Severe skin and soft tissue infection in cohort patients admitted in a teaching hospital in Belgium: identification of risk factors for surgery.

BACKGROUND: Necrotizing soft tissue infections (NSTIs) are associated with significant mortality if not promptly diagnosed and surgically treated. AIM: This study aims to compare patients with severe skin and soft tissue infection treated with or without a surgical intervention and to identify risk factors that can predict the need for early surgery. METHODS: Demographics, clinical, laboratory, Risk Indicator for Necrotizing Fasciitis (LRINEC) and imaging results were retrospectively collected. RESULTS: There were 91 non-NSTI (group 1), 26 NSTI who were operated (group 2) and eight suspected NSTI who were not operated (group 3). In the multivariate analysis, skin necrosis, tachycardia, CRP value and hyperglycemia were predictive for surgery. A performance analysis revealed AUC of 0.65 (95%CI: 0.52-0.78) as to the LRINEC score for the use of surgery. The AUC for a predictive model associating four variables (heart rate, skin necrosis, CRP and glycemia at admission) was 0.71 (95%CI: 0.59-0.84). In terms of outcome, the median length of stay (LOS) was statistically higher in group 2 vs. group 1 (seven days (5-15) vs. 34 days (20-42), p < .001) and in group 2 vs. group 3 (34 days (20-42) vs. 14 days (11-19), p = .005). The overall in-hospital mortality at 30 days was 3.2% and did not statistically differ between the three groups. CONCLUSIONS: Although the LRINEC score performed well in predicting surgery, the AUC of a model combining four predictive variables (glycemia, skin necrosis, CRP and heart rate) was superior. Further research is needed to validate this model.

Toll-like receptor 4 modulation as a strategy to treat sepsis.

Despite a decrease in mortality over the last decade, sepsis remains the tenth leading causes of death in western countries and one of the most common cause of death in intensive care units. The recent discovery of Toll-like receptors and their downstream signalling pathways allowed us to better understand the pathophysiology of sepsis-related disorders. Particular attention has been paid to Toll-like receptor 4, the receptor for Gram-negative bacteria outer membrane lipopolysaccharide or endotoxin. Since most of the clinical trial targeting single inflammatory cytokine in the treatment of sepsis failed, therapeutic targeting of Toll-like receptor 4, because of its central role, looks promising. The purpose of this paper is to focus on the recent data of various drugs targeting TLR4 expression and pathway and their potential role as adjunctive therapy in severe sepsis and septic shock.

The tetraspanin CD9 associates with the integrin alpha6beta4 in cultured human epidermal keratinocytes and is involved in cell motility.

Integrins are involved in several ways in keratinocyte physiology, including cell motility. CD9 is a member of the tetraspanin protein family which is found in association with other transmembrane proteins like the integrins. CD9 is expressed in the epidermal tissue, but this expression is not regulated by differentiation. The present work focuses on association of CD9 with the integrin alpha6beta4 in keratinocytes. In vivo, CD9 does not co-localize with alpha6beta4, and is not internalized with the integrin upon basal detachment with dispase. In vitro, CD9 is found partly in co-localization with alpha6beta4 and is internalized with the integrin after keratinocyte detachment with dispase. Using blocking antibodies in a phagokinetic tracks assay, we show that CD9, and to a lesser extent alpha6beta4, but not the tetraspanin CD82, promote motility of subconfluent keratinocytes on collagen I. Our observations also suggest that CD9 is involved in the formation of lamellipodia. We also report that the phorbol ester TPA has no effect on CD9 expression and association with alpha6beta4, but increases keratinocyte motility, possibly through modulation of integrin subunits expression, or through upregulation of collagenase-1 expression. Together, these results confirm that CD9 associates with alpha6beta4 in cultured keratinocytes, possibly in order to regulate the function of the integrin, and that CD9 is involved in keratinocyte motility on collagen. The data suggest that regulation of adhesion characteristics by CD9 in keratinocytes may play a role in epidermal repair.