Divergent trajectories of cellular bioenergetics, intermediary metabolism and systemic redox status in survivors and non-survivors of critical illness.

BACKGROUND: Numerous pathologies result in multiple-organ failure, which is thought to be a direct consequence of compromised cellular bioenergetic status. Neither the nature of this phenotype nor its relevance to survival are well understood, limiting the efficacy of modern life-support. METHODS: To explore the hypothesis that survival from critical illness relates to changes in cellular bioenergetics, we combined assessment of mitochondrial respiration with metabolomic, lipidomic and redox profiling in skeletal muscle and blood, at multiple timepoints, in 21 critically ill patients and 12 reference patients. RESULTS: We demonstrate an end-organ cellular phenotype in critical illness, characterized by preserved total energetic capacity, greater coupling efficiency and selectively lower capacity for complex I and fatty acid oxidation (FAO)-supported respiration in skeletal muscle, compared to health. In survivors, complex I capacity at 48 h was 27% lower than in non-survivors (p = 0.01), but tended to increase by day 7, with no such recovery observed in non-survivors. By day 7, survivors' FAO enzyme activity was double that of non-survivors (p = 0.048), in whom plasma triacylglycerol accumulated. Increases in both cellular oxidative stress and reductive drive were evident in early critical illness compared to health. Initially, non-survivors demonstrated greater plasma total antioxidant capacity but ultimately higher lipid peroxidation compared to survivors. These alterations were mirrored by greater levels of circulating total free thiol and nitrosated species, consistent with greater reductive stress and vascular inflammation, in non-survivors compared to survivors. In contrast, no clear differences in systemic inflammatory markers were observed between the two groups. CONCLUSION: Critical illness is associated with rapid, specific and coordinated alterations in the cellular respiratory machinery, intermediary metabolism and redox response, with different trajectories in survivors and non-survivors. Unravelling the cellular and molecular foundation of human resilience may enable the development of more effective life-support strategies.MRC, Evelyn Trust, Intensive Care Society, Royal Free Charit

Tribute to Professor David Bruck

A tribute to Professor David I. Bruck, who served on the faculty of the Washington and Lee University School of Law from 2004 to 2020. Bruck directed W&L\u27s death penalty defense clinic, the Virginia Capital Case Clearinghouse, also known as VC3 . He became Professor of Law, Emeritus in 2020

Elevated serum levels of soluble CD154 in children with juvenile idiopathic arthritis

<p>Abstract</p> <p>Objective</p> <p>Cytokines play important roles in mediating inflammation in autoimmunity. Several cytokines are elevated in serum and synovial fluid samples from children with Juvenile Idiopathic Arthritis (JIA). Soluble CD154 (sCD154) is elevated in other autoimmune disorders, but has not been characterized in JIA. Our objectives were to determine if sCD154 is elevated in JIA, and to examine correlations between sCD154 and other inflammatory cytokines.</p> <p>Methods</p> <p>Serum from 77 children with JIA and 81 pediatric controls was analyzed for interleukin (IL)1β, IL2, IL4, IL5, IL6, IL8, IL10, IL12, IL13, sCD154, interferon-γ (IFNγ), soluble IL2 receptor (sIL2R), and tumor necrosis factor-α (TNFα), using the Luminex Multi-Analyte Profiling system. Differences in levels of cytokines between cases and controls were analyzed. Logistic regression was also performed.</p> <p>Results</p> <p>sCD154 was significantly elevated in cases compared to controls (p < 0.0001). IL1β, IL5, IL6, IL8, IL13, IFNγ, sIL2R, and TNFα were also significantly elevated in JIA. Levels of sCD154 were highly correlated with IL1β, IL6, IL8, and TNFα (p < 0.0001). Logistic regression analysis suggested that IL6 (odds ratio (OR): 1.4, p < 0.0001), sCD154 (OR: 1.1, p < 0.0001), and TNFα (OR: 1.1, p < 0.005) were positively associated with JIA, while IL10 (OR: 0.5, p < 0.002) was protective. sCD154 was elevated in all JIA subtypes, with highest levels among more severe subtypes. IL1β, IL6, IL8, sIL2R and TNFα were also elevated in several JIA subtypes.</p> <p>Conclusion</p> <p>Serum levels of sCD154, IL1β, IL6, IL8, sIL2R and TNFα are elevated in most JIA subtypes, suggesting a major role for sCD154, and these cytokines and cytokine receptors in the pathogenesis of JIA.</p

Assistants in nursing : scope of practice and pressure injury prevention

There is greater focus on patientcentred care supported by the National Safety and Quality Health Service Standards (ACSQHC 2017) as well as a focus on Hospital Acquired Complications (ACSQHC 2018). In NSW one model has been the introduction of Assistants in Nursing (AIN) as part of the nursing skill mix. The AIN role was initially introduced to provide basic support to qualified nurses by assisting patients with personal care needs (Afzal et al. 2018). With current nursing workforce shortages and changing healthcare environments hospitals are increasingly utilising AINs in the acute care environment (Duffield et al. 2014). The AIN role now includes activities that were previously undertaken by regulated nurses. The AIN has become a member of the nursing acute care team. As an unregulated position, qualifications for AINs are not mandatory (Mason 2013). Courses designed for AINs are available in both the public and private sector but these courses vary in both length and content. In NSW, an AIN can have completed preparation for the role ranging from a six week course; a nationally recognised qualification such as the Certificate III Health Services Assistance; one year of an undergraduate nursing course, or ‘equivalent experience’ (NSW Health 2018). Therefore, an individual AIN’s knowledge and experience can vary, leading to confusion around AINs scope of practice and clinical competency

Taking the pressure off in the Emergency Department: evaluation of the prophylactic application of a low shear, soft silicon sacral dressing on high risk medical patients

Pressure injuries are key clinical indicators of care standard. In Australia, pressure injuries increase length of hospital stay by 4·31 and cost $285 million annually. This pilot study examined the effectiveness of sacral dressing in reducing the preva

Microbial Persistence, Replacement and Local Antimicrobial Therapy in Recurrent Bone and Joint Infection

We report microbiological results from a cohort of recurrent bone and joint infection to define the contributions of microbial persistence or replacement. We also investigated for any association between local antibiotic treatment and emerging antimicrobial resistance. Microbiological cultures and antibiotic treatments were reviewed for 125 individuals with recurrent infection (prosthetic joint infection, fracture-related infection, and osteomyelitis) at two UK centres between 2007 and 2021. At re-operation, 48/125 (38.4%) individuals had an organism from the same bacterial species as at their initial operation for infection. In 49/125 (39.2%), only new species were isolated in culture. In 28/125 (22.4%), re-operative cultures were negative. The most commonly persistent species were Staphylococcus aureus (46.3%), coagulase-negative Staphylococci (50.0%), and Pseudomonas aeruginosa (50.0%). Gentamicin non-susceptible organisms were common, identified at index procedure in 51/125 (40.8%) and at re-operation in 40/125 (32%). Gentamicin non-susceptibility at re-operation was not associated with previous local aminoglycoside treatment (21/71 (29.8%) vs. 19/54 (35.2%); p = 0.6). Emergence of new aminoglycoside resistance at recurrence was uncommon and did not differ significantly between those with and without local aminoglycoside treatment (3/71 (4.2%) vs. 4/54 (7.4%); p = 0.7). Culture-based diagnostics identified microbial persistence and replacement at similar rates in patients who re-presented with infection. Treatment for orthopaedic infection with local antibiotics was not associated with the emergence of specific antimicrobial resistance

Profiling anti-cyclic citrullinated peptide antibodies in patients with juvenile idiopathic arthritis

Abstract Background Anti-citrullinated protein/peptide antibodies (ACPA), have high specificity for rheumatoid arthritis (RA). Some children with juvenile idiopathic arthritis (JIA), phenotypically resemble RA and test positive for rheumatoid factor (RF) a characteristic biomarker of RA. We investigated the prevalence of ACPA and its relationship to other serologic markers associated with RA in a well-characterized JIA cohort. Methods Cases were 334 children with JIA, 30 of whom had RF + polyarticular JIA. Sera from all cases and 50 healthy pediatric controls were investigated by ELISA at a single time point for anti-cyclic citrullinated peptide (anti-CCP) IgG, RF IgM, IgA and IgG, anti-RA33 IgG, and antinuclear antibodies (ANA). Comparisons between cases and controls were made using Chi-square or Fisher exact tests and T-tests. Results The prevalence of RF was 8% among controls, and 12% among cases (ns). The prevalence of ACPA was 2% in controls and 14.3% in cases (OR 8.2, p Conclusions ACPAs are detectable in 14% of children with JIA. Children with positive ACPA but negative RF are frequent, and may define a distinct subset of children with JIA. ACPA testing should be included in the classification of JIA.</p

Elevated serum levels of soluble CD154 in children with juvenile idiopathic arthritis-0

The 25and 75percentile. The solid horizontal line within the box denotes the median value and the dashed lines represent the mean values. The Whiskers above and below the boxes show the 90and 10percentiles respectively. Four subjects had levels greater than 1000 pg/ml.<p><b>Copyright information:</b></p><p>Taken from "Elevated serum levels of soluble CD154 in children with juvenile idiopathic arthritis"</p><p>http://www.ped-rheum.com/content/6/1/8</p><p>Pediatric Rheumatology Online Journal 2008;6():8-8.</p><p>Published online 28 May 2008</p><p>PMCID:PMC2430568.</p><p></p