Pre-natal and post-natal diagnosis of congenital upper limb differences: The first 3 years of the Australian Hand Difference Register.

AIMS: Children with a congenital upper limb difference (CoULD) are a diverse group who often require multidisciplinary care and long-term support for functional and social impacts. The Australian Hand Difference Register (AHDR) provides a national database of children born with a CoULD and aims to facilitate research and improve health care for affected children. Using data from the first 3 years of its operation, we analysed the demographic and clinical features of participating families, including type of CoULDs and the frequency of pre-natal and syndromic diagnoses. METHODS: Families were recruited from tertiary plastic surgery, orthopaedic and genetics clinics, as well as by self-referral. Hand differences were classified by the consulting physician according to the Oberg-Manske-Tonkin classification system. Primary carers were invited to complete an online questionnaire covering demographic information, pregnancy and newborn outcomes and diagnostic details. RESULTS: Between August 2017 and September 2020, 822 families consented and 320 questionnaires were reviewed. CoULDs were detected pre-natally in 66 (20.6%) and post-natally in 248 children (77.5%); data for 6 (1.9%) children were missing. The most common CoULDs were radial polydactyly, symbrachydactyly with ectodermal elements and radial longitudinal deficiency, hypoplastic thumb. Twenty-seven children (8.4%) had an associated syndrome, 7 diagnosed pre-natally and 19 post-natally; the most common were VACTERL association, Poland anomaly, Holt-Oram and ectrodactyly-ectodermal dysplasia-clefting syndromes. CONCLUSIONS: The AHDR is a valuable resource for understanding the relative frequencies of CoULDs. Participation will assist future research into the diagnostic journeys of children with CoULDs, including risk factors, diagnosis and psychosocial impacts.

Extravasation injury in a paediatric population.

BACKGROUND: Extravasation occurs when a drug is inadvertently administered outside of the vein. Depending on the substance involved, this may lead to tissue necrosis with significant long-term morbidity. Children, particularly neonates, are particularly susceptible to extravasation with up to 70% of children in neonatal intensive care unit having some form of extravasation injury. These injuries are commonly referred to plastic surgeons for ongoing management. METHODS: We prospectively collected information on all extravasation injuries referred to the plastic surgery department in a children's hospital over an 18-month period. Data collected included the agent involved in the extravasation, treatment and outcomes. RESULTS: In total, there were 43 extravasation injuries recorded on the hospital risk management system during the period of this study. All of these were referred to the plastic surgery team for ongoing management. Five patients (11%) underwent washout of their injuries. Three patients (7%) suffered injuries, which led to significant tissue necrosis, delayed healing and prolonged morbidity. CONCLUSION: Smaller infants, particularly those being cared for in an intensive care setting, are at increased risk for extravasation injury. Early referral and treatment of high-risk extravasation injuries may reduce the incidence of tissue loss and morbidity.

The use of vascularised bone capping to prevent and treat amputation stump spiking in the paediatric population.

BACKGROUND: Overgrowth of the stump skeleton is a major complication seen in children after an amputation. In advanced cases, perforation of the bone spike through the skin can occur. Many surgical treatments have been employed to treat and prevent this, with best results seen when non-vascularised osteo-chondral bone grafts are placed to try to mimic a trans-articular amputation. We reviewed our outcomes using vascularized bone flaps to prevent and treat spiking. PATIENTS AND METHODS: Between 2000 and 2016 we carried out six vascularised osteo-cartilaginous bone capping procedures. Five patients underwent the procedure as an adjunct to primary amputation and in a single patient it was used to treat established bone spiking. Trauma accounted for three cases, with the other three being tumour, vascular malformation and ischemia. Three patients had pedicled bone flaps placed on the amputation stump and three underwent free tissue transfer (free calcaneus, free scapular angle, and free proximal tibia). Five cases involved lower limb amputations, with one in the upper limb. RESULTS: One patient had an early post-operative complication in the form of partial skin flap necrosis that required debridement and skin grafting. All bone flaps survived. Mean follow-up was 6.5 years. All patients had bony union with no development of stump spiking. Two patients required further procedures unrelated to the bone flaps. CONCLUSION: Vascularised bone flaps to cap amputation stumps may be a safe and effective method of preventing and treating long-bone stump spiking following amputation in children.

Paediatric fingertip composite grafts: Do they all go black?

BACKGROUND: Fingertip injuries are amongst the most frequently seen hand injuries in the paediatric population. The present study evaluated the composite graft survival rate in distal digital amputations with respect to injury type, amputation level and time to surgery. METHODS: We performed a retrospective review of patients who underwent composite grafting of fingertip injuries over an 11-year period at a paediatric hospital. All children who underwent non-vascularized replantation of amputated fingertips were included. Patients were excluded if they failed to attend at least one follow-up appointment. Demographic information was recorded. The nature and level of injury and time to surgery was also recorded. Graft viability was characterized as no take, partial take, or complete take. The number of secondary procedures and number and duration of follow-up appointments were recorded. RESULTS: A total of 105 patients underwent fingertip composite grafting, of whom 96 were suitable for inclusion in this study. The median age was 2.4 years (0-16 years); there were 48 boys (46%) and 57 girls (54%). Thirty-one patients had no graft take (32%), 50 patients had partial take (52%) and 15 patients had complete take (16%). Only two patients underwent secondary revision (2%). The median number of follow-up appointments was 4, and the mean follow-up time was 68 days. Time to surgery or level of amputation did not have a statistically significant influence on outcome. CONCLUSIONS: Over two-thirds of composite grafts in children showed some degree of take, albeit partially in the majority. Morbidity was low, and most children did not require further surgery.

Identification of functional elements in the murine Gabp alpha/ATP synthase coupling factor 6 bi-directional promoter.

The GA-repeat binding protein (GABP) is a ubiquitous transcription factor involved in transcriptional regulation of genes encoding proteins involved in a variety of cellular processes including adipocyte differentiation, mitochondrial respiration, and neuromuscular signaling. GABP is composed of two subunits; the GABP alpha subunit is a member of the Ets-family of transcription factors, and the unrelated ankyrin repeat containing GABP beta subunit. We previously identified a bidirectional promoter directing the expression of Gabpa (GAA) gene in one direction and ATP Synthase Coupling Factor 6 (Atp5j) (CF6) gene in the other [Chinenov, Y., Coombs, C. and Martin, M. E., 2000a. "Isolation of a bi-directional promoter directing the expression of the mouse GABP alpha and ATP Synthase Coupling Factor 6 genes. Gene 261:311-320.]. In this study we characterize sequence elements and regulatory factors contributing to the promoter activities of the GAA/CF6 bidirectional promoter. The core of the GAA/CF6 bidirectional promoter is retained within a 400 bp sequence and contains four GABP binding sites, a Sp1/3 binding site and an YY1 binding site. Site-directed mutagenesis demonstrated that while no single factor binding site was essential for promoter activity in either direction, the GA1 site located proximal to the previously mapped transcription start sites functioned cooperatively with the other GABP binding sites and with the Sp1/3 and YY1 sites to provide transcriptional activation of the GAA and CF6 promoters. The other GABP sites and the Sp1/3 and YY1 binding sites were functionally redundant for basal promoter activities in both directions. Electrophoretic mobility shift assays identified multiple DNA-protein complexes containing GABP alpha, GABP beta, Sp1, Sp3 or YY1 proteins, including one ternary complex containing GABP alpha, GABP beta and Sp1 proteins. Binding of GABP to the GAA/CF6 bi-directional promoter provides the potential for autoregulation of GABP alpha expression and confirms the importance of GABP in the coordinate expression of respiratory chain components.