Systematic review of molecular mechanism of action of negative-pressure wound therapy.

BACKGROUND: Negative-pressure wound therapy (NPWT) promotes angiogenesis and granulation, in part by strain-induced production of growth factors and cytokines. As their expression profiles are being unravelled, it is pertinent to consider the mode of action of NPWT at the molecular level. METHODS: MEDLINE (January 1997 to present), Embase (January 1997 to present), PubMed (no time limit), the Cochrane Database of Systematic Reviews and the Cochrane Controlled Trials Register were searched for articles that evaluated the influence of NPWT on growth factor expression quantitatively. RESULTS: Sixteen studies met the inclusion criteria. Tumour necrosis factor expression was reduced in acute and chronic wounds, whereas expression of interleukin (IL) 1ß was reduced in acute wounds only. Systemic IL-10 and local IL-8 expression were increased by NPWT. Expression of vascular endothelial growth factor, fibroblast growth factor 2, transforming growth factor ß and platelet-derived growth factor was increased, consistent with mechanoreceptor and chemoreceptor transduction in response to stress and hypoxia. Matrix metalloproteinase-1, -2, -9 and -13 expression was reduced but there was no effect on their enzymatic inhibitor, tissue inhibitor of metalloproteinase 1. CONCLUSION: Cytokine and growth factor expression profiles under NPWT suggest that promotion of wound healing occurs by modulation of cytokines to an anti-inflammatory profile, and mechanoreceptor and chemoreceptor-mediated cell signalling, culminating in angiogenesis, extracellular matrix remodelling and deposition of granulation tissue. This provides a molecular basis for understanding NPWT.

Validation of a one-stop carpal tunnel clinic including nerve conduction studies and hand therapy.

INTRODUCTION: Carpal tunnel syndrome is the most common hand disorder. We describe a pathway that includes clinical assessment, neurophysiological testing, surgery and physical therapy all at the same visit. METHODS: All referrals for carpal tunnel syndrome were screened for inclusion in a 'one-stop' surgeon-led clinic. Prospective clinical data collected included patient reported outcome measures and satisfaction scores, touch threshold, pinch and grip strength. Patients were assessed clinically, underwent nerve conduction studies and surgery as indicated, all on the same day. Baseline and one-year follow-up data were analysed for 57 patients (62 hands). RESULTS: There was significant improvement in all domains of the Boston Carpal Tunnel and Michigan hand Outcomes questionnaires, grip strength and touch threshold. There were no adverse events. The total mean operating time was 12.8 minutes (range: 5-15 minutes) and the mean tourniquet time was 2.5 minutes (range: 1-11 minutes). Using a dual theatre model produced a short mean turnaround time of 14.8 minutes (range: 2-37 minutes). Patient satisfaction as judged using a Picker questionnaire was very high. CONCLUSIONS: A highly efficient clinical service involving both diagnostics and treatment can be delivered at a single hospital visit while maintaining optimal outcomes and high patient satisfaction.

The microbiological basis for a revised antibiotic regimen in high-energy tibial fractures: preventing deep infections by nosocomial organisms.

BACKGROUND: Deep surgical site infections (SSI's) complicate Gustilo IIIB tibial fractures in 8-13% of cases. Antibiotic prophylaxis typically covers environmental contaminants. However, nosocomial organisms are usually implicated in deep infection. We used the microbiological profile of infected Gustilo IIIB tibial fractures to define a new, dynamic prophylactic regimen which recognises the need for prophylaxis against nosocomial organisms at the time of definitive closure. METHODS: The microbiological profiles of Gustilo IIIB tibial fractures presenting over a 2-year period from January 2006 to December 2007 were reviewed. The environmental contaminants were compared with the organisms isolated from deep SSI's and correlated with the prophylactic antibiotic regimen used. RESULTS: Fifty-two patients were included. Nine developed a deep tissue infection. The pathogens implicated included resistant Enterococci, Pseudomonas, Enterobacter and MRSA. Standard antibiotic prophylaxis provided cover for these combinations in only one of nine cases. This would have improved to eight of nine cases with the use of teicoplanin and gentamicin, given as a one-time dose during definitive soft-tissue closure. Specimens taken from wound debridement were neither sensitive nor specific for the subsequent development of deep infection and did not predict the organisms responsible. CONCLUSIONS: Following high-energy open fracture, a single prophylactic antibiotic regimen directed against environmental wound contaminants does not provide cover for the organisms responsible for deepest SSI's and may have depopulated the niche, promoting nosocomial contamination prior to definitive closure. We advocate a dynamic prophylactic strategy, tailoring a second wave of prophylaxis against nosocomial organisms at the time of definitive wound closure, and at the same time avoiding the potential complications of prolonged antibiotic use.

Strategies to ensure success of microvascular free tissue transfer.

Free tissue transfer has revolutionised tissue reconstruction. Surgical technique is just one of many perioperative factors that determine the eventual outcome of the procedure. Many of these factors can be modified to ensure success. A search of the MEDLINE database using search terms related to perioperative management of free tissue transfer was performed. Further articles were identified by performing related-article searches in MEDLINE. The various perioperative factors that have been demonstrated to affect clinical outcome are discussed along with the current evidence for their optimisation. We present an algorithm for the management of patients undergoing free tissue transfer.

Improving lower limb salvage following fractures with vascular injury: a systematic review and new management algorithm.

BACKGROUND: Lower limb fractures with vascular injuries are associated with a high rate of secondary amputation. Reducing ischaemic time is vital for limb salvage. However, the optimal sequence of surgical management remains unclear. We aimed to review the literature to establish an evidence-based management algorithm. METHODS: All identifiable English language or translated literature related to the surgical sequence of lower limb fractures with vascular injuries was reviewed. RESULTS: A total of 101 cases described in 10 publications (median age: 31; range: 2.5-76) were suitable for analysis. The mean MESS was 4.2. The limb-salvage rate with an ischaemic time of less than 6h was 87%, falling to 61% when ischaemic time exceeded 6h. A preoperative angiography caused a significant delay. The rate of re-vascularisation within 6h improved from 46% (33 of 71) to 90% (27 of 30) with the use of a shunt (p=0.04), with a mean ischaemic time of 3.8h (+/-1.7h, 1 standard deviation (SD)) versus 7.6h (+/-3.8h, 1SD) in those re-vascularised using grafts (p<0.001). The amputation rate of 27% was reduced to 13% by using shunts. CONCLUSION: Early recognition of vascular injury is vital. Formal angiograms are unnecessary and cause crucial delays. A vascular shunt can significantly reduce ischaemic time, enabling unhurried assessment of the feasibility of limb salvage, debridement of demonstrably non-viable tissue and safe skeletal fixation prior to definitive vascular and soft-tissue repair.

Comparison of zones 1 to 4 flexor tendon repairs using absorbable and unabsorbable four-strand core sutures.

Absorbable sutures behave favourably in vitro and in an animal model. We report the outcome of flexor tendon injuries in a series of 272 consecutive patients treated over 45 months with a mean follow-up of 4 (range 3-12) months. Five hundred and seventy-six tendons were repaired in 416 digits. The patients were not randomised and all repairs were performed using a Strickland four-strand core technique. In 191 (73%) patients an absorbable core suture was used (Group 1) and in 81 (27%) a non-absorbable material was used (Group 2). There were six ruptures (2%) in Group 1 and two (2%) in Group 2. Using the original Strickland criteria, there were 72% excellent/good and 28% fair/poor results in the absorbable core suture group, and 73% and 27%, respectively, in the non-absorbable core suture group. This study suggests that appropriate absorbable core sutures can be used safely for flexor tendon repair.

Management of severe open tibial fractures: the need for combined orthopaedic and plastic surgical treatment in specialist centres.

Although it is widely accepted that grade IIIB open tibial fractures require combined specialised orthopaedic and plastic surgery, the majority of patients in the UK initially present to local hospitals without access to specialised trauma facilities. The aim of this study was to compare the outcome of patients presenting directly to a specialist centre (primary group) with that of patients initially managed at local centres (tertiary group). We reviewed 73 consecutive grade IIIB open tibial shaft fractures with a mean follow-up of 14 months (8 to 48). There were 26 fractures in the primary and 47 in the tertiary group. The initial skeletal fixation required revision in 22 (47%) of the tertiary patients. Although there was no statistically-significant relationship between flap timing and flap failure, all the failures (6 of 63; 9.5%) occurred in the tertiary group. The overall mean time to union of 28 weeks was not influenced by the type of skeletal fixation. Deep infection occurred in 8.5% of patients, but there were no persistently infected fractures. The infection rate was not increased in those patients debrided more than six hours after injury. The limb salvage rate was 93%. The mean limb functional score was 74% of that of the normal limb. At review, 67% of patients had returned to employment, with a further 10% considering a return after rehabilitation. The times to union, infection rates and Enneking limb reconstruction scores were not statistically different between the primary and tertiary groups. The increased complications and revision surgery encountered in the tertiary group suggest that severe open tibial fractures should be referred directly to specialist centres for simultaneous combined management by orthopaedic and plastic surgeons.

Functional outcome following extensor synovectomy and excision of the distal ulna in patients with rheumatoid arthritis.

We prospectively measured hand and wrist function in rheumatoid patients undergoing excision of the distal ulna. Range of motion, visual analogue pain scores and grip strength were measured in 22 wrists, and the Jebsen hand function test was administered to seven patients, preoperatively and at 3 and 12 months. At 1 year there were improvements in forearm pronation (P=0.04), supination (P=0.03) and wrist extension (P=0.02), but a reduction in flexion (P=0.009). Active radial deviation was reduced and ulnar deviation increased. There was a significant improvement in grip strength (P=0.05) and reduction in wrist pain (P=<0.0001). At 1 year the Jebsen hand function test showed improvements in simulated feeding, stacking checkers, and lifting large empty cans. Excision of the distal ulna in rheumatoid patients results in an improvement in some aspects of hand function.

Influence of human skin injury on regeneration of sensory neurons.

The regeneration of sensory nerve fibres is regulated by trophic factors released from their target tissue, particularly the basal epidermis, and matrix molecules. Means to modulate this response may be useful for the treatment of neuromas and painful hypertrophic scars and of sensory deficits in skin grafts and flaps. We have developed an in vitro model of sensory neuron regeneration on human skin in order to study the mechanisms of sensory dysfunction in pathological conditions. Adult rat sensory neurons were co-cultured with unfixed cryosections of normal or injured (crushed) human skin for 72 h. Neurons were immunostained for growth-associated protein-43 and the neurite lengths of neuronal cell bodies situated in various skin regions were measured. Two-way analysis of variance was performed. Neurites of sensory cell bodies on epidermis of normal skin were the shortest, with a mean +/- SEM of 75+/-10 micrometer, whereas those of cells on the dermo-epidermal junction were the longest, with a mean +/- SEM of 231+/-18 micrometer. Neurons on the dermo-epidermal junction of injured skin had significantly longer neurites than those on the same region of normal skin (mean +/- SEM = 289+/-21 micrometer). Regeneration of sensory neurons may be influenced by extracellular matrix molecules, matrix-binding growth factors and trophic factors. Altered substrate or trophic factors in injured skin may explain the increase of neurite lengths. This in vitro model may be useful for studying the molecular mechanisms of sensory recovery and the development of neuropathic pain following peripheral nerve injury.

Research options for plastic surgical trainees.

A period of formal research training has become a popular option for many plastic surgical trainees. In this article, we discuss the range of postgraduate research options available and provide information that will allow plastic surgical trainees to make an informed choice about their relative suitability.

Allogeneic skin substitutes applied to burns patients.

Early re-surfacing of burn wounds remains the ideal but is limited by the availability of skin graft donor sites. Cultured grafts overcome these problems and autologous keratinocytes can be grown in culture and placed on a dermal substitute, but this results in delay and requires two operations. We developed an organotypic skin substitute, which achieves cover in one procedure, and have previously found allogeneic cell survival up to 2.5 years after grafting onto clean elective wounds (tattoo removal). Here, we report a short series using the same model applied to burns patients with less than 20% total body surface area affected. The skin substitutes consisted of allogeneic dermal fibroblasts embedded in a collagen gel overlain with allogeneic epidermal keratinocytes, and were grafted to patients with tangentially excised burns. A side-by-side comparison with meshed split-thickness autografts was performed. No grafts became infected. The allogeneic skin substitute showed little effective take at 1 week, and by 2 weeks only small islands of keratinocytes survived. These sites were subsequently covered with meshed split-thickness autograft, which took well. It is concluded that further development of this model is needed to overcome the hostile wound bed seen in burns patients.

Synovial chondromatosis of the metacarpophalangeal joint.

We describe a case of synovial chondromatosis in a metacarpophalangeal joint with invasion of local structures. The degree of local tissue involvement was not demonstrated on the preoperative MRI scans. This case highlights that synovial chondromatosis can be invasive and that even the best preoperative imaging may not demonstrate this.

Production of cytokines, vascular endothelial growth factor, matrix metalloproteinases, and tissue inhibitor of metalloproteinases 1 by tenosynovium demonstrates its potential for tendon destruction in rheumatoid arthritis.

OBJECTIVE: To investigate the role of proinflammatory cytokines, vascular endothelial growth factor (VEGF), matrix metalloproteinases (MMPs), and tissue inhibitor of metalloproteinases 1 (TIMP-1) in the destruction of tendons by tenosynovium in rheumatoid arthritis (RA). METHODS: Synovial specimens were obtained from encapsulating tenosynovium (n = 17), invasive tenosynovium (n = 13), and wrist joints (n = 17) in 18 RA patients undergoing wrist extensor tenosynovectomy. Synovial membrane cells were dissociated from connective tissue by enzyme digestion and cultured in vitro for 48 hours, and harvested supernatants were assayed for the cytokines tumor necrosis factor alpha (TNFalpha) and interleukin-6 (IL-6), VEGF, MMPs 1, 2, 3, and 13, and TIMP-1 by enzyme-linked immunosorbent assay. Gelatin zymography was performed to demonstrate enzyme activity. Statistical analysis was performed using Student's paired 2-tailed t-tests for parametric data and the Wilcoxon signed rank test for nonparametric data. RESULTS: MMP-1 and MMP-13 levels were approximately 2.5-fold higher in invasive tenosynovium compared with encapsulating tenosynovium. Levels of MMP-2 were approximately 1.5-fold higher in invasive tenosynovium compared with both encapsulating tenosynovium and wrist joint synovium. MMP-13 (P = 0.009) and IL-6 (P = 0.03) levels were significantly lower in encapsulating tenosynovium compared with wrist joint synovium. Levels of VEGF, TIMP-1, TNFalpha, and MMP-3 were similar in all synovial sample groups. Zymography demonstrated enzyme activity in all synovium samples from all 9 patients assessed. CONCLUSION: Tenosynovium produces proinflammatory cytokines and proteolytic enzymes that are important in the tissue degradation seen in RA. Increased production of the enzymes MMP-1, MMP-2, and MMP-13 by invasive tenosynovium suggests a possible explanation for the worse prognosis and increased rupture rate associated with invasive tenosynovitis in RA. Production of VEGF by tenosynovium suggests that angiogenesis may have a role in tenosynovial proliferation and invasion of tendons.

Pyoderma gangrenosum occurring in a lower limb fasciocutaneous flap--a lesson to learn.

Pyoderma gangrenosum is a destructive cutaneous disease characterised by progressive painful ulceration. The occurrence of pyoderma gangrenosum at a surgical site is rare (especially if there is no predisposing illness), but is well recognised. We present a case of a 63-year-old man who developed erythematous ulcerative lesions due to pyoderma gangrenosum in and around a lower limb fasciocutaneous flap used to cover an exposed total knee prosthesis. The lesions were initially confused with postoperative wound infection. No predisposing disorder, other than the rarely reported association with osteoarthritis, was found. The diagnosis is important because its rapid detection not only avoids unnecessary treatment but also allows for prompt intervention with oral steroids. This case is presented to alert surgeons to the presence of pyoderma gangrenosum and its diagnostic confusion with postoperative wound infection.

Closed continuous irrigation in the treatment of hand infections.

We report our experience with a closed continuous irrigation system in 12 patients with hand infections: six cases of flexor tenosynovitis, three cases of septic arthritis and three palmar abscesses. Four of these patients had undergone previous surgical debridement and peroperative washout without elimination of the infection. The continuous irrigation system consists of two fenestrated tubes placed within the infected space, with the tip of the smaller calibre inlet tube positioned just inside the larger outlet tube. Resolution of infection was achieved in all 12 cases and all regained complete functional recovery. The closed continuous irrigation system is easy to manage, with no leakage of fluid; hand therapy may be started early and the patient is mobile throughout.

Excision of the distal ulna in rheumatoid arthritis. Is the price too high?

Patients with rheumatoid arthritis who underwent excision of the distal ulna were reviewed and the operated wrist was compared with the non-operated side in the 40 patients who had the procedure performed unilaterally. Radiological assessment showed that the radiocapitate measurement of carpal translocation was the most consistent and that excision of the distal ulna was not associated with statistically significant collapse, ulnar translocation or radial rotation of the carpus. 61% of wrists spontaneously developed a radial shelf or limited radiocarpal fusion following excision of the distal ulna, compared to 21% of non-operated wrists. However, there was no statistically significant difference in carpal collapse or ulnar translocation between these two groups.

Pre-operative distraction lengthening for radial longitudinal deficiency.

Patients treated for total radial aplasia have been reviewed. It was possible to re-align the carpus by radialization in five out of six limbs treated with pre-operative distraction, but in only one out of six treated without distraction. The average improvement in radial angulation in the non-distraction group was 19 degrees and in the distraction group 38 degrees. The average improvement in radial translation was 16 mm and 17 mm in the two groups respectively. Pre-operative distraction with the Kessler device permits re-alignment of the hand without skeletal resection or excessive tension on the radial neurovascular structures.