Developing an Injury-Free 15 Hour Preservation Protocol of Donor Porcine Kidneys Using Normothermic Machine Perfusion.

Normothermic machine perfusion (NMP) offers a superior alternative to hypothermic preservation but is currently time limited. Extending this time could electivise transplantation and enable physiologic assessments of functionality. Porcine kidneys were retrieved, stored on ice for 3.5 hours before being placed onto a NMP circuit for 12 hours. Hemodynamics, biochemistry, and urine output were assessed. After 12 hours, kidneys were scored using the clinical assessment score. Biopsies were collected for histological assessment. Kidneys demonstrated continual improvements in hemodynamics. Perfusate sodium concentrations remained within physiologic parameters. Sodium bicarbonate increased over-time with corresponding decreases in lactate, demonstrating active renal gluconeogenesis and Cori cycle processes. Urine production began immediately and was sustained, indicating renal functionality. Under the clinical perfusion assessment score, all kidneys received a score of 1 and would be considered suitable for transplantation. Histological assessment revealed kidneys were injury free. Our NMP protocol safely preserves kidneys for over 15 hours. Successful perfusion was achieved with stable hemodynamics and biochemistry, with maintained urination. Importantly, kidneys remained in optimal health, with no evidence of injury. This may enable electivisation of transplantation, while reducing hypothermic injury.

The contribution of the donor vascularised hand and face allograft in transplant rejection: An immunological perspective.

Overcoming immunological rejection remains a barrier to the safe adoption of Vascularised Composite Allotransplantation (VCA). To mitigate this risk, clinical protocols have been derived from solid organ transplantation, targeting recipient immunomodulation, yet VCA is unique. Face and hand composite allografts are composed of multiple different tissues, each with their own immunological properties. Experimental work suggests that allografts carry variable numbers and populations of donor leukocytes in an organ specific manner. Ordinarily, these passenger leukocytes are transferred from the donor graft into the recipient circulation after transplantation. Whether alloantigen presentation manifests as acute allograft rejection or transplant tolerance is unknown. This review aims to characterise the immunological properties of the constituent parts of the donor face and hand, the potential fate of donor leukocytes and to consider theoretical graft specific interventions to mitigate early rejection.

An Unexpected Late Recurrence of Breast Irradiation-Induced Angiosarcoma Following Autologous Microvascular Breast Reconstruction.

The authors present the case of a 68-year-old female who developed recurrent angiosarcoma, a rare but recognized complication after breast irradiation therapy in the treatment of breast cancer. Microvascular breast reconstruction was performed after the completion of 10 years of disease-free clinical surveillance. Abdominal tissue was harvested and transferred onto the chest wall with restoration of its blood supply using microsurgical techniques to recreate the breast. Unexpectedly, local recurrence of irradiation-induced angiosarcoma was confirmed in the reconstructed breast 12 years later, a unique finding, given the long latent period and recruitment of tissues from a distant site. It is vital to consider the potential of late recurrence before embarking on complex reconstructions, and this should be discussed with patients who have a history of angiosarcoma. This further emphasizes the importance of long-term surveillance in such a rare, yet aggressive tumor at specialist centers.

Reconstructive surgery for treating pressure ulcers.

BACKGROUND: There are several possible interventions for managing pressure ulcers (sometimes referred to as pressure injuries), ranging from pressure-relieving measures, such as repositioning, to reconstructive surgery. The surgical approach is usually reserved for recalcitrant wounds (where the healing process has stalled, or the wound is not responding to treatment) or wounds with full-thickness skin loss and exposure of deeper structures such as muscle fascia or bone. Reconstructive surgery commonly involves wound debridement followed by filling the wound with new tissue. Whilst this is an accepted means of ulcer management, the benefits and harms of different surgical approaches, compared with each other or with non-surgical treatments, are unclear. This is an update of a Cochrane Review published in 2016. OBJECTIVES: To assess the effects of different types of reconstructive surgery for treating pressure ulcers (category/stage II or above), compared with no surgery or alternative reconstructive surgical approaches, in any care setting. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was January 2022. SELECTION CRITERIA: Published or unpublished randomised controlled trials (RCTs) that assessed reconstructive surgery in the treatment of pressure ulcers. DATA COLLECTION AND ANALYSIS: Two review authors independently selected the studies, extracted study data, assessed the risk of bias and undertook GRADE assessments. We would have involved a third review author in case of disagreement. MAIN RESULTS: We identified one RCT conducted in a hospital setting in the USA. It enrolled 20 participants aged between 20 and 70 years with stage IV ischial or sacral pressure ulcers (involving full-thickness skin and tissue loss). The study compared two reconstructive techniques for stage IV pressure ulcers: conventional flap surgery and cone of pressure flap surgery, in which a large portion of the flap tip is de-epithelialised and deeply inset to obliterate dead space. There were no clear data for any of our outcomes, although we extracted some information on complete wound healing, wound dehiscence, pressure ulcer recurrence and wound infection. We graded the evidence for these outcomes as very low-certainty. The study provided no data for any other outcomes. AUTHORS' CONCLUSIONS: Currently there is very little randomised evidence on the role of reconstructive surgery in pressure ulcer management, although it is considered a priority area. More rigorous and robust research is needed to explore this intervention.

Bionic Prostheses: The Emerging Alternative to Vascularised Composite Allotransplantation of the Limb.

Twenty years have surpassed since the first vascularised composite allotransplantation (VCA) of the upper limb. This is an opportunity to reflect on the position of VCA as the gold standard in limb reconstruction. The paucity of recipients, tentative clinical outcomes, and insufficient scientific progress question whether VCA will remain a viable treatment option for the growing numbers of amputees. Bionic technology is advancing at a rapid pace. The prospect of widely available, affordable, safely applied prostheses with long-standing functional benefit is appealing. Progress in the field stems from the contributions made by engineering, electronic, computing and material science research groups. This review will address the ongoing reservations surrounding VCA whilst acknowledging the future impact of bionic technology as a realistic alternative for limb reconstruction.

Renal hemofiltration prevents metabolic acidosis and reduces inflammation during normothermic machine perfusion of the vascularized composite allograft: A preclinical study.

INTRODUCTION: Recent experimental evidence suggests normothermic machine perfusion of the vascularized composite allograft results in improved preservation compared to static cold storage, with less reperfusion injury in the immediate post-operative period. However, metabolic acidosis is a common feature of vascularized composite allograft perfusion, primarily due to the inability to process metabolic by-products. We evaluated the impact of combined limb-kidney perfusion on markers of metabolic acidosis and inflammation in a porcine model. METHODS: Ten paired pig forelimbs were used for this study, grouped as either limb-only (LO, n = 5) perfusion, or limb-kidney (LK, n = 5) perfusion. Infrared thermal imaging was used to determine homogeneity of perfusion. Lactate, bicarbonate, base, pH, and electrolytes, along with an inflammatory profile generated via the quantification of cytokines and cell-free DNA in the perfusate were recorded. RESULTS: The addition of a kidney to a limb perfusion circuit resulted in the rapid stabilization of lactate, bicarbonate, base, and pH. Conversely, the LO circuit became progressively acidotic, correlating in a significant increase in pro-inflammatory cytokines. Global perfusion across the limb was more homogenous with LK compared to LO. CONCLUSION: The addition of a kidney during limb perfusion results in significant improvements in perfusate biochemistry, with no evidence of metabolic acidosis.

Artificial intelligence in the management and treatment of burns: a systematic review.

BACKGROUND: Artificial intelligence (AI) is an innovative field with potential for improving burn care. This article provides an updated review on machine learning in burn care and discusses future challenges and the role of healthcare professionals in the successful implementation of AI technologies. METHODS: A systematic search was carried out on MEDLINE, Embase and PubMed databases for English-language articles studying machine learning in burns. Articles were reviewed quantitatively and qualitatively for clinical applications, key features, algorithms, outcomes and validation methods. RESULTS: A total of 46 observational studies were included for review. Assessment of burn depth (n = 26), support vector machines (n = 19) and 10-fold cross-validation (n = 11) were the most common application, algorithm and validation tool used, respectively. CONCLUSION: AI should be incorporated into clinical practice as an adjunct to the experienced burns provider once direct comparative analysis to current gold standards outlining its benefits and risks have been studied. Future considerations must include the development of a burn-specific common framework. Authors should use common validation tools to allow for effective comparisons. Level I/II evidence is required to produce robust proof about clinical and economic impacts.

A post-preservation vascular flush removes significant populations of donor leukocytes prior to lung transplantation.

BACKGROUND: Donor leukocytes are intrinsically involved in acute lung allograft rejection, via self-presentation of donor antigens to recipient leukocytes. Therapeutic modalities to remove donor leukocytes are currently unavailable. We evaluated if a vascular flush immediately following preservation can be used for this purpose. METHODS: A post-preservation flush was performed with STEEN solution in n = 6 porcine lungs following static cold storage. The first 500 ml effluent from the left atrium was collected and an inflammatory profile performed. RESULTS: A total of 1.17 billion (±2.8 × 108) viable leukocytes were identified within the effluent. T cells were the dominant cell population, representing 82% of the total mobilised leukocytes, of which <0.01% were regulatory T cells. IL-18 was the most abundant cytokine, with a mean concentration of 84,216 pg (±153,552 pg). In addition, there was a mean concentration of 8819 ng (±4415) cell-free mitochondrial DNA. CONCLUSION: There is an immediate transfer of donor leukocytes, cytokines and damage-associated molecular patterns following reperfusion. Such a pro-inflammatory donor load may enhance alloantigen presentation and drive recipient alloimmune responses. A post-preservation flush may therefore be an effective method for reducing the immune burden of the donor lung prior to transplantation.

Scar orientation: Principles in plastic surgery.

For biopsy proven skin cancers that are deemed to be high risk, a wide local excision (WLE) is recommended to reduce the risk of local recurrence. For this reason, it is pragmatic to account for the likelihood of a WLE at the time of the initial biopsy. We illustrate a staged approach to excision of lesions to facilitate this, bearing in mind the optimal reconstruction is primary closure. In our experience as plastic surgeons, having to perform a locoregional flap or skin graft prevents the opportunity to perform a local anesthetic procedure. This increases the risk of postoperative complications, especially if adjuvant radiotherapy further exposes reconstructed tissues to radiation toxicity. Collectively, this often results in an inferior aesthetic outcome. We value the referrals from allied colleagues and want to share the principles we adhere to when planning an excision biopsy, which aid in the delivery of the optimal reconstruction.

The future application of nanomedicine and biomimicry in plastic and reconstructive surgery.

Plastic surgery encompasses a broad spectrum of reconstructive challenges and prides itself upon developing and adopting new innovations. Practice has transitioned from microsurgery to supermicrosurgery with a possible future role in even smaller surgical frontiers. Exploiting materials on a nanoscale has enabled better visualization and enhancement of biological processes toward better wound healing, tumor identification and viability of tissues, all cornerstones of plastic surgery practice. Recent advances in nanomedicine and biomimicry herald further reconstructive progress facilitating soft and hard tissue, nerve and vascular engineering. These lay the foundation for improved biocompatibility and tissue integration by the optimization of engineered implants or tissues. This review will broadly examine each of these technologies, highlighting areas of progress that reconstructive surgeons may not be familiar with, which could see adoption into our armamentarium in the not-so-distant future.

Combined Karapandzic-Abbé/Estlander/Stein flap for subtotal and total lower lip reconstruction.

BACKGROUND: Lower lip reconstruction remains a challenging task due to multi-functional and high aesthetic requirements that have to be achieved for successful outcome. This is particularly true to near-total lower lip defects, encompassing over 70% of lower lip loss due to cancer, trauma or burns. Despite the fact that numerous flaps and their modifications have been described over the past century, only a few valuable techniques and concepts withstood the test of time for sub-total lower lip defects, each having their own drawbacks. We describe a new approach to these defects combining bilateral Karapandzic and Abbe/Estlander/Stein flaps, not reported so far, and present our long term outcomes. METHODS: From 2012 to 2016, five patients with T4 lower lip squamous cell carcinoma (SCC) underwent near-total and total lower lip resection and reconstruction with a combination of bilateral Karapandzic flap and double Abbé/Estlander/Stein flaps from the upper lip. RESULTS: Our patients were between 44 and 88 years old (mean 66.6). All flaps healed uneventfully in all patients. Patients were followed up between 18 and 60 months (mean follow up 33.6 months). There were no local tumor recurrencies. All patients were able to eat perorally whilst reconstructed lips were fully functional. No drooling was observed and aesthetic outcomes were excellent. CONCLUSIONS: Combined bilateral Karapandzic and Abbe/Estlander/Stein flaps can produce excellent functional and aesthetic outcomes in near total and total lower lip reconstructions and should be considered a reliable reconstructive option in patients with more then 70% of lower lip loss.

Corrigendum: Fat harvest using a closed-suction drain.

[This corrects the article on p. 288 in vol. 43.].

Ex-vivo flush of the limb allograft reduces inflammatory burden prior to transplantation.

BACKGROUND: Passenger leucocytes and inflammatory debris transferred from the donor limb to the recipient can induce allorecognition, which activates the host immune response. This is the first study to evaluate whether the transfer of this inflammatory burden can be reduced via post-preservation flush prior to revascularisation, and whether this is influenced by ischaemia. METHODS: Bilateral forelimbs from the same pig were procured and infused with preservation flush and stored on ice. Each limb from the same pig underwent a post-preservation intravascular flush with isotonic solution at either 2 or 6 h. Venous effluent underwent flow cytometry to phenotype leucocyte populations, with additional quantification of cytokines and cell-free DNA. RESULTS: We identified large populations of viable leucocytes in the flush effluent (8.65 × 108 ± 3.10 × 108 cells at 2 h and 1.02 × 109 ± 2.63 × 108 at 6 h). This comprised T cells, B cells, NK cells and monocytes. Post-preservation flush yielded significant concentrations of pro-inflammatory cytokines including IL-6, IL-18, GM-CSF, IL-1ß, IL1α and CXCL-8 and mitochondrial DNA. The regulatory cytokine, IL-10 was undetectable. CONCLUSIONS: This study supports the finding that a post-preservation flush removes leucocytes and inflammatory components that are responsible for direct presentation. This study also gives an indication of how ischaemia impacts on the inflammatory burden transferred to the recipient upon reperfusion.

Strategies to Reduce Ischemia Reperfusion Injury in Vascularized Composite Allotransplantation of the Limb.

An important and often underinvestigated contributor to solid organ transplant rejection is ischemia reperfusion injury. This pathophysiological response releases damaging reactive oxygen species and cell stress signals that initiate inflammation, which has a critical role in priming the immune system for allorecognition. In time, this renders graft dysfunction and how this response is mediated in composite tissues remains unknown. Current protocols are drawn from solid organ transplantation with little scientific basis as to how this informs current hand transplantation practices. In addition to preservation flush and allograft cooling, machine perfusion is placing itself experimentally as a concept that could act to promote viability and increase the critical ischemic window, which is especially beneficial at a time of limited donors. With the increasing prevalence worldwide of hand transplantation, we review the potential contribution of ischemia reperfusion injury to hand allograft rejection including both current and experimental strategies.

Characterizing the early inflammatory contribution of the donor kidney following reperfusion.

BACKGROUND: Donor kidneys contain a large reservoir of passenger leucocytes that contribute to acute rejection via direct alloantigen presentation and pro-inflammatory cytokine secretion. However, the early contribution of these cells following revascularization has not previously been described. We performed a secondary, high-volume preservation flush following cold storage to characterize the inflammatory contribution of the donor kidney upon reperfusion. METHODS: Porcine kidneys were retrieved using a protocol analogous to current UK clinical practice. Following 2 h of cold static preservation, kidneys underwent a secondary flush with Ringer's solution. The venous effluent was collected and leucocytes phenotyped via flow cytometry. Inflammatory mediators, including cytokines and cell-free DNA, were then assessed to determine the inflammatory contribution of the donor kidney. RESULTS: Upon reperfusion, a significant population of donor-derived CD45 + leucocytes mobilized from the renal vasculature via the renal vein [mean 4.738 × 10 8 (SD 1.348 × 10 8 )]. Within this population, T cells were dominant, representing >60% of the leucocyte repertoire. Granulocytes, monocytes and natural killer cells were also identified, but in comparatively lower numbers. Significant concentrations of cytokines and cell-free DNA were also eluted upon reperfusion. CONCLUSIONS: The donor kidney contains a significant immune load that rapidly mobilizes following reperfusion. Performing a secondary preservation flush prior to implantation may reduce this inflammatory burden via diversion of donor leucocytes and inflammatory mediators from entry into the recipient circulation. This may modulate direct presentation and reduce the inflammatory contribution of the donor kidney following transplantation.

Reconstructive Microsurgery: The Future Is Today.

This reconstructive microsurgery course will run yearly and was borne and popularized from its infant meeting the year before, primarily focused on perforator flaps. It is a 2-day course updating residents/registrars to attending physicians/consultants about the most topical advancements in microvascular reconstructive surgery. The course is held at the New York University Langone Hospital in the United States.The timetable is primarily lecture based with the advantage of live-surgical procedures by world-renowned faculty. The timetable includes, but not limited to, facial/hand vascularized composite allotransplantation, upper/lower limb, breast, head and neck, transgender, and lymphedema surgery. Lectures were highly informative and there was ample time for case discussion with the appreciation that managing complex situations often requires input from other colleagues. The faculty focused on the lessons they have learned and potential pitfalls to avoid. The faculty was comprised of leading experts in reconstructive microsurgery from Europe, Korea, and throughout the United States.The primary emphasis of the course was to appreciate the global recognition in advances in microsurgery.

Alveolar Bone Grafting: Donor Site Review of 100 Consecutive Cases in Cleft Lip and Palate.

OBJECTIVE: Review of patients who underwent secondary alveolar bone grafting for total inpatient stay, postoperative complications, and postoperative analgesic requirements. DESIGN: Retrospective analysis of medical records. SETTING: Tertiary care center as part of a regional cleft lip and palate network. PATIENTS: All patients who underwent secondary alveolar bone grafting from the iliac crest. INTERVENTIONS: Local anesthetic was infiltrated overlying the anterior iliac crest. An incision was made to conform to the future skin crease and avoid muscle dissection. The cartilaginous cap was incised and raised, and cancellous bone was then harvested. The cavity was packed with hemostatic cellulose and closed in layers. All patients received postoperative antibiotics. All patients were prescribed regular paracetamol (acetaminophen) and ibuprofen if there were no contraindications. Oral morphine was available when requested. MAIN OUTCOME MEASURES: Length of stay, postoperative analgesic requirements, and postoperative donor site and oral complications. RESULTS: From 100 consecutive patients, 92 (92%) of the patients were discharged the day after surgery; one (1%) patient required four nights of monitoring for postoperative pyrexia of unknown origin. All patients received regular paracetamol, and the majority (86%) did not require oral morphine. Complications included seroma (4%), superficial donor site abscess (1%), postoperative pyrexia of unknown origin (2%), gingival bleeding (2%), and oral infection (2%). CONCLUSION: The findings suggest that donor site pain may be well controlled with simple, regular analgesia. Children tolerated this procedure well and were safely discharged the day after surgery. Alveolar bone grafting from the iliac crest was found to have low complication rates.

Reconstructive surgery for treating pressure ulcers.

BACKGROUND: The management of pressure ulcers involves several interventions ranging from pressure-relieving measures such as repositioning, to treatments that can include reconstructive surgery. Such surgery may be considered for recalcitrant wounds when full thickness skin loss arises and deeper structures such as muscle fascia and even bone are exposed. The surgery commonly involves wound debridement followed by the addition of new tissue into the wound. Whilst reconstructive surgery is an accepted means of ulcer management, the benefits and harms of surgery compared with non-surgical treatments, or alternative surgical approaches are not clear. OBJECTIVES: To assess the effects of reconstructive surgery for healing pressure ulcers (stage II or above), comparing surgery with no surgery or comparing alternative forms of surgery in any care setting. SEARCH METHODS: We searched the following electronic databases to identify reports of relevant randomised clinical trials (searched 26 September 2016): the Cochrane Wounds Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL. We also searched three clinical trials registers and reference lists of relevant systematic reviews, meta-analyses and health technology assessment reports. SELECTION CRITERIA: Published or unpublished randomised controlled trials that assessed reconstructive surgery in the treatment of pressure ulcers. DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection. We planned that two review authors would also assess the risk of bias and extract study data. MAIN RESULTS: We did not identify any studies that met the review eligibility criteria nor any registered studies investigating the role of reconstructive surgery in the management of pressure ulcers. AUTHORS' CONCLUSIONS: Currently there is no randomised evidence that supports or refutes the role of reconstructive surgery in pressure ulcer management. This is a priority area and there is a need to explore this intervention with more rigorous and robust research.

Audiologic changes after pinna augmentation.

No studies to date have objectively assessed whether pinna morphology affects sound intensity detected within the external auditory canal (EAC). Commonly performed procedures on the EAC are carried out for acquired and congenital pathology, together with correction of ear deformities. Our aim was to use an experimental model to identify whether a relationship exists between pinna shape and its subsequent effect on the hearing subject. An anatomically accurate and life-size model made of rubber composite was used for this study. Serial sections (small wedge, defect open; small wedge, defect closed; large wedge, defect open; large wedge, defect closed [equivalent to a protruding ear]; and pinnectomy) were undertaken, and the sound intensity changes assessed at the junction between the EAC and middle ear (tympanic membrane position) using an AURICAL Plus (Otometrics; Taastrup, Denmark) sound processor. A statistically significant loss was demonstrated for wedge-excised models, which was greatest at 180° azimuth. This loss was significantly reduced when the wedge defects were closed. A statistically significant improvement was demonstrated in the protruding ("bat") ear model compared with the normal ear at 0° azimuth. In this model, gain in sound intensity is adversely affected by pinna wedge resection. Because this change may be increased in those with protruding ears, this factor is important to consider for all cosmetic and noncosmetic operations to the pinna, and it supports the notion that the pinna is not a simple funnel.