Effects of corticotropin-releasing hormone on proopiomelanocortin derivatives and monocytic HLA-DR expression in patients with septic shock

Matejec, Reginald; Kayser, Friederike; Schmal, Frauke; Uhle, Florian; Bödeker, Rolf‐Hasso; Maxeiner, H; Kolbe, J.

doi:10.1016/j.peptides.2013.07.013

Cited by 4 publications

(1 citation statement)

References 31 publications

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“…MC1R is expressed by cutaneous melanocytes, where it has a key role in determining skin and hair pigmentation. 13 However, other cell types in the skin also express MC1R, including keratinocytes, fibroblasts, endothelial cells, and antigen-presenting cells. 5,14 In this respect, MC1R is expressed by leukocytes and macrophages where it mediates the anti-inflammatory and immunomodulatory properties of melanocortins.…”

Section: Discussionmentioning

confidence: 99%

MC1R gene polymorphisms are associated with dysfunctional immune responses and wound infection after burn injury

Carter

Sood

Seaton

et al. 2018

Journal of Surgical Research

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Background: Systemic inflammatory response syndrome (SIRS) is associated with organ failure and infectious complications after major burn injury. Recent evidence has linked melanocortin signaling to anti-inflammatory and wound-repair functions, with mutations in the melanocortin 1 receptor (MC1R) gene leading to increased inflammatory responses. Our group has previously demonstrated that MC1R gene polymorphisms are associated with postburn hypertrophic scarring. Thus, we hypothesized that MC1R single nucleotide polymorphisms (SNPs) would be associated with increased burn-induced SIRS and increased infectious complications. Methods: We performed a retrospective cohort study of adults (>18 y of age) admitted to our burn center with >20% total body surface area (TBSA) partial/full thickness burns between 2006 and 2013. We screened for five MC1R SNPs (V60L, V92M, R151C, R163Q, T314T) by polymerase chain reaction from genomic DNA isolated from blood samples. We performed a detailed review of each patient chart to identify age, sex, race, ethnicity, %TBSA burned, burn wound infections (BWIs), and 72-hr intravenous fluid volume, the latter a surrogate for a dysfunctional inflammatory response to injury. Association testing was based on multivariable regression. Results: Of 106 subjects enrolled, 82 had complete data for analysis. Of these, 64 (78%) were male, with a median age of 39 and median burn size of 30% TBSA. A total of 36 (44%) subjects developed BWIs. The median total administered IV crystalloid in first 72h was 24.6 L. In multivariate analysis, the R151C variant allele was a significant independent risk factor for BWI (adjusted prevalence ratio 2.03; 95% CI: 1.21–3.39; P = 0.007), and the V60L variant allele was independently associated with increased resuscitation fluid volume (P = 0.021). Conclusions: This is the first study to demonstrate a significant association between genetic polymorphisms and a nonfatal burn-induced SIRS complication. Our findings suggest that MC1R polymorphisms contribute to dysfunctional responses to burn injury that may predict infectious and inflammatory complications.

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Section: Discussionmentioning

confidence: 99%

MC1R gene polymorphisms are associated with dysfunctional immune responses and wound infection after burn injury

Carter

Sood

Seaton

et al. 2018

Journal of Surgical Research

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Interventions for necrotizing soft tissue infections in adults

Hua

Bosc

Sbidian

et al. 2018

Cochrane Database of Systematic Reviews

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We found very little evidence on the effects of medical and surgical treatments for NSTI. We cannot draw conclusions regarding the relative effects of any of the interventions on 30-day mortality or serious adverse events due to the very low quality of the evidence.The quality of the evidence is limited by the very small number of trials, the small sample sizes, and the risks of bias in the included trials. It is important for future trials to clearly define their inclusion criteria, which will help with the applicability of future trial results to a real-life population.Management of NSTI participants (critically-ill participants) is complex, involving multiple interventions; thus, observational studies and prospective registries might be a better foundation for future research, which should assess empiric antimicrobial therapy, as well as surgical debridement, along with the placebo-controlled comparison of adjuvant therapy. Key outcomes to assess include mortality (in the acute phase of the condition) and long-term functional outcomes, e.g. quality of life (in the chronic phase).

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