101 research outputs found
The clinical use of hyperbaric oxygen in the treatment of Danish patients with diabetic foot ulcers
How biomarkers reflect the prognosis and treatment of necrotising soft tissue infections and the effects of hyperbaric oxygen therapy:the protocol of the prospective cohort PROTREAT study conducted at a tertiary hospital in Copenhagen, Denmark
Effect of Hyperbaric Oxygen Therapy on whole blood cyanide concentrations in carbon monoxide intoxicated patients from fire accidents
<p>Abstract</p> <p>Background</p> <p>Hydrogen cyanide (HCN) and carbon monoxide (CO) may be important components of smoke from fire accidents. Accordingly, patients admitted to hospital from fire accidents may have been exposed to both HCN and CO. Cyanide (CN) intoxication results in cytotoxic hypoxia leading to organ dysfunction and possibly death. While several reports support the use of hyperbaric oxygen therapy (HBO) for the treatment of severe CO poisoning, limited data exist on the effect of HBO during CN poisoning. HBO increases the elimination rate of CO haemoglobin in proportion to the increased oxygen partial pressure and animal experiments have shown that in rats exposed to CN intoxication, HBO can increase the concentration of CN in whole blood.</p> <p>Objective</p> <p>The purpose of the present study was to determine whole blood CN concentrations in fire victims before and after HBO treatment.</p> <p>Materials and methods</p> <p>The patients included were those admitted to the hospital because of CO intoxication, either as fire victims with smoke inhalation injuries or from other exposures to CO. In thirty-seven of these patients we measured CN concentrations in blood samples, using a Conway/microdiffusion technique, before and after HBO. The blood samples consisted of the remaining 2 mL from the arterial blood gas analysis. CN concentration in blood from fire victims was compared to 12 patients from non-fire accidents but otherwise also exposed to CO intoxication.</p> <p>Results</p> <p>The mean WB-CN concentration before patients received HBO did not differ significantly between the two groups of patients (p = 0.42). The difference between WB-CN before and after HBO did not differ significantly between the two groups of patients (p = 0.7). Lactate in plasma before and after did not differ significantly between the two groups of patients. Twelve of the 25 fire patients and one of the non-fire patients had been given a dose of hydroxycobalamin before HBO.</p> <p>Discussion and Conclusion</p> <p>CN concentrations in blood from patients admitted to hospital with CO intoxication and smoke inhalation exposure did not differ significantly from controls. Accordingly, we were not able to detect any changes in CN concentrations in blood after treatment with HBO.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov identifier: NCT00280579</p
Treatment with 24Â h-delayed normo- and hyperbaric oxygenation in severe sepsis induced by cecal ligation and puncture in rats
Abstract Background Septic shock remains a leading cause of death worldwide. Hyperbaric oxygen treatment (HBO2) has been shown to alter the inflammatory response during sepsis and to reduce mortality. A therapeutic window of HBO2 treatment has been demonstrated experimentally, but optimal timing remains uncertain. We investigated the effects of 24 h delayed normobaric oxygen (NBO2) and HBO2 treatment on the endogenous production of the inflammatory markers interleukin (IL)-6, tumor necrosis factor (TNF)-α and IL-10, and on mortality in rats with cecal ligation and puncture (CLP) induced sepsis. Method Fifty-five male Sprague-Dawley rats underwent CLP and were randomized to the following groups: 1) HBO2 2.5 bar absolute pressure (pabs); 2) NBO2 1.0 bar pabs; 3) Control (no-treatment), and they were individually monitored for 72 h with intermittent blood sampling. Results IL-6, TNF-α, and IL-10 were increased 24 h after the procedure, and IL-6 was significantly higher in non-survivors than in survivors. The level of IL-10 was significantly higher at hour 48 in the HBO2 group compared to control (p = 0.01), but this was not the case at other time points. No other significant differences in cytokine levels were found for any group comparisons. Delayed NBO2 and HBO2 treatment failed to change the mortality in the animals. Conclusion High levels of IL-6 in non-surviving animals with sepsis suggest that IL-6 is a potential biomarker. We found a significantly higher concentration of IL-10 in the HBO2 group at hour 48 vs. control animals. However, 24 h–delayed treatment with HBO2 did not change the levels of pro-inflammatory cytokines and survival, suggesting that earlier intervention may be required to obtain an anti-inflammatory effect
SuPAR correlates with mortality and clinical severity in patients with necrotizing soft-tissue infections:results from a prospective, observational cohort study
Abstract 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. In a prospective, observational cohort study, suPAR was measured in 200 NSTI patients. We compared admission suPAR levels in survivors and non-survivors, patients with septic shock and non-shock, amputation and non-amputation, correlations with Simplified Acute Physiology Score II (SAPS II) and the Sequential Organ Failure Assessment (SOFA) score. Admission suPAR levels were higher in septic shock vs. non-septic shock patients (9.2 vs. 5.8 ng/mL, p-value < 0.001) and non-survivors vs. survivors (11 vs. 6.1 ng/mL, p-value < 0.001) and correlated with SAPS II (r = 0.52, p < 0.001) and SOFA score (r = 0.64, p < 0.001). Elevated suPAR upon admission was associated with 90-day mortality (log-rank test p < 0.001), however not after adjustment for age, sex, and SOFA score. The AUC for suPAR and 90-day mortality was 0.77. We found that suPAR is a promising candidate for prognosis and severity in patients with NSTI
A single session of hyperbaric oxygen therapy demonstrates acute and long-lasting neuroplasticity effects in humans:A replicated, randomized controlled clinical trial
Associations of Plasma Nitrite, L-Arginine and Asymmetric Dimethylarginine With Morbidity and Mortality in Patients With Necrotizing Soft Tissue Infections
Neutrophil-derived reactive agents induce a transient SpeB negative phenotype in Streptococcus pyogenes
Background
Streptococcus pyogenes (group A streptococci; GAS) is the main causative pathogen of monomicrobial necrotizing soft tissue infections (NSTIs). To resist immuno-clearance, GAS adapt their genetic information and/or phenotype to the surrounding environment. Hyper-virulent streptococcal pyrogenic exotoxin B (SpeB) negative variants caused by covRS mutations are enriched during infection. A key driving force for this process is the bacterial Sda1 DNase.
Methods
Bacterial infiltration, immune cell influx, tissue necrosis and inflammation in patient´s biopsies were determined using immunohistochemistry. SpeB secretion and activity by GAS post infections or challenges with reactive agents were determined via Western blot or casein agar and proteolytic activity assays, respectively. Proteome of GAS single colonies and neutrophil secretome were profiled, using mass spectrometry.
Results
Here, we identify another strategy resulting in SpeB-negative variants, namely reversible abrogation of SpeB secretion triggered by neutrophil effector molecules. Analysis of NSTI patient tissue biopsies revealed that tissue inflammation, neutrophil influx, and degranulation positively correlate with increasing frequency of SpeB-negative GAS clones. Using single colony proteomics, we show that GAS isolated directly from tissue express but do not secrete SpeB. Once the tissue pressure is lifted, GAS regain SpeB secreting function. Neutrophils were identified as the main immune cells responsible for the observed phenotype. Subsequent analyses identified hydrogen peroxide and hypochlorous acid as reactive agents driving this phenotypic GAS adaptation to the tissue environment. SpeB-negative GAS show improved survival within neutrophils and induce increased degranulation.
Conclusions
Our findings provide new information about GAS fitness and heterogeneity in the soft tissue milieu and provide new potential targets for therapeutic intervention in NSTIs.publishedVersio
Efectos y beneficios del entrenamiento de fuerza en pacientes con cáncer: revisión sistemática de la literatura
Introduction: cancer is among the diseases having the greatest mortality rates and the cause of many disabilities worldwide. The practice of exercise is developed as an adjuvant therapy along with the cancer treatment to reduce mortality and disability in the different types of cancer.Objective: to identify the effects of strength training on cancer patients.Methods: a complete review of the medical literature was conducted until December 2018, scientific articles published in indexed bases from 2015 to 2018. The studies included were in population over 18 years old with cancer diagnosis regardless of sociodemographic characteristics, type or stage of cancer. The data extracted were on the population, intervention and control groups, type of cancer, period, frequency of intervention and results.Results: during the first search 36071 titles of clinical study were found in specialized journals. 10 experimental studies were chosen. Multiple positive effects were found, as well as components that should be taken into account when performing strength training on cancer patients or cancer survivors.Conclusions: strength training in patients with cancer or survivors of this disease, helps them to improve their symptoms as well as their quality of life, strength, improved mobility and pain, among others. Also, strength training is beneficial to patients without causing adverse effects or long-term complications.IntroducciĂłn: El cáncer se encuentra entre las enfermedades con mayor mortalidad y causante de un gran nĂşmero de discapacidades a nivel mundial. El ejercicio surge como un coadyuvante del tratamiento oncolĂłgico para disminuir la mortalidad y discapacidad en los diferentes tipos de cáncer.Objetivo: Identificar los efectos del entrenamiento de fuerza en pacientes con cáncer.MĂ©todo:  Se realizĂł una revisiĂłn de la literatura hasta diciembre del 2018, de artĂculos cientĂficos publicados en bases de indexadas desde 2015 y hasta 2018. Los estudios incluidos fueron en poblaciĂłn mayor a 18 años con diagnĂłstico de cáncer sin importar caracterĂsticas sociodemográficas, tipo o estadio del cáncer. Los datos extraĂdos fueron sobre la poblaciĂłn, grupos de intervenciĂłn y control, tipo de cáncer, periodo, frecuencia de la intervenciĂłn y resultados.Resultados: Durante la primera bĂşsqueda 36071 tĂtulos de estudios clĂnicos fueron encontrados en revistas especializadas. Al final 10 estudios de carácter experimental fueron seleccionados. En dichos estudios, mĂşltiples efectos fueron encontrados, asĂ como componentes que se deben tener en cuenta a realizar un entrenamiento de fuerza en pacientes con cáncer o sobrevivientes del mismo.Conclusiones: El entrenamiento de fuerza en pacientes con cáncer o sobrevivientes de esta enfermedad, les ayuda a mejorar su sintomatologĂa al igual que su calidad de vida, fatiga, fuerza, mejorĂa en la movilidad y el dolor, entre otros. AsĂ mismo, el entrenamiento de fuerza es beneficioso para los pacientes sin causar efectos adversos o complicaciones a largo plazo
Analysis of host-pathogen gene association networks reveals patient-specific response to streptococcal and polymicrobial necrotising soft tissue infections
Background: Necrotising soft tissue infections (NSTIs) are rapidly progressing bacterial infections usually caused by either several pathogens in unison (polymicrobial infections) or Streptococcus pyogenes (mono-microbial infection). These infections are rare and are associated with high mortality rates. However, the underlying pathogenic mechanisms in this heterogeneous group remain elusive.
Methods: In this study, we built interactomes at both the population and individual levels consisting of host-pathogen interactions inferred from dual RNA-Seq gene transcriptomic profiles of the biopsies from NSTI patients.
Results: NSTI type-specific responses in the host were uncovered. The S. pyogenes mono-microbial subnetwork was enriched with host genes annotated with involved in cytokine production and regulation of response to stress. The polymicrobial network consisted of several significant associations between different species (S. pyogenes, Porphyromonas asaccharolytica and Escherichia coli) and host genes. The host genes associated with S. pyogenes in this subnetwork were characterised by cellular response to cytokines. We further found several virulence factors including hyaluronan synthase, Sic1, Isp, SagF, SagG, ScfAB-operon, Fba and genes upstream and downstream of EndoS along with bacterial housekeeping genes interacting with the human stress and immune response in various subnetworks between host and pathogen.
Conclusions: At the population level, we found aetiology-dependent responses showing the potential modes of entry and immune evasion strategies employed by S. pyogenes, congruent with general cellular processes such as differentiation and proliferation. After stratifying the patients based on the subject-specific networks to study the patient-specific response, we observed different patient groups with different collagens, cytoskeleton and actin monomers in association with virulence factors, immunogenic proteins and housekeeping genes which we utilised to postulate differing modes of entry and immune evasion for different bacteria in relationship to the patients’ phenotype.publishedVersio
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