Indications and Results of Reconstructive Techniques with Flaps Transposition in Patients Requiring Complex Thoracic Surgery: A 12-Year Experience.

BACKGROUND: Flap transposition is an infrequent but far from exceptional thoracic surgical procedure. The aim of this retrospective study was to report our experience in a referral unit of general thoracic surgery analyzing the early results after flap transposition. METHODS: We retrospectively analyzed the clinical records, surgical notes, and postoperative results of a cohort of patients who underwent flap transposition in our unit from November 2000 to February 2013. RESULTS: Overall, a surgical approach adopting flap reconstruction techniques was performed in 81 patients (54 males, 27 females) with a median age of 62 years (range 20-87). Flap transposition was necessary to reconstruct chest wall after resection for malignancy (27 patients), to repair intrathoracic viscera perforation (15 patients), and to fill residual cavities secondary to pulmonary/pleural infection (39 patients). A pedicle muscle flap was transposed in most of cases (64 pts, 79 %), while in the remaining 17 cases (11 %), an omental flap was used. There were no immediate postoperative complications, while three in-hospital deaths occurred due to respiratory or multiorgan failure. Among patients undergone flap transposition to fill a residual cavity, we observed a recurrent bronchopleural fistula in three patients (7.7 %); such patients were treated by repeat flap transposition (2 cases) and by repeat cavernostomy (1 case). CONCLUSION: Flap transposition may be indicated as part of a multimodal treatment for severely ill patients requiring complex thoracic surgery.

Skin donors and human skin allografts: evaluation of an 11-year practice and discard in a referral tissue bank.

The Saint Louis hospital tissue bank provides skin allografts to pediatric and adult burn units in the Paris area. The aim of this study was to analyze our activity during the last 11 years focusing on the reasons for skin discard. Skin is procured solely from the back of the body, which is divided into 10 zones that are harvested and processed separately. This retrospective study included all skin donors harvested between June 2002 and June 2013, representing a total of 336 donors and 2770 zones. The donors were multiorgan heart-beating donors in 91 % of cases (n = 307). The main reason for discarding harvested skin was microbial contamination, detected in 99 donors (29 %). Most contaminants were of low pathogenicity. Other reasons for discard included positive serologic tests for 2 donors [17 zones (0.61 %)], unsuitable physical skin characteristics for 3 zones (0.11 %), the donor's medical history for 53 zones (1.91 %), and technical issues with processing or distribution for 61 zones (2.2 %). In our experience, microbial contamination continues to be the main reason for discarding potential skin allografts. However, discards are limited by separate harvesting and processing of multiple zones in each donor.

Technical note: comparison of the PrestoBlue and LDH release assays with the MTT assay for skin viability assessment.

MTT assay is the gold standard for assessing skin sample viability but it is time-consuming. Here we compared the MTT test with two other assays for the assessment of skin viability. The MTT, PrestoBlue (colorimetric method) and LDH release assays were applied to fresh and cryopreserved skin. Skin viability was considered proportional to the optical density values of the relevant analytes. PrestoBlue did not reliably distinguish between fresh and cryopreserved skin. The LDH release assay did not allow us to establish a viability index. We recommend the MTT assay for assessing skin viability.

Citrullinated Histone H3, a Marker for Neutrophil Extracellular Traps, Is Associated with Poor Prognosis in Cutaneous Squamous Cell Carcinoma Developing in Patients with Recessive Dystrophic Epidermolysis Bullosa.

Recessive dystrophic epidermolysis bullosa (RDEB) is a rare severe hereditary skin disease characterized by skin and mucosa fragility, resulting in blister formation. The most severe complication in RDEB patients is the development of cutaneous squamous cell carcinoma (SCC), leading to premature death. There is a great deal of evidence suggesting a permissive tumor microenvironment (TME) as a driver of SCC development in RDEB patients. In a cohort of RDEB patients, we characterized the immune profiles of RDEB-SCCs and compared them with clinical, histopathological, and prognostic features. RDEB-SCCs were subdivided into four groups based on their occurrence (first onset or recurrences) and grading according to clinical, histopathological parameters of aggressiveness. Thirty-eight SCCs from 20 RDEB patients were analyzed. Five RDEB patients experienced an unfavorable course after the diagnosis of the first SCC, with early recurrence or metastasis, whereas 15 patients developed multiple SCCs without metastasis. High-risk primary RDEB-SCCs showed a higher neutrophil-to-lymphocyte ratio in the tumor microenvironment and an increased proportion of neutrophil extracellular traps (NETs). Additionally, citrullinated histone H3, a marker of NETs, was increased in the serum of RDEB patients with high-risk primary SCC, suggesting that this modified form of histone H3 may serve as a potential blood marker of unfavorable prognosis in RDEB-SCCs.

Severe adult burn survivors. What information about skin allografts?

During the acute phase of a severe burn, surgery is an emergency. In this situation, human skin allografts constitute an effective temporary skin substitute. However, information about the use of human tissue can not be given to the patients because most of the allografted patients are unconscious due to their injury. This study explored the restitution of information on skin donation to patients who have been skin allografted and who have survived their injury. A qualitative study was conducted due to the limited number of patients in ability to be interviewed according to our medical and psychological criteria. 12 patients who had been treated between 2002 and 2008 were interviewed. Our results show that 10 of them ignored that they had received skin allografts. One of the two patients who knew that they had received allografts knew that skin had been harvested from deceased donor. All patients expressed that there is no information that should not be delivered. They also expressed their relief to have had the opportunity to discuss their case and at being informed during their interview. Their own experience impacted their view in favor of organ and tissue donation.

[The surgical treatment of pressure ulcers]. / La chirurgie de l'escarre.

The whole context of the treatment must be taken into account. The aim is to treat the patient and avoid a recurrence. Not all pressure ulcers are suitable for surgery and patients must be rigorously assessed, which requires a coherent approach by all the medical and allied health care teams in order to harmonise practices. This coordination must lead to the acceptance of the surgical procedure and the implementation of a care approach which will ensure its success both with regard to the preoperative preparation and the immediate post-operative period as well as the long-term.

Highly Efficient Ex Vivo Correction of COL7A1 through Ribonucleoprotein-Based CRISPR/Cas9 and Homology-Directed Repair to Treat Recessive Dystrophic Epidermolysis Bullosa.

Recessive dystrophic epidermolysis bullosa (RDEB) is a rare and severe genetic skin disease responsible for blistering of the skin and mucosa after minor trauma. RDEB is caused by a wide variety of variants in COL7A1 encoding type VII Collagen, the major component of anchoring fibrils that form key attachment structures for dermal-epidermal adherence. In this study, we achieved highly efficient COL7A1 editing in primary RDEB keratinocytes and fibroblasts from 2 patients homozygous for the c.6508C>T (p.Gln2170∗) variant through CRISPR/Cas9-mediated homology-directed repair. Three guide RNAs targeting the c.6508C>T variant or harboring sequences were delivered together with high-fidelity Cas9 as a ribonucleoprotein complex. Among them, one achieved 73% cleavage activity in primary RDEB keratinocytes and RDEB fibroblasts. Then, we treated RDEB keratinocytes and RDEB fibroblasts with this specific ribonucleoprotein complex and the corresponding donor template delivered as single-stranded oligodeoxynucleotide and achieved up to 58% of genetic correction as well as type VII Collagen rescue. Finally, grafting of corrected 3-dimensional skin onto nude mice induced re-expression and normal localization of type VII Collagen as well as anchoring fibril formation at the dermal-epidermal junction 5 and 10 weeks after grafting. With this promising nonviral approach, we achieved therapeutically relevant specific gene editing that could be applicable to all variants in exon 80 of COL7A1 in primary RDEB cells.

Viability of cryopreserved human skin allografts: effects of transport media and cryoprotectant.

Human skin allografts can be preserved by different methods. In our clinical practice, human skin allografts are harvested on multi-organ and tissue donors, transferred at +4°C in Ringer Lactate, cryopreserved with 15% Glycerol and held in the vapor phase of a liquid nitrogen freezer until delivery to the burn center. The aim of this experimental study was to evaluate the impact of transport medium and cryoprotectant on the viability of human skin allografts. For this purpose, we compared skin samples harvested from 19 multi-organ and tissue donors with two different transport media and two different cryoprotectants. Viability was assessed by the MTT assay after harvesting at laboratory reception, during storage (at +4°C) at day 2 and day 7, and after cryopreservation and thawing. Histopathological analysis was performed for each MTT assay. Results indicate that, when stored at +4°C, skin retains more viability with RPMI, whereas Glycerol and DMSO are equivalent cryoprotectants regardless of the transport medium. In conclusion, our protocol could be improved by the utilization of RPMI as transport medium.

Plastic surgery in bariatric patients: a nationwide study of 17,000 patients on the national administrative database.

BACKGROUND: Bariatric patients are often candidates for plastic surgery. However, the rate of postbariatric procedures is not known. OBJECTIVES: The aim of this study was to analyze the rate of plastic surgery, and factors related to surgery, in bariatric patients. SETTING: University hospital, France. METHODS: This was a cohort study based on administrative data. All adult patients who received bariatric surgery in France between 2007 and 2013 were included to estimate the rate of plastic surgery and related predictive factors. Data are reported according to the reporting of studies conducted using observational routinely collected data guidelines for observational studies on administrative data. RESULTS: Among the 183,514 patients who underwent bariatric surgery in the study period, 23,120 plastic surgeries were performed on 17,695 patients, including abdominoplasty (62%), dermolipectomy of the upper or lower limbs (25%), and reconstruction of the breast (14%). The rates of plastic surgery were 13%, 18%, and 21% at 3, 5, and 7 years post-bariatric surgery, respectively. Multivariate analysis revealed that patients who had a biliopancreatic diversion or a gastric bypass had a hazard ratio of 2.67 and 2.67 for subsequent plastic surgery, respectively, compared with patients who had adjustable gastric banding. Women had a 2-fold probability of surgery compared with men (hazard ratio 2.02). Important variability in the rate of surgery was found among different hospitals; rates ranged from 6.1% to 41.3% at 5 years. CONCLUSIONS: This study showed that 21% of bariatric patients undergo plastic surgery. Large variability exists among hospitals, suggesting that several unmeasured factors may limit access to contouring surgery.

Sarcoidosis and Wound Healing After Cellulitis of the Lower Limb: Is Methotrexate Responsible for Skin Graft Failure?

The authors report the case of a 53-year-old man with diffuse cutaneous and mediastinal pulmonary sarcoidosis and well-controlled steroid-induced diabetes. He was hospitalized for cellulitis of his left leg. His standard treatment for sarcoidosis consisted of prednisone and methotrexate. Prednisone was stopped at his admission. He received antibiotics for 4 weeks to treat the cellulitis. In parallel, the leg wound was treated with daily silver sulfadiazine applications until necrosis removal, then by skin autografting. Four successive procedures were performed, but all failed despite lack of surgical problem or local infection. Methotrexate was stopped after the fourth grafting procedure failed; the fifth, and final, autografting procedure was successfully performed.

Removal of subcutaneous lipomas: Interest of liposuction.

Subcutaneous lipomas are very common tumors. We report our experience of treatment by liposuction in carefully selected patients, initially referred for conventional surgical excision.

Gene-Corrected Fibroblast Therapy for Recessive Dystrophic Epidermolysis Bullosa using a Self-Inactivating COL7A1 Retroviral Vector.

Patients with recessive dystrophic epidermolysis bullosa (RDEB) lack type VII collagen and therefore have severely impaired dermal-epidermal stability causing recurrent skin and mucosal blistering. There is currently no specific approved treatment for RDEB. We present preclinical data showing that intradermal injections of genetically corrected patient-derived RDEB fibroblasts using a Good Manufacturing Practices grade self-inactivating COL7A1 retroviral vector reverse the disease phenotype in a xenograft model in nude mice. We obtained 50% transduction efficiency in primary human RDEB fibroblasts with an average low copy number (range = 1-2) of integrated provirus. Transduced fibroblasts showed strong type VII collagen re-expression, improved adhesion properties, normal proliferative capabilities, and viability in vitro. We show that a single intradermal injection of 3 × 10(6) genetically corrected RDEB fibroblasts beneath RDEB skin equivalents grafted onto mice allows type VII collagen deposition, anchoring fibril formation at the dermal-epidermal junction, and improved dermal-epidermal adherence 2 months after treatment, supporting functional correction in vivo. Gene-corrected fibroblasts previously showed no tumorigenicity. These data show the efficacy and safety of gene-corrected fibroblast therapy using a self-inactivating vector that has now been good manufacturing grade-certified and pave the way for clinical translation to treat nonhealing wounds in RDEB patients.

Assessment of a Standardized Pre-Operative Telephone Checklist Designed to Avoid Late Cancellation of Ambulatory Surgery: The AMBUPROG Multicenter Randomized Controlled Trial.

OBJECTIVES: To assess the impact of a standardized pre-operative telephone checklist on the rate of late cancellations of ambulatory surgery (AMBUPROG trial). DESIGN: Multicenter, two-arm, parallel-group, open-label randomized controlled trial. SETTING: 11 university hospital ambulatory surgery units in Paris, France. PARTICIPANTS: Patients scheduled for ambulatory surgery and able to be reached by telephone. INTERVENTION: A 7-item checklist designed to prevent late cancellation, available in five languages and two versions (for children and adults), was administered between 7 and 3 days before the planned date of surgery, by an automated phone system or a research assistant. The control group received standard management alone. MAIN OUTCOME MEASURES: Rate of cancellation on the day of surgery or the day before. RESULTS: The study population comprised 3900 patients enrolled between November 2012 and September 2013: 1950 patients were randomized to the checklist arm and 1950 patients to the control arm. The checklist was administered to 68.8% of patients in the intervention arm, 1002 by the automated phone system and 340 by a research assistant. The rate of late cancellation did not differ significantly between the checklist and control arms (109 (5.6%) vs. 113 (5.8%), adjusted odds ratio [95% confidence interval] = 0.91 [0.65-1.29], (p = 0.57)). Checklist administration revealed that 355 patients (28.0%) had not undergone tests ordered by the surgeon or anesthetist, and that 254 patients (20.0%) still had questions concerning the fasting state. CONCLUSIONS: A standardized pre-operative telephone checklist did not avoid late cancellations of ambulatory surgery but enabled us to identify several frequent causes. TRIAL REGISTRATION: ClinicalTrials.gov NCT01732159.

[Medical specialty choice: what impact of teaching? Results of a survey of two medical schools]. / L'enseignement et l'enseignant influencent le choix de la spécialité médicale. Enquête auprès de 207 étudiants.

BACKGROUND: Determinants of career choice are numerous. The impact of teaching has not yet been reported. OBJECTIVES: The objectives were to assess determinants of career choice among DCEM 4 (sixth year) medical students at Paris Descartes University and Pierre-et-Marie-Curie University; and to determine the impact of teaching on career choice. MATERIALS AND METHODS: Prospective study based on an online survey, after the 2011 National Grading Examination, among 865 DCEM 4 students. Collection of socio-demographic data, commonly reported determinants of medical specialty choice, and the impact of the teaching on this choice. RESULTS: Two hundred and seven (24%) students (67% female) answered the survey. During their medical studies, students changed their mind on their career choice an average of 3 times (range 0-10). Nearly 60% of them made their final choice during the fifth year. Choices varied significantly between the beginning and end of the studies (P<0.0001), with interest in surgical and pediatric careers falling significantly (P<0.0001 and p=0.0003 respectively). At the time of expressing the final choice, surgical careers were mainly chosen by male students (19.8% of males vs. 9.9% of females, P=0.04), whereas medical careers were chosen equally by males and females (37.7% vs. 35.5%, P=0.75). The main determinant was interest in the specialty (96% of students), followed by perceived quality of life (56% of students). Teaching was a determinant for 74% of students, of whom 88% were influenced by the teaching they received during their clinical training. In 42% of cases, the teacher did not belong to the university corpus. In 10% of cases, students were discouraged from their choice by a teacher (a university professor in 50%). DISCUSSION AND CONCLUSION: Our results highlight the impact of both teaching and the teacher on medical students' career choice. If career choice is now compelled in France by the "careers law", teaching is more than ever an effective way of interesting students in specialties which might appear less attractive. At a time when the selection of candidates for hospital-university careers is mainly based on publications, this study calls for reflection on the evaluation of these candidates' teaching qualities.

[Skin allograft, from the donor to the burn patient]. / La greffe de peau, du donneur au patient brûlé.

Severely burned patients are treated through the use of donor skin or skin allografts. It is a vital treatment. From the donor to the recipient, the process involves numerous procedures which are performed in accordance with ethical and medical safety rules.