scholarly journals Increase in the Complement Activation Product C4d and the Terminal Complement Complex sC5b-9 Is Associated with Disease Severity and a Fatal Outcome in Necrotizing Soft-Tissue Infection

2021 ◽  
pp. 1-11
Author(s):  
Morten Hedetoft ◽  
Martin Bruun Madsen ◽  
Cecilie Bo Hansen ◽  
Ole Hyldegaard ◽  
Peter Garred
Keyword(s):  
Soft Tissue ◽  
Disease Severity ◽  
Soft Tissue Infection ◽  
Complement Activation ◽  
Sofa Score ◽  
Tissue Infection ◽  
Necrotizing Soft Tissue Infection ◽  
High Baseline ◽  
Terminal Complement Complex ◽  
Terminal Complement

The hyperinflammatory burden is immense in necrotizing soft-tissue infection (NSTI). The complement system is a key during the innate immune response and may be a promising target to reduce the inflammatory response, potentially improving the clinical outcome. However, complement activation and its association to disease severity and survival remain unknown in NSTI. Therefore, we prospectively enrolled patients with NSTI and sampled blood at admission and once daily for the following 3 days. Plasma C4c, C4d, C3bc, and C3dg and the terminal complement complex (TCC) were evaluated using ELISA techniques. In total, 242 patients were included with a median age of 62 years, with a 60% male predominance. All-cause 30-day mortality was 17% (95% confidence interval [CI] 13–23) with a follow-up of &#x3e;98%. C4c and C3dg were negatively correlated with Simplified Acute Physiology Score II (<i>Rho</i> −0.22, <i>p</i> &#x3c; 0.001 and <i>Rho</i> −0.17, <i>p</i> = 0.01). Patients with septic shock (<i>n</i> = 114, 47%) had higher levels of baseline TCC than those in non-shock patients (18 vs. 14, <i>p</i> &#x3c; 0.001). TCC correlated with the Sequential Organ Failure Assessment (SOFA) score (<i>Rho</i> 0.19, <i>p</i> = 0.004). In multivariate Cox regression analysis (adjusted for age, sex, comorbidity, and SOFA score), high baseline C4d (&#x3e;20 ng/mL) and the combination of high C4d and TCC (&#x3e;31 arbitrary units/mL) were associated with increased 30-day mortality (hazard ratio [HR] 3.26, 95% CI 1.56–6.81 and HR 5.12, 95% CI 2.15–12.23, respectively). High levels of both C4d and TCC demonstrated a negative predictive value of 0.87. In conclusion, we found that in patients with NSTI, complement activation correlated with the severity of the disease. High baseline C4d and combination of high C4d and TCC are associated with increased 30-day mortality. Low baseline C4d or TCC indicates a higher probability of survival.

scholarly journals Associations between YKL-40 and markers of disease severity and death in patients with necrotizing soft-tissue infection

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Morten Hedetoft ◽  
Marco Bo Hansen ◽  
Martin Bruun Madsen ◽  
Julia Sidenius Johansen ◽  
Ole Hyldegaard
Keyword(s):  
Renal Replacement Therapy ◽  
Soft Tissue ◽  
Replacement Therapy ◽  
Disease Severity ◽  
Soft Tissue Infection ◽  
Simplified Acute Physiology Score ◽  
Tissue Infection ◽  
Acute Physiology Score ◽  
Necrotizing Soft Tissue Infection ◽  
Risk Of Death

Abstract Background Necrotizing soft-tissue infection (NSTI) is a severe and fast-progressing bacterial infection. Prognostic biomarkers may provide valuable information in treatment guidance and decision-making, but none have provided sufficient robustness to have a clinical impact. YKL-40 may reflect the ongoing pathological inflammatory processes more accurately than traditional biomarkers as it is secreted by the activated immune cells, but its prognostic yields in NSTI remains unknown. For this purpose, we investigated the association between plasma YKL-40 and 30-day mortality in patients with NSTI, and assessed its value as a marker of disease severity. Methods We determined plasma YKL-40 levels in patients with NSTI (n = 161) and age-sex matched controls (n = 65) upon admission and at day 1, 2 and 3. Results Baseline plasma YKL-40 was 1191 ng/mL in patients with NSTI compared with 40 ng/mL in controls (p < 0.001). YKL-40 was found to be significantly higher in patients with septic shock (1942 vs. 720 ng/mL, p < 0.001), and in patients receiving renal-replacement therapy (2382 vs. 1041 ng/mL, p < 0.001). YKL-40 correlated with Simplified Acute Physiology Score II (Rho 0.33, p < 0.001). Baseline YKL-40 above 1840 ng/mL was associated with increased risk of 30-day mortality in age-sex-comorbidity adjusted analysis (OR 3.77, 95% CI; 1.59–9.24, p = 0.003), but after further adjustment for Simplified Acute Physiology Score II no association was found between YKL-40 and early mortality. Conclusion High plasma YKL-40 to be associated with disease severity, renal-replacement therapy and risk of death in patients with NSTI. However, YKL-40 is not an independent predictor of 30-day mortality.

Soluble ICAM-1 is Modulated by Hyperbaric Oxygen Treatment and Correlates with Disease Severity and Mortality in Patients with Necrotizing Soft-tissue Infection

2021 ◽  
Author(s):  
Morten Hedetoft ◽  
Claus Moser ◽  
Peter Østrup Jensen ◽  
Julie Vinkel ◽  
Ole Hyldegaard
Keyword(s):  
Soft Tissue ◽  
Inflammatory Response ◽  
Adhesion Molecules ◽  
Disease Severity ◽  
Hyperbaric Oxygen ◽  
Soft Tissue Infection ◽  
Tissue Infection ◽  
Collateral Damage ◽  
Necrotizing Soft Tissue Infection ◽  
Saps Ii

The inflammatory response in patients with necrotizing soft-tissue infection (NSTI) is excessive and often causes collateral damage, thereby worsening disease severity and prognosis. Shedding of endothelial adhesion molecules may be a key regulatory mechanism to modulate the inflammatory response in septic NSTI patients. Hyperbaric oxygen (HBO2) treatment has demonstrated an effect on adhesion molecules. However, endothelial shedding and its association with NSTI disease severity and prognosis is not fully understood. We hypothesized that shedding of intercellular adhesion molecule-1, and the resulting release of the soluble isoform sICAM-1, is modified by HBO2 treatment, and secondly, that sICAM-1 concentrations are associated with severity of disease and mortality in patients with NSTI. We measured sICAM-1 in 80 patients with NSTI immediately before and after first session of HBO2 treatment as well as on the following day. We found an overall sICAM-1 level of 594 ng/mL (IQR 406-817). HBO2 significantly (p=0.01) increased sICAM-1 by a median of 45.1 ng/mL, which remained elevated until the following day; this effect was more pronounced in patients with septic shock. Furthermore, sICAM-1 was significantly correlated with disease severity (SAPS II; rho 0.24, p=0.04) and low sICAM-1 was found to be an independent predictor for 90-day mortality in age-sex-SAPS II adjusted analysis (Odds Ratio 14.0, 95% CI 1.82-341.4, p=0.03). These results support the hypothesis that endothelial shedding is an important pathophysiological mechanism in NSTI, and suggest that HBO2 treatment may induce immunomodulatory effects that potentially decreases collateral damage and mortality.

Group G Streptococcal Necrotizing Soft Tissue Infection

2016 ◽  
Vol 78 (6) ◽  
pp. 644-649
Author(s):  
Eriko MAEHARA ◽  
Gaku TSUJI ◽  
Yukihiro MIZOTE ◽  
Naohide TAKEUCHI ◽  
Masutaka FURUE
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Infection ◽  
Tissue Infection ◽  
Necrotizing Soft Tissue Infection

Can Paronychia Cause a Remote Necrotizing Soft Tissue Infection?

2011 ◽  
Vol 40 (1) ◽  
pp. e11-e13 ◽  
Author(s):  
Julian E. Losanoff ◽  
Anne E. Missavage ◽  
Paul Linneman ◽  
Boyd E. Terry
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Infection ◽  
Tissue Infection ◽  
Necrotizing Soft Tissue Infection

scholarly journals Hyperbaric oxygen treatment impacts oxidative stress markers in patients with necrotizing soft-tissue infection

2021 ◽  
pp. jim-2021-001837
Author(s):  
Morten Hedetoft ◽  
Peter Østrup Jensen ◽  
Claus Moser ◽  
Julie Vinkel ◽  
Ole Hyldegaard
Keyword(s):  
Oxidative Stress ◽  
Septic Shock ◽  
Soft Tissue ◽  
Hyperbaric Oxygen ◽  
Soft Tissue Infection ◽  
Tissue Infection ◽  
Heme Oxygenase 1 ◽  
Necrotizing Soft Tissue Infection ◽  
Before And After ◽  
Nitrite Nitrate

Necrotizing soft-tissue infection (NSTI) is a rare, severe, and fast-progressing bacterial infection associated with a high risk of developing sepsis or septic shock. Increasing evidence indicates that oxidative stress is crucial in the development and progression of sepsis, but its role in NSTI specifically has not been investigated. Some patients with NSTI receive hyperbaric oxygen (HBO2) treatment as the restoration of oxidative stress balance is considered an important mechanism of action, which HBO2 facilitates. However, a gap in knowledge exists regarding the effect of HBO2 treatment on oxidative stress in patients with NSTI. In the present observational study, we aimed to investigate HBO2 treatment effects on known markers of oxidative stress in patients with NSTI. We measured plasma myeloperoxidase (MPO), superoxide dismutase (SOD), heme oxygenase-1 (HO-1) and nitrite+nitrate in 80 patients with NSTI immediately before and after their first HBO2 treatment, and on the following day. We found that HBO2 treatment was associated with a significant increase in MPO and SOD by a median of 3.4 and 8.8 ng/mL, respectively. Moreover, we observed an HBO2 treatment-associated increase in HO-1 in patients presenting with septic shock (n=39) by a median of 301.3 pg/mL. All markers were significantly higher in patients presenting with septic shock compared to patients without shock, and all markers correlated with disease severity. High baseline SOD was associated with 90-day mortality. In conclusion, HBO2 treatment was associated with an increase in MPO and SOD in patients with NSTI, and oxidative stress was more pronounced in patients with septic shock.

scholarly journals A case of Apophysomyces trapeziformis necrotizing soft tissue infection

2013 ◽  
Vol 17 (12) ◽  
pp. e1240-e1242 ◽  
Author(s):  
Jose F. Echaiz ◽  
Carey-Ann D. Burnham ◽  
Thomas C. Bailey
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Infection ◽  
Tissue Infection ◽  
Necrotizing Soft Tissue Infection
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