Necrotizing fasciitis caused by mono-bacterial gram-negative infection with E. coli - the deadliest of them all: A case series and review of the literature.

INTRODUCTION: Unlike other skin and soft tissue infections, necrotizing fasciitis (NF) is a very rare but potentially fatal condition. Common organisms causing NF are poly-microbial (type I) infection with mixed organisms and mono-bacterial gram-positive infection with mainly streptococci (type II). Mono-bacterial gram-negative NF is a rare form of NF that is not included in the current classification. CASE SERIES: We report four cases of mono-bacterial gram-negative NF caused by E. coli. All patients presented in septic shock and showed landscape-like skin necrosis and pain out of proportion. Radical debridement and escalation of antibiotic treatment was performed in all patients. Short-term survival was 50%. Two patients died of multiorgan failure. Two patients survived short term: One patient was amputated through the knee but died six months later of metastatic prostate cancer. One patient was covered with split thickness skin grafts and died three months later of catheter-associated sepsis with endocarditis. DISCUSSION: Recent findings suggest adding a type III fasciitis, which is caused by mono-bacterial gram-negative organisms. As patients are getting older with even more comorbidities, mono-bacterial gram-negative NF will be an increasing problem for physicians treating soft tissue and skin infections.In oncologic diseases, liver cirrhosis, renal diseases or otherwise immunocompromised patients, mono-bacterial gram-negative NF with E. coli is underestimated. Therefore, in these patients, antibiotic treatment should cover Gram-negative organisms including E. coli. However even with adjusted antibiotic treatment and radical debridement, the short-term survival and long-term outcome are poor.

Neuromuscular reinnervation efficacy using a YFP model.

INTRODUCTION: The gold standard reconstruction for facial reanimation is the functional muscle transfer. The reinnervation of a muscle is never complete, and clinical results are variable with 20% not achieving a satisfactory outcome. We hypothesise that this may be due to a mismatch between the characteristics of the donor nerve and transferred muscle. METHOD: 81 YFP-16 and 14 YFP-H mice were studied in three intervention groups over three time periods. Two parameters were investigated: the number and surface area of reinnervated neuromuscular junctions and regenerating axons. An assessment was made of motor unit proportions. RESULTS: All cases of nerve repair and nerve graft, the neuromuscular junctions (NMJ) were completely reinnervated by regenerating axons. The number and calibre of the regenerating axons were significantly different from controls for both intervention groups. The motor units were smaller in both intervention groups. DISCUSSION: Reinnervation occurs after nerve repair or graft; however, the arbour was reinnervated by large numbers of much smaller axons. These axons showed some evidence of remodelling in the repair group, but not in the graft group. Neither group achieved the parameters of the control group. There were persistent qualitative changes to the morphology of both axons and junctions. Imaging documented both synkinesis and alterations that resemble those seen in ageing. CONCLUSION: Overall, the efficacy of reinnervation is very high with all NMJ reoccupied by regenerating axons. The way small axons are remodelled is different in the nerve repairs compared with the nerve grafts.

Reanimation surgery in patients with acquired bilateral facial palsy.

Acquired bilateral facial palsy is rare and causes difficulty with speech and eating, but dynamic reanimation of the face can reduce the effect of these problems. Of 712 patients who had these procedures during our study period, two had an acquired bilateral facial paralysis. In both, reanimation was completed in a single operation using a free-functional transfer of the latissimus dorsi muscle that was coapted to the masseteric branch of the trigeminal nerve. Both patients achieved excellent non-spontaneous excursion and an improvement in function. Careful evaluation of the available donor nerves including thorough examination and electromyographic testing should always be completed before operation.

Reanimation of the brow and eye in facial paralysis: Review of the literature and personal algorithmic approach.

Facial palsy patients suffer 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. There are a multitude of treatment modalities available and the surgeon has the challenging prospect of choosing the correct intervention to yield the best outcome for a patient. The accurate assessment of the eye in facial paralysis is described and by approaching the brow and the eye separately the treatment options and indications are discussed having been broken down into static and dynamic modalities. Based on our unit's experience of more than 35 years and 1000 cases of facial palsy, we have developed a detailed approach to help manage these patients optimally. The aim of this article is to provide the reader with a systematic algorithm that can be used when consulting a patient with eye problems associated with facial palsy.

The growth factors involved in flexor tendon repair and adhesion formation.

Flexor tendon injuries remain a significant clinical problem, owing to the formation of adhesions or tendon rupture. A number of strategies have been tried to improve outcomes, but as yet none are routinely used in clinical practice. Understanding the role that growth factors play in tendon repair should enable a more targeted approach to be developed to improve the results of flexor tendon repair. This review describes the main growth factors in tendon wound healing, and the role they play in both repair and adhesion formation.

The use of a free vascularised fibula to reconstruct the radius following the resection of an osteosarcoma in a paediatric patient.

Osteosarcoma is the most common high grade bone malignancy in children and the surgical treatment traditionally involves amputation. In our case, a 6-year-old girl was diagnosed with an osteosarcoma of the left distal radius after presenting with forearm pain. After initially being offered an amputation, a second opinion was sought and a limb salvage procedure was offered using a free vascularised fibula bone flap. This resulted in limb preserving surgery which allowed the potential for growth with the maximal preservation of function.

A review of fetal scarless healing.

Wound healing is a complex process involving a number of processes. Fetal regeneration has been shown to have a number of differences compared to scar-forming healing. This review discusses the number of differences identified in fetal regeneration. Understanding these differences may result in new therapeutic targets which may reduce or even prevent scarring in adult healing.

The mechanics of flexor tendon adhesions.

The mechanics of adhesions at a local tissue level have not been extensively studied. This study compared microstrains and macrostrains in adhesions of immobilized and mobilized partially lacerated flexor digitorum profundus tendons in a New Zealand White rabbit model. At 2 weeks, 50 digits were randomized to either gross tensile testing or micromechanical assessment, in which the movement of fluorescently labelled cell nuclei, acting as dynamic markers, was visualized using real-time confocal microscopy. The structural stiffness and load at failure of immobilized adhesions were 140% and 160% of that of mobilized adhesions, respectively, and both differences were statistically significant. Micromechanically, different patterns of loading and failure were observed. Mobilized adhesions exhibited over a three-fold higher local strain, which was less uniformly distributed. Confocal microscopy provided an accurate measure of local strain. For the first time, it has been possible to visualize, define, and quantify local adhesion tissue mechanics. Mobilization appears to favour the formation of sites expressing increased local strain responses or those predisposed to heterogeneity and localized failure.

The attachment of intrinsic and extrinsic, mobilized and immobilized adhesion cells to collagen and fibronectin.

This study investigated the attachment of intrinsic and extrinsic, mobilized and immobilized adhesion cells to the extracellular matrix. Five New Zealand White rabbit forepaws were dissected to isolate the flexor tendon core, tendon surface and synovial sheath, which were explanted separately. A further 10 animals were subjected to flexor tendon injuries, randomized to either mobilization or immobilization, and adhesions were explanted at 2 weeks. Cell groups were tested for attachment to collagen type-I or fibronectin and morphometric analysis was made. The attachment of intrinsic tendon cells and adhesion cells from mobilized tendons to both matrix proteins was statistically significantly greater than that of extrinsic tendon cells and adhesion cells from immobilized tendons. Adhesion cells from mobilized tendons were statistically significantly more elongated, which may correlate with the deposition of a more organized matrix. Because the synovial sheath cells were least attached to matrix proteins, selective treatments that reduce cell attachment may be used to exclude them, without inhibiting intrinsic tendon healing.

Shear-aggregated fibronectin with anti-adhesive properties.

Biomaterials based on proteins, such as fibronectin, have the potential to guide cell and tissue behaviour during healing as a function of their unique mechanical and bioactive properties. Fibronectin has been reported as a scaffold for attachment of fibroblasts and subsequent deposition of collagen. We have recently developed a derivative process of shear-aggregated fibronectin that prevents cell attachment without causing cell death. This has potential applications in clinical situations where adhesions form across gliding surfaces and cause loss of function, e.g. peritoneal or flexor tendon adhesions. This in vitro study tested this derivative fibronectin biomaterial and its effects on aggressive adhesion-forming cells, using rabbit flexor tendon synovial fibroblasts. We investigated degradation of the novel biomaterial, and attachment of fibroblasts to glass coated with the biomaterial, relative to fibroblast attachment to uncoated and fibronectin-coated glass. We assessed infiltration of the derivative fibronectin biomaterial by fibroblasts and cytotoxicity of the biomaterial to fibroblasts. The interaction between fibroblasts and the derivative fibronectin biomaterial was visualized using time-lapse photography. The derivative fibronectin biomaterial dissolved by 88% of its mass by 3 weeks. Fibroblast attachment to the novel biomaterial was significantly reduced at 6 h. After 24 h of exposure to the novel biomaterial, fibroblasts did not migrate into it, there was no cell death and no attachment was seen using time-lapse. This novel derivative fibronectin biomaterial combines inhibition of fibroblast attachment with barrier effects and has suitable mechanical properties for surgical use in preventing adhesions in vivo.

The role of an MMP inhibitor in the regulation of mechanical tension by Dupuytren's disease fibroblasts.

Mechanical tension and contracture are two related facets of tissue biology. This study assessed the effect of ilomastat, a broad-spectrum matrix metalloprotease (MMP) inhibitor, on generation of tension by Dupuytren's disease fibroblasts. Nodule and cord-derived fibroblasts were isolated from five patients with Dupuytren's disease; flexor retinaculum acted as the control. A culture force monitor (CFM) provided an in vitro model of tissue organization to assess development of mechanical tension, lattice contraction and spatial remodelling by fibroblasts. Responses to ilomastat were compared to treatment with a control peptide. Nodule and cord-derived fibroblasts exhibited a two-fold increase in tension compared with flexor retinaculum. Ilomastat significantly inhibited development of tension by nodule and cord but not flexor retinaculum derived fibroblasts at 100 microM. These results imply that MMP activity mediates regulation of tensile strength by Dupuytren's disease fibroblasts and may be an important therapeutic target in patients with Dupuytren's disease.

Diagnosis of skin lesions by trainee surgeons: experience improves accuracy.

INTRODUCTION: Accurate clinical diagnosis depends on the reliable recognition of signs and symptoms. This expertise comes from experience in seeing patients which has been traditionally gained over a long training period. Shortened specialist training (Modernising Medical Careers) has led to a greater reliance on structured teaching and skills transfer programmes. The accuracy of clinical diagnosis and the rate at which diagnostic skills improve during training is important for the assessment of trainees, and the delivery of care. PATIENTS AND METHODS: This study assessed the accuracy of clinical diagnosis of skin lesions by two junior plastic surgery trainees. They were asked to diagnose 120 consecutive skin lesions seen in a pigmented skin lesion clinic in 2005, with the histological diagnosis being confirmed following subsequent excision. The process was repeated a year later in 2006 to enable the rate of correct diagnosis to be compared. RESULTS: Initially, 53.3% of diagnoses were correct. A year later, this had risen to 65.0%. Twenty-two different skin pathologies were present in excised specimens, and skin cancers comprised 30%. The trainees demonstrated 93.8% sensitivity in their initial diagnosis of malignancy (95% CI, 79.2-99.2) and 97.4% a year later (95% CI, 86.5-99.9). However, specificity was 69.3% (95% CI, 58.6-78.7) in 2005 and 71.6% (95% CI, 60.5-71.4) in 2006. CONCLUSIONS: Accuracy in the diagnosis of the wide range of skin conditions presenting to an out-patient clinic was shown to increase over a 1-year period. We feel that this improvement resulted from regular clinical exposure supported by a structured learning programme. The shortening of the specialist training period may affect the acquisition of diagnostic skills by trainees and impact on the confidence with which they commence consultant practice.

In vitro flexor tendon cell response to TGF-beta1: a gene expression study.

PURPOSE: Adhesion formation around zone II flexor tendon repairs remains an important clinical challenge. Tendon healing is complex, and when uncontrolled it may lead to adhesion formation. Transforming growth factor-beta1 (TGF-beta1) is a multipotent growth factor known to be involved in wound healing and scar formation. It has also been shown to have a role in both tendon healing and adhesion formation. METHODS: Uninjured rabbit flexor tendons were divided into endotenon, epitenon, and sheath cells and cultured separately. The in vitro effect of TGF-beta1 gene expression was determined on quiescent tendon cells using real-time polymerase chain reaction for collagen type 1, collagen type 3, fibronectin, plasminogen activator inhibitor-1 (PAI-1), and tissue plasminogen activator (t-PA). RESULTS: Endotenon-derived cells showed a statistically significant down-regulation of collagen type I gene expression in response to TGF-beta1 compared with untreated endotenon cells and with both epitenon and sheath cells at a number of time points. However, endotenon cells showed an increase in collagen type 3 gene expression compared with untreated cells and epitenon cells. All cells showed a statistically significant increase in fibronectin in the later time points compared with the untreated cells. Endotenon-derived cells showed an early increase in PAI-1, whereas sheath cells showed a later increase. CONCLUSIONS: We have shown that cells cultured from 3 separate parts of the flexor tendon-sheath complex respond in different ways when stimulated with TGF-beta1. The down-regulation of collagen types 1 and 3 in endotenon cells may give further insight into the effects of TGF-beta1 in tendon healing. Also, the upregulation of fibronectin and PAI-1, combined with a down-regulation of tissue plasminogen activator, could explain the association of TGF-beta1 with tendon adhesion formation. Treatments aimed at improving tendon healing and the prevention of adhesions may arise from modification of the effects of TGF-beta1.

Transforming growth factor beta1 signalling, wound healing and repair: a multifunctional cytokine with clinical implications for wound repair, a delicate balance.

Transforming growth factor beta1 (TGFbeta1) is a multifunctional cytokine known to be involved in a number of human diseases. It is believed to play an important role in wound healing and repair, as it is a key regulator of the production and remodelling of the extracellular matrix through its effect on mesenchymal cells. Over the last few years, it has become evident that the signalling pathway of TGFbeta is complex with numerous receptor-ligand interactions, intracellular pathways and a number of mechanisms, which not only control the signalling but may also decide the response to the TGFbeta signal. This review focuses on TGFbeta1 signalling and the role that TGFbeta1 plays in wound healing, repair and scarring.

A comparison of one- versus two-stage surgery in an experimental model of functional muscle transfer with interposed nerve grafting.

Functional muscle transfer (FMT) combined with cross-facial nerve grafting (CFNG) is the gold standard treatment of chronic unilateral facial palsy, performed by most surgeons over two operative stages to minimise FMT denervation atrophy. Proponents of one-stage surgery cite shorter total recovery time, fewer operative procedures and a possible beneficial neurotrophic effect of muscle attachment. This study aimed to compare one- and two-stage surgery in terms of neural and muscle reinnervation and FMT force production. Forty New Zealand white rabbits underwent one- or two-stage rectus femoris FMT and interposed nerve grafting under different reinnervation conditions. For two-stage surgery, nerve grafting was followed by FMT after three months and by final experiments after a further six months, whereas one-stage groups experienced nerve grafting and FMT together and final experiments after nine months. Outcomes compared were nerve graft and rectus nerve morphometry, FMT reinnervation measured using PGP 9.5, and FMT force production. Statistical analysis was performed by means of the independent samples t-test or the Mann-Whitney Rank Sum test using Statistics Package for the Social Sciences version 11.0.4 for Mac OS X. Nerve graft reinnervation was similar for respective one- and two-stage surgery groups or favoured one-stage surgery. There was no significant difference between respective groups in terms of rectus nerve morphometry, muscle reinnervation, or absolute, weight-adjusted or weight- and control-adjusted tetanic force production. One-stage surgery offers potential advantages including a reduction in the number of surgical procedures, a shorter total recovery time and beneficial economic and healthcare delivery implications. This data supports previous clinical and experimental studies and questions the basis for performing facial reanimation by FMT combined with CFNG over two separate operative stages.

Ki-67 expression in melanoma. A potential method of risk assessment for the patient with a positive sentinel node.

Melanoma patients with a positive sentinel node biopsy generally proceed to regional lymph node dissection, though ultimately only around 20% have evidence of tumour in their "non-sentinel" nodes. A means to identify patients at high risk of non-sentinel node involvement could potentially spare a large number of patients a procedure with significant morbidity. The proliferation marker Ki-67 has been associated with tumour progression in primary melanoma but has not been extensively studied in metastases. The study aims to investigate Ki-67 in primary melanoma and lymph node metastases and investigate any relationship with disease progression. Tissue Arrays of primary melanoma (n=79) and lymph node metastases (n=92) were constructed from paraffin embedded tissue and Ki-67 expression examined by immunohistochemistry. Staining positivity and intensity were assessed and correlated with standard staging criteria and clinical outcome. High Ki-67 expression was associated with both Breslow thickness (chi(2)=8.54, p=0.035) and presence of ulceration (Fisher's Exact test p=0.003) in primary melanoma. In lymph node metastases high Ki-67 expression correlated with Nodal (N) Stage (chi(2)=8.193, p=0.0 17). High Ki-67 expression is associated with melanoma progression and multiple lymph node involvement. This might potentially form the basis of a risk analysis for patients with positive sentinel nodes.

Ectopic nail formation in the hand.

This paper reports an unusual case of ectopic nail formation, reviews the literature and proposes a simple classification of this anomaly.