Key pathways and genes that are altered during treatment with hyperbaric oxygen in patients with sepsis due to necrotizing soft tissue infection (HBOmic study).

Background: For 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 (HBO) treatment. HBO 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.

Hyperbaric oxygen treatment in the management of necrotising soft-tissue infections: results from a Danish nationwide registry study.

Objectives: Application of hyperbaric oxygen (HBO) treatment in the multidisciplinary setting of necrotising soft-tissue infection (NSTI) is debated as a considerable number of studies are of low quality with marked prognostication bias due to inadequately addressing disease severity. The objective of this study was to associate HBO treatment with mortality in patients with NSTI including disease severity as a prognostic variable.

Design: Nationwide population-based register study.

Investigating the Effects of Hyperbaric Oxygen Treatment in Necrotizing Soft Tissue Infection With Transcriptomics and Machine Learning (the HBOmic Study): Protocol for a Prospective Cohort Study With Data Validation.

Background: Necrotizing 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 (HBO) 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.

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.

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.

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

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.

Effect of immunoglobulin G on cytokine response in necrotising soft-tissue infection: A post hoc analysis.

Background: A marked inflammatory response in necrotising soft-tissue infection (NSTI) may contribute to the severe clinical course. Intravenous polyspecific immunoglobulin G (IVIG) is used by some as adjuvant treatment for NSTI, but in the randomised INSTINCT trial, no effect of IVIG in NSTI patients was seen on physical quality of life. In experimental studies, IVIG may induce immunosuppressive effects by reducing the pro-inflammatory response and neutralising circulating superantigens.

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

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 (HBO) treatment as the restoration of oxidative stress balance is considered an important mechanism of action, which HBO facilitates.

Adjunctive hyperbaric oxygen treatment for necrotising soft-tissue infections: A systematic review and meta-analysis.

Introduction: Surgical 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.

Hyperbaric oxygen treatment is associated with a decrease in cytokine levels in patients with necrotizing soft-tissue infection.

Background: The 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 (HBO ) 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 HBO treatment and assessed the overall inflammatory response during the first 3 days after admission.

Soluble ICAM-1 is modulated by hyperbaric oxygen treatment and correlates with disease severity and mortality in patients with necrotizing soft-tissue infection.

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 patients with septic NSTI. Hyperbaric oxygen (HBO) treatment has demonstrated an effect on adhesion molecules.

[Hyperbaric oxygen therapy].

Hypoxia triggers hypoxia-inducible factor (HIF). Not only hypoxia triggers downstream HIF target genes for transcription, as intermittent hyperoxia also possesses similar capabilities, suggesting that fluctuations in oxygen availability may be equally important for inducing HIF transcription. This review describes some of the mechanisms, whereby intermittent hyperbaric hyperoxia may explain some of the observations during hyperbaric oxygen therapy such as enhanced wound healing, angiogenesis and tissue healing, and concludes that oxidative stress enhances certain antibiotics in infection control.

Incidence, comorbidity and mortality in patients with necrotising soft-tissue infections, 2005-2018: a Danish nationwide register-based cohort study.

Objective: To assess the incidence, comorbidities, treatment modalities and mortality in patients with necrotising soft-tissue infections (NSTIs) in Denmark.

Design: Nationwide population-based registry study.

Setting: Denmark.

Measurement of peripheral arterial tonometry in patients with diabetic foot ulcers during courses of hyperbaric oxygen treatment.

Introduction: Treatment of diabetic foot ulcers is complex and often protracted. Hyperbaric oxygen treatment (HBOT) improves wound healing in diabetic ulcers and serves as an important adjunct to regular diabetic wound care. Endothelial dysfunction plays a central role in diabetes-related vascular complications and may be evaluated by a non-invasive technique called peripheral arterial tonometry which measures a reactive hyperaemia index (RHI).

Patient's characteristics and outcomes in necrotising soft-tissue infections: results from a Scandinavian, multicentre, prospective cohort study.

Purpose: Necrotising soft-tissue infections (NSTI) are characterised by necrosis, fast progression, and high rates of morbidity and mortality, but our knowledge is primarily derived from small prospective studies and retrospective studies.

Methods: We performed an international, multicentre, prospective cohort study of adults with NSTI describing patient's characteristics and associations between baseline variables and microbiological findings, amputation, and 90-day mortality.

Results: We included 409 patients with NSTI; 402 were admitted to the ICU.

SuPAR correlates with mortality and clinical severity in patients with necrotizing soft-tissue infections: results from a prospective, observational cohort study.

Necrotizing soft tissue infections (NSTI) have a 90-day mortality rate of 18-22%. Tools are needed for estimating the prognosis and severity of NSTI upon admission. We evaluated soluble urokinase-type plasminogen activator receptor (suPAR) levels at admission as a prognostic marker of NSTI severity and mortality.

Neuronal nitric oxide inhibition attenuates the protective effect of HBO2 during cyanide poisoning.

Purpose: Experiments have shown that hyperbaric oxygen (HBO2) therapy reduces cyanide-induced cerebral distress. The exact mechanism behind HBO2's neuroprotective effect is unknown, but has been proposed to be mediated by an increased neuronal nitric oxide (NO) bioavailability, which may compete with cyanide for the active site of cytochrome oxidase in the mitochondrial respiratory chain. We hypothesized that the ameliorating effect of HBO2 is caused by an increased bioavailability of NO, which can be attenuated by injection of the selective neuronal NO synthase inhibitor, 7-nitroindazole, preceding the HBO2 procedure.

Decompression illness treated in Denmark 1999-2013.

Introduction: The incidence, diver characteristics and symptomatology of decompression illness (DCI) in Denmark has not been assessed since 1982, and the presence of long-term residual symptoms among divers receiving hyperbaric oxygen therapy in Denmark has never been estimated to our knowledge.

Methods: We undertook a retrospective study of the incidence and characteristics of DCI cases in Denmark for the period of 1999 to 2013. Medical records and voluntary questionnaires were reviewed, extracting data on age, gender, weight, height, diver certification level, diving experience, number of previous dives, type of diving, initial type of hyperbaric treatment and DCI symptoms.

Postural stability in patients with decompression sickness evaluated by means of Quantitative Romberg testing.

Objective: The present study was designed to retrospectively evaluate the use of quantitative Romberg's testing on postural stability during the course of hyperbaric oxygen (HBO2) therapy in patients presenting with decompression sickness (DCS).

Methods: The Quantitative Romberg test was used to evaluate postural stability in 33 patients with DCS treated between May 2009 and August 2014. Postural stability was assessed before and after each session of HBO2 therapy.

Evaluation of endothelial function by peripheral arterial tonometry and relation with the nitric oxide pathway.

Endothelial dysfunction is an important component in the development of cardiovascular diseases. Endothelial function may be evaluated by peripheral arterial tonometry (PAT) which measures the vasodilator function in the microvasculature of the fingertip during reactive hyperaemia. The reactive hyperaemia index (RHI) is decreased in the presence of cardiovascular risk factors and thus far several studies have shown that PAT-RHI may provide reliable prediction of outcome.