The Need for Basic, Translational, and Clinical Research in the Field of Hypertrophic Scars

Hypertrophic scar (HTS) is a fibrotic skin disorder that is marked by excessive inflammation and extracellular matrix deposition in response to cutaneous traumatic injuries such as burns, lacerations, incisions, and abrasions. HTS has various risk factors, available treatments, and treatment effectiveness. Research at the basic, translational, and clinical levels are in their infancy compared to fibrotic diseases in other organ systems. This chapter will review current in vitro and in vivo modeling, and highlight research needs to address gaps in the study of HTS. The following topics will be discussed in the chapter: a. Basic Science Research i. Seminal findings ii. Limitations to these models iii. Suggestions for topics of future research b. Translational Science Research i. Seminal findings ii. Limitations to these models iii. Suggestions for topics of future research c. Clinical Research i. Seminal findings ii. Limitations to these models iii. Suggestions for topics of future research

Hypopigmented burn hypertrophic scar contains melanocytes that can be signaled to re-pigment by synthetic alpha-melanocyte stimulating hormone in vitro.

There are limited treatments for dyschromia in burn hypertrophic scars (HTSs). Initial work in Duroc pig models showed that regions of scar that are light or dark have equal numbers of melanocytes. This study aims to confirm melanocyte presence in regions of hypo- and hyper-pigmentation in an animal model and patient samples. In a Duroc pig model, melanocyte presence was confirmed using en face staining. Patients with dyschromic HTSs had demographic, injury details, and melanin indices collected. Punch biopsies were taken of regions of hyper-, hypo-, or normally pigmented scar and skin. Biopsies were processed to obtain epidermal sheets (ESs). A subset of ESs were en face stained with melanocyte marker, S100β. Melanocytes were isolated from a different subset. Melanocytes were treated with NDP α-MSH, a pigmentation stimulator. mRNA was isolated from cells, and was used to evaluate gene expression of melanin-synthetic genes. In patient and pig scars, regions of hyper-, hypo-, and normal pigmentation had significantly different melanin indices. S100β en face staining showed that regions of hyper- and hypo-pigmentation contained the same number of melanocytes, but these cells had different dendricity/activity. Treatment of hypo-pigmented melanocytes with NDP α-MSH produced melanin by microscopy. Melanin-synthetic genes were upregulated in treated cells over controls. While traditionally it may be thought that hypopigmented regions of burn HTS display this phenotype because of the absence of pigment-producing cells, these data show that inactive melanocytes are present in these scar regions. By treating with a pigment stimulator, cells can be induced to re-pigment

Evidence summaries tailored to health policy-makers in low- and middle-income countries

Q1Artículo de investigación54-61Objective To describe how the SUPPORT collaboration developed a short summary format for presenting the results of systematic reviews to policy-makers in low- and middle-income countries (LMICs).Methods We carried out 21 user tests in six countries to explore users’ experiences with the summary format. We modified the summaries based on the results and checked our conclusions through 13 follow-up interviews. To solve the problems uncovered by the user testing, we also obtained advisory group feedback and conducted working group workshops.Findings Policy-makers liked a graded entry format (i.e. short summary with key messages up front). They particularly valued the section on the relevance of the summaries for LMICs, which compensated for the lack of locally-relevant detail in the original review. Some struggled to understand the text and numbers. Three issues made redesigning the summaries particularly challenging: (i) participants had a poor understanding of what a systematic review was; (ii) they expected information not found in the systematic reviews and (iii) they wanted shorter, clearer summaries. Solutions included adding information to help understand the nature of a systematic review, adding more references and making the content clearer and the document quicker to scan.Conclusion Presenting evidence from systematic reviews to policy-makers in LMICs in the form of short summaries can render the information easier to assimilate and more useful, but summaries must be clear and easy to read or scan quickly. They should also explain the nature of the information provided by systematic reviews and its relevance for policy decisions