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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. 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. 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. 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. Protocole Hospitalier de Recherche Clinique (PHRC) National.

Vascularized composite allografts (VCAs) allow reconstruction of devastating injuries and amputations, yet require lifelong immunosuppression that is associated with significant morbidity. Induction of immune tolerance of VCAs would permit widespread use of these procedures. VCAs are acquired from deceased donors most likely to be -MHC-mismatched (in contrast to living-related renal transplant donor-recipient pairs matched at one MHC haplotype). After achieving VCA tolerance in a swine model equivalent to clinical living-related renal transplants (single-haplotype MHC mismatches: e.g., \"mother-daughter\"/haploidentical), we tested our protocol in MHC class I, class II, and fully-MHC-mismatched pairs. Although class II mismatched swine demonstrated similar results as the haploidentical scenario (stable mixed chimerism and tolerance), our protocol failed to prevent rejection of class I and full mismatch VCAs. Here, we describe a new adapted conditioning protocol that successfully achieved tolerance across MHC class-I-mismatch barriers in swine. Swine were treated with non-myeloablative total body and thymic irradiation two days prior to infusion of bone marrow cells from an MHC class I-mismatched donor. They also received a short-term treatment with CTLA4-Ig (Belatacept ) and anti-IL6R mAb (Tociluzimab ) and were transplanted with an osteomyocutaneous VCA from the same donor. Stable mixed chimerism and tolerance of MHC class-I-mismatched VCAs was achieved in 3 recipients. Allograft tolerance was associated with a sustained lack of anti-donor T cell response and a concomitant expansion of double negative CD4 CD8 T cells producing IL-10. This study demonstrates the first successful mixed chimerism-induced VCA tolerance in a large animal model across a MHC class-I-mismatch. Future studies aimed at fully-mismatched donor-recipient pairs are under investigation with this protocol.

The risk to benefit ratio of face transplantation with a composite tissue allograft remains debatable, although this procedure is technically feasible. We report here a 1-year follow-up of a patient who underwent face transplantation with a composite tissue allograft. On Jan 21, 2007, a 29-year-old man with neurofibromatosis type 1 underwent resection of a massive plexiform neurofibroma diffusely infiltrating the middle and lower part of his face. The main goal was to restore both the cutaneous appearance and function of the face, including, in particular, control of orbicularis oculi and oris muscle contraction. The issues of immunosuppressive therapy, psychological outcome, and social reintergration were addressed, together with the monitoring of graft rejection by biopsies of the skin and mucosa. The initial postoperative course was uncomplicated. Two episodes of clinical rejection occurred on days 28 and 64. The second episode was associated with cytomegalovirus infection. Both episodes resolved favourably, with no further clinical signs of rejection, making the reduction of immunosuppressive treatment possible. A year after surgery, the functional outcome was very good, with successful sensory and motor reinnervation in the transplanted territory. Psychological recovery was excellent, with complete social reintegration. This case demonstrates the feasibility of surgically removing a large part of the face and replacing it with a composite tissue allograft. This facial repair procedure, which seems to have a satisfactory risk to benefit ratio, could be offered in rare and selected cases. Programme Hospitalier de Recherche Clinique.

Vascularized Composite Allotransplantation (VCA) including Facial Transplantation (FT) emerged as a unique solution for anatomically restoring faces after disfigurement. It became a clinical reality after the first successful face transplantation in 2005.1 VCA is a rapidly growing new field in plastic surgery; and from November 2005 to the time of this writing in September 2018, 44 transplants have been performed worldwide. It is clear that many more transplantations will be performed in the future. The main concern in VCA remains the risk of chronic rejection2 and graft loss3 despite life-long immunosuppression. Scientists are actively working on new strategies to reduce the burden of immunosuppression and prevent immune rejection. The most promising approach is the development of tolerance protocols through the induction of mixed chimerism4. Indeed, it is the sole strategy to have demonstrated long-term tolerance in solid organ transplantation in humans.5 Currently, the gold standard in reconstructive surgery remains the use of autologous tissue. This strategy is still very useful to replace limited missing body parts (like mandible) by tissue transfer (for example, osteomyocutaneous flap). However, the functional sensory organs (mouth, eyes) cannot be restored adequately by these conventional surgical techniques.The goal of face transplantation is not only to restore the patient’s appearance but also, to create a new physiognomy that will allow the facially disfigured person to adapt and reintegrate into life. Before the advent of VCA, the complexity of the face made surgeons unable to reestablish an “acceptable outcome,” leaving disfigured patients little chance of social rehabilitation. Nowadays VCA surgery, while offering new hope, represents an important challenge (even for the top facility) for the surgical6 and medical7 team. First, there must be a high level of cooperation between the various specialists including surgeons, anesthesiologists and nephrologists. Secondly, the management of immune rejection remains a primary on-going concern due to the untreatable chronic rejection effect.8

IntroductionTypically, 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 methodsForty 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.ResultsWe 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.ConclusionsWith 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.

Background Neurofibromatosis type 1 (NF1) is a common dominant tumor predisposition syndrome affecting 1 in 3,500 individuals. The hallmarks of NF1 are the development of peripheral nerve sheath tumors either benign (dermal and plexiform neurofibromas) or malignant (MPNSTs). Results To comprehensively characterize the role of microRNAs in NF1 tumorigenesis, we analyzed 377 miRNAs expression in a large panel of dermal and plexiform neurofibromas, and MPNSTs. The most significantly upregulated miRNA in plexiform neurofibromas was miR-486-3p that targets the major tumor suppressor gene, PTEN . We confirmed PTEN downregulation at mRNA level. In plexiform neurofibromas, we also report aberrant expression of four miRNAs involved in the RAS-MAPK pathway (miR-370, miR-143, miR-181a, and miR-145). In MPNSTs, significant deregulated miRNAs were involved in PTEN repression (miR-301a, miR-19a, and miR-106b), RAS-MAPK pathway regulation (Let-7b, miR-195, and miR-10b), mesenchymal transition (miR-200c, let-7b, miR-135a, miR-135b, and miR-9), HOX genes expression (miR-210, miR-196b, miR-10a, miR-10b, and miR-9), and cell cycle progression (miR-195, let-7b, miR-20a, miR-210, miR-129-3p, miR-449a, and miR-106b). Conclusion We confirmed the implication of PTEN in genesis of plexiform neurofibromas and MPNSTs in NF1. Markedly deregulated miRNAs might have potential diagnostic or prognostic value and could represent novel strategies for effective pharmacological therapies of NF1 tumors.

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.

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. 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. 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. 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. Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris.

Long-term patient monitoring and strict control by an institutional review board is necessary to ensure that the assumed increased technical risks of face transplantation are outweighed by the potential benefits in each case, from inclusion to long-term follow-up. References 1 JR Diaz-Siso, ED Rodriguez, Facial transplantation: knowledge arrives, questions remain, Lancet, Vol. 388, 2016, 1355-1356 2 L Lantieri, P Grimbert, N Ortonne, Face transplant: long-term follow-up and results of a prospective open study, Lancet, Vol...