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Skin models mimicking features of psoriasis‐related inflammation are needed to support the development of new drugs in dermatology. Reconstructed skin models lack tissue complexity, including a fully competent skin barrier, and presence and/or diversity of immune cells. Here, we describe InflammaSkin®, a novel human Th17‐driven ex vivo skin inflammation model. In this model, skin‐resident T cells are in situ activated by intradermal injection of anti‐CD3 and anti‐CD28 antibodies and Th17 cell polarization is sustained by culture in a chemically defined medium supplemented with IL‐1β, IL‐23 and TGF‐β for seven days. The acquired Th17 signature is demonstrated by the sustained secretion of IL‐17A, IL‐17AF, IL‐17F, IL‐22, IFN‐γ, and to some degree IL‐15 and TNF‐α observed in the activated ex vivo skin inflammation model compared with the non‐activated skin model control. Furthermore, expression of S100A7 and Keratin‐16 by keratinocytes and loss of epidermal structure integrity occur subsequently to in situ Th17cell activation, demonstrating cellular crosstalk between Th17 cells and keratinocytes. Finally, we demonstrate the use of this model to investigate the modulation of the IL‐23/IL‐17 immune axis by topically applied anti‐inflammatory compounds. Taken together, we show that by in situ activation of skin‐resident Th17 cells, the InflammaSkin® model reproduces aspects of inflammatory responses observed in psoriatic lesions and could be used as a translational tool to assess efficacy of test compounds.

Background Calf shape is an essential aesthetic parameter of the leg, and calf atrophy can lead to complex problems. The functional consequences of calf atrophy are generally moderate. Prefilled silicone gel implants represent the vast majority of currently placed prostheses, but this technique does not ensure optimal adaptation of the implant shape due to loss of volume. Objectives The aim of this study was to describe an innovative procedure for correcting acquired calf atrophy based on 3-dimensional (3D) modeling. Methods The study involved 22 patients treated for calf atrophy caused by illness. Implants were made with solid rubber silicone, and 3D reconstructions were created by computer-aided design based on computed tomography scans. The implants were introduced through a horizontal popliteal incision. Results Forty-one implants were placed. No cases of infection, hematoma, or compartment syndrome were encountered. We experienced 1 case of skin necrosis and 1 case of periprosthetic seroma. In addition, lipofilling was performed in 5 cases. Two patients sought to benefit from a surgical reduction in implant size. Conclusions Our innovative procedure to correct calf atrophy with custom solid rubber silicone implants produces a calf shape that better adapts to volume loss than prefilled silicone gel implants. The material maintains its shape and facilitates retrofitting of the prosthesis. There is no risk of hull formation or breakage, and the life span of the implants is limitless. This 3D computer-aided design approach has optimized our reconstructions. Level of Evidence: 4

Isolated scaphotrapeziotrapezoid (STT) osteoarthritis has functional consequences on the wrist. The main objective of our study was to evaluate the functional outcomes of patients managed surgically during the last 12 years at the Toulouse University Hospital, regardless of the surgical technique used, for isolated STT osteoarthritis. We performed a single-center retrospective observational study using the CCAM database. The inclusion criteria were patients treated surgically for isolated STT osteoarthritis who did not respond to conservative treatment, with at least 6 months of clinical and radiological follow-up. Twenty-four patients were treated between 2006 and 2018. Partial arthroplasty of the distal pole of the scaphoid with or without interposition and total trapeziectomy had been performed on these patients. The mean follow-up was 79±46.8 months. The wrist range of motion (ROM) and the Kapandji score were not significantly reduced postoperatively. The mean postoperative QuickDASH score was 29.15±8.46. The mean pain assessed using a visual analog scale was 6.6±1.17 preoperatively versus 1.25±1.51 postoperatively (P=0.003). Statistical subgroup analysis found no predictive factor for a better postoperative QuickDASH score, and no surgical technique was superior at halting the progression of intracarpal misalignment and postoperative ROM. Surgical treatment of isolated STT osteoarthritis resistant to conservative treatment leads to significant functional improvement, particularly in terms of pain, without altering the wrist's overall mobility.

Flap reconstruction techniques are increasingly desired by French's patients and it represents almost half of breast reconstruction indications in 2017. The main reasons of this statistics are the growing concerns of the patients with breast implant of developing BIA-ALCL, as well as their desire of having a more natural reconstruction results without having any foreign bodies. The multiplication of autologous reconstruction techniques, especially microsurgical techniques which has been popularized in the recent years, makes possible to propose a reconstruction to the majority of patients without an implant. This type of reconstructions is associated with a significant number of complications; thus, a proper selection of patient should be done and a good knowledge of the surgical technique by the surgeon to reduce the complication. Our proposed study is divided into two main parts, the complications of the flap and the complications at the donor site. Based on the experience of our plastic surgery department in immediate and delayed breast reconstruction, the objective of this article is to describe and to analyze the possible complications of breast reconstruction by a flap and their surgical management in intra and post operatively. Our goal is to provide an algorithm for our young colleagues in order to obtain better understanding of this type of interventions difficulties and to provide an appropriate care in the event of complication, also to provide optimal care to the patients who wish to undergo autologous flap reconstructions.

Summary Ectodermic dysplasia corresponds to genetic pathologies characterized by two or more defects that involved ectodermal-derived structures. Breast anomalies in female patients were uncommon. Just a few articles in the literature retrieved this association. The main anomalies concerning breast region were amastia and areolar complex malformation. Two types of reconstruction have been already studied: implants with or without tissue preexpansion, and autologous flap like latissimus dorsi or DIEP. We described in this article a series of three female patients issue from the same family. They presented various type of breast malformation with other defects characteristics of ectodermic dysplasia. They all benefit of a bilateral breast reconstruction by implants on a one-staged reconstruction. Patients and surgeon were satisfied of the reconstruction. This case series demonstrate that reconstruction by implants without tissue preexpansion was a good choice in this pathology.

International audience; No abstract available

Introduction Smoking prevalence in the overall population in France was 27% in 2017. There are few data about smoking prevalence in hospital workers. The aim of this study was to assess prevalence of current smoking in student and staff populations at Lyon University Hospital. Secondary objectives were to identify main variables associated with current smoking and willingness to quit. Methods We designed a single center, cross-sectional survey, using printed questionnaires. During one day, all registered staff and students were surveyed. We used optical reading to extract information from questionnaires. We performed univariate and multivariate analysis adjusted on most relevant factors. Results We analyzed 9712 questionnaires. The participating rates were high: 40.6% in the student cohort and 51.5% in the staff cohort. The proportion of current cigarette users was 26% in students and 25% in staff. In multivariate analysis, current smoking was significantly associated with: younger age, male sex, occupation type (e.g. logistical staff, and paramedical students), overnight work, and e-cigarette use. Among smokers, 53% reported a willingness to quit. In multivariate analysis, number of quit attempts, and feeling symptoms from tobacco were associated with willingness to quit. Conclusions Current smoking is less frequent in our cohorts of hospital staff and students than in the general French population. However, there are deep disparities in current smoking prevalence underlining a heterogeneous population. Among smokers, the majority reported a willingness to quit and some predictive factors may help to target this audience.

Background: The thumb plays a key role in hand function for precise dexterity. The surgical treatment of full avulsions of the digital skin sheath by tearing (ring syndrome) is complex and the management of these lesions is challenging for the reconstructive surgeon. When replantation is not possible, other alternatives are available if the covering tissue is thin and flexible. Case presentation: A 30-year-old male, tobacco addict, had a thumbsequelae similar to a stage III ring finger. Revascularization attempt failed and the skin envelope necrosed secondarily. A groin pocket flapgraft allowed a conservation of his thumb with a satisfactory aesthetic and functional result. Conclusions: We described a thumb coverage by a groin flapgraft using an original pocket design. This simple and safe procedure, in the carefully selected patient can successfully address functional and aesthetic concerns simultaneously, with minimal sequelae at the donor site. This technique can be used to treat a cutaneous tearing of the other fingers.

International audience; Following a long period dominated by random fasciocutaneous flaps or muscle flaps, solutions to cover the lower limb have been largely diversified by the advent of so-called "perforator" flaps. Extended knowledge of vascular anatomy has propagated the development of this innovative procedure, in the objective of reducing morbidity. The existence of close to 400 perforator vessels in the body makes it possible to offer new flap perspectives for many defects, which were sometimes previously impossible to manage before except by free flap. For us, perforator flaps have become the current first-line solutions for small to medium size loss of substances. Understanding of vascular physiology and surgical experience are essential in choosing indications, detecting perforators, and modeling flaps to be optimally positioned in the reconstructive decisional algorithm. New skills are needed to master this type of reconstruction and limit failures, which implies a learning curve not only for flap design, perforator detection and surgical procedure, but also for monitoring and management of complications. In this manuscript, we outline the concepts and principles of the majority of the pedicled perforator flaps available for coverage of the lower limb, based on experience of more than 400 perforator flaps suitable for this localization.

Background:The purpose of this study was to assess the efficacy of botulinum toxin in reducing the frequency of migraine headaches.Methods:The MEDLINE, Embase, and Cochrane Library databases were searched to identify randomized, double-blind, placebo-controlled trials that compared patients receivin

Background Plastic surgery is a transversal discipline that many people misunderstand, including general practitioners, medical students, paramedics and the public. Plastic surgeons often collaborate with physiotherapists for post-acute care and rehabilitation. They ensure optimal post-operative recovery of the patient. Herein, the authors assessed the medical knowledge and perceptions of plastic surgery by physiotherapists working outside health centers and explored their attitudes towards classic reconstructive surgery scenarios. Methods To assess physiotherapists' medical knowledge and perceptions of plastic surgery, the authors conducted an online questionnaire survey. A total of 1,262 physiotherapists responded. Results The physiotherapists confirmed the suspected lack of knowledge regarding the plastic surgery field. Although they were generally aware that plastic surgeons perform cosmetic procedures and treat burns, they were largely unaware that plastic surgeons perform hand surgeries and microsurgical operations. More than 70% of them stated that they did not have the necessary knowledge to properly manage patients in this specialty. This lack of knowledge can sometimes have a negative impact on patients' recovery, particularly for fear of making a mistake. Conclusions Physiotherapists, outside the hospital, have an incomplete conception of plastic surgery. They would need a specific plastic surgery training in order to manage these patients in an optimal way.

To achieve adequate nasal proportions, nostril surgery can be a complementary technique useful in facial surgery. To help surgeons with the decision to realize nostril surgery, we conducted a systematic review to summarize reported cases on surgical procedures with a specific interest on indications, surgical procedures and postoperative outcomes. A therapeutic algorithm is also proposed. We carried out this review in accordance with the PRISMA criteria. Twenty-two eligible studies were identified using Medical databases, including 1599 patients. A qualitative and quantitative analysis was carried out. Excision techniques were realized on 728 patients (45.5%), followed by cinching sutures on 642 patients (40%) and combined techniques: excision techniques with flap advancement techniques in 189 cases (12%), excision techniques with flap advancement techniques and cinching suture in 40 patients (2.5%). When excessive alar flaring was present, alar wedge resection was preferred in the 92% of followed by alar and sill resection. Cinching sutures were realized when excessive alar flaring was associated with a vertical alar axis, in cases of wide alar base, of associated orthognathic surgery. When excessive alar flaring was associated with wide alar bases, indications changed basing on the associated deformities. In 795 patients, nostril surgery was conducted simultaneously with rhinoplasty. Nostril surgery through excision techniques, cinching sutures or flaps advancement techniques, reveals good outcomes and can be complementary to rhinoplasty or orthognathic surgery. Through this systematic review, we tried to orient surgeons to find the best treatment for nostril base surgery. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Background: Methylxanthines including caffeine and theobromine are widely consumed compounds and were recently shown to interact with bovine copper-containing amine oxidase. To the best of our knowledge, no direct demonstration of any interplay between these phytochemicals and human primary amine oxidase (PrAO) has been reported to date. We took advantage of the coexistence of PrAO and monoamine oxidase (MAO) activities in human subcutaneous adipose tissue (hScAT) to test the interaction between several methylxanthines and these enzymes, which are involved in many key pathophysiological processes. Methods: Benzylamine, methylamine, and tyramine were used as substrates for PrAO and MAO in homogenates of subcutaneous adipose depots obtained from overweight women undergoing plastic surgery. Methylxanthines were tested as substrates or inhibitors by fluorimetric determination of hydrogen peroxide, an end-product of amine oxidation. Results: Semicarbazide-sensitive PrAO activity was inhibited by theobromine, caffeine, and isobutylmethylxanthine (IBMX) while theophylline, paraxanthine, and 7-methylxanthine had little effect. Theobromine inhibited PrAO activity by 54% at 2.5 mM. Overall, the relationship between methylxanthine structure and the degree of inhibition was similar to that seen with bovine PrAO, although higher concentrations (mM) were required for inhibition. Theobromine also inhibited oxidation of tyramine by MAO, at the limits of its solubility in a DMSO vehicle. At doses higher than 12 % v/v, DMSO impaired MAO activity. MAO was also inhibited by millimolar doses of IBMX, caffeine and by other methylxanthines to a lesser extent. Conclusions: This preclinical study extrapolates previous findings with bovine PrAO to human tissues. Given that PrAO is a potential target for anti-inflammatory drugs, it indicates that alongside phosphodiesterase inhibition and adenosine receptor antagonism, PrAO and MAO inhibition could contribute to the health benefits of methylxanthines, especially their anti-inflammatory effects.

Simultaneous lesions of both proper digital arteries of the thumb are common in hand trauma surgery. The purpose of this anatomical study was to determine if the dorsal arterial network could be sufficient to ensure the vascularization of the thumb skin sheath. We carried out a cadaveric study on 22 hands. The ulnar and radial proper digital arteries of the thumb were ligated at the base of the first phalanx. Red dye was injected into the radial artery and blue dye into the ulnar artery at the wrist level. Visual evaluation of skin staining and systematic photographs was done at 1, 3 and 10 min after injection of dyes. Staining of the thumb sheath was obtained in 100% of the dissections and complete in 91.91% of cases. Staining originated from mixed radial and ulnar artery origins in 81.82% of cases. It was incomplete in 9.09% of cases with a missing on the dorsoradial edge of the proximal phalanx. In one dissection, the whole hand skin was only stained red, and in another dissection only stained blue. The dorsal vascular network ensures the substitution of the skin vascularization in more than 90% of cases when ligating the proper digital arteries of the thumb. A clinical impression of good skin vascularization after injury of both proper digital arteries might lead the surgeon not to perform systematic revascularization, but the risk of variable damages of adjacent tissues due to an interruption of one major arterial system requires a palmar arterial anastomosis whenever possible.

International audience; The proximally based medial plantar flap is considered to be the reference standard for heel reconstruction. Although less well-studied, a distally based medial plantar flap is a suitable alternative when used to cover a distal foot defect, especially of the hallux, first metatarsal, or metatarsophalangeal joint. Our objective was to provide a complete description and propose a classification of the different surgical procedures used to harvest this flap. A review of the data reported in the MEDLINE database until May 2017 concerning the distally based medial plantar flap was performed. We have illustrated the different surgical procedures through a case series. Three approaches or "types" of flap have been described, and we have proposed a classification for reconstructive surgeons. In type 1, the plantar pedicle is ligatured before division into the medial and lateral plantar artery. In type 2, the medial plantar pedicle is cut proximally just after division. In type 3, the flap is harvested to include the fasciocutaneous perforator vessels, as an advancement flap or a propeller perforator flap. A distally based medial plantar flap affords adequate and reliable coverage of the weightbearing zone. Because the donor site drawbacks are minimal, this flap is a useful option for distal foot reconstruction, and reconstructive surgeons should remember this flap. The type 1 flap appears to be associated with a minimal risk of flap necrosis, even in those with diabetes or arteriopathy, and can cover even the most distal defect.

Burns to the cephalic extremities are particularly implicated in problems of self-image and alterations to personal social relations. The aim of this study was to objectively assess the quality-of-life (QoL) of patients suffering from face-and-neck burns through our newly created scale: The Burn-Specific Health Scale for Face and Neck (BSHS-FN).After constructing the BSHS-FN, we compared QoL of patients with or without face-and-neck burns. SF-36, the French version of the BSHS-B (Burn Specific Health Scale-Brief), and the BSHS-FN were administrated to 53 patients divided into two groups: GB group (general burns, 26 patients) and FN group (face-neck burns, 27 patients).QoL evaluated using the SF-36 had a higher average total score in GB patients compared to FN patients, but there were no significant difference between the two groups (54.3±18.5 vs. 47.0±17.3, respectively, p=0.11). In contrast, in BSHS-B the total score was significantly different between the two groups with a higher score recorded for the GB group (71.9±13.4 [median: 72.8] in the GB group vs. 62.2±14.4 [median: 64.4] in the FN group). In percentage terms, total score of BSHS-FN for GB group was 79.1±10.1, while total score for FN group was 53.6±13.1 (p0.001), with the highest score for the Face and Neck domain in GB group (99.7±1.1, p0.001) CONCLUSION: The BSHS-FN seemed to be more appropriate to assess QoL for FN burn patients. This study supports its application in routine clinical practice and in international studies.

BACKGROUND Poland syndrome is historically associated with hypoplasia of the pectoral major muscle and abnormalities of the upper limbs. The authors propose an innovative procedure for correcting Poland syndrome thoracic malformations using three-dimensional modeling. Moreover, the authors evaluated aesthetic improvement, satisfaction, and quality of life after reconstruction with computer-aided design customized silicone implants. METHODS Since 1993, the authors have treated 129 patients for Poland syndrome. Before 2007, the implants were made from plaster molds; since 2007, they have been made using three-dimensional computer-aided design. Patient satisfaction was assessed using a standardized questionnaire, and quality of life was evaluated using the Medical Outcomes Study 36-Item Short-Form Health Survey. RESULTS Lipofilling was performed in combination with computer-aided design in one-third of cases, and breast prostheses were required in 24 percent of cases. We found three exposed prostheses and two infections. Cosmetic results were excellent in more than 90 percent of cases, and more than 80 percent of patients were very satisfied or satisfied, with no significant difference between men and women (p = 0.382). The Medical Outcomes Study 36-Item Short-Form Health Survey scores revealed significant improvements in role emotional (p < 0.05), emotional well-being (p < 0.001), and social functioning (p < 0.001). CONCLUSIONS Correcting Poland syndrome using a computer-aided design silicone implant fulfilled aesthetic and psychological demands, and significant improvements were seen in quality of life. The technique is simple and reliable and yields high-quality results, and three-dimensional computer-aided design has optimized the authors' reconstructions. Nevertheless, associated procedures and secondary corrections remain necessary to obtain optimal results. CLINICAL QUESTION/LEVEL OF EVIDENCE Therapeutic, IV.

The safety of electric vehicles under crash event depends on the mechanical behavior of Lithium-ion cells under large deformation at high strain rates. Here, an extensive experimental campaign is performed on large-format pouch cells under out-of-plane indentation with two indenter shapes and speeds ranging from a few millimeters per minute up to ten meters per seconds, spanning six decades of strain rates. It reveals that the displacement at the onset of short circuit decreases with increasing strain rates, while a non-monotonic relationship is observed between the strain rate and the maximum force as well as the macroscopic cell tangent stiffness. Based on the experimental results, a phenomenological constitutive model is proposed making use of a Deshpande-Fleck yield locus and strain-rate dependent hardening. An internal variable is introduced to capture the softening at intermediate strain rates. The calibrated model is able to accurately reproduce the experimental data and is further validated on a hemispherical indentation performed at two meters per seconds.

This is the peer reviewed version of the following article: "Risk of hospital admission for liver injury in users of NSAIDs and nonoverdose paracetamol: Preliminary results from the EPIHAM study", which has been published in final form at https://onlinelibrary.wiley.com/doi/full/10.1002/pds.4640.This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.; International audience; Purpose: The SALT study found similar per-user risks of acute liver failure (ALF) leading to transplantation (ALFT) between NSAIDs and a three-fold higher risk in non-overdose paracetamol (NOP) users. The objective of EPIHAM was to identify the risks of hospital admission for acute liver injury (ALI) associated with NSAIDs and NOP. Methods: Case-population study included in the 1/97 sample of the French population claims database. ALI was identified from hospital discharge summaries, from 2009 to 2013. Exposure for cases was dispensation of NSAID or NOP resulting in exposure within 30 days before admission. Population exposure was number of patients using the drugs over the study timeframe and total number of DDD dispensed. Results: Of 63 cases of ALI, 13 had been exposed to NSAIDs and 24 to NOP. Events per million DDD [95%CI] ranged from 0.46 [0.09-1.34] (ketoprofen) to 1.43 [0.04-7.97] (diclofenac combinations), 0.43 [0.23-0.73] all NSAIDs combined, 0.58 [0.37-0.86] for NOP. There was no association with average duration of treatment. Per patient risk ranged from 19.5 [5.31-49.9] (ibuprofen) per million users to 37.2 [19.8-63.6] all NSAIDs combined, 58.0 [37.2-86.3] for NOP. There was a linear relationship between average treatment duration and per-user risk (R2=0.51, p

Autologous fat transfer, or lipofilling, is a common technique used for soft tissue reconstruction. It has been used for many years, but the technique is associated with a significant graft resorption rate (20% to 80%). To improve the fat graft survival rate, several methods have been tested, and one has appeared more promising: cell-assisted lipotransfer (CAL). In the CAL method, fat is enriched with adipose-derived stromal cells (ASC), contained in the stromal vascular fraction (SVF) obtained after enzymatic digestion of fat or after cell culture to improve the fat survival rate. In this concise review, we present the clinical indications, and the technical principles of CAL, as well as a presentation of ASC. To conclude, we present the main results (efficacy, complications and safety) obtained from different studies of this technique.

Compelling evidence suggests that volatile organic compounds (VOCs) have potentially harmful effects to the skin. However, knowledge about cellular signaling events and toxicity subsequent to VOC exposure to human skin cells is still poorly documented. The aim of this study was to focus on the interaction between 5 different VOCs (hexane, toluene, acetaldehyde, formaldehyde and acetone) at doses mimicking chronic low level environmental exposure and the effect on human keratinocytes to get better insight into VOC-cell interactions. We provide evidence that the proteasome, a major intracellular proteolytic system which is involved in a broad array of processes such as cell cycle, apoptosis, transcription, DNA repair, protein quality control and antigen presentation, is a VOC target. Proteasome inactivation after VOC exposure is accompanied by apoptosis, DNA damage and protein oxidation. Lon protease, which degrades oxidized, dysfunctional, and misfolded proteins in the mitochondria is also a VOC target. Using human skin explants we found that VOCs prevent cell proliferation and also inhibit proteasome activity in vivo. Taken together, our findings provide insight into potential mechanisms of VOC-induced proteasome inactivation and the cellular consequences of these events.

Small bowel adenocarcinoma (SBA) complicating Crohn's disease (CD) is rare and generally found incidentally on surgical specimens. We report our experience in CD-associated SBA observed this last decade in a tertiary referral centre in order to update its incidence, clinical presentation and pathological features. All SBAs diagnosed in patients who underwent surgery for CD between 2006 and 2016 were retrospectively included. Clinico-pathological characteristics were reviewed, and follow-up was updated. SBA was diagnosed in 9 (1.7%) of 522 patients who underwent SB resection(s) after a median CD duration of 15 years [0-32]. The median age at diagnosis was 46 years. Seven (78%) patients had obstructive symptoms refractory to medical treatment. Pre-operative biopsy revealed neoplasia in five (56%) patients (dysplasia in three and SBA in two) justifying the surgery. Two (29%) of the seven patients with imaging had features suggestive of cancer. In all specimens, SBA developed in active ileitis with adjacent dysplasia. Stage I low-grade tubulo-glandular adenocarcinoma was observed in 33% of patients. Stage IV high-grade adenocarcinoma was observed in 56% of patients, and mucinous/signet ring cell differentiation predominated in 44% of patients. Molecular analysis showed no BRAF mutation, a KRAS mutation in one case and a microsatellite instability phenotype suggestive of Lynch syndrome in one case. After a median follow-up of 24 months [7-82], four (44%) patients died with advanced stage IV SBA. This surgical series confirms that CD-associated SBA is rare with an incidence of 1.7%. Adjacent dysplasia was present in all specimens and was identified before surgery in all patients who benefit from ileal biopsies. This strengthens the importance of screening all longstanding CD by endoscopy if surgery is not considered.

International audience; We hypothesized that skeletal muscle contraction produces a cellular stress signal, triggering adipose tissue lipolysis to sustain fuel availability during exercise. The present study aimed at identifying exercise-regulated myokines, also known as exerkines, able to promote lipolysis. Human primary myotubes from lean healthy volunteers were submitted to electrical pulse stimulation (EPS) to mimic either acute intense or chronic moderate exercise. Conditioned media (CM) experiments with human adipocytes were performed. CM and human plasma samples were analyzed using unbiased proteomic screening and/or ELISA. Real-time qPCR was performed in cultured myotubes and muscle biopsy samples. CM from both acute intense and chronic moderate exercise increased basal lipolysis in human adipocytes. Growth and differentiation factor 15 (GDF15) gene expression and secretion increased rapidly upon skeletal muscle contraction. GDF15 protein was upregulated in CM from both acute and chronic exercise–stimulated myotubes. We further showed that physiological concentrations of recombinant GDF15 protein increased lipolysis in human adipose tissue, while blocking GDF15 with a neutralizing antibody abrogated EPS CM-mediated lipolysis. We herein provide the first evidence to our knowledge that GDF15 is a potentially novel exerkine produced by skeletal muscle contraction and able to target human adipose tissue to promote lipolysis.

The management of pilonidal sinus disease is still not standardized. Currently, the two main procedures are a lay-open excision procedure with secondary healing or coverage with local flaps. The authors present their experience with a one-stage excision-coverage with an innovative parasacral artery perforator flap propeller designed to respect the aesthetic unity of the buttocks.Study patients were managed with this procedure in the Toulouse, Montpellier, and Rennes university hospitals between 2012 and 2018. Data were collected on clinical and surgical details, immediate and late postoperative complications, and long-term recurrence. Aesthetic satisfaction was evaluated with a self-evaluation questionnaire.The authors operated on 228 consecutive patients for pilonidal sinus disease with an aesthetically shaped parasacral artery perforator flap. The median patient age was 23.5 years, the median operative time was 46 minutes, the median flap length was 9.3 cm (range, 6.5 to 14 cm), and the median flap width was 4.1 cm (range, 4 to 6.5 cm). There were five distal necroses but no complete flap necrosis. There were six postoperative hematomas, 11 infections, and 18 wound dehiscences. The median follow-up period was 27.9 months. Median hospital length of stay was 4.2 days. Three recurrences of pilonidal sinus disease and six instances of hidradenitis suppurativa were detected. Approximately 82 percent of the women and more than 85 percent of the men were "satisfied" or "very satisfied" with the aesthetic outcome, without significant differences between the sexes (p = 0.901).The aesthetically shaped parasacral artery perforator flap combines very satisfactory results regarding recurrence and postoperative recovery with cosmetic outcome. This procedure is technically more demanding than other flap procedures, although it is accessible to numerous surgeons as the first-line treatment for pilonidal sinus disease after initial learning.Therapeutic, IV.

Summary Background In France, when someone presents with chest pain, it is recommended to call a health emergency number. The patient talks with an emergency doctor at a medical dispatch centre, who decides whether (or not) to send a Mobile Intensive Care Unit (MICU). Patients with an ST-segment elevation myocardial infarction (STEMI) should have an MICU as their first medical contact, to speed up confirmation of diagnosis and enable them to benefit from reperfusion therapy as quickly as possible. Aim To evaluate the proportion of patients with STEMI benefiting from an optimal care pathway, and to identify the key factors leading to this pathway. Methods RESCAMIP was a multicentre registry conducted between May 2015 and May 2017 in Midi-Pyrenees. All patients treated for STEMI within 12 hours of symptoms onset, without initially going into cardiac arrest, were included. Results Data from 1371 patients with STEMI were analysed; 60% had an MICU as their first medical contact. In-hospital mortality was 4%. Factors associated with calling the medical dispatch centre when presenting chest pain were: age > 65 years (odds ratio [OR] 1.37, 95% confidence interval [CI] 1.02–1.83), personal history of cardiovascular disease (OR 1.9, 95% CI 1.22–2.96) and having cardiovascular risk factors (OR 1.84, 95% CI 1.35–2.5). Factors associated with sending an MICU as first medical contact were: male sex (OR 2.11, 955 CI 1.49–2.99) and personal history of cardiovascular disease (OR 1.69, 95% CI 1.07–2.65). Conclusions The proportion of patients with STEMI going through non-optimal pathways was 40% in our area. We note that there are sex-based inequalities in accessing MICUs.

International audience; Many treatments have been described for pilonidal disease, but recurrence cannot be completely eliminated. The aim of this study was to perform a meta-analysis of randomised, controlled trials comparing flap repair vs the laying open technique and/or excision and direct closure techniques in the treatment of chronic pilonidal sinus disease. The primary outcome measure was the recurrence rate. Secondary outcomes were complete wound-healing time, duration of the incapacity to work, quality of life and patient satisfaction, postoperative pain, wound infection, bleeding or haematoma, skin wound complications, and duration of hospital stay. Seventeen studies were included. The meta-analysis demonstrated a lower risk of recurrence, a shorter duration of incapacity to work, a lower risk of wound infections, a lower risk of skin wound complications, and a shorter duration of hospitalisation in favour of flap vs direct closure. A shorter time to complete wound healing and a shorter duration of incapacity to work for flap vs the laying open technique were observed. Superiority of flap repair vs direct closure in pilonidal sinus treatment was demonstrated in this meta-analysis. These results suggest avoiding primary direct closure in clinical practice. Compared with the laying open technique, flaps result in faster healing and a shorter time to return to activities.

This is the accepted manuscript of this article.; International audience; Introduction: Acute liver injury (ALI) is a major reason for stopping drug development or removing drugs from the market. Hospitalisation for ALI is relatively rare for marketed drugs, justifying studies in large-scale databases such as the nationwide Système National des Données de Santé (SNDS) that covers 99% of the French population.Methods: SNDS was queried over 2010-2014 for all hospital admissions for acute toxic liver injuries not associated with a possible other cause, using a case-population approach. Exposures of interest were drugs dispensed from 7 to 60 days before date of admission. Individual drugs were analysed by their frequency (if ≥ 5 cases), and by the ratio of exposed cases to the number of exposed subjects and to exposed patient-time in the general population over the same time-frame.Results: Over 5 years, 4,807 cases of ALI were identified, mean age 54.5, 59% women, 76% exposed to at least one of 249 different drugs. Drugs most commonly identified were non-overdose paracetamol (31% of cases), esomeprazole or omeprazole (18%), phloroglucinol, domperidone, coamoxiclav, furosemide, atorvastatin (more than 250 cases each). When compared to population exposures, the highest per-person risks were observed with antimycobacterial antibiotics with 1 case for 1,000 or fewer users, followed by colestyramine and erythromycin (around 1/5,300), antiepileptic drugs, anticoagulants, anti-Alzheimer drugs (1/6,000 - 1/10,000 users). When a person-time approach is considered, the drugs with the highest per-tablet risk were still the antituberculosis drugs followed by a number of other antibiotics. Conclusions: This nationwide study describes drugs associated with ALI, according to absolute population burden, to per-patient and per-tablet risk. Some of these associations may be spurious, others causal, and others yet were unexpected. Systematic analysis of drug classes will look for outliers within each class that could raise signals of unexpected hepatic toxicity.

Objectives: The Quebec Trauma Care Continuum (TCC) was initiated in 1991 with the objective of providing accessible, continuous, efficient, and high quality services for all injury cases in the province.Methods: The TCC design relied on three key components: (i) the designation of a network of acute care and rehabilitation facilities with specific mandates and responsibilities; (ii) the elaboration of transfer protocols, standing agreements, and governing structures to ensure fluid and optimal patient flow; and (iii) the close monitoring of several indicators to facilitate the continuous evaluation and improvement of the network.Results: Between 1992 and 2002, in-hospital mortality following major trauma decreased from 51.8 percent to 8.6 percent, followed by an additional 24 percent drop between 1999 and 2012. We also observed a 16 percent decrease in average LOS but no change in the incidence of complications or unplanned readmissions. These changes translate into 186 lives saved per year and cost savings, due to shorter LOS, of 6.3 million CD$ per year. The risk-adjusted incidence of in-hospital mortality following major injury between 2006 and 2012 (7 percent) was the lowest of all Canadian provinces.Conclusions: Strategic transformation of a network's structure and processes, supported by continuous monitoring of validated quality indicators, can lead to significant and sustainable improvements in clinical outcomes. It is hoped that the Quebec trauma story will inspire other jurisdictions and other healthcare sectors.

Resume Introduction Les techniques modernes de conception assistee par ordinateur et de prototypage 3D pour la fabrication d’implants sur mesure en elastomere de silicone sont en plein essor. Elles ont largement modifie les indications chirurgicales dans notre unite. Materiels et methodes En presentant leur experience de 611 cas operes entre 1993 et 2016, les auteurs detaillent la technologie de conception a partir de coupes scanner, la copie virtuelle du corps et la fabrication de l’implant unique parfaitement adapte a l’anatomie de chacun. Les techniques operatoires sont decrites pour les trois principales indications : le thorax en entonnoir ou pectus excavatum (474 cas) sous ses differents types selon une classification de CHIN modifiee et completee est corrige de facon remarquable et simple, rendant obsoletes les techniques remodelantes de chirurgie thoracique, peu injustifiable au plan de l’apport fonctionnel ; le syndrome de Poland (116 cas) ou l’utilisation d’un implant sur mesure pour la compensation du volume musculaire est souvent utilise, mais peut etre complete par un transfert de tissu adipeux ou un implant mammaire classique en plusieurs temps operatoires ; les atrophies de jambe (21 cas) beneficient de ce choix d’implants sur mesure en elastomere de volume previsible et mis en place en sous-aponevrotique. Resultats Les resultats sont excellents pour les pectus excavatum mais plus delicats a optimiser avec parfois des techniques complementaires pour les deux autres indications. Les complications sont rares et souvent benignes et les implants ont une duree de vie illimitee. La qualite de vie, le confort psychologique et l’estime de soi sont ameliores avec une morbidite reduite et sans avoir subi une experience chirurgicale trop douloureuse. Conclusion Les techniques de reconstruction des malformations congenitales a l’aide d’implant en silicone sur mesure ouvrent un nouveau champ d’activite a notre specialite chirurgicale avec des possibilites tres vastes.

Tuberous breast deformity is a congenital breast anomaly with different clinical signs. The most consistent sign is the constricting ring at the base of the breast. There is deficiency in the horizontal and/or vertical dimensions of the breast and often herniation of breast parenchyma toward the nipple-areola complex with areola enlargement. Breast asymmetry is frequently associated. This anomaly occurs only in females, during breast development at puberty. The incidence is unknown because of minor forms more difficult to diagnose. This deformity produces psychological morbidity and encourages the patients to consult. In 1999, Grolleau publishes a classification with three types of tuberous breast deformity. The goals of the surgical treatment are the expansion of the constricted base, the redistribution of volume, the correction of areolar size and of herniated subareolar breast tissue. In type II and III, the simple use of breast implant involves the "memory" of the previous inframammary fold line. To avoid this complication, it is necessary to make a glandular rearrangement with parenchymal flaps like Puckett and Ribeiro. It is a real challenge for the plastic surgeon who must reshape the breast and obtain a symmetry of volume. It would be delusive to think all types of tuberous breast can be corrected with the same one-step technique. It is often necessary to plan several surgeries and patient must always be informed about the strategy.

International audience; Background: The use of stromal vascular fraction and adipose-derived stromal cells in tissue regeneration is now being increasingly investigated, and studies have demonstrated that adipose-derived stromal cells present differentiation and immunomodulatory capacities. The development of a rapid, inexpensive, and enzyme-free technique to isolate adipose-derived stromal cell-enriched stromal vascular fraction is a major goal for stem cell therapy. Therefore, the authors compared innovative mechanical procedures to the gold standard technique, collagenase digestion. Methods: Stromal vascular fraction was prepared from 21 liposuctions using either enzymatic digestion or two different mechanical methods: high vortexing/centrifugation and dissociation by intersyringe processing. The effects of tissue processing on cell count, viability, proliferation, clonogenic enrichment, and the phenotypes of the different native cell were determined. Adipose-derived stromal cell phenotypes from the different protocols, and their differentiation and immunosuppressive potential, were compared. Results: Enzymatic digestion isolated more viable cells than dissociation by intersyringe processing and vortexing/centrifugation. The expansion rate and clonogenic enrichment were higher for stromal vascular fraction isolated with collagenase. The proportion of adipose-derived stromal cells was higher in stromal vascular fraction extracted with dissociation than with enzymatic digestion and vortexing/centrifugation (p < 0.01). Interestingly, all cultured adipose-derived stromal cells displayed similar differentiation and immunosuppressive capacities. Conclusions: Enzymatic digestion extracts more adipose-derived stromal cells, but intersyringe dissociation enables the rapid extraction of adipose-derived stromal cell-enriched stromal vascular fraction. Moreover, mechanical methods enable adipose-derived stromal cell isolation with stemness and immunosuppressive properties, similar to enzymatic digestion. Such mechanical procedures could allow easier and more rapid isolation of adipose-derived stromal cell-enriched stromal vascular fraction for practitioners. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V. Copyright © 2016 by the American Society of Plastic Surgeons.

Background The recent development of perforator flaps has changed the reconstructive strategy for common integumental defects and has refocused the attention of microsurgeons to donor site morbidity. We asked a representative panel of microsurgeons about the free flap they would use to cover a common integumental defect on their own body to investigate the best free-flap donor sites. Methods In total, 100 practitioners participated in the “FreeFlap4U” study, representing 77.3% of the French national plastic surgery teams practicing microsurgery. To assess changing attitudes, we also compared microsurgeons below 40 years of age (called junior microsurgeons, JMs) with those above 40 years of age (called senior microsurgeons, SMs). Results Perforator flaps were preferred for the first line (JMs) and second line (JMs and SMs) of treatment compared with other flaps. JMs emphasized lower donor site morbidity, whereas SMs favored reliability ( p = 0.013) and considered perforator flaps as a second-line treatment. Radial forearm and transverse rectus abdominis flaps were largely dismissed due to high morbidity. Some microsurgeons were influenced by the potential secondary benefit of the integument sample at the donor site. Conclusions Microsurgeons interviewed clearly moved toward perforator flaps, such as the anterolateral thigh, thoracodorsal artery perforator, and superficial circumflex iliac artery types, to cover common integumental defects. In the coming years, we believe that this choice, emitted by the microsurgeons for themselves, will be applied extensively by these surgeons for their patients.

Venous insufficiency is the main cause of failure and surgical revision in free flap surgery. Achieving a double venous anastomosis is frequently proposed to improve flap drainage. However, this procedure remains controversial. The authors evaluated, through a meta-analysis, the benefit of double venous anastomoses in the venous thrombosis, surgical revision, and failure rates of free flaps in head and neck oncologic reconstruction.A systematic literature review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria in the MEDLINE, PubMed Central, Cochrane Library, and EMBASE databases. Statistical heterogeneity evaluation and then fixed effects and random effects models were used.Sixteen articles were included involving 3684 flaps. The overall success rate was 96.15 percent. The authors reported a failure rate of 1.51 percent in the group with two anastomoses versus 5.03 percent in the group with single anastomoses (OR, 0.64; 95 percent CI, 0.277 to 1.522; p = 0.320). The authors found a venous thrombosis rate of 2.74 percent in the group with two anastomoses versus 4.54 percent in the group with single anastomoses (OR, 0.535; 95 percent CI, 0.334 to 0.858; p = 0.009). There were also more surgical revisions in the single venous anastomoses group, 11.87 percent versus 6.04 percent (OR, 0.474; 95 percent CI, 0.349 to 0.643; p0.001).This meta-analysis supports that performing a double venous anastomosis confers protective effects in venous thrombosis and surgical revision, thus reducing free flap failure. The authors recommend the achievement of double venous anastomosis whenever it is feasible in head and neck oncologic reconstruction.Therapeutic, IV.

Background:. Venous congestion is a frequent problem in flap surgery. Other than surgical revision, there are a multitude of procedures in the literature to tackle this problem, but their effectiveness is not clear. Through a systematic review, we aimed to identify and evaluate the different interventions available for managing flap venous congestion. Methods:. The MEDLINE, PubMed central, Embase, and Cochrane databases were searched. The study selection process was adapted from the PRISMA statement. All English and French original articles describing or comparing a method for managing flap venous congestion were included. For each article, a level of evidence was assigned, as defined by the Oxford Centre for Evidence-based Medicine. Lastly, we specifically analyzed the effectiveness of postoperative non-surgical methods. No formal analysis was performed. Results:. Through literature searches carried out in various databases, we identified 224 articles. Finally, 72 articles were included. The majority of these studies had a low-level evidence. A total of 17 different methods (7 pre- and intraoperative, and 10 postoperative) were found. Concerning non-surgical methods, the most represented were leeches, local subcutaneous injection of heparin with scarification, venocutaneous catheterization, negative pressure therapy, and hyperbaric oxygen therapy. Conclusions:. Risks of venous congestion of flaps must always be present in a surgeon’s mind, at every stage of flap surgery. Apart from studies on the use of leeches, which have a significant follow-up and large enough patient numbers to support their efficacy, the low-level evidence associated with studies of other methods of venous congestion management does not allow us to draw a scientifically valid conclusion about their effectiveness.

Pectus excavatum is the most common thoracic deformity, often familial [1]. The incidence thereof is 1/300 to 1/1000 births and the sex ratio 3:1 to 5:1 in the literature, 6:4 in our experience due to the success of women’s and asymmetric case treatments. In the absence of any cardiac or respiratory impairment, the condition is a mere morphological deformation, but with a strong psychological impact for most of the authors [2–8].

Poland syndrome is associated with varying degrees of thoracic abnormalities and malformations of the upper limbs. The pathognomonic anomaly is agenesis of the sternocostal fibers of the pectoralis major [1]. Breast asymmetry occurs frequently in women [2] but the rate of hand malformations varies widely [3]. Poland syndrome is a rare malformation, as the incidence is estimated at only 1 per 30,000 births [4]. There appears to be a male predominance (3:1), and the majority of studies attest to lateralization of Poland syndrome on the right side. The etiology of the syndrome remains unknown but a vascular origin, as supported by Bavinck and Weaver [5], could explain the existence of associated syndromes (pectus, tuberous breasts).

Pectus excavatum, or “funnel chest,” is the most common congenital malformation of the thorax. In the literature, the sex ratio is mostly 5 men to 1 woman; in our 25-year experience of 600 cases, it was 3 men to 2 women owing to the quality of our plastic surgeon and the specific recruitment of breast anomalies due partly or totally to pectus excavatum.