Defects in ear canal development can cause severe hearing loss as sound waves fail to reach the middle ear. Here we reveal new mechanisms that control human canal development and highlight for the first time the complex system of canal closure and reopening. These processes can be perturbed in mutant mice and in explant culture, mimicking the defects associated with canal aplasia. The more superficial part of the canal forms from an open primary canal that closes and then reopens. In contrast, the deeper part of the canal forms from an extending solid meatal plate that opens later. Closure and fusion of the primary canal was linked to loss of periderm, with failure in periderm formation in Grhl3 mutant mice associated with premature closure of the canal. Conversely, inhibition of cell death in the periderm resulted in an arrest of closure. Once closed, re-opening of the canal occurred in a wave, triggered by terminal differentiation of the epithelium. Understanding these complex processes involved in canal development sheds light on the underlying causes of canal aplasia.

A 40-year-old woman with antiphospholipid syndrome presented with a 5-day history of right upper quadrant (RUQ) pain, radiating posteriorly, associated with fever and vomiting. She was admitted 1-week prior with an upper respiratory infection and erythema multiforme. Clinical assessment revealed sepsis with RUQ tenderness and positive Murphy's sign. Laboratory results showed raised inflammatory markers, along with renal and liver impairment. CT showed bilateral adrenal infarction and inferior vena cava thrombus. The patient was managed for sepsis and started on heparin. Further immunological investigations revealed a diagnosis of systemic lupus erythematous, an exacerbation of which culminated in lupus myocarditis. This case illustrates the importance of promptly recognising adrenal insufficiency in patients with antiphospholipid syndrome and the possible causative agents, which require careful consideration and exclusion to prevent further thrombotic events. It also highlights the importance of undertaking imaging, namely CT, in patients with antiphospholipid syndrome presenting with abdominal pain as well as considering concomitant autoimmune conditions.

BackgroundAutologous fat grafting is an emerging therapeutic option for cutaneous wounds. The regenerative potential of autologous fat relates to the presence of adipose-derived stem cells (ADSCs) within the stromal vascular fraction (SVF). ADSCs are capable of differentiating into fibroblasts and keratinocytes, as well as secreting soluble mediators with angiogenic and anti-inflammatory properties. However, to date, there has been no comprehensive assessment of the wound healing literature in humans. This systematic review aims to critically evaluate the efficacy and safety of autologous fat grafting in acute and chronic cutaneous wounds with an appraisal of the quality of evidence available.MethodsFollowing PRISMA guidelines, MEDLINE, Embase and Cochrane Library databases will be searched from inception to December 2017. All primary clinical studies in which wounds are treated with lipotransfer, cell-assisted lipotransfer (CAL), SVF products or isolated ADSCs will be eligible for inclusion. Study screening and data extraction will be conducted by two authors in duplicate. Our primary outcome measure will be the proportion of completely healed wounds at 12 weeks. Secondary outcome measures will include the proportion of partially healed wounds at 12 weeks; the mean wound surface area reduction at 12 weeks; the mean time to wound healing; and adverse event rates. The quality of evidence for each summary outcome measure will be assessed using the GRADE approach.DiscussionIn light of the growing popularity of autologous fat grafting for wound healing, a systematic appraisal of the available evidence is timely. If autologous fat grafting is associated with a positive treatment effect, we will compare these outcomes to those achieved using alternative wound management strategies. This review also aims to determine if one or more autologous fat grafting techniques are superior and whether this varies according to patient- and wound-specific factors. We anticipate that these results will guide future research and inform clinical practice.Systematic review registrationPROSPERO CRD42017081499

Background: There is a growing interest in the regenerative potential of autologous fat. Adipose-derived stem cells, within the stromal vascular fraction of lipoaspirate samples, demonstrate anti-inflammatory, immunomodulatory, and angiogenic properties. This systematic review aimed to determine the efficacy and safety of autologous fat therapies for wound healing, with an evaluation of the quality of evidence provided by the literature. Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we searched Ovid Medline, Embase, and Cochrane Library databases from inception to November 2018. We included all human studies where wounds were treated with lipotransfer, cell-assisted lipotransfer, stromal vascular fraction products, or isolated adipose-derived stem cells. Study screening and data extraction were performed by 2 authors. The quality of evidence was evaluated using the GRADE approach. Results: The search strategy returned 5027 citations. From these, 10 observational case series were included in the qualitative synthesis; there were no randomized controlled trials. Patient characteristics, wound etiology, and intervention type differed markedly between studies, precluding formal meta-analysis. Autologous fat grafting was associated with satisfactory wound healing in all studies with low complication rates. However, the quality of evidence was consistently very low. Conclusions: Autologous fat grafting is an emerging therapeutic option for challenging wounds, although there is insufficient evidence to conclusively demonstrate its effectiveness and adverse event profile. Based on the literature to date, it is unclear whether one type of autologous fat therapy is superior. Well-designed, blinded, prospective randomized controlled trials with adequate methodologic details and objective outcome measure reporting are essential. PROSPERO ID: CRD42017081499.