Approaches to the Management of Synkinesis: A Scoping Review.

Postparalysis facial synkinesis (PPFS) can develop in any facial palsy and is associated with significant functional and psychosocial consequences for affected patients. While the prevention of synkinesis especially after Bell's palsy has been well examined, much less evidence exists regarding the management of patients with already established synkinesis. Therefore, the purpose of this review is to summarize the available literature and to provide an overview of the current therapeutic options for facial palsy patients with established synkinesis. A systematic literature review was undertaken, following the Preferred Reporting Items of Systematic Reviews and Meta-analyses 2020 guidelines. MEDLINE via PubMed and Cochrane Library were searched using the following strategy: ([facial palsy] OR [facial paralysis] OR [facial paresis]) AND (synkinesis) AND ([management] OR [guidelines] OR [treatment]). The initial search yielded 201 articles of which 36 original papers and 2 meta-analyses met the criteria for inclusion. Overall, the included articles provided original outcome data on 1,408 patients. Articles were divided into the following treatment categories: chemodenervation (12 studies, 536 patients), facial therapy (5 studies, 206 patients), surgical (10 studies, 389 patients), and combination therapy (9 studies, 278 patients). Results are analyzed and discussed accordingly. Significant heterogeneity in study population and design, lack of control groups, differences in postoperative follow-up, as well as the use of a variety of subjective and objective assessment tools to quantify synkinesis prevent direct comparison between treatment modalities. To date, there is no consensus on how PPFS is best treated. The lack of comparative studies and standardized outcome reporting hinder our understanding of this complex condition. Until higher quality scientific evidence is available, it remains a challenge best approached in an interdisciplinary team. An individualized multimodal therapeutic concept consisting of facial therapy, chemodenervation, and surgery should be tailored to meet the specific needs of the patient.

Axonal Regeneration Through Autologous Grafts: Does the Axonal Load Influence Regeneration?

INTRODUCTION: Two-stage free functional muscle transfers for long-standing facial palsy can yield unpredictable results. Earlier studies have demonstrated incomplete regeneration across neurorrhaphies in native nerve and higher donor axonal counts correlating with improved outcomes but axonal count in nerve grafts have not been as thoroughly reviewed. To investigate the impact of varying axonal counts in autologous grafts on functional outcomes of repair. MATERIALS AND METHODS: Animals were allocated into three groups: Direct Nerve Repair (DNR, n = 50), Small Nerve Graft (SNG, n = 50), and Large Nerve Graft (LNG, n = 50). All grafts were inset into the Posterior Auricular Nerve with ear movement recovery (EMR) monitored as functional outcome. At various postoperative weeks (POWs), excised specimens were imaged with electron microscopy. Axonal counts were measured proximal to, distal (DAC) to, and within grafts. Total Success Ratio (TSR) was calculated. RESULTS: In DNR, DAC was significantly lower than proximal axonal counts at all POWs, with maximum TSR of 80%. TSR for LNG and SNG were significantly lower at all POWs when compared to DNR, with maximums of 56% and 38%, respectively. LNG had a significantly larger DAC than SNG at POW12 and beyond. A direct relationship was present between DAC and EMR for all values. CONCLUSIONS: Higher native axonal count of autologous nerve grafts resulted in higher percentage of regeneration across neurorrhaphies.

Imaging Peripheral Nerve Regeneration: A New Technique for 3D Visualization of Axonal Behavior.

BACKGROUND: Peripheral nerve assessment has traditionally been studied through histological and immunological staining techniques in a limited cross-sectional modality, making detailed analysis difficult. A new application of serial section electron microscopy is presented to overcome these limitations. METHODS: Direct nerve repairs were performed on the posterior auricular nerve of transgenic YFP-H mice. Six weeks postoperatively the nerves were imaged using confocal fluorescent microscopy then excised and embedded in resin. Resin blocks were sequentially sectioned at 100 nm, and sections were serially imaged with an electron microscope. Images were aligned and autosegmented to allow for 3D reconstruction. RESULTS: Basic morphometry and axonal counts were fully automated. Using full 3D reconstructions, the relationships between the axons, the Nodes of Ranvier, and Schwann cells could be fully appreciated. Interactions of individual axons with their surrounding environment could be visualized and explored in a virtual three-dimensional space. CONCLUSIONS: Serial section electron microscopy allows the detailed pathway of the regenerating axon to be visualized in a 3D virtual space in comparison to isolated individual traditional histological techniques. Fully automated histo-morphometry can now give accurate axonal counts, provide information regarding the quality of nerve regeneration, and reveal the cell-to-cell interaction at a super-resolution scale. It is possible to fully visualize and "fly-through" the nerve to help understand the behavior of a regenerating axon within its environment. This technique provides future opportunities to evaluate the effect different treatment modalities have on the neuroregenerative potential and help us understand the impact different surgical techniques have when treating nerve injuries.

Complex Reconstruction After Sarcoma Resection and the Role of the Plastic Surgeon: A Case Series of 298 Patients Treated at a Single Center.

BACKGROUND: More than 1000 new patients present to the London Sarcoma Unit each year and between 5% and 10% require plastic surgery intervention. Advancements in radiotherapy and chemotherapy protocols combined with higher expectations for limb preservation has led to increased reconstructive challenges. Frequently, primary closure is achievable; however, larger tumors often require specialist reconstruction. STUDY DESIGN: A retrospective chart review of all referred patients from the London Sarcoma Unit requiring reconstruction between February 2006 and January 2015 was performed. Patients who underwent primary amputation were excluded. RESULTS: The total number of operations performed was 298 and the mean follow-up was 16 months (12-46 months). 51% of patients had major comorbidities. Patients could be separated into early (0-1 week postoperatively, n = 167) and late reconstructions (>1 week postoperatively, n = 131). 32 patients were reconstructed with skin grafts, 137 patients were managed with regional flaps and 129 patients were treated with free flaps. CONCLUSIONS: A patient with 3 or more major comorbidities resulted in a significantly increased risk of reconstructive failure (P < 0.05). Our experience has lead us to adhere to the following guidelines: (1) All patients should be reviewed in a multidisciplinary team meeting. (2) After primary excision, patients should be managed with a vacuum dressing until margins are clear. (3) Definitive reconstruction should be performed by a specialist reconstructive surgeon.

Free Functional Platysma Transfer for Restoration of Spontaneous Eye Closure in Facial Paralysis.

BACKGROUND: Facial palsy patients experience an array of problems ranging from functional to psychological issues. With regard to the eye, lacrimation, lagophthalmos, and the inability to spontaneously blink are the main symptoms and, if left untreated, can compromise the cornea and vision. This article reports the outcomes of 23 free functional vascularized platysma transfers used for reanimation of the eye in unilateral facial paralysis. METHODS: Data were collected prospectively for all patients undergoing reanimation of the paralyzed eye using free functional platysma transfer. The only exclusion criterion was that a minimum of a 2-year follow-up was required. Patients were assessed preoperatively and postoperatively and scored using the eFACE tool focusing on eye-symmetry with documentation of blink reflex. RESULTS: A total of 26 free functional platysma transfers were completed between 2011 and 2018; three patients were excluded because of inadequate follow-up. The mean age was 9.1 ± 7.1 years and there were 12 boys and 11 girls. Preoperatively, no patients had evidence of a blink reflex in comparison to 22 patients at 2-year follow-up. There was a statistically significant improvement in palpebral fissure ( P < 0.001) and full eye closure ( P < 0.001) scores at 2-year follow-up; however, there was no statistically significant difference in gentle eye closure ( P = 0.15). CONCLUSIONS: This is the first report of free functional platysma long-term outcomes in eye reanimation. The results demonstrate that successful restoration of the blink reflex can be achieved and full eye closure is obtainable following surgery. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Short- and Long-Term Complications of Free Anterolateral Thigh Flap Reconstructions: A Single-Centre Experience of 92 Consecutive Cases.

Background: The anterolateral thigh (ALT) flap has been amongst the most versatile components of the reconstructive surgeon's armamentarium. The authors utilise these flaps for a variety of reconstructive procedures including lower limb reconstruction; postsarcoma excision; and open fractures. Few studies have discussed the extent of recipient site morbidity and subsequent revisional procedures. We will report our experience of the ALT flap in 92 consecutive reconstructions with focus on recipient site complications and revisional procedures. Methods: Retrospective data collection was done from 92 patients who underwent ALT flap reconstruction-for various large soft tissue defects-at our unit at the Royal Free Hospital, London. We evaluated primary recipient site complications and the requirements for secondary operations after flap transfer. Results: All flaps survived with the exception of 3 cases (97% survival rate) in which irreversible venous thrombosis was encountered. 16 of 92 patients (17%) required a second recipient site operation for the following: 7 patients experienced major recipient site complications that warranted early return to theatre and 9 patients required a secondary revision thinning procedure(s). 8 of the 16 patients (50%) requiring second operations had construction on their lower leg/ankle/feet (p value = 0.10). Conclusions: Our data demonstrated effective use of the ALT flap in the management of soft tissue reconstructive surgery. Partial flap necrosis was the main complication at the recipient site. In future work, secondary thinning procedures, particularly at the ankle/foot, should be separated from flap-specific complications. Furthermore, we demonstrate tailoring ALT thickness can be performed safely without compromising flap viability.

Posttraumatic Vascular Anomalies in Hand Surgery-A Case-based Approach.

The field of vascular anomalies (VA) has been subject to changes during the last few decades. The current classification of the International Society for the Study of Vascular Anomalies (ISSVA) offers a simple diagnostic structure. Hand surgeons commonly appear to have limited exposure to VA. Already recognized for more than 120 years, pyogenic granuloma (PG) is by far the most commonly described VA by different disciplines with accordingly diverse treatment strategies and theories behind it. Arteriovenous fistula (AVF), venous aneurysms (VAN), and venous malformations (VM) are, however, rare in hand surgery. With a compilation of four illustrative cases of posttraumatic entities such as AVF, VAN, VM, and PG, we would like to highlight possible daily exposure to VA in the general hand surgery practice. We discuss diagnostic and therapeutic options as well as the current literature with focus on posttraumatic VA.

Predicting risk factors that lead to free flap failure and vascular compromise: A single unit experience with 565 free tissue transfers.

BACKGROUND: Even though the benefit of free tissue transfer is uncontested in complex reconstructive cases, vascular compromise and/or flap failure remain a challenge for the surgeon and identification of possible risk factors can aid in the preoperative planning. The aim of this study was to identify the individual risk factors leading to flap failure and/or vascular compromise in free tissue transfers in a single institution over a period of 10 years and to create an index predicting these problems, as well as finding predictors of other postoperative complications. METHODS: Data from all the patients undergoing free tissue transfers between 2009 and 2018 were retrospectively analyzed (demographics, comorbidities, flap failure, vascular compromise, and other complications). The results from the univariate and multivariate analyses were used to create an index. RESULTS: A predictability index with three classes (low, moderate, and high risk) was calculated for each patient, based on defect etiology and the presence of coronary heart disease, diabetes, smoking, peripheral arterial vascular disease, and arterial hypertension. A patient with moderate-risk index had 9.3 times higher chances of developing vascular compromise than those in the low-risk group, while a high-risk index had 18.6 higher odds (p=0.001). American Society of Anesthesiologists (ASA) classification was found to be a predictor of complications in free tissue transfer (p=0.001). CONCLUSION: If patients at a high risk of vascular compromise could be identified preoperatively through this predictability index, patient counseling could be improved and the surgeon might adapt the reconstructive plan and choose an alternative reconstructive strategy.

Workhorse Free Functional Muscle Transfer Techniques for Smile Reanimation in Children with Congenital Facial Palsy: Case Report and Systematic Review of the Literature.

BACKGROUND: Pediatric facial palsy represents a rare multifactorial entity. Facial reanimation restores smiling, thus boosting self-confidence and social integration of the affected children. The purpose of this paper is to present a systematic review of microsurgical workhorse free functional muscle transfer procedures with emphasis on the long-term functional, aesthetic, and psychosocial outcomes. MATERIALS AND METHODS: We performed a literature search of the PubMed database from 1995 to 2019 using the following search strategy: "facial paralysis"[Title/Abstract] OR "facial palsy"[Title]. We used as limits: full text, English language, age younger than 18 years, and humans. Two independent reviewers performed the online screening process using Covidence. Forty articles met the inclusion criteria. The protocol was aligned with the PRISMA statement (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and was registered at the International Prospective Register of Systematic Reviews (PROSPERO, CRD42019150112) of the National Institute for Health Research. RESULTS: Free functional muscle transfer procedures include mainly segmental gracilis, latissimus dorsi, and pectoralis minor muscle transfer. Facial reanimation procedures with the use of the cross-face nerve graft (CFNG) or masseteric nerve result in almost symmetric smiles. The transplanted muscle grows harmoniously along with the craniofacial skeleton. Muscle function and aesthetic outcomes improve over time. All children presented improved self-esteem, oral commissure opening, facial animation, and speech. CONCLUSIONS: A two-stage CFNG plus an FFMT may restore a spontaneous emotive smile in pediatric facial palsy patients. Superior results of children FFMT compared to adults FFMT are probably attributed to greater brain plasticity.

The effect of epigallocatechin-3-gallate, a constituent of green tea, on transforming growth factor-beta1-stimulated wound contraction.

Dermal fibrosis, or scarring, following surgical incisions, traumatic wounds and burns presents a major clinical burden. Transforming growth factor (TGF)-beta1 is a major factor known to stimulate fibroblast proliferation, collagen production, and the differentiation of fibroblast to myofibroblast promoting wound contraction. Furthermore, excessive or prolonged TGF-beta1 has been shown to be associated with scarring. Green tea contains high amounts of polyphenols with the major polyphenolic compound being epigallocatechin-3-gallate (EGCG). EGCG has been shown to be anti-inflammatory, anti-oxidant, and may improve wound healing and scarring, though its precise effect on TGF-beta1 remains unclear. This study aimed at determining the effect of EGCG on TGF-beta1 collagen contraction, gene expression and the differentiation of fibroblast to myofibroblast. EGCG appears to affect the role that TGF-beta1 plays in fibroblast populated collagen gel contraction and this seems to be through both myofibroblast differentiation and connective tissue growth factor gene expression and reduces the expression of collagen type I gene regulation.

The quantitative assessment of wrinkle depth: turning the microscope on botulinum toxin type A.

This prospective study was designed to produce a quantitative model for wrinkle depth assessment, and to compare scientific and clinical methods of evaluation, in the context of botulinum toxin type A treatment. Ten patients were assessed at baseline and 3 weeks after treatment using silicone masks and standardized photography in forehead, glabellar, and lateral canthal areas, at rest and during maximal expression. Wrinkle depth was measured on masks using multiphoton microscopy. Clinical improvement was judged by a panel of observers according to the Hay scale. There was a statistically significant improvement in wrinkle depth after treatment in all areas. Dynamic rhytides demonstrated greatest improvement, notably in the forehead (89% reduction). The objective improvement in static rhytides (43%-56%) has not previously been demonstrated. Clinical evaluation was less accurate than scientific methodology for static lines. This model may have a place in comparing products or treatment regimes, particularly when changes are subtle.

The Propeller Flap for Traumatic Distal Lower-Limb Reconstruction: Risk Factors, Pitfalls, and Recommendations.

BACKGROUND: Defects in the distal third of the leg are difficult to cover and often require free tissue transfer, even for defects of limited sizes. Propeller flaps have been designed specifically as an alternative to free tissue transfer but at times have been associated with unacceptably high complication rates. We therefore aimed to prospectively assess our own institutional experience with this technique and to define its role in lower-limb reconstruction. METHODS: All patients who had been managed with reconstruction of the distal part of the leg with a propeller flap between 2014 and 2017 were included in the study. Demographic, clinical, and follow-up data on the patients and surgical procedures were recorded with special focus on the complication profile. RESULTS: Twenty-six patients underwent propeller flap reconstruction of the distal part of the leg: 12 flaps were based on the posterior tibial artery, and 14 were based on the peroneal artery. Postoperative complications developed in association with 1 of the 12 flaps based on the posterior tibial artery, compared with 8 of the 14 flaps based on the peroneal artery (p = 0.015). Moreover, the presence of a higher Charlson comorbidity index (≥2) was strongly associated with the development of postoperative complications (p < 0.001). CONCLUSIONS: Propeller flaps are a reliable option for traumatic reconstruction in carefully selected patients with lower-limb defects. In our experience, the rate of complications was higher for propeller flaps based on the peroneal artery and for patients with a Charlson comorbidity index of ≥2, whereas posterior tibial artery-based propeller flap reconstruction was a reliable surgical option for patients with a small defect in the distal third of the lower limb. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Transforming growth factor-beta1 stimulation enhances Dupuytren's fibroblast contraction in response to uniaxial mechanical load within a 3-dimensional collagen gel.

PURPOSE: A function of fibroblasts is the generation of cytomechanical force within their surrounding extracellular matrix. Abnormalities in force generation may be the cause of many pathologic conditions including scarring, and some fibroproliferative disorders such as Dupuytren's disease, which is the focus of this report. METHODS: This work investigated the cytomechanical responses of Dupuytren's-derived fibroblasts to externally applied mechanical force using a culture force monitor model, with and without stimulation with the fibrosis-linked cytokine, transforming growth factor-beta1 (TGF-beta1). We compared these responses with cytomechanical responses of fibroblasts derived from the transverse carpal ligament. RESULTS: Dupuytren's fibroblasts display a significantly greater ability to contract a collagen matrix compared with control fibroblasts, with a maximum generated force of 131 dynes (p < .001). These cells did not exhibit a characteristic plateau phase in the contraction, which indicates a delay in achieving tensional homeostasis from Dupuytren's-derived cells. After being subjected to uniaxial overload and underload, Dupuytren's fibroblasts responded by increased force generation, whereas control fibroblasts responded by a reduction in force in response to an overload, and contraction in response to an underload. These changes were exacerbated by the addition of the profibrotic factor TGF-beta1, with a significant increase in generated force for all cell types, in particular during the early phase of fibroblast attachment and contraction, and a positive contraction gradient in response to overloading forces. CONCLUSIONS: These data suggest that cells derived from this fibrotic disease display characteristic abnormalities in force generation profiles. Their default response to loading or underloading is contraction, or increased force generation. This work highlights the role of TGF-beta1 as a mechano-transduction cytokine, which has an influence on the early phase cell of force generation, as well as a role in mechanical responses of cells to external mechanical stimuli. This, in turn, may influence the progression of Dupuytren's disease and the high rates of recurrence seen postoperatively.

Development of the interscutularis model as an outcome measure for facial nerve surgery.

INTRODUCTION: Animal models for the study of facial paralysis have been well developed, but concern has arisen regarding the accuracy of eye closure and whisker movement as outcome measures due to new data regarding interconnectivity between facial nerve branches and autonomic innervation. The posterior auricular nerve (PAN) is an isolated branch of the facial nerve which has been confirmed as the sole motor innervat or of the interscutularis muscle. This study was designed to develop a model for facial nerve palsy utilizing the PAN and interscutularis muscle. METHODS: A custom-made automated video capture system was built into a poly methyl methacrylate cage using a high definition monochrome digital camera and image sensor to record the animal as it drank from a water feeder. A copper floor pad and copper collar around the water feeder were connected to an electrical circuit for automatic saving of the video recording 10 s prior to and 30 s following the drinking event. A pre-operative baseline recording of ear movement during drinking was captured. Female YFP-16 mice at 6 weeks were assigned to sham (Sh, n = 5), nerve excision (Ex, n = 10), or nerve crush (Cr, n = 10) groups with all interventions performed on the right PAN. Sh mice were irrigated with 10 ml normal saline as were the Ex and Cr mice following operative intervention. In Ex mice, a 3 mm section of the PAN was sharply excised and nerve gap was confirmed with fluorescent microscopy. In Cr mice, the PAN was crushed 3 mm from the origin of the facial nerve trunk with size 5 jeweler's forceps for two periods of 20 s. Post-operative video recordings were collected on post-operative days (POD) 1, 10, 20, and 30. To determine the change in ear movement, the right ear was graphically compared to the left control side. RESULTS: Sh animals exhibited a statistically significant reduction in ear movement at POD01 compared to other POD recordings (p < 0.05), but no significant change in right ear movement following POD05. Ex animals had a significant reduction in right ear movement at all PODs in comparison to the left ear (p < 0.05) with no significant change in right ear movement during the study period (p = 0.94). Cr animals showed a significant reduction in right ear movement compared to the left at POD01, POD10, and POD20 (p < 0.05). At POD30, there was no significant difference between ear movement on either side (p = 0.35). There was a significant change in right ear movement during the data collection period (p < 0.05). CONCLUSION: The results show that significant differences were demonstrated between the experimental groups and that significant changes within the crush group were identifiable making this an acceptable model to develop as an accurate outcome measure following rodent facial nerve surgery.

An International Collaborative Standardizing Patient-Centered Outcome Measures in Pediatric Facial Palsy.

IMPORTANCE: Standardization of outcome measurement using a patient-centered approach in pediatric facial palsy may help aid the advancement of clinical care in this population. OBJECTIVE: To develop a standardized outcome measurement set for pediatric patients with facial palsy through an international multidisciplinary group of health care professionals, researchers, and patients and patient representatives. DESIGN, SETTING, AND PARTICIPANTS: A working group of health care experts and patient representatives (n = 21), along with external reviewers, participated in the study. Seven teleconferences were conducted over a 9-month period between December 3, 2016, and September 23, 2017, under the guidance of the International Consortium for Health Outcomes Measurement, each followed with a 2-round Delphi process to develop consensus. This process defined the scope, outcome domains, measurement tools, time points for measurements, and case-mix variables deemed essential to a standardized outcome measurement set. Each teleconference was informed by a comprehensive review of literature and through communication with patient advisory groups. Literature review of PubMed was conducted for research published between January 1, 1981, and November 30, 2016. MAIN OUTCOMES AND MEASURES: The study aim was to develop the outcomes and measures relevant to children with facial palsy as opposed to studying the effect of a particular intervention. RESULTS: The 21 members of the working group included pediatric facial palsy experts from 9 countries. The literature review identified 1628 papers, of which 395 (24.3%) were screened and 83 (5.1%) were included for qualitative evaluation. A standard set of outcome measurements was designed by the working group to allow the recording of outcomes after all forms of surgical and nonsurgical facial palsy treatments among pediatric patients of all ages. Unilateral or bilateral, congenital or acquired, permanent or temporary, and single-territory or multiterritory facial palsy can be evaluated using this standard set. Functional, appearance, psychosocial, and administrative outcomes were selected for inclusion. Clinimetric and psychometric outcome measurement tools (clinician-, patient-, and patient proxy-reported) and time points for measuring patient outcomes were established. Eighty-six independent reviews of the standard set were completed, and 34 (85%) of the 40 patients and patient representatives and 44 (96%) of the 46 health care professionals who participated in the reviews agreed that the standard set would capture the outcomes that matter most to children with facial palsy. CONCLUSIONS AND RELEVANCE: This international collaborative study produced a free standardized set of outcome measures for evaluating the quality of care provided to pediatric patients with facial palsy, allowing benchmarking of clinicians, comparison of treatment pathways, and introduction of value-based reimbursement strategies in the field of pediatric facial palsy. LEVEL OF EVIDENCE: NA.

Quantitative assessment of tissue sections by Reverse Colour Coding.

Stains and dyes are frequently used to emphasise tissue structures for viewing under microscopy but few simple objective quantification methods exist. We describe the derivation of a mathematical formula enabling calculation of the relative contribution of three different coloured components to an image, which can be applied to rapid batch assessment of tissue sections for quantification of area proportions of differently stained elements. In order to validate this method, termed Reverse Colour Coding (RCC), we compared RCC estimations with known area proportions in artificially created images to calculate absolute accuracy, and compared RCC with panel visual estimation (VE) for the assessment of actual NCAM-stained muscle slides. Our results indicate that RCC has an absolute accuracy of 98-98.5% and superior inter-observer agreement and both inter- and intra-observer variability compared with VE. Results also suggest that cognitive bias occurring with VE may be eliminated by use of RCC. We submit RCC as a more accurate and less labour-intensive method of quantifying area proportions of stained tissues on microscopic images.

Matrix metalloproteinase inhibition reduces contraction by dupuytren fibroblasts.

PURPOSE: Dupuytren's disease is a common fibroproliferative condition of the hand characterized by fibrotic lesions (nodules and cords), leading to disability through progressive digital contracture. Although the etiology of the disease is poorly understood, recent evidence suggests that abnormal matrix metalloproteinase (MMP) activity may play a role in cell-mediated collagen contraction and tissue scarring. The aim of this study was to investigate the efficacy of ilomastat, a broad-spectrum MMP inhibitor, in an in vitro model of Dupuytren fibroblast-mediated contraction. METHODS: Nodule-derived and cord-derived fibroblasts were isolated from Dupuytren patients; carpal ligament-derived fibroblasts acted as control. Stress-release fibroblast-populated collagen lattices (FPCLs) were used as a model of contraction. FPCLs were allowed to develop mechanical stress (48 hours) during treatment with ilomastat (0-100 micromol/L), released, and allowed to contract over a 48-hour period. Contraction was estimated by measuring lattice area compared with untreated cells or treatment with a control peptide. MMP-1, MMP-2, and MT1-MMP levels were assessed by zymography, Western blotting, and enzyme-linked immunosorbent assay. RESULTS: Nodule-derived fibroblasts contracted lattices (69% +/- 2) to a greater extent than did cord-derived (55% +/- 3) or carpal ligament-derived (55% +/- 1) fibroblasts. Exposure to ilomastat led to significant inhibition of lattice contraction by all fibroblasts, although a reduction in lattice contraction by nodule-derived fibroblasts was most prominent (84% +/- 8). In addition, treatment with ilomastat led to a concomitant suppression of MMP-1 and MMP-2 activity, whereas MT1-MMP activity was found to be upregulated. CONCLUSIONS: Our results demonstrate that inhibition of MMP activity results in a reduction in extracellular matrix contraction by Dupuytren fibroblasts and suggest that MMP activity may be a critical target in preventing recurrent contracture caused by this disease.

Dermal fibroblasts derived from fetal and postnatal humans exhibit distinct responses to insulin like growth factors.

BACKGROUND: It has been well established that human fetuses will heal cutaneous wounds with perfect regeneration. Insulin-like growth factors are pro-fibrotic fibroblast mitogens that have important roles in both adult wound healing and during development, although their relative contribution towards fetal wound healing is currently unknown. We have compared responses to IGF-I and -II in human dermal fibroblast strains derived from early gestational age fetal (<14 weeks) and developmentally mature postnatal skin to identify any differences that might relate to their respective wound healing responses of regeneration or fibrosis. RESULTS: We have established that the mitogenic response of fetal cells to both IGF-I and -II is much lower than that seen in postnatal dermal fibroblasts. Further, unlike postnatal cells, fetal cells fail to synthesise collagen in response to IGF-I, whereas they do increase synthesis in response to IGF-II. This apparent developmentally regulated difference in response to these related growth factors is also reflected in changes in the tyrosine phosphorylation pattern of a number of proteins. Postnatal cells exhibit a significant increase in phosphorylation of ERK 1 (p44) in response to IGF-I and conversely the p46 isoform of Shc on IGF-II stimulation. Fetal cells however only show a significant increase in an unidentified 100 kDa tyrosine-phosphorylated protein on stimulation with IGF-II. CONCLUSION: Dermal fibroblasts exhibit different responses to the two forms of IGF depending on their developmental maturity. This may relate to the developmental transition in cutaneous wound healing from regeneration to fibrosis.

Facial palsy: what can the multidisciplinary team do?

The functional and psychosocial impact of facial paralysis on the patient is significant. In response, a broad spectrum of treatment options exist and are provided by a multitude of health care practitioners. The cause and duration of the facial weakness can vary widely and the optimal care pathway varies. To optimize patient outcome, those involved in the care of patients with facial palsy should collaborate within comprehensive multidisciplinary teams (MDTs). At an international level, those involved in the care of patients with facial paralysis should aim to create standardized guidelines on which outcome domains matter most to patients to aid the identification of high quality care. This review summarizes the causes and treatment options for facial paralysis and discusses the subsequent importance of multidisciplinary care in the management of patients with this condition. Further discussion is given to the extended role of the MDT in determining what constitutes quality in facial palsy care to aid the creation of accepted care pathways and delineate best practice.

Objective sensory and functional outcomes at the donor site following endoscopic-assisted sural nerve harvest.

BACKGROUND: The sural nerve is a common choice for a nerve graft. Understanding the potential morbidity associated with its harvest is important. In this study, we describe the objective sensory and functional outcomes associated with endoscopic sural nerve harvest from a combined paediatric and adult population. METHODS: Data were collected prospectively from patients attending for follow-up between August 2015 and January 2016, who had previously undergone an endoscopic sural nerve graft harvest. Sensory loss was evaluated using a 5.07 Semmes-Weinstein monofilament. The lower extremity functional scale was used to evaluate the patients' lower limb function. Statistical comparison was made using the Student's t-test. RESULTS: The outcomes from 46 sural nerve grafts were evaluated. The mean age of the patients was 18.1 years (range 4-45 years old). The mean time since surgery was 4.3 years. Those aged ≤18 years had a significantly smaller area of sensory loss (p = 0.003), which was not related to a difference in foot size. Those who had undergone surgery >6 months previously had a significantly smaller area of sensory loss than those who had undergone surgery <6 months ago (p = 0.0002). The mean lower extremity functional scale score was 78.7/80. CONCLUSION: We demonstrated a significantly reduced post-harvest sensory deficit among a paediatric population compared to that seen in adults. Furthermore, sensory loss reduces with time. Despite the sensory loss resulting from sural nerve graft harvest, there is minimal loss of function. As such, the sural nerve continues to be an excellent donor for a nerve graft procedure.