Mesenchymal Stem Cells in Nerve Tissue Engineering: Bridging Nerve Gap Injuries in Large Animals.

Cell-therapy-based nerve repair strategies hold great promise. In the field, there is an extensive amount of evidence for better regenerative outcomes when using tissue-engineered nerve grafts for bridging severe gap injuries. Although a massive number of studies have been performed using rodents, only a limited number involving nerve injury models of large animals were reported. Nerve injury models mirroring the human nerve size and injury complexity are crucial to direct the further clinical development of advanced therapeutic interventions. Thus, there is a great need for the advancement of research using large animals, which will closely reflect human nerve repair outcomes. Within this context, this review highlights various stem cell-based nerve repair strategies involving large animal models such as pigs, rabbits, dogs, and monkeys, with an emphasis on the limitations and strengths of therapeutic strategy and outcome measurements. Finally, future directions in the field of nerve repair are discussed. Thus, the present review provides valuable knowledge, as well as the current state of information and insights into nerve repair strategies using cell therapies in large animals.

The Role of Hippo Signaling Pathway and ILK in the Pathophysiology of Human Hypertrophic Scars and Keloids: An Immunohistochemical Investigation.

BACKGROUND: Keloids and hypertrophic scars are characterized by abnormal fibroblast activation and proliferation. While their molecular pathogenesis remains unclear, myofibroblasts have been associated with their development. Hippo pathway effectors YAP/TAZ promote cell proliferation and matrix stiffening. Integrin-linked kinase (ILK), a central component of focal adhesions that mediates cell-matrix interactions, has been linked to tissue repair and fibrosis. The aim of this study was to investigate the expression of key Hippo pathway molecules and ILK in hypertrophic scars and keloids. METHODS: YAP/TAZ, TEAD4, ILK and a-SMA expression were evaluated by immunohistochemistry in keloids (n = 55), hypertrophic scars (n = 38) and normal skin (n = 14). RESULTS: The expression of YAP/TAZ, TEAD4, ILK and a-SMA was higher in fibroblasts of keloids compared to hypertrophic scars while negative in normal skin. There was a significant positive correlation between the expression of ILK and Hippo pathway effectors. CONCLUSIONS: Our results suggest that the deregulation of Hippo signaling and ILK are implicated in keloid and hypertrophic scar formation.

Defining the Ideal Breast Reconstruction Procedure After Mastectomy From the Patient Perspective: A Retrospective Analysis.

Background: An increasing number of breast cancer patients undergo immediate or secondary breast reconstruction, but the ideal method in terms of patient satisfaction remains ambiguous. We compared the 3 most common breast reconstruction techniques to determine patient satisfaction and objective outcomes. Methods: Retrospective study of 184 patients with breast cancer who underwent a reconstructive procedure between 1993 and 2011 at our institution. Procedures evaluated were implant-based reconstruction (IBR) alone, latissimus dorsi (LD) flap reconstruction with/without implant, and deep inferior epigastric perforator (DIEP) free flap reconstruction. A retrospective patient satisfaction questionnaire was sent to all women. Twenty patients from each subgroup were matched to conduct a standardized objective assessment of the sensitivity of their reconstructed breast. A blinded photographic evaluation was also performed by 3 independent observers to assess the esthetic aspect and symmetry. Results: DIEP obtained significantly higher average scores regarding the esthetic outcome, immediate reconstruction impact, and overall score in the questionnaire evaluation. The IBR had the best results in the somatosensory evaluation, with DIEP scoring better than LD. DIEP received higher scores on average than LD for the criteria of size and symmetry in the esthetic evaluation. No statistically significant differences were observed between IBR and DIEP. Conclusions: Good results were reported overall for all breast reconstruction procedures, with more reserved scores for LD. The DIEP reconstruction appeared to be the most satisfactory and best experienced reconstruction method for patients, despite the complexity of the intervention. Clinicians should be encouraged to consider DIEP as the principal choice for breast reconstruction.

Free-flap breast reconstruction: cost analysis in the Swiss healthcare system

AIM OF THE STUDY: Breast cancer is the most common type of malignancy among women. Mastectomy maintains an essential role in oncological therapy and led to the development of breast reconstruction procedures. The deep inferior epigastric perforator (DIEP) free flap became in the last decade a popular approach for breast reconstruction. Although this procedure is known to be more complex than other techniques, it offers one of the highest patient satisfaction rates. However, the cost-effectiveness of this technique has rarely been assessed; and the real cost coverage by health insurance has never been studied. This study estimated the real cost of immediate DIEP free flap breast reconstruction after unilateral mastectomy and evaluated the cost coverage by healthcare insurers according to the diagnosis-related group (DRG) reimbursement scheme in Switzerland. METHODS: Medical files of 20 consecutive patients who underwent immediate DIEP free-flap breast reconstruction between 2012 and 2017 were reviewed retrospectively. Billing data according to DRG rates were compared with an estimation of the real cost generated by the procedure. RESULTS: The mean charge according to the DRG model for one-stage DIEP free-flap reconstruction was CHF 29,573 (CHF 19,256­64,741). The mean real estimated cost was CHF 33,416 (CHF 20,633­47,036). Seven different DRG codes were used between 2012 and 2017, each offering a different definition and compensation. CONCLUSION: The DRG pricing scheme evolves through annual revisions. Progressively, more specific codes were created and used, allowing a better cost coverage for the procedure. Since 2017, the use of the dedicated code J01B has resulted in adequate cost coverage of the procedure. Since it has been widely accepted that DIEP breast reconstruction has advantages such as high patient satisfaction, we encourage the inclusion of this procedure in the reconstructive arsenal of breast cancer centres in Switzerland.

[Keloid treatment†: Where do we stand†?] / Traitement des chéloïdes: où en sommes-nous?

Keloids are debilitating skin lesions that develop often as a result of minor skin lesions. Unlike hypertrophic scars, their main clinical feature is the tendency to extend beyond the initial limits of the wound. They can be responsible for pain and itching and may appear several months after the trauma. Their pathophysiology remains unknown but various mechanisms seem to be involved. Their management includes invasive and non-invasive approaches. At present, there is no satisfactory method or consensus on their management. Since the risk of recurrence after treatment is particularly high, a combination of different methods is proposed. In this article, we present the therapeutic strategy used in our institution concerning these problematic lesions.

Les chéloïdes sont des lésions cutanées débilitantes se développant suite à un traumatisme cutané souvent mineur. Contrairement aux cicatrices hypertrophiques, leur principale caractéristique clinique est la tendance à envahir la peau saine et à s'étendre au-delà des limites initiales de la plaie. Elles peuvent être responsables de douleurs et démangeaisons et apparaître plusieurs mois après le traumatisme. Leur physiopathologie reste inconnue mais divers mécanismes semblent impliqués. Leur prise en charge comprend des approches invasives et non invasives. A l'heure actuelle, il n'y a pas de méthode satisfaisante ni de réel consensus concernant leur traitement. Le risque de récidive étant particulièrement élevé, une combinaison de différentes méthodes est proposée. Dans cet article, nous présentons la stratégie utilisée dans notre établissement concernant ces lésions complexes.

Keloid treatment: what about adjuvant radiotherapy?

Background: Keloids are debilitating fibrous skin proliferations with a high recurrence rate after surgical treatment. Postoperative radiotherapy (PORT) is a well-tolerated adjuvant treatment to reduce the risk of recurrence, but the optimal regimen for this combined treatment remains unknown. The aim of this study is to evaluate the efficacy of combining surgical excision and immediate PORT. Methods: We retrospectively reviewed the records of patients with keloid lesions treated with adjuvant PORT in the period 2005-2014 at Geneva University Hospitals. Main outcomes were the rates of complications and recurrence in patients with a minimal follow-up of 1 year, including the Patient and Observer Scar Assessment Scale satisfaction scores. Results: 10 patients with 16 keloids were eligible (mean follow-up, 37 months). Only one recurrence was reported (6%). In 12.5% of cases, mild erythema appeared in the early postoperative period. No major complications were observed. The overall patient and observer satisfaction rate was excellent. Conclusion: Surgical excision combined with immediate PORT is an effective and easy treatment with good esthetic results and an acceptable recurrence rate. It should be considered for patients with persistent keloid formation after failure of other treatments and those at high risk of relapse.

Traumatic Dislocation of the Pisiform Bone.

Pisiform dislocation is a rare wrist injury. The limited literature available describes this pathology in the form of case reports. An immediate closed reduction and immobilization is indicated for acute injury while there is a debate in the management of cases with delayed diagnosis or failed closed reduction. In this case, a 32-year-old, right-handed man visited the emergency department with pain at the ulnar side of his left wrist after a fall. The initial management involved immobilization, and the patient was referred to the authors' specialized clinic 10 days later because of persistence of important ulnar wrist pain. The choice of treatment was pisiform excision without ligament reconstruction with excellent functional results.

Cell therapies for tendons: old cell choice for modern innovation.

Although tissue engineering and cell therapies are becoming realistic approaches for medical therapeutics, it is likely that musculoskeletal applications will be among the first to benefit on a large scale. Cell sources for tissue engineering and cell therapies for tendon pathologies are reviewed with an emphasis on small defect tendon injuries as seen in the hand which could adapt well to injectable cell administration. Specifically, cell sources including tenocytes, tendon sheath fibroblasts, bone marrow or adipose-derived stem cells, amniotic cells, placenta cells and platelet-derivatives have been proposed to enhance tendon regeneration. The associated advantages and disadvantages for these different strategies will be discussed and evolving regulatory requirements for cellular therapies will also be addressed. Human progenitor tenocytes, along with their clinical cell banking potential, will be presented as an alternative cell source solution. Similar cell banking techniques have already been described with other progenitor cell types in the 1950's for vaccine production, and these "old" cell types incite potentially interesting therapeutic options that could be improved with modern innovation for tendon regeneration and repair.