Optimization of Ex Vivo Machine Perfusion and Transplantation of Vascularized Composite Allografts

Background: Machine perfusion is gaining interest as an efficient method of tissue preservation of Vascularized Composite Allografts (VCA). The aim of this study was to develop a protocol for ex vivo subnormothermic oxygenated machine perfusion (SNMP) on rodent hindlimbs and to validate our protocol in a heterotopic hindlimb transplant model. Methods: In this optimization study we compared three different solutions during 6 h of SNMP ( n = 4 per group). Ten control limbs were stored in a preservation solution on Static Cold Storage [SCS]). During SNMP we monitored arterial flowrate, lactate levels, and edema. After SNMP, muscle biopsies were taken for histology examination, and energy charge analysis. We validated the best perfusion protocol in a heterotopic limb transplantation model with 30-d follow up ( n = 13). As controls, we transplanted untreated limbs ( n = 5) and hindlimbs preserved with either 6 or 24 h of SCS ( n = 4 and n = 5). Results: During SNMP, arterial outflow increased, and lactate clearance decreased in all groups. Total edema was significantly lower in the HBOC-201 group compared to the BSA group ( P = 0.005), 4.9 (4.3-6.1) versus 48.8 (39.1-53.2) percentage, but not to the BSA + PEG group ( P = 0.19). Energy charge levels of SCS controls decreased 4-fold compared to limbs perfused with acellular oxygen carrier HBOC-201, 0.10 (0.07-0.17) versus 0.46 (0.42-0.49) respectively ( P = 0.002). Conclusions: Six hours ex vivo SNMP of rodent hindlimbs using an acellular oxygen carrier HBOC-201 results in superior tissue preservation compared to conventional SCS. (c) 2021 Elsevier Inc. All rights reserved

Exceeding the Limits of Static Cold Storage in Limb Transplantation Using Subnormothermic Machine Perfusion

Background For 50 years, static cold storage (SCS) has been the gold standard for solid organ preservation in transplantation. Although logistically convenient, this preservation method presents important constraints in terms of duration and cold ischemia-induced lesions. We aimed to develop a machine perfusion (MP) protocol for recovery of vascularized composite allografts (VCA) after static cold preservation and determine its effects in a rat limb transplantation model. Methods Partial hindlimbs were procured from Lewis rats and subjected to SCS in Histidine-Tryptophan-Ketoglutarate solution for 0, 12, 18, 24, and 48 hours. They were then either transplanted (Txp), subjected to subnormothermic machine perfusion (SNMP) for 3 hours with a modified Steen solution, or to SNMP + Txp. Perfusion parameters were assessed for blood gas and electrolytes measurement, and flow rate and arterial pressures were monitored continuously. Histology was assessed at the end of perfusion. For select SCS durations, graft survival and clinical outcomes after transplantation were compared between groups at 21 days. Results Transplantation of limbs preserved for 0, 12, 18, and 24-hour SCS resulted in similar survival rates at postoperative day 21. Grafts cold-stored for 48 hours presented delayed graft failure (p = 0.0032). SNMP of limbs after 12-hour SCS recovered the vascular resistance, potassium, and lactate levels to values similar to limbs that were not subjected to SCS. However, 18-hour SCS grafts developed significant edema during SNMP recovery. Transplantation of grafts that had undergone a mixed preservation method (12-hour SCS + SNMP + Txp) resulted in better clinical outcomes based on skin clinical scores at day 21 post-transplantation when compared to the SCS + Txp group (p = 0.01613). Conclusion To date, VCA MP is still limited to animal models and no protocols are yet developed for graft recovery. Our study suggests that ex vivo SNMP could help increase the preservation duration and limit cold ischemia-induced injury in VCA transplantation.</p

Treatment of hyperpigmentation after burn: A literature review

International audienceOBJECTIFY: Skin pigmentation disorders are one of the most frequent sequelae after burn injury. While these conditions often improve over time, some are permanent and cause severe psychological disorders (especially on the face). Given the frequency of these disorders and their benign nature, the scientific community has great difficulty postponing these patient follow-ups. Publications on their management are rare, and there is no consensus on the gold standard treatment for skin dyschromia. Herein, we performed a literature review including the various treatments currently proposed to manage these hyperpigmentations. METHODS: All reported articles up to February 2021 were reviewed on Pubmed. Studies on the treatment of hyperpigmented scars were included if they were secondary to burn injuries. Excluded articles evaluated transient treatments, such as makeup, and articles on inflammatory hyperpigmentation without etiological details or not secondary to burns. RESULTS: 201 articles were identified, and 13 studies were included. Topical creams used in inflammatory hyperpigmented lesions such as hydroquinone and first-line retinoids are controversial due to their inconstant efficacy. Various types of laser and pulsed light treatments have shown their effectiveness but can also aggravate pigmentation. CONCLUSION: Dyschromia after burn remains a therapeutic challenge. Hyperpigmentations after burn should be treated on a case-by-case basis, using data from the literature, clinical experience and measuring the risk/benefit ratio

Existing and evolving bioethical dilemmas, challenges, and controversies in vascularized composite allotransplantation: An international perspective from the Brocher Bioethics Working Group

Early results of hand and face transplants and other grafts such as those of uterus, penis, trachea, larynx, or abdominal wall have confirmed the potential for vascularized composite allotransplantation (VCA) to restore appearance, anatomy, function, independence, and social integration in patients suffering from devastating tissue deficits untreatable by conventional treatment options. Despite such promise, these novel and complex procedures face challenges and controversies that remain open to discussion and debate. Indeed, many barriers to clinical advancement and negative stakeholder perceptions still exist. The bioethical challenges surrounding VCA include but are not limited to justice and vulnerability of subjects, and their experiences with risks, benefits and outcomes, provider economy of fame, public awareness and attitudes toward transplantation, and policy and regulatory issues shaping progress of the field. The First International Workshop on Bioethical Challenges in Reconstructive Transplantation was organized by the Brocher Foundation in Hermance, Switzerland. VCA professionals representing teams from across the world examined bioethical issues in VCA related to standards for safety, efficacy, feasibility, privacy, confidentiality, and equitability. Key discussion topics from the workshop were included in a survey questionnaire implemented across VCA professionals attending the 13th Congress of International Society of VCA held in Salzburg, Austria. The insights from the Brocher workshop and International Society of VCA survey as presented here could help inform the future development of clinical practice and policy strategies in VCA to ensure value, accessibility, and acceptance of these procedures by potential donors, potential or actual recipients and their families, and providers and payers

Results of a mindfulness-based social-emotional learning program on portuguese elementary students and teachers: a quasi-experimental study

Recently, mindfulness-based social-emotional learning (SEL) approaches have been taught to children in some schools. Due to deficient methodological consistency observed in most studies, their results should be interpreted with caution. Moreover, research on how mindfulness-based SEL approaches benefit teachers is scarce, and the majority of these studies have been conducted in English-speaking countries; therefore, it is uncertain whether these approaches are suited to other cultural backgrounds. The aim of the present study was to evaluate the efficacy of the MindUp curriculum, an SEL program through mindfulness practice for Portuguese students and teachers. Participants included 454 3rd and 4th grade students and 20 teachers from state schools. A quasiexperimental (pre- and post-test) study compared outcomes for an experimental group with a waitlist control group. Data were collected from teachers and children through self-report measures. Results showed that over 50 % of the children who participated in the MindUp program scored above the control group mean in their ability to regulate emotions, to experience more positive affect, and to be more self-compassionate, and over 50 % scored lower in negative affect. In the group of teachers, over 80 % scored above the control group mean in observing, in personal accomplishment, and in self-kindness. Our results contribute to the recent research on the potential added value of mindfulness practices to a SEL program and strengthen the importance for teachers and students of adding to the academic curriculum a SEL program through mindfulness practices.Fundação para a Ciência e a Tecnologia (FCT