Enhanced recovery for acute open lower limb fracture 'fix and flap'.

INTRODUCTION: Enhanced recovery (ER) aims to achieve earlier recovery, reduced hospital length of stay (LoS) whilst improving outcomes. Our ER protocol for acute lower-limb open fracture (ALLOFs) includes dangling at day 3 and mobilising fully weight-bearing from day 5. Our aims were to evaluate the outcomes of ALLOFs using our ER protocol for limb salvage, LoS following 'fix & flap', return to theatre, rate of successful flap salvage, flap failure and deep infection rates. METHODS: An observational study of a prospectively maintained lower limb flap database from September 2020 to January 2023 was undertaken. Search criteria encompassed patients with a Gustilo IIIB/C injury and a free flap reconstruction. Exclusions were for local/perforator flaps, soft tissue injury only, fracture related/prosthetic joint infections, or chronic osteomyelitis cases. RESULTS: 161 patients were available for analysis, 126 male (78 %) and 35 female (22 %) with a median age of 40 years (12-79, interquartile range 30.0). 81 % of cases were high-energy injuries. For all patients, the median time to definitive fixation and soft tissue coverage from injury was 4 days (0-30, interquartile range 2). 18 cases (11.2 %) required return to theatre for flap exploration; 11 cases were successfully salvaged (61 %). Nine free flaps failed (5.4 %). The median total LoS from admission was 10 days (6 to 46, interquartile range 5), with a median LoS following definitive fixation and soft tissue coverage of 7 days (4 to 20, interquartile range 3). The median follow-up period was 18 months (12 to 38.2, interquartile range 9), with a deep infection rate of 6.5 %. CONCLUSION: In isolated ALLOFs, our ER protocol is safe and effective in shortening the LoS. Our outcomes sit comfortably within acceptable ranges of contemporary literature for return to theatre, flap salvage/failure and deep infection. Our ER protocol actively involves our allied health professional colleagues early to facilitate discharge.

Thrombophilia and Preoperative Deep Venous Thrombosis and Their Effect on Free Flap Survival: A Scoping Review.

Background: A proper preoperative planning is essential to prevent flap failure. However, venous workup for flaps has not been commonly performed or utilized as a preoperative screening tool. A scoping review was conducted to explore preoperative venous system screening, including deep vein thrombosis diagnosis, and its effect on flap survival rate. This review identified existing gaps of knowledge and emphasized potential research areas for future studies. Methods: Two independent reviewers searched 3 electronic databases from inception to September 2020. Retrieved appropriate articles were selected systematically by title, abstract, and full review of the article. Studies were included if they enrolled patients who had thrombophilia or deep venous thrombosis (DVT) preoperatively and had undergone a free flap reconstruction. For eligible studies, the following information was extracted: basic demographics (sex, age, comorbidities), preoperative scans type, free flap type, clotting mode (causes), wound type, and flap survival. Results: Seventeen articles were found eligible for this review. Traumatic aetiology was found in 63 (33.6%) patients, while 124 (66.3%) patients had a non-traumatic aetiology. Preoperative screening for patients with non-traumatic aetiology was reported in 119 patients. In these patients, the flap survived in 107 (89.91%) patients. Four studies investigating patients with traumatic DVT aetiology, 60 patients (out of 63) had a preoperative computed tomography angiography or duplex. Those patients had 100% flap survival rates. Conclusion: Further investigations are required to identify venous thrombosis incidence in patients with non-traumatic thrombosis aetiology as this cohort of patients is at high risk of flap failure. Finally, the prognostic validity of available preoperative screening tools to identify high-risk patients should be assessed, such as imaging techniques, which would include venous duplex scanning, may prevent failure in free flap surgery.

Historique: Il est essentiel de procéder à une planification préopératoire appropriée pour prévenir l'échec du lambeau. Cependant, il n'est pas fréquent que le bilan veineux des lambeaux soit effectué ou utilisé comme outil de dépistage préopératoire. Les chercheurs ont réalisé une analyse exploratoire pour évaluer le dépistage du système veineux préopératoire, y compris un diagnostic de thrombose veineuse profonde et son effet sur le taux de survie des lambeaux. Cette analyse a permis de repérer les lacunes et de faire ressortir des domaines de recherche potentiels. Méthodologie: Deux analystes indépendants ont fait des recherches dans trois bases de données électroniques entre leur création et septembre 2020. Ils ont extrait systématiquement les articles appropriés en fonction de leur titre, de leur résumé et de leur analyse complète. Ils les ont conservés s'ils comprenaient des patients qui présentaient une thrombophilie ou une thrombose veineuse profonde avant l'opération et qui avaient subi une reconstruction par lambeau libre. Ils ont tiré l'information suivante des études admissibles: caractéristiques démographiques de base (sexe, âge, maladies associées), type d'imagerie préopératoire, type de lambeau libre, mode de coagulation (causes), type de plaie et survie du lambeau. Résultats: Les chercheurs ont trouvé 17 articles admissibles à l'analyse. Ils ont constaté une étiologie traumatique chez 63 patients (33,6 %), et une étiologie non traumatique chez 124 patients (66,3 %). Au total, 119 patients présentant une étiologie non traumatique ont été soumis à un dépistage préopératoire. Le lambeau a survécu chez 107 d'entre eux (89,91 %). Dans les quatre études sur les patients ayant une étiologie de thrombose veineuse profonde traumatique, 60 (sur 63) ont subi une angiographie tomographique ou un échodoppler duplex. Le taux de survie des lambeaux atteignait 100 % chez ces patients. Conclusion: D'autres explorations s'imposent pour déterminer l'incidence de thrombose veineuse chez les patients présentant une étiologie de thrombose non traumatique, car cette cohorte de patients est très vulnérable à un échec du lambeau. Enfin, il faudra évaluer la validité pronostique des outils de dépistage préopératoire visant à détecter les patients à haut risque, tels que les technologies d'imagerie, qui incluraient un échodoppler duplex, pour prévenir l'échec d'une opération à lambeau libre.

Free flaps for lower limb soft tissue reconstruction - A systematic review of complications in 'Silver Trauma' patients.

BACKGROUND: There are 12.5 million people aged 65 years and older living in the UK. The annual incidence of open fracture is 30.7 per 10,000 person-years. In females, 42.9% of all open fractures occur in patients ≥ 65 years. METHODS AND MATERIALS: Preferred Reporting for Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed, and the study is registered with PROSPERO (CRD42020209149). The aim was to compare the complication profiles of free fasciocutaneous flaps and free muscular flaps in patients aged over 60 years undergoing lower limb soft tissue reconstruction following an open lower limb fracture. The search strategy based on strict inclusion criteria included PubMed, Embase and Google Scholar. RESULTS: 15 papers were identified, including 46 patients with 10 free fasciocutaneous flaps and 41 free muscle flaps. There were 3 complications in the fasciocutaneous group (30%) and 9 complications in the muscle group (22%). There was a total of 1 secondary procedure in the fasciocutaneous group and 4 in the muscle group. DISCUSSION: There is insufficient data to provide statistical comparison between free fasciocutaneous versus free muscle flaps for lower limb reconstruction performed in those aged over 60 years. This systematic review highlights evidence for the successful use of free tissue transfer in the older population following an open fracture injury and requiring lower limb reconstruction. There is no evidence to suggest the superiority of one tissue type over the other, with the inference that well vascularised tissue is the most significant factor impacting outcome.

Identifying collagen VI as a target of fibrotic diseases regulated by CREBBP/EP300.

Fibrotic diseases remain a major cause of morbidity and mortality, yet there are few effective therapies. The underlying pathology of all fibrotic conditions is the activity of myofibroblasts. Using cells from freshly excised disease tissue from patients with Dupuytren's disease (DD), a localized fibrotic disorder of the palm, we sought to identify new therapeutic targets for fibrotic disease. We hypothesized that the persistent activity of myofibroblasts in fibrotic diseases might involve epigenetic modifications. Using a validated genetics-led target prioritization algorithm (Pi) of genome wide association studies (GWAS) data and a broad screen of epigenetic inhibitors, we found that the acetyltransferase CREBBP/EP300 is a major regulator of contractility and extracellular matrix production via control of H3K27 acetylation at the profibrotic genes, ACTA2 and COL1A1 Genomic analysis revealed that EP300 is highly enriched at enhancers associated with genes involved in multiple profibrotic pathways, and broad transcriptomic and proteomic profiling of CREBBP/EP300 inhibition by the chemical probe SGC-CBP30 identified collagen VI (Col VI) as a prominent downstream regulator of myofibroblast activity. Targeted Col VI knockdown results in significant decrease in profibrotic functions, including myofibroblast contractile force, extracellular matrix (ECM) production, chemotaxis, and wound healing. Further evidence for Col VI as a major determinant of fibrosis is its abundant expression within Dupuytren's nodules and also in the fibrotic foci of idiopathic pulmonary fibrosis (IPF). Thus, Col VI may represent a tractable therapeutic target across a range of fibrotic disorders.

Interventions to improve ergonomics in the operating theatre: A systematic review of ergonomics training and intra-operative microbreaks.

Musculoskeletal occupational injury is prevalent within the surgical community. This is a multi-factorial issue, but is contributed to by physical posture, environmental hazards and administrative deficiency. There is growing awareness of this issue, with several behavioural, educational and administrative techniques being employed. The literature on this topic is, however, sporadic and difficult to access by healthcare practitioners. The aim of this systematic review was to evaluate the literature on the current interventions used to minimise musculoskeletal occupational injury in surgeons and interventionalists. This review will focus on administrative and human factor interventions, such as intra-operative microbreaks and ergonomics training.

Ankle fractures in the elderly: an overlooked burden.

Ankle fractures in the elderly are a complex under-recognized burden which require a multidisciplinary approach to management. This article discusses the holistic approach required, including the up-to-date surgical management options and the areas for future development.

Soft-tissue reconstruction of open fractures of the lower limb: muscle versus fasciocutaneous flaps.

Early vascularized soft-tissue closure has long been recognized to be essential in achieving eventual infection-free union. The question of whether muscle or fasciocutaneous tissue is superior in terms of promoting fracture healing remains unresolved. In this article, the authors review the experimental and clinical evidence for the different tissue types and advocate that the biological role of flaps should be included as a key consideration during flap selection.

A three-digit dermofasciectomy for Dupuytren's disease.

In patients presenting to our unit with recurrent or aggressive Dupuytren's disease (DD), we favour the technique of radical excision and resurfacing popularised by Logan, who has described its use for the ulnar two digits of the hand at the same operation.(1) In patients in whom dermofasciectomy may be indicated in three or more digits, we have previously advised patients that the quality of the surgical attention and the post-operative physiotherapy might be better delivered by a staged approach. However, we demonstrate here with a case report that the technique can have excellent outcome when used for three digits at the same time. We are unaware of similar previous reports.

Comparison of the vascularity of fasciocutaneous tissue and muscle for coverage of open tibial fractures.

BACKGROUND: Early coverage with vascularized soft-tissue flaps has dramatically improved the outcome in open tibial fractures. However, the ideal tissue for covering open fractures remains controversial. Several clinical studies suggest that muscle is superior to fasciocutaneous tissue; this is attributed to the presumed higher vascularity of muscle, although experimental evidence is inconclusive. The authors' previously described novel murine fracture model, which allows exclusive comparison of both tissues, demonstrated enhanced healing beneath muscle. The present study was undertaken to compare the vascularity of muscle and fasciocutaneous tissues over the course of fracture healing. METHODS: Two experimental groups comprised mice with tibial fractures in contact with either muscle or fasciocutaneous tissues exclusively. Controls included a nontrauma group and those where soft tissues and periosteum were dissected but the tibia was not fractured. Animals were harvested between 3 and 28 days after fracture (n = 170 in total). The vascular density of the soft tissues was assessed using immunohistochemical techniques. RESULTS: Fasciocutaneous tissue was found to have a higher vascular density compared with muscle in contact with the fracture site at all time points (p < 0.0001, two-way analysis of variance), despite accelerated healing of fractures covered by muscle. CONCLUSIONS: The authors' data show that the more advanced healing of fractures covered by muscle compared with fasciocutaneous tissue is not related to the vascularity of the tissues, as the latter had a higher vascular density at all time points. Therefore, provided that a flap has sufficient vascularity to effectively reconstitute the soft-tissue envelope, other factors may be important in specifically promoting fracture healing.

Models of tibial fracture healing in normal and Nf1-deficient mice.

Delayed union and nonunion are common complications associated with tibial fractures, particularly in the distal tibia. Existing mouse tibial fracture models are typically closed and middiaphyseal, and thus poorly recapitulate the prevailing conditions following surgery on a human open distal tibial fracture. This report describes our development of two open tibial fracture models in the mouse, where the bone is broken either in the tibial midshaft (mid-diaphysis) or in the distal tibia. Fractures in the distal tibial model showed delayed repair compared to fractures in the tibial midshaft. These tibial fracture models were applied to both wild-type and Nf1-deficient (Nf1+/-) mice. Bone repair has been reported to be exceptionally problematic in human NF1 patients, and these patients can also spontaneously develop tibial nonunions (known as congenital pseudarthrosis of the tibia), which are recalcitrant to even vigorous intervention. pQCT analysis confirmed no fundamental differences in cortical or cancellous bone in Nf1-deficient mouse tibiae compared to wild-type mice. Although no difference in bone healing was seen in the tibial midshaft fracture model, the healing of distal tibial fractures was found to be impaired in Nf1+/- mice. The histological features associated with nonunited Nf1+/- fractures were variable, but included delayed cartilage removal, disproportionate fibrous invasion, insufficient new bone anabolism, and excessive catabolism. These findings imply that the pathology of tibial pseudarthrosis in human NF1 is complex and likely to be multifactorial.

Comparison of the healing of open tibial fractures covered with either muscle or fasciocutaneous tissue in a murine model.

The objective of this study was to compare the effects of soft tissue coverage by either muscle or fasciocutaneous tissue on the healing of open tibial fractures in a murine model. An open tibial fracture, stripped of periosteum with intramedullary fixation, was created in mice. Experimental groups were devised to allow exclusive comparison of either muscle alone or skin plus fascia in direct contact with healing bone. To exclusively assess the relative efficacy of muscle and fasciocutaneous tissue to promote healing of a fracture stripped of periosteum, a piece of sterile inert material (polytetrafluoroethylene) was positioned anteriorly, excluding skin and fascia (muscle group) or posteriorly, excluding muscle (fasciocutaneous group). Skeletal repair was assessed histologically and quantified by histomorphometry; quantitative peripheral computed tomography (pQCT) and mechanical testing using a four-point bending technique. This standardized, reproducible model allowed characterization of the morphology of open fracture healing. At 28 days postfracture, there was faster healing in the experimental muscle coverage group compared to skin and fascia alone. Furthermore, there was almost 50% more cortical bone content and a threefold stronger union beneath muscle compared to fasciocutaneous tissue (p < 0.05 by one-way ANOVA). Exclusive comparison of muscle and fasciocutaneous tissue in our novel murine model demonstrates that muscle is superior for the coverage of open tibial fractures for both the rate and quality of fracture healing.

Modulating angiogenesis: more vs less.

The concept of manipulation of the vascular bed to either increase or decrease the number of blood vessels has attracted considerable interest. This review focuses on angiogenesis as a therapeutic target, particularly in the context of cancer and arthritis, as well as on promoting angiogenesis in cardiovascular disease and the healing of bone fractures. Although once touted almost as a panacea for treatment of tumors, as well as other diseases associated with angiogenesis, such as diabetic retinopathy or rheumatoid arthritis, it is now clear that such enthusiasm was somewhat premature. Similarly, some clinical trials of therapeutic angiogenesis for the management of cardiovascular disease have been disappointing. Nevertheless, this exciting field of research holds promise for more targeted therapies.

From the cradle to the clinic: VEGF in developmental, physiological, and pathological angiogenesis.

Formation of new blood vessels, which is fundamental in embryonic development, occurs through a combination of angiogenesis and vasculogenesis. Angiogenesis also plays a vital role postnatally, especially in reparative processes such as wound and fracture healing. Some of these events, especially in fracture healing, recapitulate processes observed in developmental angiogenesis. However, dysregulated angiogenesis is well documented to underlie a number of pathological disorders, including rheumatoid arthritis (RA). The vascular endothelial growth factor (VEGF)/VEGF receptor system is the best characterized regulator of angiogenesis. VEGF is expressed in a range of cells in response to soluble mediators (such as cytokines and growth factors), cell-bound stimuli (such as CD40 ligand), and environmental factors (such as hypoxia). As a consequence, this molecule is vital in the modulation of physiological and pathological angiogenesis. This review will focus in particular on the role played by VEGF in embryogenesis and skeletal growth, in fracture healing (in which increased angiogenesis is likely to be beneficial in promoting union), and in RA (in which excessive angiogenesis is thought to play a significant role in disease pathogenesis). In the not-too-distant future, targeting VEGF may prove to be of benefit in the treatment of diseases associated with excessive or aberrant angiogenesis, such as malignancies and RA.