The contradictory role of androgens in cutaneous and major burn wound healing.

Wound healing is a complex process involving four overlapping phases: haemostasis, inflammation, cell recruitment and matrix remodeling. In mouse models, surgical, pharmacological and genetic approaches targeting androgen actions in skin have shown that androgens increase interleukin-6 and tumor necrosis factor-α production and reduce wound re-epithelization and matrix deposition, retarding cutaneous wound healing. Similarly, clinical studies have shown that cutaneous wound healing is slower in men compared to women. However, in major burn injury, which triggers not only local wound-healing processes but also systemic hypermetabolism, the role of androgens is poorly understood. Recent studies have claimed that a synthetic androgen, oxandrolone, increases protein synthesis, improves lean body mass and shortens length of hospital stay. However, the possible mechanisms by which oxandrolone regulates major burn injury have not been reported. In this review, we summarize the current findings on the roles of androgens in cutaneous and major burn wound healing, as well as androgens as a potential therapeutic treatment option for patients with major burn injuries.

Obstetric outcomes in major vs minor placenta praevia: A retrospective cohort study.

BACKGROUND: Placenta praevia (PP) is a rare obstetric condition associated with significant maternal and perinatal morbidity. Traditionally, the degree of PP has been classified into minor and major; however, there are very few robust studies that compare the maternal outcomes of these types of PP. AIMS: To identify any significant differences in obstetric outcomes between major and minor PP, including antepartum, intraoperative and postpartum complications. MATERIALS AND METHODS: A retrospective cohort study was conducted at the Royal Brisbane & Women's Hospital between 2009 and 2018; all women were diagnosed with PP. RESULTS: Of the total of 368 women recruited, over half of the participants were diagnosed with major PP (57%), while the remaining had minor PP. Women with major PP, compared to women with minor PP, had an increased risk of antepartum haemorrhage (odds ratio (OR) 2.77, P < 0.001), delivery at an earlier gestational age (36.1 vs 37.4 weeks), general anaesthesia (OR 3.25, P < 0.001), greater proportion of emergency lower segment (51% vs 40%) and classical caesarean (7.7% vs 3.8%), increased number of uterotonics (incidence rate ratio (IRR) 1.17, P < 0.031), greater blood loss (IRR 1.32, P < 0.001) and higher frequency of blood transfusion (IRR 2.00, P < 0.027), and longer postpartum hospital stay (IRR 1.26, P < 0.001). Hysterectomy was performed for three women with major PP, compared to one with minor PP. CONCLUSIONS: The degree of PP significantly impacts obstetric outcomes, with major PP associated with worse maternal morbidity antenatally, intraoperatively and postpartum. Therefore, to optimise patient care, this study emphasises the importance of identifying and distinguishing between different types of PP.

Androgen actions in mouse wound healing: Minimal in vivo effects of local antiandrogen delivery.

The aims of this work were to define the role of androgens in female wound healing and to develop and characterize a novel wound dressing with antiandrogens. Androgens retard wound healing in males, but their role in female wound healing has not been established. To understand androgen receptor (AR)-mediated androgen actions in male and female wound healing, we utilized the global AR knockout (ARKO) mouse model, with a mutated AR deleting the second zinc finger to disrupt DNA binding and transcriptional activation. AR inactivation enhanced wound healing rate in males by increasing re-epithelialization and collagen deposition even when wound contraction was eliminated. Cell proliferation and migration in ARKO male fibroblasts was significantly increased compared with wild-type (WT) fibroblasts. However, ARKO females showed a similar healing rate compared to WT females. To exploit local antiandrogen effects in wound healing, while minimizing off-target systemic effects, we developed a novel electrospun polycaprolactone (PCL) scaffold wound dressing material for sustained local antiandrogen delivery. Using the antiandrogen hydroxyl flutamide (HF) at 1, 5, and 10 mg/mL in PCL scaffolds, controlled HF delivery over 21 days significantly enhanced in vitro cell proliferation of human dermal fibroblasts and human keratinocytes. HF-PCL scaffolds also promoted in vivo wound healing in mice compared with open wounds but not to PCL scaffolds.