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.

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.

Face transplantation: A longitudinal histological study focusing on chronic active and mucosal rejection in a series with long-term follow-up.

The 2007 Banff working classification of skin-containing Tissue Allograft Pathology addressed only acute T cell-mediated rejection in skin. We report the longitudinal long-term histological follow-up of six face transplant recipients, focusing on chronic and mucosal rejection. We identified three patterns suggestive of chronic rejection (lichen planus-like, vitiligo-like and scleroderma-like). Four patients presented lichen planus-like and vitiligo-like chronic rejection at 52 ± 17 months posttransplant with severe concomitant acute T cell-mediated rejection. After lichen planus-like rejection, two patients developed scleroderma-like alterations. Graft vasculopathy with C4d deposits and de novo DSA led to subsequent graft loss in one patient. Chronic active rejection was frequent and similar patterns were noted in mucosae. Concordance between 124 paired skin and mucosal biopsies acute rejection grades was low (κ = 0.2, p = .005) but most grade 0/I mucosal rejections were associated with grade 0/I skin rejections. We defined discordant (grade≥II mucosal rejection and grade 0/I skin rejection) (n = 55 [70%]) and concordant (grade≥II rejection in both biopsies) groups. Mucosal biopsies of the discordant group displayed lower intra-epithelial GranzymeB/FoxP3 ratios suggesting a less aggressive phenotype (p = .08). The grading system for acute rejection in mucosa may require phenotyping. Whether discordant infiltrates reflect a latent allo-immune reaction leading to chronic rejection remains an open question.

First human facial retransplantation: 30-month follow-up.

BACKGROUND: Since the first successful facial transplantation in 2005, the benefits of this procedure in terms of aesthetics, functionality, and quality of life have been firmly established. However, despite immunosuppressive treatment, long-term survival of the allograft might be compromised by chronic antibody-mediated rejection (CAMR), leading to irreversible necrosis of the tissue. In the absence of therapeutic options, this complication is inevitably life-threatening. METHODS: We report facial retransplantation in a man, 8 years after his first facial transplantation because of extensive disfigurement from type 1 neurofibromatosis and 6 weeks after complete loss of his allograft due to severe CAMR. We describe the chronology of immune-related problems that culminated in allograft necrosis and the eventual loss of the facial transplant, the desensitisation protocol used for this highly immunosensitised recipient, the surgical technicalities of the procedure, the specific psychological management of this patient, and the results from follow-up at 30 months. FINDINGS: Although the patient had a complicated postoperative course with numerous immunological, infectious, cardiorespiratory, and psychological events, he was discharged after a hospital stay of almost 1 year. He has since been able to re-integrate into his community with acceptable restoration of his quality of life. INTERPRETATION: This clinical report of the first documented human facial retransplantation is proof-of-concept that the loss of a facial transplant after CAMR can be mitigated successfully by retransplantation combined with an aggressive desensitisation process. FUNDING: Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris.

Deep inferior epigastric perforator free flap in elderly women for breast reconstruction: The experience of a tertiary referral center and a literature review.

BACKGROUND: A general belief is to consider elderly patients as poor candidates for free flap reconstruction, which does not reflect our 20-year experience for breast reconstruction (BR). The aim of this study was to determine the safety and benefits of BR using deep inferior epigastric perforator (DIEP) free flap in the elderly population. METHODS: We conducted a retrospective study of all consecutive BRs using DIEP flaps in patients 65 years or older at the European Georges Pompidou Hospital from January 2011 to December 2019. Postoperative complications were reported as minor or major. We used a descriptive approach to analyze the main characteristics of the patients included. Surgical patient-reported outcomes and quality of life were assessed using the validated BREAST-Q questionnaire. RESULTS: Eighty-three DIEP flaps were performed in 79 patients (4 bilateral flaps) for BR. Sixty-six percent of the patients (52/79) did not present any complication. Total flap loss occurred in 3 BR (3.6%), arterial thrombosis in 4 BR (4.8%), and venous thrombosis in 8 BR (9.6%). The average duration of inpatient stay was 9.5 (±2.7) days. Forty-one of 69 eligible patients completed the questionnaire (response rate 59.4%). Patients reported high satisfaction and well-being scores. The mean Q score for psychosocial well-being was 75.4 (±16.7) and 59 (±13.3) for satisfaction with breasts. CONCLUSION: In our retrospective cohort, DIEP flap BR in elderly population had similar success and complication rates compared with those in younger patients, as well as high satisfaction scores. The free flap should be encouraged for BR in women over 65 years of age, and personal motivation as well as physiological age considered as main criteria for patient selection.

Anatomy of the axillary arch: from its incidence in human to an embryologic and a phylogenetic explanation of its origins.

INTRODUCTION: Typically, the axillary arch is defined as a fleshy slip running from latissimus dorsi to the anterior aspect of the humerus. Phylogeny seems to give the most relevant and plausible explanation of this anatomical variant as a remnant of the panniculus carnosus. However, authors are not unanimous about its origin. We report herein the incidence of axillary arch in a series of 40 human female dissections and present an embryologic and a comparative study in three domestic mammals. MATERIALS AND METHODS: Forty formalin-preserved Caucasian human female cadavers, one rat (Rattus norvegicus), one rabbit (Oryctolagus cuniculus) and one pig (Sus scrofa domesticus) cadavers were dissected bilaterally. A comparative, analytical and a descriptive studies of serial human embryological sections were carried out. RESULTS: We found an incidence of axillary arch of 2.5% (n = 1 subject of 40) in Humans. We found a panniculus carnosus inserted on the anterior aspect of the humerus only in the rat and the rabbit but not in the pig. The development of the latissimus dorsi takes place between Carnegie stage 16-23, but the embryological study failed to explain the genesis of the axillary arch variation. However, comparative anatomy argues in favour of a panniculus carnosus origin of the axillary arch. CONCLUSIONS: With an incidence of 2.5% of cases, the axillary arch is a relatively frequent variant that should be known by clinician and especially surgeons. Moreover, while embryology seems to fail to explain the genesis of this variation, comparative study gives additional arguments which suggest a possible origin from the panniculus carnosus.

The Perception of Plastic Surgery by Community-Based, Private Practice Nurses: A French National Descriptive Study.

Plastic surgery is a dynamic field but remains poorly understood by general practitioners, medical students, health professionals, and the public. The main health care professionals in the community who are involved in the follow-up of plastic surgery patients are nurses; they help to facilitate wound healing and rehabilitation in the postoperative period. In this study, the authors assessed the medical knowledge and perceptions of plastic surgery by nurses working in the community setting and explored their understanding of classical scenarios commonly encountered in reconstructive surgery. An online survey was designed to assess the demographics of nurses working in the community in France and their knowledge of plastic surgery. This was disseminated to all practicing nurses working outside of hospitals by means of an online social network from the period of April 2019 to June 2019. The survey was completed by 318 nurses. Specific training in plastic surgical nursing will be required to optimize the management of these patients following discharge from hospital. This gap in knowledge may affect patient recovery negatively.

Graft vasculopathy of vascularized composite allografts in humans: a literature review and retrospective study.

Mechanisms of chronic rejection of vascularized composite allografts (VCA) remain poorly understood and likely present along a spectrum of highly varied clinicopathological findings. Across both animal and human VCA however, graft vasculopathy (GV) has been the most consistent pathological finding resulting clinically in irreversible allograft dysfunction and eventual loss. A literature review of all reported clinical VCA cases with documented GV up to December 2018 was thus performed to elucidate the possible mechanisms involved. Relevant data extracted include C4d deposition, donor-specific antibody (DSA) formation, extent of human leukocyte antigen (HLA) mismatch, pretransplant panel reactive antibody levels, induction and maintenance immunosuppression used, the number of preceding acute rejection episodes, and time to histological confirmation of GV. Approximately 6% (13 of 205) of all VCA patients reported to date developed GV at a mean of 6 years post-transplantation. 46% of these patients have either lost or had their VCAs removed. Neither C4d nor DSA alone was predictive of GV development; however, when both are present, VCA loss appears inevitable due to progressive GV. Of utmost concern, GV in VCA does not appear to be abrogated by currently available immunosuppressive treatment and is essentially irreversible by the time of diagnosis with allograft loss a likely eventuality.

Predictive factors of success at the French National Ranking Examination (NRE): a retrospective study of the student performance from a French medical school.

BACKGROUND: The national ranking examination (NRE) marks the end of the second cycle (6th university year) of French medical studies and ranks students allowing them to choose their specialty and city of residency. We studied the potential predictive factors of success at the 2015 NRE by students attending a French School of Medicine. METHODS: From March 2016 to March 2017, a retrospective study of factors associated with the 2015 NRE success was conducted and enrolled 242 students who attended their sixth year at the school of medicine of Reims. Demographic and academic data collected by a home-made survey was studied using univariate and then multivariate analysis by generalized linear regression with a threshold of p <  0.05 deemed significant. RESULTS: The factors independently associated with a better ranking at the NRE were the motivation for the preparation of the NRE (gain of 3327 ± 527 places, p <  0.0001); to have participated in the NRE white test organized by la Revue du Praticien in November 2014 (gain of 869 ± 426 places, p <  0.04), to have participated in the NRE white test organized by la conférence Hippocrate in March 2015 (+ 613 places ±297, p <  0.04). The factors independently associated with poor NRE ranking were repeating the first year (loss of 1410 places ±286, p <  0.0001), repeating a year during university course (loss of 1092 places ±385, p <  0.005), attendance of hospital internships in 6th year (loss of 706 places ±298, p <  0.02). CONCLUSIONS: The student motivation and their white tests completion were significantly associated with success at the NRE. Conversely, repeating a university year during their course and attendance of 6th year hospital internships were associated with a lower ranking.

Medium- and Large-Sized Autologous Breast Reconstruction using a Fleur-de-lys Profunda Femoris Artery Perforator Flap Design: A Report Comparing Results with the Horizontal Profunda Femoris Artery Perforator Flap.

BACKGROUND: The volume of the profunda femoris artery perforator (PAP) flap limits its indications to small- and medium-sized breast reconstructions after modified radical mastectomy for cancer. We report a modified PAP flap design, including not only a vertical extension that increases its volume but also the skin surface, which suits larger breasts requiring immediate or delayed breast reconstructions and compare the results with our horizontal skin paddle PAP flap experience. PATIENTS AND METHODS: In our center between November 2014 and November 2016, 51 consecutive patients underwent a PAP flap breast reconstruction following breast cancer. A retrospective analysis on the collected data was performed to compare 34 patients with a bra cup smaller than C who underwent 41 horizontal PAP flap procedures, with those (n = 17) of a bra cup greater than or equal to C who underwent 21 fleur-de-lys PAP flap procedures. Demographic, anthropometric, flap and surgical characteristics, postoperative complication rates, and hospital stay were compared between the two groups. RESULTS: The average flap weight was 480 g (range: 340-735 g) for the fleur-de-lys PAP flap group compared with 222 g (range: 187-325 g) for the horizontal PAP flap procedure (p < 0.001). The mean flap dimensions were 25 × 18 cm for the fleur-de-lys PAP flap group compared with 25 × 7 cm in the horizontal PAP flap group. No flap failure was observed in the fleur-de-lys PAP flap group compared with two flap failures secondary to venous thrombosis in the horizontal PAP flap group (NS). Three patients (14%) experienced delayed healing at the donor site compared with four patients (10%) in the horizontal PAP flap group (NS). CONCLUSION: The fleur-de-lys skin paddle design not only allows an increase of the horizontal PAP flap volume, but also increases the skin surface, with an acceptable donor site morbidity. For medium- or large-sized breasts, the fleur-de-lys PAP flap seems to be ideal when a DIEP flap-based reconstruction is contraindicated.

Anatomical variations of the subscapular pedicle and its terminal branches: an anatomical study and a reappraisal in the light of current surgical approaches.

PURPOSE: While anatomical variations of the subscapular vessels are frequently encountered during axillary dissection, little is found in the literature. The aim of this cadaveric study was to define arterial and venous anatomical variations and frequencies of the subscapular vascular pedicle and its terminal/afferent vessels in women. METHODS: We performed 80 dissections of the axillary region on forty female formalin-embalmed cadavers. Each anatomical arrangement was photographed and recorded on a scheme before analysis. RESULTS: We propose a new classification of the subscapular pedicle variations. We observed three types of subscapular arterial variation. The type Ia was the most frequent arrangement (71% of our dissections), the type Ib was observed in 11% and the type II in 18% of cases. We observed four types of subscapular venous variation. The type Ia was observed in 63% of cases, the type Ib in 14%, the type II in 14% and the type III in 10% of cases. CONCLUSIONS: This knowledge of the anatomical variation arrangement and frequencies of the subscapular vascular pedicle will assist the surgeon when dissecting the axillary region for malignant or reconstructive procedures.

Partial Hand Transplant: Lessons Learned From Cadaveric Dissection Studies.

As the field of vascularized composite allotransplantation continues to expand, new upper extremity transplant candidates are being considered. We recently evaluated a bilateral amputee who had a mid-forearm amputation and a contralateral metacarpal hand amputation. In the latter limb, a "partial" hand transplant that preserved the majority of the patient's existing hand, including a partially severed thumb with intact thenar muscle function, was proposed. The feasibility of this partial hand transplant was studied in fresh-frozen cadaver limbs. This report details the proposed approach, the cadaveric dissections, and the lessons learned from these dissections. Issues of osteosynthesis, microvascular planning, and intrinsic muscle recovery are discussed, all of which are critical considerations for partial hand transplant candidates. Ultimately, the partial hand approach was felt to be inferior to a more conventional distal forearm transplant in this particular candidate. Practical, functional, and ethical implications of such decision are presented.

Face transplant: long-term follow-up and results of a prospective open study.

BACKGROUND: More than 30 face transplantations have been done worldwide since 2005 but no documented long-term follow-up has been reported in the literature. We aimed to answer remaining question about the long-term risks and benefits of face transplant. METHODS: In this single-centre, prospective, open study, we assessed 20 patients presenting with facial defects. Ten patients were selected, and, after three were secondarily excluded, seven were transplanted: two with neurofibromatosis 1, one with a burn, and four with self-inflicted facial gunshot injuries. We report the long-term outcomes of six face allotransplant recipients at an average of 6 years (range 3·4-9 years) after the transplantation. All admissions to hospital except for planned revisions and immunosuppressive follow-up therapy were reported as adverse events (safety endpoint). Predefined immunological, metabolic, surgical, and social integration endpoints were collected prospectively. Patients underwent quantitative health-related quality of life assessments through Short Form 36 health questionnaires. This study was registered with ClinicalTrials.gov, number NCT00527280. FINDINGS: Two of seven patients died: one at 65 days due to transplant destruction with concomitant pseudomonas infection and the second at 3·4 years after transplantation by suicide. The six patients alive at long-term follow-up presented with functional transplants. Safety endpoints were related to infection in the first month, acute rejection from 1 day to 7 years after transplantation, or side-effects of immunosuppressive therapy. Recurrent rejection episodes justified maintenance therapy with high-dose steroids at high levels in all patients at last follow-up, yet none of the patients developed diabetes. Three patients were found to have hypertension with one requiring therapy. All patients had a noticeable reduction in glomerular filtration rate. All recipients and their families accepted their transplant. Improvements in social integration and quality of life were highly variable among the patients and depended on baseline levels and psychiatric comorbidities. INTERPRETATION: These long-term results show the crucial effect of patients' social support and pre-existing psychiatric conditions on the risk-benefit ratio of facial transplantation. Careful preoperative patient selection and long-term postoperative follow-up programmes under strict institutional review board controls should be used for any future grafts of this type. FUNDING: Protocole Hospitalier de Recherche Clinique (PHRC) National.

The Retroauricular Approach to the Facial Nerve Trunk.

BACKGROUND: Exposure of the common trunk of the facial nerve has traditionally been approached based on principles of parotidectomy, which is associated with high rates of facial nerve palsy and landmarks that may be unreliable. On the basis of experience gained with vascularized composite allotransplantation of the face, the authors propose a retroauricular approach that may be more time-effective and safe. METHODS: In the proposed retroauricular facial nerve approach, an incision is made posterior to the ear in the retroauricular sulcus, and dissection proceeds anteriorly to the mastoid fascia to the base of the conchal bowl. The anteroinferior edge of the external auditory canal is followed as a reference structure to locate the facial nerve trunk (FNT), coursing between the stylomastoid foramen (posteromedially) and entering the parotid gland (anteriorly). Twelve unilateral FNT dissections were performed in 6 fresh human cadaver heads. Six dissections were performed for illustration and proof of concept using full facial transplant, conventional, and limited retroauricular exposures; 6 additional dissections were performed by trainees to assess reliability and replicability of technique. RESULTS: The FNT was successfully identified in all 12 dissections. Trainees tended toward being more time efficient in exploring the anatomy when using the limited retroauricular technique than with the conventional approach, 7.8 ±â€Š0.78 minutes versus 13.0 ±â€Š3.3 minutes (P = 0.089). No intraoperative injury to any critical structure was noted with either technique. CONCLUSION: A retroauricular approach to the FNT based on liberating anterior tissues from the auditory canal provides expedient and aesthetic exposure of the FNT.

Anti-HLA sensitization in extensively burned patients: extent, associated factors, and reduction in potential access to vascularized composite allotransplantation.

Extensively burned patients receive iterative blood transfusions and skin allografts that often lead to HLA sensitization, and potentially impede access to vascularized composite allotransplantation (VCA). In this retrospective, single-center study, anti-HLA sensitization was measured by single-antigen-flow bead analysis in patients with deep, second- and third-degree burns over ≥40% total body surface area (TBSA). Association of HLA sensitization with blood transfusions, skin allografts, and pregnancies was analyzed by bivariate analysis. The eligibility for transplantation was assessed using calculated panel reactive antibodies (cPRA). Twenty-nine patients aged 32 ± 14 years, including 11 women, presented with a mean burned TBSA of 54 ± 11%. Fifteen patients received skin allografts, comprising those who received cryopreserved (n = 3) or glycerol-preserved (n = 7) allografts, or both (n = 5). An average 36 ± 13 packed red blood cell (PRBC) units were transfused per patient. In sera samples collected 38 ± 13 months after the burns, all patients except one presented with anti-HLA antibodies, of which 13 patients (45%) had complement-fixing antibodies. Eighteen patients (62%) were considered highly sensitized (cPRA≥85%). Cryopreserved, but not glycerol-preserved skin allografts, history of pregnancy, and number of PRBC units were associated with HLA sensitization. Extensively burned patients may become highly HLA sensitized during acute care and hence not qualify for VCA. Alternatives to skin allografts might help preserve their later access to VCA.

The use of lipofilling to treat congenital hypoplastic breast anomalies: preliminary experiences.

BACKGROUND: Treatment options for congenital hypoplastic breast anomalies are often open, including radial scoring, parenchymal flaps, and insertion of expanders and implants. Drawbacks of open techniques involve scarring, the use of drains, and inpatient stays. The use of lipofilling to treat breast deformities is increasing, as more research is completed in this area. PATIENTS AND METHODS: We report a retrospective study of 10 patients below the age of 20 following autologous fat transfer between January 1, 2003 and January 1, 2004. (2 Poland syndrome, 3 bilateral tuberous breast, and 5 unilateral micromastia). Age, cup size, the number of sessions, time interval between each session, volumes injected, and complications were recorded. Postoperative mammography, ultrasonography, and MRI were assessed by a specialized radiologist. Patients answered a questionnaire 1 year after the procedure. RESULTS: Mean follow-up was 68 months (60-77 months) and mean age was 17.5 years (15-20 years). Mean number of fat injection sessions was 2 (1-4) and mean volume injected 285 mL per breast (200-500 mL). The time interval between each session was 5 months (3-6 months). Cup size remained unchanged after at least 5 years of follow-up. One case underwent a contralateral breast reduction. The cosmetic results considered satisfactory in almost all the patients after 1 year of follow-up. None of our patients complained of scars or defects at the donor site. All breasts imaging were normal except 1 patient with oil cysts. CONCLUSION: Our preliminary results using lipofilling to treat young patients with breast hypoplasia with lipofilling are very encouraging. The authors believe it is an alternative of choice for the correction of the young woman's breast deformities if the avoidance of scarring is preferred.

Intraoperative argatroban vessel irrigation during microsurgical anastomosis in heparin-induced thrombocytopenia patients: About two cases.

Patients with heparin-induced thrombocytopenia or confirmed allergies to heparin have a contraindication to heparin therapy, which poses a problem for intraoperative free flap irrigation in reconstruction. The use of argatroban as an alternative to heparin allowed us to perform a free flap for leg salvage and a deep inferior epigastric perforator flap for breast reconstruction without microvascular complication, with a 0.01 mg/mL solution. We reported two cases of using an alternative treatment to heparin in an emergency and planned surgeries for vessel irrigation during microsurgical anastomosis reconstruction without microvascular complications, suggesting the reliability and effectiveness of its use in case of contraindication to heparin.