Hyperbaric oxygen treatment impacts oxidative stress markers in patients with necrotizing soft-tissue infection.
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ABSTRACT:
SUBMITTER: Hedetoft M
PROVIDER: S-EPMC8485130 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundThe pathophysiological understanding of the inflammatory response in necrotizing soft-tissue infection (NSTI) and its impact on clinical progression and outcomes are not resolved. Hyperbaric oxygen (HBO2 ) treatment serves as an adjunctive treatment; however, its immunomodulatory effects in the treatment of NSTI remains unknown. Accordingly, we evaluated fluctuations in inflammatory markers during courses of HBO2 treatment and assessed the overall inflammatory response during the first 3 days after admission.MethodsIn 242 patients with NSTI, we measured plasma TNF-α, IL-1β, IL-6, IL-10, and granulocyte colony-stimulating factor (G-CSF) upon admission and daily for three days, and before/after HBO2 in the 209 patients recieving HBO2 . We assessed the severity of disease by Simplified Acute Physiology Score (SAPS) II, SOFA score, and blood lactate.ResultsIn paired analyses, HBO2 treatment was associated with a decrease in IL-6 in patients with Group A-Streptococcus NSTI (first HBO2 treatment, median difference -29.5 pg/ml; second HBO2 treatment, median difference -7.6 pg/ml), and overall a decrease in G-CSF (first HBO2 treatment, median difference -22.5 pg/ml; 2- HBO2 treatment, median difference -20.4 pg/ml). Patients presenting with shock had significantly higher baseline cytokines values compared to non-shock patients (TNF-α: 51.9 vs. 23.6, IL-1β: 1.39 vs 0.61, IL-6: 542.9 vs. 57.5, IL-10: 21.7 vs. 3.3 and G-CSF: 246.3 vs. 11.8 pg/ml; all p < 0.001). Longitudinal analyses demonstrated higher concentrations in septic shock patients and those receiving renal-replacement therapy. All cytokines were significantly correlated to SAPS II, SOFA score, and blood lactate. In adjusted analysis, high baseline G-CSF was associated with 30-day mortality (OR 2.83, 95% CI: 1.01-8.00, p = 0.047).ConclusionIn patients with NSTI, HBO2 treatment may induce immunomodulatory effects by decreasing plasma G-CSF and IL-6. High levels of inflammatory markers were associated with disease severity, whereas high baseline G-CSF was associated with increased 30-day mortality.
| S-EPMC7957267 | biostudies-literature
Project description:BackgroundFor decades, the basic treatment strategies of necrotizing soft tissue infections (NSTI) have remained unchanged, primarily relying on aggressive surgical removal of infected tissue, broad-spectrum antibiotics, and supportive intensive care. One treatment strategy that has been proposed as an adjunctive measure to improve patient outcomes is hyperbaric oxygen (HBO2) treatment. HBO2 treatment has been linked to several immune modulatory effects; however, investigating these effects is complicated due to the disease's acute life-threatening nature, metabolic and cell homeostasis dependent variability in treatment effects, and heterogeneity with respect to both patient characteristics and involved pathogens. To embrace this complexity, we aimed to explore the underlying biological mechanisms of HBO2 treatment in patients with NSTI on the gene expression level.MethodsWe conducted an observational cohort study on prospective collected data, including 85 patients admitted to the intensive care unit (ICU) for NSTI. All patients were treated with one or two HBO2 treatments and had one blood sample taken before and after the intervention. Total RNAs from blood samples were extracted and mRNA purified with rRNA depletion, followed by whole-transcriptome RNA sequencing with a targeted sequencing depth of 20 million reads. A model for differentially expressed genes (DEGs) was fitted, and the functional aspects of the obtained set of genes was predicted with GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of genes and Genomes) enrichment analyses. All analyses were corrected for multiple testing with FDR.ResultsAfter sequential steps of quality control, a final of 160 biological replicates were included in the present study. We found 394 protein coding genes that were significantly DEGs between the two conditions with FDR < 0.01, of which 205 were upregulated and 189 were downregulated. The enrichment analysis of these DEGs revealed 20 GO terms in biological processes and 12 KEGG pathways that were significantly overrepresented in the upregulated DEGs, of which the term; "adaptive immune response" (GO:0002250) (FDR = 9.88E-13) and "T cell receptor signaling pathway" (hsa04660) (FDR = 1.20E-07) were the most significant. Among the downregulated DEGs two biological processes were significantly enriched, of which the GO term "apoptotic process" (GO:0006915) was the most significant (FDR = 0.001), followed by "Positive regulation of T helper 1 cell cytokine production" (GO:2000556), and "NF-kappa B signaling pathway" (hsa04064) was the only KEGG pathway that was significantly overrepresented (FDR = 0.001).ConclusionsWhen one or two sessions of HBO2 treatment were administered to patients with a dysregulated immune response and systemic inflammation due to NSTI, the important genes that were regulated during the intervention were involved in activation of T helper cells and downregulation of the disease-induced highly inflammatory pathway NF-κB, which was associated with a decrease in the mRNA level of pro-inflammatory factors.Trial registrationBiological material was collected during the INFECT study, registered at ClinicalTrials.gov (NCT01790698).
| S-EPMC10636866 | biostudies-literature
Project description:To determine the efficacy of hyperbaric oxygen therapy (HBO) in the treatment of necrotizing soft tissue infections (NSTI), we conducted a meta-analysis of the available evidence. Data sources were PubMed, Embase, Web of Science, Cochrane Library, and reference lists. The study included observational trials that compared HBO with non-HBO, or standard care. The primary outcome was the mortality rate. Secondary outcomes were the number of debridement, amputation rate and complication rate. Relative risks or standardized mean differences with 95% confidence intervals were calculated for dichotomous and continuous outcomes, respectively. A total of retrospective cohort and case-control studies were included, including 49,152 patients, 1448 who received HBO and 47,704 in control. The mortality rate in the HBO group was significantly lower than that in the non-HBO group [RR = 0.522, 95% CI (0.403, 0.677), p < 0.05]. However, the number of debridements performed in the HBO group was higher than in the non-HBO group [SMD = 0.611, 95% CI (0.012, 1.211), p < 0.05]. There was no significant difference in amputation rates between the two groups [RR = 0.836, 95% CI (0.619, 1.129), p > 0.05]. In terms of complications, the incidence of MODS was lower in the HBO group than in the non-HBO group [RR = 0.205, 95% CI (0.164, 0.256), p < 0.05]. There was no significant difference in the incidence of other complications, such as sepsis, shock, myocardial infarction, pulmonary embolism, and pneumonia, between the two groups (p > 0.05). The current evidence suggests that the use of HBO in the treatment of NSTI can significantly reduce the mortality rates and the incidence rates of complications. However, due to the retrospective nature of the studies, the evidence is weak, and further research is needed to establish its efficacy. It is also important to note that HBO is not available in all hospitals, and its use should be carefully considered based on the patient's individual circumstances. Additionally, it is still worthwhile to stress the significance of promptly evaluating surgical risks to prevent missing the optimal treatment time.
| S-EPMC10040118 | biostudies-literature
Project description:BackgroundNecrotizing soft tissue infections (NSTIs) are complex multifactorial diseases characterized by rapid bacterial proliferation and progressive tissue death. Treatment is multidisciplinary, including surgery, broad-spectrum antibiotics, and intensive care; adjunctive treatment with hyperbaric oxygen (HBO2) may also be applied. Recent advances in molecular technology and biological computation have given rise to new approaches to infectious diseases based on identifying target groups defined by activated pathophysiological mechanisms.ObjectiveWe aim to capture NSTI disease signatures and mechanisms and responses to treatment in patients that receive the highest standard of care; therefore, we set out to investigate genome-wide transcriptional responses to HBO2 treatment during NSTI in the host and bacteria.MethodsThe Effects of Hyperbaric Oxygen Treatment Studied with Omics (HBOmic) study is a prospective cohort study including 95 patients admitted for NSTI at the intensive care unit of Copenhagen University Hospital (Rigshospitalet), Denmark, between January 2013 and June 2017. All participants were treated according to a local protocol for management of NSTI, and biological samples were obtained and stored according to a standard operational procedure. In the proposed study, we will generate genome-wide expression profiles of whole-blood samples and samples of infected tissue taken before and after HBO2 treatment administered during the initial acute phase of infection, and we will analyze the profiles with unsupervised hierarchical clustering and machine learning. Differential gene expression will be compared in samples taken before and after HBO2 treatment (N=85), and integration of profiles from blood and tissue samples will be performed. Furthermore, findings will be compared to NSTI patients who did not receive HBO2 treatment (N=10). Transcriptomic data will be integrated with clinical data to investigate associations and predictors.ResultsThe first participant was enrolled on July 27, 2021, and data analysis is expected to begin during autumn 2022, with publication of results immediately thereafter.ConclusionsThe HBOmic study will provide new insights into personalized patient management in NSTIs.Trial registrationClinicalTrials.gov NCT01790698; https://clinicaltrials.gov/ct2/show/NCT01790698.International registered report identifier (irrid)DERR1-10.2196/39252.
| S-EPMC9736759 | biostudies-literature
Project description:BACKGROUND:Necrotizing skin and soft tissue infection (NSTI) is a surgical emergency that is associated with high morbidity and mortality. This study aims to identify predictors of in-hospital death following a NSTI. MATERIAL AND METHODS:We queried the Healthcare Cost and Utilization Project (HCUP) State Inpatient Database (SID) for California between 2006 and 2011. We used conventional and advanced statistical methods to identify predictors of in-hospital mortality, which included: logistic regression, stepwise logistic regression, decision trees, and K-nearest neighbor (KNN) algorithms. RESULTS:A total of 10,158 patients had a NSTI. The full and stepwise logistic regression models had a ROC AUC in the validation dataset of 0.83 (95% CI [0.80, 0.86]) and 0.81 (95% CI [0.78, 0.83]), respectively. The KNN and decision tree model had a ROC AUC of 0.84 (95% CI [0.81, 0.85]) and 0.69 (95% CI [0.65, 0.72]), respectively. The top predictors of in-hospital mortality in the KNN and stepwise logistic model included: (1) the presence of in-hospital coagulopathy, (2) having an infectious or parasitic diagnoses, (3) electrolyte disturbances, (4) advanced age, and (5) the total number of beds in a hospital. CONCLUSION:Patients with a NSTI have high rates of in-hospital mortality. This study highlights the important factors in managing patients with a NSTI which include: correcting coagulopathy and electrolyte imbalances, treating underlying infectious processes, providing adequate resources to the elderly population, and managing patients in high-volume centers.
| S-EPMC6778025 | biostudies-literature
Project description:BackgroundNecrotizing 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.MethodsWe 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.ResultsBaseline 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.ConclusionHigh 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.
| S-EPMC8502346 | biostudies-literature
Project description:BACKGROUND:Mannose-binding lectin (MBL) and ficolins are pattern recognition molecules (PRMs) that play an important role during infection through activation of the lectin complement pathway. We assessed whether plasma PRM levels were associated with mortality in patients with necrotizing soft tissue infection (NSTI). METHODS:We conducted a prospective, observational study over 25 months involving 135 NSTI patients with a maximum follow-up of 2.7 years. Blood samples were taken upon admission. Non-infected patients served as controls. RESULTS:PRM levels were significantly lower compared with controls. A baseline Ficolin-2 level below the median was associated with mortality at the end of follow-up (p = 0.007). No significant association was found for MBL, Ficolin-1 and Ficolin-3. A Ficolin-2 level below the median had a negative predictive value of 0.94 for 28-day mortality, and a level below the optimal cut-off was independently associated with 28-day mortality when adjusted for age, sex and chronicity [hazard ratio 6.27 (95% confidence interval 2.28-17.21), p < 0.0001], also when Simplified Acute Physiology Score II was included in the analysis [hazard ratio 3.16 (95% confidence interval 1.03-9.73), p = 0.045]. CONCLUSIONS:All PRMs were significantly lower in patients with NSTI than in controls. Only baseline Ficolin-2 was associated with short- and long-term mortality. A high baseline Ficolin-2 level indicated a 94% chance of surviving the first 28 days after admission.
| S-EPMC6738884 | biostudies-literature
Project description:IntroductionSurgical intervention, broad-spectrum antibiotics and intensive care support are the standard of care in the treatment of necrotising soft-tissue infections (NSTI). Hyperbaric oxygen treatment (HBOT) may be a useful adjunctive treatment and has been used for almost 60 years, but its efficacy remains unknown and has not been systematically appraised. The aim was to systematically review and synthesise the highest level of clinical evidence available to support or refute the use of HBOT in the treatment of NSTI.MethodsThe review was prospectively registered (PROSPERO; CRD42020148706). MEDLINE, EMBASE, CENTRAL and CINAHL were searched for eligible studies that reported outcomes in both HBOT treated and non-HBOT treated individuals with NSTI. In-hospital mortality was the primary outcome. Odds ratio (ORs) were pooled using random-effects models.ResultsThe search identified 486 papers of which 31 were included in the qualitative synthesis and 21 in the meta-analyses. Meta-analysis on 48,744 patients with NSTI (1,237 (2.5%) HBOT versus 47,507 (97.5%) non-HBOT) showed in-hospital mortality was 4,770 of 48,744 patients overall (9.8%) and the pooled OR was 0.44 (95% CI 0.33-0.58) in favour of HBOT. For major amputation the pooled OR was 0.60 (95% CI 0.28-1.28) in favour of HBOT. The dose of oxygen in these studies was incompletely reported.ConclusionsMeta-analysis of the non-random comparative data indicates patients with NSTI treated with HBOT have reduced odds of dying during the sentinel event and may be less likely to require a major amputation. The most effective dose of oxygen remains unclear.
| S-EPMC8081587 | biostudies-literature
Project description:Background:Group A Streptococcus pyogenes (GAS) causes necrotizing soft tissue infections (NSTIs) necessitating exploration, surgical debridement, and possibly limb amputation. Case presentation:A 45-year-old man presented with traumatic injury of the left carpal region, vomiting, and diarrhea. The swelling and pain in the left forearm worsened with sensorimotor deficits, and his skin color deteriorated. Emergent exploration was performed for limb preservation; GAS was detected in an exudate, and debridement was performed on postoperative day 2 for streptococcal toxic shock syndrome. He recovered uneventfully and was discharged; however, he returned after 2 months with GAS-induced STI at the same site and received antimicrobial treatment. Conclusion:Exploration and subsequent debridement are crucial for effective treatment of NSTI.
| S-EPMC7649489 | biostudies-literature
Project description:BackgroundThe Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score may distinguish necrotizing soft tissue infection (NSTI) from non-NSTI. The association of higher preoperative LRINEC scores with escalations of intraoperative anesthesia care in NSTI is unknown and may be useful in communicating illness severity during patient handoffs.Materials and methodsWe conducted a retrospective cohort study of first operative debridement for suspected NSTI in a single referral center from 2013 to 2016. We assessed the association between LRINEC score and vasopressors, blood products, crystalloid, invasive monitoring, and minutes of operative and anesthesia care.ResultsWe captured 332 patients undergoing their first operative debridement for suspected NSTI. For every 1-point higher LRINEC score, there was a higher risk of norepinephrine and vasopressin use (relative risk [RR] = 18%, 95% confidence interval [CI] [10%, 26%] and [10%, 27%], respectively), packed red blood cell use (RR = 28% [95% CI 13%, 45%]), and additional crystalloid (17.57 mL/h [95% CI 0.37, 34.76]). Each additional LRINEC point was associated with longer anesthesia (3.42 min, 95% CI 0.94, 5.91) and operative times (2.35 min, 95% CI 0.29, 4.40) and a higher risk of receiving invasive arterial monitoring (RR 1.11, 95% CI 1.05, 1.18). The negative predictive value for an LRINEC score < 6 was > 90% for use of vasopressors and packed red blood cells.ConclusionsPreoperative LRINEC scores were associated with escalations in intraoperative care in patients with NSTI. A low score may predict patients unlikely to require vasopressors or blood and may be useful in standardized handoff tools for patients with NSTI.
| S-EPMC6451873 | biostudies-literature