Publications (33)79.26 Total impact
- [Show abstract] [Hide abstract] ABSTRACT: Expression of major histocompatibility antigens class-2 (MHC-II) under non-inflammatory conditions is not usually associated with the nervous system. Comparative analysis of immunogenicity of human embryonic/fetal brain-derived neural stem cells (hNSCs) and human mesenchymal stem cells with neurogenic potential from umbilical cord (UC-MSCs) and paediatric adipose tissue (ADSCs), while highlighting differences in their immunogenicity, led us to discover subsets of neural cells co-expressing the neural marker SOX2 and MHC-II antigen in vivo during human CNS development. MHC-II proteins in hNSCs are functional, and differently regulated upon differentiation along different lineages. Mimicking an inflammatory response using the inflammatory cytokine IFNγ induced MHC-II up-regulation in both astrocytes and hNSCs, but not in UC-MSCs and ADSCs, either undifferentiated or differentiated, though IFNγ receptor expression was comparable. Together, hypoimmunogenicity of both UC-MSCs and ADSCs supports their suitability for allogeneic therapy, while significant immunogenicity of hNSCs and their progeny may at least in part underlie negative effects reported in some patients following embryonic neural cell grafts. Crucially, we show for the first time that MHC-II expression in developing human brains is not restricted to microglia as previously suggested, but is present in discrete subsets of neural progenitors and appears to be regulated independently of inflammatory stimuli.
- [Show abstract] [Hide abstract] ABSTRACT: The surgical treatment of defects caused by noma is challenging for the surgeon and the patient. Local flaps are preferred, but sometimes, because of the nature of the disease, there is not enough local tissue available. We describe our experience of free tissue transfer in Ethiopia. Between 2008 and 2014, 34 microsurgical procedures were done over 11 missions with the charity Facing Africa, predominantly for the treatment of defects caused by noma (n=32). The mean duration of operation was 442minutes (range 200 - 720). Six minor wound infections were treated conservatively and did not affect outcome, a return to theatre was required in 4 patients with wound infections and one with a haemorrhage; 2 flaps failed and 2 partially failed, one patient developed an oronasal fistula, and one had an infection at the donor site that required a repeat graft. In settings where resources are limited, free flaps can be used when local tissue is not available and they cause less morbidity than pedicled tissue transfer.
- [Show abstract] [Hide abstract] ABSTRACT: We describe a series of 8 patients who had total reconstruction of the nose during 4 separate missions to Ethiopia. The aetiology was noma (n=3), assault (n=2), acid burn (n=1), squamous cell carcinoma (n=1), and a sequela of meningococcal septicaemia (n=1). Reconstruction was with forehead flaps when adequate tissue was available (n=6) and with radial forearm flaps when it was not (n=2). Some reconstructive approaches require procedures to be done in stages, and in settings where resources are limited, difficulties with the continuity of care and provision for the management of complications, must be overcome.
- [Show abstract] [Hide abstract] ABSTRACT: Background Mirror ear, also known as polyotia, is an infrequently reported form of external ear malformation characterized by morphologic and dimensional similarity to a normal pinna. The condition has been described in association with various syndromes, and in isolation. However, as the data with specific relevance to polyotia is sparse, not only are the precise causative processes of mirror ear unknown, but the paucity of documented cases also lends the operative approach to be daunting. Methods Six patients with eight mirror ears underwent surgical reconstruction at Great Ormond Street Hospital for Children. All children were followed from infancy and reviewed in a multidisciplinary setting to coordinate aspects of their care—including plastic surgery, maxillofacial surgery, dentistry, audiology, speech and language pathology, and psychiatry where relevant. Concurrent surgical procedures in addition to mirror ear correction occurred in four patients. Results Pleasing results were achieved in all cases, as reconstruction employed a bespoke approach. Nonetheless, there were unifying principles adhered to, which began in the planning stages by assessing the morphology of the anomalous ear and evaluating the accessory cartilage available for utilization. Deliberate positioning of the incisions, exploiting cartilage remnants to fill the depression of the mirrored ear, and manipulation of excess tissue to reconstruct an anatomically sound tragus were crucial to achieving agreeable aesthetic results. Conclusions Given that it is rarely encountered, the successful reconstruction of a mirrored ear requires a thoughtful surgical approach. With this report, we provide a comprehensive review of this unique type of ear deformity, significantly add to the documented cases of polyotia, and describe our operative technique to recreate a tragus that throws a natural shadow in the conchal bowl and shields the external auditory meatus. Level of evidence: level V, therapeutic study.
- [Show abstract] [Hide abstract] ABSTRACT: Human somatic stem cells with neural differentiation potential can be valuable for developing cell-based therapies, including treatment of birth-related defects, while avoiding issues associated with cell reprogramming. Precisely defining the "identity" and differentiation potential of somatic stem cells from different sources, has proven difficult, given differences in sets of specific markers, protocols used and lack of side-by-side characterization of these cells in different studies. Therefore, we set to compare expression of mesenchymal and neural markers in human umbilical cord-derived mesenchymal stem cells (UC-MSCs), paediatric adipose-derived stem cells (p-ADSCs) in parallel with human neural stem cells (NSCs). We show that UC-MSCs at a basal level express mesenchymal and so-called “neural” markers, similar to that we previously reported for the p-ADSCs. All somatic stem cell populations studied, independently from tissue and patient of origin, displayed a remarkably similar expression of surface markers, with the main difference being the restricted expression of CD133 and CD34 to NSCs. Expression of certain surface and neural markers was affected by the expansion medium used. As predicted, UC-MSCs and p-ADSCs demonstrated tri-mesenchymal lineage differentiation potential, though p-ADSCs display superior chondrogenic differentiation capability. UC-MSCs and p-ADSCs responded also to neurogenic induction by up-regulating neuronal markers, but crucially they appeared morphologically immature when compared with differentiated NSCs. This highlights the need for further investigation into the use of these cells for neural therapies. Crucially, this study demonstrates the lack of simple means to distinguish between different cell types and the effect of culture conditions on their phenotype, and indicates that a more extensive set of markers should be used for somatic stem cell characterization, especially when developing therapeutic approaches.
Chapter: Congenital ear anomalies
Chapter: Vascular anomalies
Chapter: Congenital melanocytic naevi
- [Show abstract] [Hide abstract] ABSTRACT: Extravasation is an iatrogenic injury that may produce soft tissue necrosis requiring surgical reconstruction (Rose et al., 2008) and (Goon et al., 2006).(1)(,2) Previous review of extravasation injuries within our hospital showed that early referral to plastic surgeons and washout of high-risk cases lead to favourable outcome in 86% of patients (Gault, 1993).(3) Hospital-wide guidelines were introduced in 2005. This paper closes the audit loop by evaluating extravasation injuries outcome following the introduction of these guidelines. All patients referred to the plastic surgery department for extravasation injuries between October 2008 and October 2009 were reviewed. A favourable outcome was defined as resolution without tissue loss requiring surgical reconstruction. Patients were excluded if they sustained the extravasation in other institution. A total of 82 extravasation injuries in 78 patients were reviewed during the audit period. Mean age was 3.2 years (Median 0.2 years, Minimum 0 day, and maximum 16.7 years). The injuries were more frequent on the left half of the body (52%) and involving the upper limbs (59%). Mean time to referral was 8 h, with 60% of patients referred within 6 h of the injury, 30% in 6-12 h, and 10% referred after more than 12 h 26% of the injuries required washout treatment - the rest was treated conservatively. Tissue necrosis occurred in 3 cases (4%) but required no surgical intervention due to the small area affected. Our audit showed an improved outcome of extravasation injury following introduction of hospital-wide guidelines of early referral to specialist team and washout of high-risk cases. Copyright © 2015 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.
- [Show abstract] [Hide abstract] ABSTRACT: Terminal myelocystocele is a severe form of spinal dysraphism characterized by cystic expansion of the terminal spinal cord that herniates through a deficiency of the posterior sacral spinal elements to fuse with the subcutaneous fat. Postnatal enlargement of the subcutaneous fluid-filled sac may result in progressive neurological deficit and threaten the viability of the overlying skin. Surgical repair entails spinal cord untethering, resection of nonfunctional neural elements and watertight reconstruction of the terminal thecal sac. Young age at the time of surgery, large dural defect, attenuated tissues and locally altered CSF dynamics frequently mean that wound complications including CSF leakage and pseudomeningocele formation are common. With consideration of these requirements, we describe our surgical technique in terminal myelocystocele repair, which combines a novel surgical incision and for the first time in a neurosurgical setting, the use of a de-epithelialized skin flap to augment the closure. We report successful operative outcomes in three infant patients with terminal myelocystocele.
- [Show abstract] [Hide abstract] ABSTRACT: Background: The incidence of midline frontonasal dermoid cysts is one in 20,000 to one in 40,000. These lesions may have intracranial extension. This is explained by the anatomy and embryology of nasofrontal development. Skin involvement may also be extensive. Incomplete excision frequently leads to recurrence. The authors report their experience and pathway for management of midline dermoids. Methods: Databases were searched to identify patients who had undergone surgery for removal of a dermoid cyst. Preoperative imaging and indications for surgery were reviewed. Cases were grouped according to surgical approach, and outcomes and complications were identified. Results: Fifty-five patients were treated. Magnetic resonance imaging or computed tomography was used to delineate the anatomy, and surgical excision was expedited if there was a history of infection, especially if imaging suggested intracranial extension. Twelve patients were treated endoscopically (one was converted to open). Eleven required transcranial approaches for intracranial extension (20 percent). Of these, one lesion breached the dura. The remaining 32 patients had dermoids excised with an open approach (direct, bicoronal, or rhinoplasty). There were no recurrences in the open group and there was one recurrence in the transcranial group. This was treated by reexcision. Conclusion: Midline dermoid cysts are relatively uncommon. However, knowledge of the pathogenesis of these lesions together with the authors' experience over 15 years has allowed them to develop a protocol-driven approach, with a low incidence of complications.
- [Show abstract] [Hide abstract] ABSTRACT: Treacher Collins syndrome (TCS), mandibulofacial dysostosis, or Franceschetti–Zwahlen–Klein syndrome, is a rare genetic disorder characterised by dysgenesis of the hard and soft tissues of the first and second branchial arches. Early operations focus on maintaining the airway, protecting the eyes, and supporting auditory neurological development. Later operations include staged reconstruction of the mouth, face, and external ear. Bimaxillary surgery can improve the maxillomandibular facial projection, but correction of malar, orbital rim, and temporal defects may be more difficult. We present a clinical review of the syndrome with a chronological approach to the operations.
- [Show abstract] [Hide abstract] ABSTRACT: Context: The hormone fibroblast growth factor 21 (FGF21) is a key metabolic regulator in the adaptation to fasting. In food-restricted mice, inhibition of skeletal growth is mediated by the antagonistic effect of FGF21 on GH action in the liver and growth plate. Objective: The objective of the study was to assess the role of FGF21 in growth regulation in humans using postnatal growth failure of very preterm infants as a model. Design: FGF21 levels were measured serially in very preterm infants, and their linear growth evaluated from birth to term-equivalent age. Primary chondrocytes obtained from pediatric donors were used to test whether FGF21 can directly interfere with GH signaling. Results: A negative association (β -.415, P < .005, linear regression model) of FGF21 levels with the change in SD score for length was found. In primary chondrocytes, FGF21 upregulated basal and GH-induced SOCS2 expression and inhibited GH-induced STAT5 phosphorylation as well as GH-induced COLII and ALP expression. Finally, FGF21 inhibited GH-induced IGF-1 expression and cell proliferation, indicating GH resistance. However, FGF21 did not affect IGF-1-induced cell proliferation. Conclusions: Elevated FGF21 serum levels during the first weeks of life are independently associated with postnatal growth failure in preterm infants. Furthermore, our data provide mechanistic insights into GH resistance secondary to prematurity and may offer an explanation for the growth failure commonly seen in chronic conditions of childhood.
- [Show abstract] [Hide abstract] ABSTRACT: OBJECTIVES Jeune syndrome (asphyxiating thoracic dystrophy) is a rare disorder characterized by skeletal dysplasia, reduced diameter of the thoracic cage and extrathoracic organ involvement. Fatal, early respiratory insufficiency may occur. Two-stage lateral thoracic expansion has been reported, addressing each side sequentially over 3–12 months. While staged repair theoretically provides less invasive surgery in a small child with respiratory distress, we utilized a single stage, bilateral procedure aiming to rapidly maximize lung development. Combined bilateral surgery also offered the chance of rapid recovery, and reduced hospital stay. We present our early experience of this modification of existing surgical treatment for an extremely rare condition, thought to be generally fatal in early childhood.
- [Show abstract] [Hide abstract] ABSTRACT: Postpneumonectomy syndrome is a rare complication following pneumonectomy with its related change in mediastinal configuration. Symptoms range from airway obstruction to esophageal symptoms, leading at times to a persistent requirement for respiratory support. Surgery is often beneficial, which is in the form of placement of a prosthesis, with variable results. We report 2 cases of postpneumonectomy syndrome: one with successful relief, and the other in which the saline-filled prosthesis failed to achieve the desired result.
- [Show abstract] [Hide abstract] ABSTRACT: Postpneumonectomy syndrome (PPS) is a rare syndrome whereby the airway and oesophagus become obstructed due to extreme rotation of the mediastinum after pneumonectomy. Our treatment of this condition involved mediastinal repositioning and placement of a saline filled tissue expander into the pleural space. This has not been reported in the plastic surgical literature and we describe technical difficulties and how they were overcome. © 2014 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.
- [Show abstract] [Hide abstract] ABSTRACT: Unlabelled: Scaffold cellularization for cartilage engineering can aid implant properties, their retention and minimize repeated intervention, particularly in paediatric reconstructive craniofacial surgery. We developed novel bionanoscaffolds using paediatric adipose tissue-derived stem cells (hADSCs), an accessible autologous cell source, and POSS-PCU. Little is known about cellular responses to this nanomaterial, though it was used in human. We assessed: 1) POSS-PCU cellularization and bioaffinity to hADSCs; 2) hADSC chondrogenic differentiation ability in POSS-PCU; 3) whether bionanoscaffolds became encased within a vascular network and/or vascularised. POSS-PCU supported ADSC survival and proliferation and their migration and differentiation into cartilage within the nanoscaffold. Furthermore, after CAM-grafting, bionanoscaffolds were rapidly surrounded by blood vessels without any apparent negative reaction and erythrocytes of host origin were detected inside the scaffold, suggesting invasion from some capillaries. Altogether, this study demonstrates that POSS-PCU displays excellent bioactivity and hADSC/POSS-PCU bionanoscaffolds offer much promise for autologous cell-based tissue engineering for clinical applications. From the clinical editor: In this study, human adipose tissue derived stem cells were used in combination with POSS-PCU nanoscaffolds to generate cartilage tissue demonstrating excellent bioactivity for autologous cell-based tissue engineering for clinical applications.
- [Show abstract] [Hide abstract] ABSTRACT: Autologous microtia reconstruction is generally performed in two stages. The second stage presents a unique opportunity to carry out other complementary procedures. The present study describes our approach to microtia reconstruction, wherein the second stage of reconstruction is combined with final refinements to the ear construct and/or additional procedures to enhance facial contour and symmetry. Retrospective analysis of patients who underwent two-stage microtia reconstruction by a single surgeon (NWB) was conducted in order to ascertain those that had ancillary procedures at the time of the second stage. Patient and operative details were collected. Thirty-four patients (male, 15, median age and age range at second stage, 11 and 10-18 years, respectively) who had complementary procedures executed during the second stage of auricular reconstruction were identified. Collectively, these included centralizing genioplasty (n = 1), fat transfer (n = 22), ear piercing (n = 7), and contralateral prominauris correction (n = 7). Six patients had correction for unilateral isolated microtia and in the remaining 28 patients, auricular reconstruction for microtia associated with a named syndrome. All patients reported a high rate of satisfaction with the result achieved and the majority (85%) reported no perceived need for additional surgical refinements to the ear or procedure(s) to achieve further facial symmetry. No peri- or post-operative complications were noted. Combining the final stage of autologous microtia reconstruction with other ancillary procedures affords a superior aesthetic outcome and decreased patient morbidity.
Great Ormond Street Hospital for Children NHS Foundation Trust
Londinium, England, United Kingdom
- Department of Plastic Surgery