A Review of Perforator Flaps for Burn Scar Contractures of Joints.

OBJECTIVE: Perforator flaps are one possible surgical treatment for burn scar contractures; however, a review of evidence on this topic is lacking. METHODS: MEDLINE was searched for articles related to perforator flaps for burn contractures. Following title and abstract screen, full texts were searched to identify articles describing perforator flaps for burn scar joint contractures. Data were extracted and summarized descriptively. Only articles that contained ≥10 patients with burn scar contracture were considered. RESULTS: Two hundred forty-eight articles were identified, of which 17 met criteria for review. Of these, 16 were low-quality case series, while 1 was an open randomized controlled trial. In total, perforator flaps were performed on 339 patients (age range: 3-75 years), with the most common contracture locations being cervical (n = 218) and knee (n = 41). Nine of the 17 articles described a rehabilitation strategy. In general, functional outcomes were excellent, with the majority of patients experiencing return of normal joint range of motion and no recontracture. Compared to full-thickness skin grafts, perforator flaps showed greater improvements in joint range of motion. Cosmetically, perforator flaps were shown to have good color match with surrounding tissue, good contour around anatomical landmarks, and improved overall patient appearance. The most common complications were marginal flap necrosis (n = 26 patients) and venous congestion (n = 17 patients). CONCLUSIONS: Preliminary evidence from low-quality case series and 1 high-quality trial suggests perforator flaps may be successful for resurfacing released burn scar contractures; however, there is a need for additional trials comparing perforator flaps to other approaches.

OBJECTIF: Les lambeaux perforateurs font partie des traitements chirurgicaux des contractures des cicatrices de brûlure, mais il n'y a pas d'analyse des données probantes sur le sujet. MÉTHODOLOGIE: Les chercheurs ont effectué une recherche dans MEDLINE pour extraire les articles liés aux lambeaux perforateurs pour les contractures causées par des brûlures. Après un filtrage en fonction des titres et des résumés, ils ont fouillé les textes intégraux et retenu les articles décrivant les lambeaux perforateurs pour corriger les contractures causées par des cicatrices de brûlure. Ils ont extrait les données et procédé à un résumé descriptif. Ils n'ont évalué que les articles portant sur au moins dix patients ayant des contractures causées par des cicatrices de brûlure. RÉSULTATS: Les chercheurs ont extrait 248 articles, dont 17 respectaient les critères d'analyse. De ce nombre, 16 étaient des séries de cas de faible qualité et un, un essai aléatoire et contrôlé ouvert. Au total, 339 patients (de trois à 75 ans) ont reçu des lambeaux perforateurs, et les contractures étaient surtout situées dans la région du cou (n = 218) et du genou (n = 41). Neuf des 17 articles décrivaient une stratégie de réadaptation. En général, les résultats fonctionnels étaient excellents, car la majorité des patients retrouvaient une amplitude de mouvements normale et n'avaient plus de contractures. Par rapport aux greffes cutanées pleine épaisseur, les lambeaux perforateurs assuraient une plus grande amélioration de l'amplitude du mouvement articulaire. Sur le plan esthétique, les lambeaux perforateurs assuraient un bel appariement de couleur par rapport aux tissus avoisinants, un beau contour des repères anatomiques et une amélioration globale de l'apparence. Les principales complications étaient une nécrose du lambeau marginal (n = 26 patients) et une congestion veineuse (n = 17 patients). CONCLUSIONS: D'après les données probantes préliminaires de séries de cas de faible qualité et d'un essai de haute qualité, les lambeaux perforateurs peuvent être utiles pour le resurfaçage de contractures causées par des cicatrices de brûlure. D'autres études devront être réalisées pour comparer les lambeaux perforateurs à d'autres approches.

Gene expression analysis of Xenopsylla cheopis (Siphonaptera: Pulicidae) suggests a role for reactive oxygen species in response to Yersinia pestis infection.

Fleas are vectors for a number of pathogens including Yersinia pestis, yet factors that govern interactions between fleas and Y. pestis are not well understood. Examining gene expression changes in infected fleas could reveal pathways that affect Y. pestis survival in fleas and subsequent transmission. We used suppression subtractive hybridization to identify genes that are induced in Xenopsylla cheopis (Rothschild) (Siphonaptera: Pulicidae) in response to oral or hemocoel infection with Y. pestis. Overall, the transcriptional changes we detected were very limited. We identified several genes that are likely involved in the production or removal of reactive oxygen species (ROS). Midgut ROS levels were higher in infected fleas and antioxidant treatment before infection reduced ROS levels and resulted in higher bacterial loads. An ROS-sensitive mutant strain of Y. pestis lacking the OxyR transcriptional regulator showed reduced growth early after infection. Our results indicate that ROS may limit Y. pestis early colonization of fleas and that bacterial strategies to overcome ROS may enhance transmission.

PhoP and OxyR transcriptional regulators contribute to Yersinia pestis virulence and survival within Galleria mellonella.

The virulence of Yersinia pestis KIM6+ was compared with multiple isolates of Yersinia pseudotuberculosis and Yersinia enterocolitica toward larvae of the greater wax moth Galleria mellonella. Although Y. pestis and Y. pseudotuberculosis were able to cause lethal infection in G. mellonella, these species appeared less virulent than the majority of Y. enterocolitica strains tested. Y. pestis survived primarily within hemocytes of G. mellonella, and induced a strong antibacterial peptide response that lasted for at least 3 days in surviving larvae. Immunization with dead bacteria to induce an antibacterial response led to increased survival of the larvae following infection. Mutant strains lacking the either phoP or oxyR, which were less resistant to antibacterial peptides and hydrogen peroxide respectively, were attenuated and restoration of the wild-type genes on plasmids restored virulence. Our results indicate that the Y. pseudotuberculosis-Y. pestis lineage is not as virulent toward G. mellonella as are the majority of Y. enterocolitica isolates. Further, we have shown that G. mellonella is a useful infection model for analyzing Y. pestis host-pathogen interactions, and antibacterial peptide resistance mediated by phoP and reactive oxygen defense mediated by oxyR are important for Y. pestis infection of this insect.

Germinal center B cell and T follicular helper cell development initiates in the interfollicular zone.

We identify the interfollicular (IF) zone as the site where germinal center B cell and T follicular helper (Tfh) cell differentiation initiates. For the first 2 days postimmunization, antigen-specific T and B cells remained confined within the IF zone, formed long-lived interactions, and upregulated the transcriptional repressor Bcl6. T cells also acquired the Tfh cell markers CXCR5, PD-1, and GL7. Responding B and T cells migrated to the follicle interior directly from the IF zone, T cell immigration preceding B cells by 1 day. Notably, in the absence of cognate B cells, Tfh cells still formed and migrated to the follicle. However, without such B cells, PD-1, ICOS, and GL7 were no longer expressed on follicular Bcl6(hi) T cells that nevertheless persisted in the follicle. Thus, Ag-specific B cells are required for the maintenance of the PD-1(hi)ICOS(hi)GL7(hi) Tfh cell phenotype within the follicle, but not for their initial differentiation in the IF zone.

Langerhans cells are not required for graft-versus-host disease.

Graft-versus-host disease (GVHD) is initiated and maintained by antigen-presenting cells (APCs) that prime alloreactive donor T cells. APCs are therefore attractive targets for GVHD prevention and treatment. APCs are diverse in phenotype and function, making understanding how APC subsets contribute to GVHD necessary for the development of APC-targeted therapies. Langerhans cells (LCs) have been shown to be sufficient to initiate skin GVHD in a major histocompatibility complex-mismatched model; however, their role when other host APC subsets are intact is unknown. To address this question, we used mice genetically engineered to be deficient in LCs by virtue of expression of diphtheria toxin A under the control of a BAC (bacterial artificial chromosome) transgenic hu-man Langerin locus. Neither CD8- nor CD4-mediated GVHD was diminished in recipients lacking LCs. Similarly, CD8- and CD4-mediated GVHD, including that in the skin, was unaffected if bone marrow came from donors that could not generate LCs, even though donor LCs engrafted in control mice. Engraftment of donor LCs after irradiation in wild-type hosts required donor T cells, with immunofluorescence revealing patches of donor and residual host LCs. Surprisingly, donor LC engraftment in Langerin-diphtheria toxin A (DTA) transgenic hosts was independent of donor T cells, suggesting that a Langerin(+) cell regulates repopulation of the LC compartment.