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Axons successfully repaired with polyethylene glycol (PEG) fusion tecnology restored axonal continuity thereby preventing their Wallerian degeneration and minimizing muscle atrophy. PEG fusion studies in animal models and preliminary clinical trials involving patients with digital nerve repair have shown promise for this therapeutic approach. PEG fusion is safe to perform, and given the enormous potential benefits, there is no reason not to explore its therapeutic potential.
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Traumatismos dos Nervos Periféricos , Polietilenoglicóis , Humanos , Polietilenoglicóis/uso terapêutico , Polietilenoglicóis/administração & dosagem , Traumatismos dos Nervos Periféricos/cirurgia , Animais , Regeneração NervosaRESUMO
Background: External neurolysis is an important approach to treating symptomatic peripheral nerve entrapment. In cases of recurrent neurolysis or particularly extensive neurolysis, a paucity of overlying soft tissue for closure over the freshly liberated nerve presents a challenge to long-term surgical success as primary closure of this tissue may predispose the patient to recalcitrant epineural scarring. We report the intermediate term outcomes of the use of adipofascial perforator flaps as a means of vascularised tissue resurfacing of nerves in these difficult scenarios. Methods: We retrospectively reviewed patients undergoing external neurolysis for painful peripheral nerve lesions who subsequently had soft tissue reconstruction with local adipofascial flaps. Data with regard to age, gender, limb involved, duration of symptoms, number of prior surgeries, operative time, type of flap, vascular basis of flap, duration of follow-up, visual analogue pain score, monofilament sensory testing and complications were collected. Results: We included six patients (four women) with a minimum follow-up period of 17 months (range: 17-25 months). Age ranged from 39 to 60 years of age. Four cases involved the upper extremity and two the lower extremity. Symptoms had been present between 1 and 10 years. All operations utilised a local adipofascial flap perfused by a named perforating vessel emanating from an adjacent axial vessel. Operative time for flap creation and inset was 74 minutes, on average. There was one minor complication owing to superficial wound dehiscence. All patients reported substantial pain relief (≥five-point reduction on visual analogue scale; scores 0-3 at last follow-up) and objective sensory testing demonstrated improvement. Conclusions: Our report pays particular attention to surgical technique that is applicable to both upper and lower extremities in addition to intermediate term safety and pain outcomes. Level of Evidence: Level IV (Therapeutic).
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Retalho Perfurante , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Retalho Perfurante/irrigação sanguínea , Estudos Retrospectivos , Nervos Periféricos/cirurgia , DorRESUMO
Painful arthritis of the small joints of the hand is a common condition affecting older adults, with distal interphalangeal joint and thumb carpometacarpal joint being the two most common locations. Younger adults may also develop painful arthritis after trauma and with inflammatory arthropathy. Traditional surgical approaches address the structure of the joints with either arthrodesis or arthroplasty with or without an implant. In recent decades, denervation has been reported as an alternative treatment for painful small joints that are mobile and stable. Publications on denervation often report faster surgery and recovery times than traditional surgeries that manipulate the small joint bony structures. This article reviews the history, anatomy, surgical techniques, and outcomes of denervation of the small joints of the hand.
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Denervação , Humanos , Denervação/métodos , Polegar/inervação , Polegar/cirurgia , Articulações dos Dedos/cirurgia , Articulações dos Dedos/inervação , Articulações Carpometacarpais/cirurgia , Articulações Carpometacarpais/inervação , Artrite/cirurgia , Resultado do Tratamento , Articulação da Mão/cirurgia , Artralgia/cirurgia , Artralgia/etiologiaRESUMO
Vascularized composite allotransplantation (VCA) of the upper extremity is an established restorative procedure for selected patients with acquired upper limb loss. The majority of upper limb VCAs performed worldwide have been for victims of various forms of trauma. However, in the developed world, amputation following severe sepsis seems to be an increasingly common indication for referral to hand transplant programs. Unlike trauma patients with isolated limb injuries, patients with amputations as a complication of sepsis have survived through a state of global tissue hypoperfusion and multisystem organ failure with severe, enduring effects on the entire body's physiology. This article reviews the unique considerations for VCA candidacy in postsepsis patients with upper limb amputation. These insights may also be relevant to postsepsis patients undergoing other forms of transplantation or to VCA patients requiring additional future solid organ transplants.
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Transplante de Mão , Transplante de Órgãos , Sepse , Alotransplante de Tecidos Compostos Vascularizados , Humanos , Alotransplante de Tecidos Compostos Vascularizados/efeitos adversos , Alotransplante de Tecidos Compostos Vascularizados/métodos , Transplante Homólogo , Transplante de Órgãos/efeitos adversos , Sepse/etiologiaRESUMO
INTRODUCTION: Female plastic surgeons publish fewer and lower impact articles. To better understand how to address this gender gap, we explored the temporal trends in female senior authorship and evaluated predictive factors for female senior authorship. METHODS: A retrospective review of articles published in the 3 highest impact plastic surgery journals published from 2010 to 2020 was conducted. Trends with female senior authorship across time were analyzed with respect to study type, subspeciality, and geographical origin. RESULTS: Of the 5425 articles included, 13% (n = 720) had a female senior author, and female senior authorship increased across time ( R = 0.84, P = 0.033). Over the decade, an increased proportion of cohort studies ( R = 0.82, P = 0.045), systematic reviews ( R = 0.96, P = 0.003), breast-related articles ( R = 0.88, P = 0.022), and reconstruction-related articles ( R = 0.83, P = 0.039) were published by female senior authors. Subspecialty and geography predicted female senior authorship; articles focused on aesthetic (odds ratio [OR] = 1.3, P = 0.046) and breast (OR = 1.7, P < 0.001) subspecialties or those originating from Canada (OR = 1.7 P = 0.019), Europe (OR = 1.5, P < 0.001), and Latin America (OR = 3.0, P < 0.001) were more likely to have a female senior author. Articles from East Asia were less likely to have female senior authors (OR = 0.7, P = 0.005). CONCLUSION: Female senior authorship in plastic surgery has increased over the last decade, and the proportion of female plastic surgeons leading cohort studies and systematic reviews is increasing. Sex of the senior author is influenced by plastic surgery subspecialty and geographical origin, but article type did not impact the odds of female senior authorship.
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Procedimentos de Cirurgia Plástica , Cirurgia Plástica , Humanos , Feminino , Autoria , Estudos Retrospectivos , BibliometriaRESUMO
LEARNING OBJECTIVES: After studying this article, the participant should be able to: 1. Understand the goals of lower extremity reconstruction and identify clinical scenarios favoring amputation. 2. Understand lower extremity amputation physiology and biomechanics. 3. Review soft-tissue considerations to achieve durable coverage. 4. Appreciate the evolving management of transected nerves. 5. Highlight emerging applications of osseointegration and strategies to improve myoelectric prosthetic control. SUMMARY: Plastic surgeons are well versed in lower extremity reconstruction for traumatic, oncologic, and ischemic causes. Limb amputation is an increasingly sophisticated component of the reconstructive algorithm and is indicated when the residual limb is predicted to be more functional than a salvaged limb. Although plastic surgeons have traditionally focused on limb salvage, they play an increasingly vital role in optimizing outcomes from amputation. This warrants a review of core concepts and an update on emerging reconstructive techniques in amputee care.
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BACKGROUND: Polyethylene glycol (PEG) can fuse severed closely-apposed axolemmas and restore axonal continuity. We evaluated the effects of PEG-fusion on functional recovery in a rodent forelimb model of peripheral nerve injury. METHODS: The median nerves of male Lewis rats (n=5 per group) were transected and repaired with standard suture repair (SR), SR with PEG (PEG), or SR with PEG and 1% methylene blue (PEG+MB); a sham surgery group was also included. Proximal stimulation produced compound nerve (CAPS) and muscle (CMAPs) action potentials recorded distally. The contralateral limb of each animal acted as an internal control for grip strength measurements. RESULTS: CAPs and CMAPs immediately returned in all PEG and PEG+MB animals, but not in SR animals. PEG and PEG+MB groups demonstrated earlier return of function by post-operative day (POD) 7 (62.6 ±7.3% and 50.9 ±6.7% of contralateral limb grip strength, respectively) compared to SR group, in which minimal return of function was not measurable until POD 21. At POD 98, the PEG group grip strength recovered to 77.2 ±2.8% while the PEG+MB grip strength recovered to 79.9 ±4.4%, compared to 34.9 ±1.8% recovery in the SR group (p<0.05). The PEG and PEG+MB groups reached 50% of the Sham group grip strength on POD 3.8 and 6.3, respectively, whereas the SR group did not reach 50% grip strength recovery of the Sham group throughout the study period. CONCLUSION: PEG-fusion plus neurorrhaphy with or without methylene blue re-established axonal continuity, shortened recovery time, and augmented functional recovery compared to suture neurorrhaphy alone.
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PURPOSE: Thumb carpometacarpal (CMC) joint denervation is a relatively novel method for the management of osteoarthritis-associated pain by selective transection of articular nerve branches of the CMC joint. This study compared functional/patient-reported outcomes after CMC denervation with those after trapeziectomy and ligament reconstruction with tendon interposition (T + LRTI) over a 2-year follow-up period. We hypothesized that the outcomes of denervation and T + LRTI would be similar over the course of the study and at the final 2-year follow-up. METHODS: Adults with Eaton stage 2-4 disease, no evidence of CMC subluxation, and no history of thumb injury/surgery were included. Pain scores, brief Michigan Hand Questionnaire (bMHQ), Kapandji score, 2-point discrimination, and grip/key/3-point pinch strength were measured at 3-, 6-, 12-, and 24-months after surgery. On average, T + LRTI patients underwent 7 weeks of splinting, with release to full activity at 3 months; denervation patients were placed in a soft postoperative dressing for 2 weeks, with release to full activity as tolerated at 3 weeks. RESULTS: Thirty-three denervation and 20 T + LRTI patients were included. Preoperative characteristics were similar between both groups. Two denervation patients underwent secondary T + LRTI during the study period; one denervation patient underwent fat grafting to the CMC joint at an outside institution. Data prior to secondary surgeries were included in the analysis. The average tourniquet times (minutes) for denervation and T + LRTI were 43.5 ± 11.8 and 82.7 ± 14.2 minutes, respectively. For denervation and T + LRTI, the postoperative bMHQ scores were significantly higher than those at baseline at all time points. No significant differences were found between both groups for bMHQ, sensation, or strength measures. CONCLUSIONS: Carpometacarpal denervation is well tolerated, with shorter tourniquet times and faster return to full activity than T + LRTI. For the study cohort, the conversion rate to T + LRTI at 2 years was 9%. Both procedures demonstrated durable improvement in bMHQ compared with the preoperative state with similar long-term outcomes over 2 years of follow-up. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic II.
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Articulações Carpometacarpais , Osteoartrite , Trapézio , Adulto , Humanos , Articulações Carpometacarpais/cirurgia , Estudos Prospectivos , Seguimentos , Trapézio/cirurgia , Osteoartrite/cirurgia , Tendões/cirurgia , Ligamentos/cirurgia , Dor/cirurgia , DenervaçãoRESUMO
BACKGROUND: Publications measure academic productivity; they can affect research funding and career trajectory. There is a trend of increased authors per publication in surgery journals. We sought to determine whether authorship inflation exists in the plastic surgery literature and identify independent predictors of the number of co-authors. METHODS: We performed a bibliometric analysis of articles published in 3 high impact plastic surgery journals at 2-year intervals between 2010 and 2020. For each publication, we collected details on year of publication, article type, plastic surgery topic, gender of senior author, geographical origin of study, and the number of authors. RESULTS: A total of 5593 articles were collected. The median number of authors per article increased over time (ρ = 0.20, P < 0.001). Cohort studies, basic science investigations, literature reviews, and systematic reviews experienced a significant increase in the number of authors per article from 2010 to 2020 (P < 0.001). The rise in the number of authors was consistent across all plastic surgery topics (P < 0.001). Both male and female senior authors had a significant increase in the number of co-authors (P < 0.001). The regression model demonstrated that article type (cohort studies, basic science investigations, and systematic reviews) predicted more co-authors, whereas geographical region (Africa, Middle East, South and Southeast Asia, and United Kingdom and Ireland) and plastic surgery topics (aesthetic and hand surgery) predicted fewer authors. CONCLUSIONS: The number of authors per publication is increasing in plastic surgery. Author proliferation was consistent across most article types and unaffected by gender. Possible reasons behind this trend include research complexity, increased collaboration, or gift authorship.
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Procedimentos de Cirurgia Plástica , Cirurgiões , Cirurgia Plástica , Humanos , Masculino , Feminino , Autoria , BibliometriaRESUMO
OBJECTIVE: To identify the most important health-related quality of life (HRQOL) domains and patient-reported outcomes after upper extremity transplantation (UET) in individuals with upper extremity amputation. DESIGN: Verbatim audio-recordings of individual interviews and focus groups were analyzed using qualitative, grounded theory-based methods to identify important domains of HRQOL and provide guidance for outcomes measurement after UET. SETTING: Individual interviews were conducted by phone. Focus groups were conducted at 5 upper extremity vascularized composite allotransplantation (VCA) centers in the US and at an international conference of VCA experts. PARTICIPANTS: Individual phone interviews were conducted with 5 individuals with lived experience of UET. Thirteen focus groups were conducted with a total of 59 clinical professionals involved in UET. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Not applicable. RESULTS: Twenty-eight key HRQOL domains were identified, including physical functioning and medical complications, positive and negative emotional functioning, and social participation, relations, and independence. We identified key constructs for use in evaluation of the potentially substantial physical, medical, social, and emotional effects of UET. CONCLUSIONS: This study provides an overview of the most important issues affecting HRQOL after UET, including several topics that are unique to individuals with UET. This information will be used to establish systematic, comprehensive, and longitudinal measurement of post-UET HRQOL outcomes.
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Qualidade de Vida , Extremidade Superior , Humanos , Extremidade Superior/cirurgia , Amputação Cirúrgica , Grupos FocaisRESUMO
Vascularized Composite Allotransplantation (VCA) involves transplantation of multiple tissues from a donor to a recipient (e.g., skin, muscle, bone). Little is known about the US public's perceptions of and attitudes toward VCA organ donation. This multi-site, cross-sectional, mixed methods study involved focus groups and surveys to assess members of the general public's attitudes about VCA, and willingness and barriers to donate VCA organs. Qualitative data were analyzed by thematic analysis; quantitative data were analyzed by descriptive statistics. In focus groups (n = 6, 42 participants), most participants were female (57%) and Black (62%) with mean age of 42.6 years. Three main themes emerged: 1) awareness and perceptions of VCA, 2) purpose of VCA donation, 3) and barriers to VCA donation. Participants had heard little about VCA and sought information about VCA donation. Participants perceived VCA as challenging their concepts of "normality" and voiced concerns that VCA would create "Frankenstein[s]." Barriers to VCA donation included disruptions to end-of-life arrangements and information gaps regarding the donation process. Participants reported moderate to high willingness to donate their hands (69%) and face (50%) Public education efforts should address the specific needs and concerns of the public to facilitate VCA donation and family authorization.
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Transplante de Órgãos , Alotransplante de Tecidos Compostos Vascularizados , Feminino , Humanos , Adulto , Masculino , Estudos Transversais , Opinião Pública , Doadores de TecidosRESUMO
We review data showing that peripheral nerve injuries (PNIs) that involve the loss of a nerve segment are the most common type of traumatic injury to nervous systems. Segmental-loss PNIs have a poor prognosis compared to other injuries, especially when one or more mixed motor/sensory nerves are involved and are typically the major source of disability associated with extremities that have sustained other injuries. Relatively little progress has been made, since the treatment of segmental loss PNIs with cable autografts that are currently the gold standard for repair has slow and incomplete (often non-existent) functional recovery. Viable peripheral nerve allografts (PNAs) to repair segmental-loss PNIs have not been experimentally or clinically useful due to their immunological rejection, Wallerian degeneration (WD) of anucleate donor graft and distal host axons, and slow regeneration of host axons, leading to delayed re-innervation and producing atrophy or degeneration of distal target tissues. However, two significant advances have recently been made using viable PNAs to repair segmental-loss PNIs: (1) hydrogel release of Treg cells that reduce the immunological response and (2) PEG-fusion of donor PNAs that reduce the immune response, reduce and/or suppress much WD, immediately restore axonal conduction across the donor graft and re-innervate many target tissues, and restore much voluntary behavioral functions within weeks, sometimes to levels approaching that of uninjured nerves. We review the rather sparse cellular/biochemical data for rejection of conventional PNAs and their acceptance following Treg hydrogel and PEG-fusion of PNAs, as well as cellular and systemic data for their acceptance and remarkable behavioral recovery in the absence of tissue matching or immune suppression. We also review typical and atypical characteristics of PNAs compared with other types of tissue or organ allografts, problems and potential solutions for PNA use and storage, clinical implications and commercial availability of PNAs, and future possibilities for PNAs to repair segmental-loss PNIs.
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Traumatismos dos Nervos Periféricos , Polietilenoglicóis , Aloenxertos/fisiologia , Axônios/patologia , Humanos , Regeneração Nervosa/fisiologia , Traumatismos dos Nervos Periféricos/patologia , Nervo Isquiático/patologia , Transplante Homólogo , Degeneração Walleriana/patologiaRESUMO
BACKGROUND: Upper extremity (UE) transplantation is a complex undertaking that may require emergent or elective secondary surgery (SS) days to years following transplant. Various patient and transplantation may help determine what SS is needed. In this study, we characterize the SS needed by our UE transplant patients. METHODS: We retrospectively reviewed 6 patients who underwent hand and UE transplantation by one of the authors. Transplantation and SS details were obtained from medical records. Hand and arm function was quantified both subjectively (patient-reports) and objectively (Disabilities of the Arm, Shoulder, and Hand Score; Carroll test; Action Research Arm Tests; Box and Block test). RESULTS: Six patients underwent transplantation for a total of 10 transplanted limbs. Five transplants were performed below and 5 above the elbow. Mean time post-transplantation at last follow-up was 5 years (range: 1-9 years). In all, 66.7% of the patients required SS: total 7 surgeries comprising 13 procedures. The most common procedures were to improve hand function-nerve decompressions and tendon transfer, both in above-elbow transplant. Both patients showed a mean improvement of 15 points on Carroll scores. One above-elbow transplant had a brachioplasty for excess skin and another had a hematoma evacuation immediately after transplantation. Procedures in the below-elbow transplants included multiple incision and drainages for a septic wrist and an open reduction and internal fixation for a forearm fracture. CONCLUSION: Patients receiving UE transplantation often require one or more secondary procedures which may vary with level of transplantation. Secondary surgery should be an important aspect of pretransplant planning and cost-effectiveness determinations. LEVEL OF EVIDENCE: Level IV.
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Articulação do Cotovelo , Extremidade Superior , Articulação do Cotovelo/cirurgia , Mãos , Humanos , Redução Aberta , Estudos Retrospectivos , Extremidade Superior/cirurgiaRESUMO
Corticosteroid injection (CSI) is a commonly used tool in hand surgery that is often given little consideration as a potential detriment to vaccination efficacy. The authors reviewed guidelines issued by relevant societies for the timing of CSI around the severe acute respiratory syndrome coronavirus 2 vaccination period and the evidence used to support them. Ultimately, providers and patients should be adequately educated on the theoretical risks and benefits before proceeding with CSI immediately before, during, or immediately after coronavirus disease 2019 vaccination.
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COVID-19 , SARS-CoV-2 , Corticosteroides , Humanos , Injeções , VacinaçãoRESUMO
PURPOSE: Distal radius fractures are the most common long bone fracture in the United States, with an estimated incidence of 640,000 cases per year. Operative fixation presents a theoretical risk factor for the development of upper-extremity venous thromboembolism (UE-VTE). Additionally, patients presenting with distal radius fracture commonly have preexisting comorbidities that further increase the risk of UE-VTE. Finally, UE-VTE is considered the highest risk for eventual development of pulmonary embolism. Despite this, scant attention has been paid to studying UE-VTE in this population. The purpose of this study was to measure the incidence of this complication and to identify possible medical factors that increased the risk of developing UE-VTE. METHODS: We queried the Truven MarketScan Commercial Claims and Encounters Database for all patients who experienced a distal radius fracture and were subsequently treated with open reduction and internal fixation between 2012 and 2016. Patients were identified using relevant Common Procedural Terminology codes. Demographic and medical variables were tabulated. Our primary outcome was the development of ipsilateral UE-VTE or pulmonary embolism in the first 60 days after surgery. RESULTS: The study included 24,494 patients. The mean age was 50.7 years (range, 18-91), and 58% were women. There were 79 cases (0.3%) of UE-VTE and 19 cases of pulmonary embolism in the study population (24.1% of all UE-VTE cases; 0.08% of total sample). Multivariable logistic regression showed that coexisting heart failure and estrogen use were associated with increased risk of UE-VTE. CONCLUSIONS: Although uncommon, the development of UE-VTE after open reduction and internal fixation for distal radius fractures is a concerning complication. Coexisting heart failure and estrogen use are associated with increased risk of UE-VTE. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic II.
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Fraturas do Rádio , Tromboembolia Venosa , Feminino , Fixação Interna de Fraturas/efeitos adversos , Humanos , Incidência , Pessoa de Meia-Idade , Fraturas do Rádio/epidemiologia , Fraturas do Rádio/cirurgia , Estudos Retrospectivos , Fatores de Risco , Estados Unidos/epidemiologia , Extremidade Superior , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/etiologiaRESUMO
Complete transection of peripheral mixed nerves immediately produces loss of sensory perception, muscle contractions and voluntary behavior mediated by the severed distal axons. In contrast to natural regeneration (~1 mm/d) of proximal axons that may eventually reinnervate denervated targets, re-innervation is restored within minutes by PEG-fusion that consists of neurorrhaphy and a sequence of well specified hypo- and isotonic calcium-free or calcium-containing solutions, the anti-oxidant methylene blue (MB) and the membrane fusogen polyethylene glycol (PEG). In this study, we examined the relative efficacy of PEG-fusion with no MB (0%), 0.5% MB, or 1% MB on the recovery of voluntary behaviors by female Sprague-Dawley rats with a complete mid-thigh severance of their sciatic nerve bathed in extracellular fluid or calcium-containing isotonic saline. The recovery of voluntary behaviors is the most relevant measure of success of any technique to repair peripheral nerve injuries. We assessed recovery by the sciatic functional index, a commonly used measure of voluntary hindlimb behaviors following complete sciatic transections. We reported that both 1% MB and 0.5% MB in sterile distilled water in our PEG-fusion protocol with neurorrhaphy significantly increased the rate and extent of behavioral recovery compared to PEG plus neurorrhaphy alone. Furthermore, 0.5% MB was as effective as 1% MB in voluntary behavioral recovery as assessed by the sciatic functional index. Since sterile 1% MB is no longer clinically available, we therefore recommend that 0.5% MB be included in upcoming human clinical trials to evaluate the safety and efficacy of PEG-fusion. All animal procedures were approved by the University of Texas Institutional Animal Care and Use Committee (AUP-2019-00225) on September 9, 2020.
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In vascularized composite allotransplantation (VCA), invasive tissue biopsies remain the gold standard in diagnosing rejection carrying significant morbidity. We aimed to show feasibility of tape-stripping for noninvasive immune monitoring in VCA. Tape-stripping was performed on allografts and native skin of upper extremity transplant recipients. Healthy nontransplanted individuals served as controls. The technique was also used in swine on naïve skin in nontransplanted animals, native skin of treated, transplanted swine, nonrejecting VCAs, and rejecting VCAs. Extracted protein was analyzed for differences in cytokine expression using Luminex technology. Significantly decreased levels of INFγ and IL-1Ra were seen between human allograft samples and native skin. In swine, rejecting grafts had increased IL-1Ra compared to naïve and native skin, decreased levels of GM-CSF compared to native skin, and decreased IL-10 compared to nonrejecting grafts. Unsupervised hierarchical clustering revealed rejecting grafts separated from the nonrejecting (P = 0.021). Variable importance in projection scores identified GM-CSF, IL-1Ra, and IL-2 as the most important profiles for group discrimination. Differences in cytokine expression are detectable in human VCA patient native skin and VCA graft skin using a noninvasive tape-stripping method. Swine studies suggest that differences in cytokines between rejecting and nonrejecting grafts are discernable.
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Rejeição de Enxerto , Alotransplante de Tecidos Compostos Vascularizados , Animais , Humanos , Imunidade , Transplante de Pele , Suínos , Extremidade SuperiorRESUMO
Ablation/segmental loss peripheral nerve injuries (PNIs) exhibit poor functional recovery due to slow and inaccurate outgrowth of regenerating axons. Viable peripheral nerve allografts (PNAs) as growth-guide conduits are immunologically rejected and all anucleated donor/host axonal segments undergo Wallerian degeneration. In contrast, we report that ablation-type sciatic PNIs repaired by neurorrhaphy of viable sciatic PNAs and a polyethylene glycol (PEG)-fusion protocol using PEG immediately restored axonal continuity for many axons, reinnervated/maintained their neuromuscular junctions, and prevented much Wallerian degeneration. PEG-fused PNAs permanently restored many sciatic-mediated behaviors within 2-6 weeks. PEG-fused PNAs were not rejected even though host/donors were neither immunosuppressed nor tissue-matched in outbred female Sprague Dawley rats. Innate and adaptive immune responses to PEG-fused sciatic PNAs were analyzed using electron microscopy, immunohistochemistry, and quantitative reverse transcription polymerase chain reaction for morphological features, T cell and macrophage infiltration, major histocompatibility complex (MHC) expression, apoptosis, expression of cytokines, chemokines, and cytotoxic effectors. PEG-fused PNAs exhibited attenuated innate and adaptive immune responses by 14-21 days postoperatively, as evidenced by (a) many axons and cells remaining viable, (b) significantly reduced infiltration of cytotoxic and total T cells and macrophages, (c) significantly reduced expression of inflammatory cytokines, chemokines, and MHC proteins, (d) consistently low apoptotic response. Morphologically and/or biochemically, PEG-fused sciatic PNAs often resembled sciatic autografts or intact sciatic nerves. In brief, PEG-fused PNAs are an unstudied, perhaps unique, example of immune tolerance of viable allograft tissue in a nonimmune-privileged environment and could greatly improve the clinical outcomes for PNIs relative to current protocols.
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Imunidade Adaptativa/fisiologia , Imunidade Inata/fisiologia , Polietilenoglicóis/administração & dosagem , Nervo Isquiático/imunologia , Nervo Isquiático/transplante , Neuropatia Ciática/terapia , Imunidade Adaptativa/efeitos dos fármacos , Aloenxertos/imunologia , Aloenxertos/transplante , Animais , Feminino , Imunidade Inata/efeitos dos fármacos , Masculino , Ratos , Ratos Sprague-Dawley , Neuropatia Ciática/imunologia , Transplante Homólogo/métodosRESUMO
BACKGROUND: Peripheral nerve damage resulting in pain, loss of sensation, or motor function may necessitate a reconstruction with a bridging material. The RANGER® Registry was designed to evaluate outcomes following nerve repair with processed nerve allograft (Avance® Nerve Graft; Axogen; Alachua, FL). Here we report on the results from the largest peripheral nerve registry to-date. METHODS: This multicenter IRB-approved registry study collected data from patients repaired with processed nerve allograft (PNA). Sites followed their own standard of care for patient treatment and follow-up. Data were assessed for meaningful recovery, defined as ≥S3/M3 to remain consistent with previously published results, and comparisons were made to reference literature. RESULTS: The study included 385 subjects and 624 nerve repairs. Overall, 82% meaningful recovery (MR) was achieved across sensory, mixed, and motor nerve repairs up to gaps of 70 mm. No related adverse events were reported. There were no significant differences in MR across the nerve type, age, time-to-repair, and smoking status subgroups in the upper extremity (p > .05). Significant differences were noted by the mechanism of injury subgroups between complex injures (74%) as compared to lacerations (85%) or neuroma resections (94%) (p = .03) and by gap length between the <15 mm and 50-70 mm gap subgroups, 91 and 69% MR, respectively (p = .01). Results were comparable to historical literature for nerve autograft and exceed that of conduit. CONCLUSIONS: These findings provide clinical evidence to support the continued use of PNA up to 70 mm in sensory, mixed and motor nerve repair throughout the body and across a broad patient population.
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Traumatismos dos Nervos Periféricos , Procedimentos de Cirurgia Plástica , Aloenxertos , Humanos , Regeneração Nervosa , Procedimentos Neurocirúrgicos , Traumatismos dos Nervos Periféricos/cirurgia , Nervos Periféricos/cirurgia , Recuperação de Função FisiológicaRESUMO
: Vascularized composite allotransplantation (VCA) is a relatively new field in reconstructive medicine. Likely a result of the unique tissue composition of these allografts-including skin and often a bone marrow component-the immunology and rejection patterns do not always mimic those of the well-studied solid organ transplantations. While the number and type of VCAs performed is rapidly expanding, there is still much to be discovered and understood in the field. With more patients, new findings and patterns emerge and add to our understanding of VCA. Here, we present a case report of an upper extremity transplant recipient with trauma-induced rejection.