Poland-Möbius syndrome: a case report implicating a novel mutation of the PLXND1 gene and literature review.

BACKGROUND: Möbius (Moebius) and Poland's syndromes are two rare congenital syndromes characterized by non-progressive bilateral (and often asymmetric) dysfunction of the 6th and 7th cranial nerves and hypoplasia of the pectoral muscles associated with chest wall and upper limb anomalies respectively. Manifest simultaneously as Poland-Möbius (Poland-Moebius) syndrome, debate continues as to whether this is a distinct nosological entity or represents phenotypic variation as part of a spectrum of disorders of rhomboencephalic development. Etiological hypotheses implicate both genetic and environmental factors. The PLXND1 gene codes for a protein expressed in the fetal central nervous system and vascular endothelium and is thus involved in embryonic neurogenesis and vasculogenesis. It is located at chromosome region 3q21-q22, a locus of interest for Möbius syndrome. CASE PRESENTATION: We present the first report of a patient with Poland-Möbius syndrome and a mutation in the PLXND1 gene. A child with Poland-Möbius syndrome and a maternally inherited missense variant (NM_015103.2:ex14:c.2890G > Ap.V964M) in the PLXND1 gene is described. In order to contextualize these findings, the literature was examined to identify other confirmed cases of Poland-Möbius syndrome for which genetic data were available. Fourteen additional cases of Poland-Möbius syndrome with genetic studies are described in the literature. None implicated the PLXND1 gene which has previously been implicated in isolated Möbius syndrome. CONCLUSIONS: This report provides further evidence in support of a role for PLXND1 mutations in Möbius syndrome and reasserts the nosological link between Möbius and Poland's syndromes. LEVEL OF EVIDENCE: Level V, Descriptive Study.

Extremity Ischemia After Jellyfish Envenomation: A Case Report and Systematic Review of the Literature.

BACKGROUND: Extremity ischemia and necrosis after jellyfish envenomation can be mutilating and cause long-term functional deficits. The best way to manage these presentations is unknown. OBJECTIVE: The aim of this review was to establish an evidence-based consensus for the management of extremity ischemia after jellyfish envenomation. METHODS: A systematic review of cases of extremity ischemia and necrosis after envenomation by marine cnidarians was performed to clarify what is and what is not known about management and outcomes, to draw conclusions about how best to manage these rare presentations, and to establish an evidence-based algorithm. RESULTS: The ischemic sequelae of envenomation typically evolves over a few days. Close medical supervision is necessary to react promptly to the evolving clinical scenario. In the literature, 15 different pharmacologic classes have been used to manage these presentations. Only IV infusions of prostaglandin derivatives and intra-arterial thrombolytics have been found to improve the clinical picture and avoid the need for surgical fasciotomy and debridement in some cases. Anticoagulants, antiplatelet agents, steroids, antibiotics, and nitrates, which are among the most commonly prescribed pharmacologic agents, have not been observed to alter the clinical picture. CONCLUSIONS: Surgery for compartment syndrome and necrosis are common sequelae of extremity envenomation by marine cnidarians. Only prompt use of IV prostaglandins or intra-arterial thrombolytics can halt ischemic progression and avoid the need for surgery. An algorithm is proposed to guide management of these rare and mutilative presentations.

Correction of Thumb Duplication: A Systematic Review of Surgical Techniques.

Surgical intervention for thumb duplication can be divided into three categories: simple excision of the accessory thumb, excision of the accessory thumb with reconstruction from available "spare parts," and combining the two thumbs into one, as described by Bilhaut. This prospectively PROSPERO registered systematic review evaluates the overall, aesthetic and functional outcomes for the latter two options (reconstruction from spare parts vs. combining two thumbs into one), aiming to facilitate evidence-based decision making when addressing thumb duplication and direct future research. The review was performed in accordance with the Cochrane Handbook of Systematic Reviews and PRISMA statement. Embase, PubMed, Medline, and Cochrane databases were systematically searched. Studies offering comparisons of techniques were included. Risk of bias was assessed using the Risk of Bias In Non-randomized Studies-of Intervention tool. The quality of the evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation. Ten retrospective observational studies were included. Data did not consistently allow analysis by procedure type. Four studies reported similar overall outcomes between techniques, while two specifically reported poor overall outcomes for the Bilhaut procedure. Two studies reported comparatively worse aesthetic outcomes for the Bilhaut procedure with four studies reporting comparatively improved functional outcomes for this procedure. Overall, interpretation of outcomes was challenging with no patient-reported outcome measures used. The quality of the evidence was universally "very low" due to all studies being at risk of methodological bias. Based on the available evidence, surgical techniques for thumb duplication correction appear comparable regarding overall outcome. There is limited evidence suggesting reconstruction with spare parts offers superior aesthetic outcomes at the expense of stability. The level of evidence is III.

RADIATE - Radial Dysplasia Assessment, Treatment and Aetiology: protocol for the development of a core outcome set using a Delphi survey.

BACKGROUND: Radial dysplasia (RD) is a disfiguring, potentially disabling congenital upper limb anomaly. Multiple surgical techniques are in current use, with little agreement on the optimal treatment approach. At present, no core outcome set exists specifically for RD, and the literature is dominated by retrospective case series. A recent systematic review by this group demonstrated significant heterogeneity on which outcomes are measured and how they are measured. METHODS/DESIGN: The RADIATE study will conduct a three-round online Delphi process, involving adult RD patients, the parents of children with RD, hand surgeons and hand therapists. The initial list of outcomes was drawn from our recent systematic review and will be supplemented by suggestions from the stakeholder groups. Following the Delphi process, outcomes that meet the consensus in definition will be ratified at a final consensus meeting. We will then follow the COSMIN guidelines to select outcome measurement instruments. Where appropriate, these will overlap with the outcome measures specified in the forthcoming standard set for congenital upper limb anomalies published by the International Consortium for Health Outcomes Measurement. DISCUSSION: The Radial Dysplasia Assessment, Treatment and Aetiology (RADIATE) study aims to address the uncertainty in the treatment of RD, and to begin to answer the question 'What is the most appropriate treatment of the forearm and hand for children with RD?' by establishing a core outcome set. TRIAL REGISTRATION: COMET initiative study, 902 . Registered in May 2016.

Free tissue transfer in patients with sickle cell disease: Considerations for multi-disciplinary peri-operative management.

INTRODUCTION AND AIMS: Sickle cell disease (SCD) is an increasingly common condition in the UK. The safety of free tissue transfer in these patients is controversial, and no specific guidelines exist. The aim of this paper is to create recommendations for the plastic surgical multidisciplinary team for use in the assessment and management of SCD patients undergoing free tissue transfer and reconstruction. METHOD: A literature review was performed in PubMed of 'sickle [TiAb] AND plast* adj3 surg*. RESULTS: Sickle cell disease is explained, as is the relative peri-operative risk in different genotypes of SCD. Acute and chronic manifestations of SCD are described by system, for consideration at pre-operative assessment and post-operative review. The evidence surrounding free tissue transfer and SCD is discussed and the outcomes in published cases summarised. An algorithm for peri-operative multi-disciplinary management is outlined and justified. CONCLUSION: Free tissue transfer theoretically carries a high risk of a crisis, due not only to long anaesthetic times, but the potential requirement for tourniquet use, and the relatively hypoxic state of the transferred tissue. This paper outlines a useful, practical algorithm to optimise the safety of free tissue transfer in patients with SCD.

The Vascularized Medial Femoral Corticoperiosteal Flap for Thumb Reconstruction.

We present an interesting method of shaping a vascularized medial femoral condyle (MFC) flap into a "neophalanx" for phalangeal reconstruction. Our patient presented with limited strength and function secondary to fracture nonunion of the proximal phalanx of the dominant thumb. Following excision of the pseudarthrosis, an MFC corticoperiosteal flap was harvested, sculpted into a prism shape and inset. The superomedial genicular pedicle was anastomosed to the princeps pollicis artery and a cephalic tributary. On follow-up, new bone growth was seen on radiographs and the patient had substantially improved function, with full metacarpophalangeal extension, a Kapandji score of 9, and a markedly reduced Disabilities of the Arm, Shoulder and Hand score of 2.68. The MFC flap is useful for reconstruction of bony defects, with minimal donor morbidity. This versatile vascularized flap can be crafted to requisite shapes and is useful for small defects in the hand, including phalangeal reconstruction.

Hand disease in scleroderma: a clinical correlate for chronic hand transplant rejection.

ABSTRACT: Chronic rejection remains a potential long-term consequence of hand composite tissue allotransplantation (CTA). Scleroderma has already been proposed as a model for chronic facial allograft rejection based on potential parallels of observed progression of disease and pathophysiology course. This study proposes a similar model for how chronic rejection may manifest itself in the context of hand CTA through the functional and psychological assessment of patients with scleroderma, should it occur. METHODS: 100 consecutive patients with a clinical diagnosis of scleroderma were recruited into the study. Subjective assessment of static hand disfigurement was carried out through the use of standardised digital photographs. Hand function was assessed through the measurement of active range of motion (AROM) and using the activities of daily living (ADL) and Disabilities of the Arm, Shoulder & Hand (DASH) questionnaire. Psychological and quality of life evaluation comprised the Hospital Anxiety Depression Scale (HADS) and the SF36 health survey. RESULTS: Examination of standardised digital photographs of subjects revealed a variety of hand changes characteristic of scleroderma, ranging from mild to moderate through to severe. Objective assessment of hand disfigurement did not correlate with duration of disease, nor psychological distress. However, individuals with worsening disfigurement demonstrated poorer AROM. Longitudinally no deterioration in terms of function was seen over time in terms of the DASH and ADL results. Nevertheless deterioration of function did have a significant impact on quality of life. Overall HADS showed 22% of individuals as suffering from clinical levels of anxiety and 10% from clinical depression. CONCLUSION: Chronic rejection has not yet occurred in any of the hand transplants performed to date. Scleroderma results in a spectrum of chronic functional and psychological disability that provides a model for the potential outcome of chronic hand allograft rejection. Findings from this study provide insight into the impact of this progressive disease for patients and contribute to the information and consent process for patients considering hand composite tissue transplantation.

A quantitative comparison of psychological and emotional health measures in 360 plastic surgery candidates: is there a difference between aesthetic and reconstructive patients?

This study examines the utility of the aesthetic and reconstructive categorization for making treatment decisions in patients seeking facial surgery. A total of 360 patients with aesthetic or combined functional aesthetic deficits were included. Validated psychological scales were used as outcome measures. All subjects showed clinically significant levels of appearance-related distress, with highest levels in the aesthetic and lowest levels in the functionally impaired group. Significant gender differences were not found on any psychological measures. A small negative correlation was found between age and distress. These findings challenge the validity of restricting treatment on the basis of an aesthetic distinction, since this is the group demonstrating the highest level of need. Neither age nor gender is a reliable discriminator. Subjective assessment of noticeability of disfigurement and associated psychological distress may be more useful in prioritizing treatment in systems with limited resources.

Hypoxia and angiogenesis in rheumatoid arthritis.

PURPOSE OF REVIEW: Angiogenesis is a prominent feature of rheumatoid synovitis. Although new blood vessels deliver oxygen to the augmented inflammatory cell mass, the neovascular network is dysfunctional and fails to restore tissue oxygen homeostasis, so that the rheumatoid joint remains a markedly hypoxic environment. The purpose of this review is to discuss the role of hypoxia and angiogenesis in the pathogenesis of rheumatoid arthritis. RECENT FINDINGS: Vascular pathologic change, in the form of angiogenesis, is important in the perpetuation of rheumatoid arthritis and, in the form of endothelial dysfunction, contributes to associated cardiovascular comorbidity. Recent data suggest that tumor necrosis factor-alpha blockade may modify the vascular pathologic changes in rheumatoid arthritis. Angiogenesis is a prominent feature of rheumatoid synovitis. Emerging evidence based on ultrasonographic vascular imaging and angiogenic biomarkers implicates angiogenesis in the active phase of erosive disease. Many factors contribute to the profoundly hypoxic environment that can arise within the joint affected by rheumatoid arthritis. At a cellular level, hypoxia is detected by a mechanism that regulates cytoplasmic concentrations of hypoxia-inducible factor-1alpha. After translocation to the nucleus, hypoxia-inducible factor-1alpha binds its partner hypoxia-inducible factor-1beta to form a heterodimeric, functional transcription factor, hypoxia-inducible factor-1, which activates a gene program associated with angiogenesis, glycolysis, and adaptation to pH. SUMMARY: Despite the luxuriant vasculature associated with rheumatoid arthritis synovitis, the joint affected by rheumatoid arthritis is hypoxic. Repetitive cycles of hypoxia and reoxygenation together with oxidants produced by phagocytic cells promote chronic oxidative stress within the microenvironment of the affected joint, leading to the generation of reactive oxygen species with the potential to contribute to tissue damage.