β) in immune cells within and out of [...] Read more.

Amyloid-β peptide (Aβ_1-42), the cleavage product of the evolutionary highly conserved amyloid precursor protein, presumably plays a pathogenic role in Alzheimer’s disease. Aβ_1-42 can induce the secretion of the pro-inflammatory cytokine intereukin-1β (IL-1β) in immune cells within and out of the nervous system. Known interaction partners of Aβ_1-42 are α7 nicotinic acetylcholine receptors (nAChRs). The physiological functions of Aβ_1-42 are, however, not fully understood. Recently, we identified a cholinergic mechanism that controls monocytic release of IL-1β by canonical and non-canonical agonists of nAChRs containing subunits α7, α9, and/or α10. Here, we tested the hypothesis that Aβ_1-42 modulates this inhibitory cholinergic mechanism. Lipopolysaccharide-primed monocytic U937 cells and human mononuclear leukocytes were stimulated with the P2X7 receptor agonist 2′(3′)-O-(4-benzoylbenzoyl)adenosine-5′-triphosphate triethylammonium salt (BzATP) in the presence or absence of nAChR agonists and Aβ_1-42. IL-1β concentrations were measured in the supernatant. Aβ_1-42 dose-dependently (IC₅₀ = 2.54 µM) reversed the inhibitory effect of canonical and non-canonical nicotinic agonists on BzATP-mediated IL-1β-release by monocytic cells, whereas reverse Aβ_42-1 was ineffective. In conclusion, we discovered a novel pro-inflammatory Aβ_1-42 function that enables monocytic IL-1β release in the presence of nAChR agonists. These findings provide evidence for a novel physiological function of Aβ_1-42 in the context of sterile systemic inflammation. Full article

(This article belongs to the Special Issue Sepsis: Current Clinical Practices and New Perspectives)

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14 pages, 2372 KiB

Open AccessArticle

Decreased Thymic Output Contributes to Immune Defects in Septic Patients

by Natascha Sommer, Steffen Noack, Andreas Hecker, Holger Hackstein, Gregor Bein, Norbert Weissmann, Werner Seeger, Konstantin Mayer and Matthias Hecker

J. Clin. Med. 2020, 9(9), 2695; https://doi.org/10.3390/jcm9092695 - 20 Aug 2020

Cited by 8 | Viewed by 2460 | Correction

Abstract

Background: Prolonged immunosuppression and hypoinflammation, termed compensatory anti-inflammatory response syndrome (CARS), contribute to high morbidity and mortality in the late phase of sepsis. Although apoptosis is a well-known cause of lymphopenia in sepsis, the contribution of thymic output to immune alterations in sepsis [...] Read more.

Background: Prolonged immunosuppression and hypoinflammation, termed compensatory anti-inflammatory response syndrome (CARS), contribute to high morbidity and mortality in the late phase of sepsis. Although apoptosis is a well-known cause of lymphopenia in sepsis, the contribution of thymic output to immune alterations in sepsis and potential compensatory mechanisms are largely unknown. Methods: We investigate the release of CD4+ T cells from the thymus and their peripheral proliferation by evaluating T-cell receptor excision circles (TREC) and the expression of CD31 as markers for recent thymic emigrants (RTE) and their proliferative offspring in septic patients with relevant lymphopenia in the CARS phase. Moreover, we determine the aging of T cells by measuring telomere characteristics. Results: In septic patients, we found decreased CD4+ T-helper cell numbers, while CD8+ T cell numbers were unchanged. As a possible cause, we detected increased apoptosis of CD4+ T-helper cells and decreased levels of IL-7, which promotes the maturation of T cells in the thymus. Accordingly, the relative number of mature CD4+ T cells, TREC-containing CD4+ T cells, and CD31+ RTEs (characteristic of thymic output) was decreased, while the relative number of CD31-T cells (peripherally expanded naïve T cells) was increased. Furthermore, the telomere length decreased, although telomerase activity and markers for the shelterin complex were increased specifically in CD4+ but not in CD8+ T cells. Conclusion: We thus conclude that, in addition to T-cell apoptosis, decreased thymic output and increased aging of CD4+ T cells may contribute to lymphopenia and immunosuppression in sepsis. Increased proliferation of peripheral T cells cannot compensate for these effects. Full article

(This article belongs to the Special Issue Sepsis: Current Clinical Practices and New Perspectives)

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14 pages, 1144 KiB

Open AccessArticle

Blood Levels of Free-Circulating Mitochondrial DNA in Septic Shock and Postsurgical Systemic Inflammation and Its Influence on Coagulation: A Secondary Analysis of a Prospective Observational Study

by Emmanuel Schneck, Fabian Edinger, Matthias Hecker, Natascha Sommer, Oleg Pak, Norbert Weissmann, Andreas Hecker, Martin Reichert, Melanie Markmann, Michael Sander and Christian Koch

J. Clin. Med. 2020, 9(7), 2056; https://doi.org/10.3390/jcm9072056 - 30 Jun 2020

Cited by 20 | Viewed by 2519

Abstract

Major surgery is regularly associated with clinical signs of systemic inflammation, which potentially affects the rapid identification of sepsis. Therefore, this secondary analysis of an observational study aims to determine whether NADH dehydrogenase 1 (ND1) mitochondrial DNA (mtDNA) could be used as a [...] Read more.

Major surgery is regularly associated with clinical signs of systemic inflammation, which potentially affects the rapid identification of sepsis. Therefore, this secondary analysis of an observational study aims to determine whether NADH dehydrogenase 1 (ND1) mitochondrial DNA (mtDNA) could be used as a potential biomarker for the discrimination between septic shock and postsurgical systemic inflammation. Overall, 80 patients were included (septic shock (n = 20), cardiac artery bypass grafting (CABG, n = 20), major abdominal surgery (MAS, n = 20), and matched controls (CTRL, n = 20)). Quantitative PCR was performed to measure ND1 mtDNA. Thromboelastography was used to analyze the coagulatory system. Free-circulating ND1 mtDNA levels were significantly higher in septic shock patients compared to patients suffering from post-surgical inflammation ({copies/µL}: CTRL: 1208 (668–2685); septic shock: 3823 (2170–7318); CABG: 1272 (417–2720); and MAS: 1356 (694–2845); CTRL vs. septic shock: p < 0.001; septic shock vs. CABG: p < 0.001; septic shock vs. MAS: p = 0.006; CABG vs. MAS: p = 0.01). ND1 mtDNA levels in CABG patients showed a strong positive correlation with fibrinogen (correlation coefficient [r]= 0.57, p < 0.001) and fibrinogen-dependent thromboelastographic assays (maximum clot firmness, EXTEM: r = 0.35, p = 0.01; INTEM: r = 0.31, p = 0.02; FIBTEM: r = 0.46, p < 0.001). In conclusion, plasma levels of free-circulating ND1 mtDNA were increased in septic shock patients and were discriminative between sepsis and surgery-induced inflammation. Furthermore, this study showed an association between ND1 mtDNA and a fibrinogen-dependent pro-coagulatory shift in cardiac surgical patients. Full article

(This article belongs to the Special Issue Sepsis: Current Clinical Practices and New Perspectives)

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15 pages, 3577 KiB

Open AccessArticle

Immunomodulation by an Omega-6 Fatty Acid Reduced Mixed Lipid Emulsion in Murine Acute Respiratory Distress Syndrome

by Matthias Hecker, Matthias Rose, Andreas Hecker, Hartmut Dietrich, Martina B. Schaefer, Natascha Sommer, Werner Seeger and Konstantin Mayer

J. Clin. Med. 2020, 9(7), 2048; https://doi.org/10.3390/jcm9072048 - 29 Jun 2020

Cited by 5 | Viewed by 2762

Abstract

Background: Acute respiratory distress syndrome (ARDS) is associated with both high morbidity and mortality in intensive care units worldwide. Patients with ARDS often require parenteral nutrition with lipid emulsions as essential components. In the present study, we assessed the immunomodulatory and apoptotic effects [...] Read more.

Background: Acute respiratory distress syndrome (ARDS) is associated with both high morbidity and mortality in intensive care units worldwide. Patients with ARDS often require parenteral nutrition with lipid emulsions as essential components. In the present study, we assessed the immunomodulatory and apoptotic effects of a modern, n-6-reduced lipid emulsion mixture in murine ARDS. Methods: Mice received an infusion of either normal saline solution, pure long-chain triglyceride (LCT) emulsion, or SMOF (soybean oil, medium-chain triglycerides, olive oil, and fish oil) before a lipopolysaccharide (LPS) challenge. Mice were sacrificed at different time points (0, 24, or 72 h) after ARDS induction, and an analysis of inflammatory cytokines, protein concentrations, and the cellular composition of the alveolar and interstitial compartments was performed with special focus on alveolar apoptosis and necrosis. Results: Mice infused with SMOF showed decreased leukocyte invasion, protein leakage, myeloperoxidase activity, and cytokine production in alveolar spaces after LPS challenge compared to animals that received LCT. There were fewer cells in the lung interstitium of the SMOF group compared to the LCT group. Both lipid emulsions exerted pro-apoptotic and pro-necrotic properties on alveolar immune cells, with significantly increased necrosis in mice infused with LCT compared to SMOF. Conclusion: SMOF has both anti-inflammatory and pro-resolving influences in murine ARDS. Partial replacement of n-6 fatty acids with n-3/n-9 fatty acids may therefore benefit critically ill patients at risk for ARDS who require parenteral nutrition. Full article

(This article belongs to the Special Issue Sepsis: Current Clinical Practices and New Perspectives)

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17 pages, 620 KiB

Open AccessArticle

Early Respiratory Impairment and Pneumonia after Hybrid Laparoscopically Assisted Esophagectomy—A Comparison with the Open Approach

by Martin Reichert, Maike Lang, Matthias Hecker, Emmanuel Schneck, Michael Sander, Florian Uhle, Markus A. Weigand, Ingolf Askevold, Winfried Padberg, Veronika Grau and Andreas Hecker

J. Clin. Med. 2020, 9(6), 1896; https://doi.org/10.3390/jcm9061896 - 17 Jun 2020

Cited by 9 | Viewed by 2555

Abstract

Patients undergoing esophageal cancer surgery are at high risk of developing severe pulmonary complications. Beneficial effects of minimally invasive esophagectomy had been discussed recently, but the incidence of perioperative respiratory impairment remains unclear. This is a retrospective single-center cohort study of patients, who [...] Read more.

Patients undergoing esophageal cancer surgery are at high risk of developing severe pulmonary complications. Beneficial effects of minimally invasive esophagectomy had been discussed recently, but the incidence of perioperative respiratory impairment remains unclear. This is a retrospective single-center cohort study of patients, who underwent open (OE) or laparoscopically assisted, hybrid minimally invasive abdomino-thoracic esophagectomy (LAE) for cancer regarding respiratory impairment (PaO₂/FiO₂ ratio (P/FR) < 300 mmHg) and pneumonia. No differences were observed in the cumulative incidence of reduced P/FR between OE and LAE patients. Of note, until postoperative day (POD) 2, P/FR did not differ among both groups. Thereafter, the rate of patients with respiratory impairment was higher after OE on POD 3, 5, and 10 (p ≤ 0.05) and tended being higher on POD 7 and 9 (p ≤ 0.1). Although the duration of LAE procedure was slightly longer (total: p = 0.07, thoracic part: p = 0.004), the duration of surgery (Spearman’s rank correlation coefficient (r_sp) = −0.267, p = 0.006), especially of laparotomy (r_sp = −0.242, p = 0.01) correlated inversely with respiratory impairment on POD 3 after OE. Pneumonia occurred on POD 5 (1–25) and 8.5 (3–14) after OE and LAE, respectively, with the highest incidence after OE (p = 0.01). In conclusion, respiratory impairment and pulmonary complications occur frequently after esophagectomy. Although early respiratory impairment is independent of the surgical approach, postoperative pneumonia rate is reduced after LAE. Full article

(This article belongs to the Special Issue Sepsis: Current Clinical Practices and New Perspectives)

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8 pages, 322 KiB

Open AccessArticle

Urinary Tract Infection in Febrile Children with Sickle Cell Disease Who Present to the Emergency Room with Fever

by Nehal Patel, Ahmad Farooqi, Michael Callaghan and Usha Sethuraman

J. Clin. Med. 2020, 9(5), 1531; https://doi.org/10.3390/jcm9051531 - 19 May 2020

Cited by 4 | Viewed by 3188

Abstract

Sickle cell disease (SCD) patients are thought to be at higher risk for urinary tract infections (UTIs) compared to the general population secondary to increased sickling, abnormal urinary acidification, and an inability to concentrate the urine. The incidence of UTI in febrile children [...] Read more.

Sickle cell disease (SCD) patients are thought to be at higher risk for urinary tract infections (UTIs) compared to the general population secondary to increased sickling, abnormal urinary acidification, and an inability to concentrate the urine. The incidence of UTI in febrile children with SCD in the United States is unknown. Our objectives were to determine the rate of UTI among febrile SCD children and describe the risk factors for UTI in this population. We conducted a retrospective chart review of all febrile SCD patients <4 years of age who presented to a pediatric emergency department from 2012–2017 and who had a sterile sample of urine for analysis. A total of 167 febrile patients with SCD with 464 visits were identified. The majority were African American (95.2%), female (58.7%), and had hemoglobin SS (HbSS) (65.3%). The rate of UTI was 4.1%. All patients with a UTI were African American females with a median age of 19 months (IQR 12–30). On regression analysis, no risk factors were associated with a UTI. We found the rate of UTI in febrile young children with SCD was comparable to non-SCD children. Larger studies are required to identify the presence of risk factors for UTI in this population. Full article

(This article belongs to the Special Issue Sepsis: Current Clinical Practices and New Perspectives)

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13 pages, 589 KiB

Open AccessArticle

Impact of Early C-Reactive Protein/Albumin Ratio on Intra-Hospital Mortality Among Patients with Spontaneous Intracerebral Hemorrhage

by Michael Bender, Kristin Haferkorn, Michaela Friedrich, Eberhard Uhl and Marco Stein

J. Clin. Med. 2020, 9(4), 1236; https://doi.org/10.3390/jcm9041236 - 24 Apr 2020

Cited by 24 | Viewed by 3308

Abstract

Objective: The impact of increased C-reactive protein (CRP)/albumin ratio on intra-hospital mortality has been investigated among patients admitted to general intensive care units (ICU). However, it was not investigated among patients with spontaneous intracerebral hemorrhage (ICH). This study aimed to investigate the impact [...] Read more.

Objective: The impact of increased C-reactive protein (CRP)/albumin ratio on intra-hospital mortality has been investigated among patients admitted to general intensive care units (ICU). However, it was not investigated among patients with spontaneous intracerebral hemorrhage (ICH). This study aimed to investigate the impact of CRP/albumin ratio on intra-hospital mortality in patients with ICH. Patients and Methods: This retrospective study was conducted on 379 ICH patients admitted between 02/2008 and 12/2017. Blood samples were drawn upon admission and the patients’ demographic, medical, and radiological data were collected. The identification of the independent prognostic factors for intra-hospital mortality was calculated using binary logistic regression and COX regression analysis. Results: Multivariate regression analysis shows that higher CRP/albumin ratio (odds ratio (OR) = 1.66, 95% confidence interval (CI) = 1.193–2.317, p = 0.003) upon admission is an independent predictor of intra-hospital mortality. Multivariate Cox regression analysis indicated that an increase of 1 in the CRP/albumin ratio was associated with a 15.3% increase in the risk of intra-hospital mortality (hazard ratio = 1.153, 95% CI = 1.005–1.322, p = 0.42). Furthermore, a CRP/albumin ratio cut-off value greater than 1.22 was associated with increased intra-hospital mortality (Youden’s Index = 0.19, sensitivity = 28.8, specificity = 89.9, p = 0.007). Conclusions: A CRP/albumin ratio greater than 1.22 upon admission was significantly associated with intra-hospital mortality in the ICH patients. Full article

(This article belongs to the Special Issue Sepsis: Current Clinical Practices and New Perspectives)

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10 pages, 352 KiB

Open AccessArticle

Impact of Vitamin C and Thiamine Administration on Delirium-Free Days in Patients with Septic Shock

by Jong Eun Park, Tae Gun Shin, Ik Joon Jo, Kyeongman Jeon, Gee Young Suh, Minsu Park, Hojeong Won, Chi Ryang Chung and Sung Yeon Hwang

J. Clin. Med. 2020, 9(1), 193; https://doi.org/10.3390/jcm9010193 - 10 Jan 2020

Cited by 13 | Viewed by 4893

Abstract

Sepsis is a common cause of delirium in the intensive care unit (ICU). Recently, vitamin C and thiamine administration has been gaining interest as a potential adjunct therapy for sepsis. We investigated the impact of early vitamin C and thiamine administration on ICU [...] Read more.

Sepsis is a common cause of delirium in the intensive care unit (ICU). Recently, vitamin C and thiamine administration has been gaining interest as a potential adjunct therapy for sepsis. We investigated the impact of early vitamin C and thiamine administration on ICU delirium-free days among critically ill patients in septic shock. We performed a single-center, retrospective study of patients who visited the emergency department (ED) from January 2017 to July 2018. We categorized patients into a treatment (received vitamin C and thiamine) and control group. We compared delirium-free days within 14 days after ICU admission using propensity score matching. Of 435 patients with septic shock, we assigned 89 propensity score-matched pairs to the treatment and control groups. The median delirium-free days did not differ between treatment (11, interquartile range [IQR] 5–14 days) and control (12, IQR 6–14 days) groups (p = 0.894). Secondary outcomes were not different between the two groups, including delirium incidence and 28-day mortality. These findings were consistent after subgroup analysis for patients who met the sepsis-3 definition of septic shock. Vitamin C and thiamine administration showed no association with ICU delirium-free days among patients in septic shock. Full article

(This article belongs to the Special Issue Sepsis: Current Clinical Practices and New Perspectives)

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19 pages, 2527 KiB

Open AccessArticle

Flow Cytometry-Based Quantification of Neutrophil Extracellular Traps Shows an Association with Hypercoagulation in Septic Shock and Hypocoagulation in Postsurgical Systemic Inflammation—A Proof-of-Concept Study

by Emmanuel Schneck, Franziska Mallek, Julia Schiederich, Emil Kramer, Melanie Markmann, Matthias Hecker, Natascha Sommer, Norbert Weissmann, Oleg Pak, Gabriela Michel, Andreas Hecker, Winfried Padberg, Andreas Boening, Michael Sander and Christian Koch

J. Clin. Med. 2020, 9(1), 174; https://doi.org/10.3390/jcm9010174 - 8 Jan 2020

Cited by 16 | Viewed by 6508

Abstract

This proof-of-concept study aimed to evaluate a novel method of flow cytometry-based quantification of neutrophil extracellular traps (NETs) in septic shock patients and to identify possible interactions between the number of free-circulating NETs and alterations of the coagulatory system. Patients suffering from septic [...] Read more.

This proof-of-concept study aimed to evaluate a novel method of flow cytometry-based quantification of neutrophil extracellular traps (NETs) in septic shock patients and to identify possible interactions between the number of free-circulating NETs and alterations of the coagulatory system. Patients suffering from septic shock, a matched control group (CTRL), and patients suffering from systemic inflammation after cardiac (CABG) or major abdominal surgery (MAS) were enrolled in this prospective proof-of-concept study. Compared to the matched controls, free-circulating NETs were significantly elevated in septic shock and postsurgical patients (data are presented in median (IQR)); septic shock: (2.7 (1.9–3.9); CABG: 2.7 (2.1–3.7); MAS: 2.7 (2.1–3.9); CTRL: 1.6 (1–2); CTRL vs. septic shock: p = 0.001; CTRL vs. CABG: p < 0.001; CTRL vs. MAS: p < 0.001). NETs correlated positively with FIBTEM mean clot firmness (MCF) in septic shock patients (r = 0.37, p < 0.01) while they correlated negatively in surgical patients (CABG: r = −0.28, p < 0.01; MAS: r = −0.25, p = 0.03). Flow-cytometric quantification of NETs showed a significant increase in free-circulating NETs under inflammatory conditions. Furthermore, this study hints to an association of the number of NETs with hypercoagulation in septic shock patients and hypocoagulation in surgery-induced inflammation. Full article

(This article belongs to the Special Issue Sepsis: Current Clinical Practices and New Perspectives)

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13 pages, 388 KiB

Open AccessArticle

Epidemiology and Trends of Sepsis in Young Adults Aged 20–44 Years: A Nationwide Population-Based Study

by Carmen Bouza and Teresa López-Cuadrado

J. Clin. Med. 2020, 9(1), 77; https://doi.org/10.3390/jcm9010077 - 27 Dec 2019

Cited by 8 | Viewed by 3953

Abstract

Background: While sepsis may have especially marked impacts in young adults, there is limited population-based information on its epidemiology and trends. Methods: Population-based longitudinal study on sepsis in adults aged 20–44 years using the 2006–2015 Spanish national hospital discharge database. Cases are identified [...] Read more.

Background: While sepsis may have especially marked impacts in young adults, there is limited population-based information on its epidemiology and trends. Methods: Population-based longitudinal study on sepsis in adults aged 20–44 years using the 2006–2015 Spanish national hospital discharge database. Cases are identified by an ICD-9-CM coding strategy. Primary endpoints are incidence and in-hospital mortality. Trends are assessed for annual percentage change (AAPC) in rates using Joinpoint regression models. Results: 28,351 cases are identified, representing 3.06‰ of all-cause hospitalisations and a crude incidence of 16.4 cases/100,000 population aged 20–44. The mean age is 36 years, 58% of cases are men, and around 60% have associated comorbidities. Seen in one third of cases, the source of infection is respiratory. Single organ dysfunction is recorded in 45% of cases. In-hospital mortality is 24% and associated with age, comorbidity and extent of organ dysfunction. Incidence rates increase over time in women (AAPC: 3.8% (95% CI: 2.1, 5.5)), whereas case-fatality decline with an overall AAPC of −5.9% (95% CI −6.6, −5.2). Our results indicate that sepsis is common in young adults and associated with high in-hospital mortality, though it shows a decreasing trend. The substantial increase in incidence rates in women needs further research. Full article

(This article belongs to the Special Issue Sepsis: Current Clinical Practices and New Perspectives)

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11 pages, 574 KiB

Open AccessArticle

Favorable 90-Day Mortality in Obese Caucasian Patients with Septic Shock According to the Sepsis-3 Definition

by Caspar Mewes, Carolin Böhnke, Tessa Alexander, Benedikt Büttner, José Hinz, Aron-Frederik Popov, Michael Ghadimi, Tim Beißbarth, Dirk Raddatz, Konrad Meissner, Michael Quintel, Ingo Bergmann and Ashham Mansur

J. Clin. Med. 2020, 9(1), 46; https://doi.org/10.3390/jcm9010046 - 24 Dec 2019

Cited by 13 | Viewed by 2936

Abstract

Septic shock is a frequent life-threatening condition and a leading cause of mortality in intensive care units (ICUs). Previous investigations have reported a potentially protective effect of obesity in septic shock patients. However, prior results have been inconsistent, focused on short-term in-hospital mortality [...] Read more.

Septic shock is a frequent life-threatening condition and a leading cause of mortality in intensive care units (ICUs). Previous investigations have reported a potentially protective effect of obesity in septic shock patients. However, prior results have been inconsistent, focused on short-term in-hospital mortality and inadequately adjusted for confounders, and they have rarely applied the currently valid Sepsis-3 definition criteria for septic shock. This investigation examined the effect of obesity on 90-day mortality in patients with septic shock selected from a prospectively enrolled cohort of septic patients. A total of 352 patients who met the Sepsis-3 criteria for septic shock were enrolled in this study. Body-mass index (BMI) was used to divide the cohort into 24% obese (BMI ≥ 30 kg/m²) and 76% non-obese (BMI < 30 kg/m²) patients. Kaplan-Meier survival analysis revealed a significantly lower 90-day mortality (31% vs. 43%; p = 0.0436) in obese patients compared to non-obese patients. Additional analyses of baseline characteristics, disease severity, and microbiological findings outlined further statistically significant differences among the groups. Multivariate Cox regression analysis estimated a significant protective effect of obesity on 90-day mortality after adjustment for confounders. An understanding of the underlying physiologic mechanisms may improve therapeutic strategies and patient prognosis. Full article

(This article belongs to the Special Issue Sepsis: Current Clinical Practices and New Perspectives)

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Review

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14 pages, 1046 KiB

Open AccessReview

Sepsis-Associated Encephalopathy: From Delirium to Dementia?

by Ha-Yeun Chung, Jonathan Wickel, Frank M. Brunkhorst and Christian Geis

J. Clin. Med. 2020, 9(3), 703; https://doi.org/10.3390/jcm9030703 - 5 Mar 2020

Cited by 145 | Viewed by 16407

Abstract

Sepsis is a major cause of death in intensive care units worldwide. The acute phase of sepsis is often accompanied by sepsis-associated encephalopathy, which is highly associated with increased mortality. Moreover, in the chronic phase, more than 50% of surviving patients suffer from [...] Read more.

Sepsis is a major cause of death in intensive care units worldwide. The acute phase of sepsis is often accompanied by sepsis-associated encephalopathy, which is highly associated with increased mortality. Moreover, in the chronic phase, more than 50% of surviving patients suffer from severe and long-term cognitive deficits compromising their daily quality of life and placing an immense burden on primary caregivers. Due to a growing number of sepsis survivors, these long-lasting deficits are increasingly relevant. Despite the high incidence and clinical relevance, the pathomechanisms of acute and chronic stages in sepsis-associated encephalopathy are only incompletely understood, and no specific therapeutic options are yet available. Here, we review the emergence of sepsis-associated encephalopathy from initial clinical presentation to long-term cognitive impairment in sepsis survivors and summarize pathomechanisms potentially contributing to the development of sepsis-associated encephalopathy. Full article

(This article belongs to the Special Issue Sepsis: Current Clinical Practices and New Perspectives)

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