The Evolution of Current Concept of the Reconstructive Ladder in Plastic Surgery: The Emerging Role of Translational Medicine

Plastic surgeons have used the reconstructive ladder for many decades as a standard directory for complex trauma reconstruction with the goal of repairing body structures and restoring functionality. This consists of different surgical maneuvers, such as secondary intention and direct tissue closure, as well as more complex methods such as local tissue transfer and free flap. The reconstructive ladder represents widely known options achievable for tissue reconstruction and wound closure that puts at the bottom rung the simplest methods of reconstruction and strengthens the complexity by moving upward. Regenerative medicine and surgery constitute a quickly spreading area of translational research that can be employed by minimally invasive surgical strategies, with the aim of regenerating cells and tissues in vivo in order to reestablish normal function through the intrinsic potential of cells, in combination with biomaterials and appropriate biochemical stimuli. These translational procedures have the aim of creating an appropriate microenvironment capable of supporting the physiological cellular function to generate the desired cells or tissues and to generate parenchymal, stromal, and vascular components on demand, and above all to produce intelligent materials capable of determining the fate of cells. Smart technologies have been grown that give extra “rungs” on the classic reconstructive ladder to integrate a more holistic, patient-based approach with improved outcomes. This commentary presents the evolution of the traditional concept of the reconstructive ladder in the field of plastic surgery into a new course with the aim of achieving excellent results for soft tissue reconstruction by applying innovative technologies and biologically active molecules for a wide range of surgical diseases

SeqBreed : a python tool to evaluate genomic prediction in complex scenarios

Background: Genomic prediction (GP) is a method whereby DNA polymorphism information is used to predict breeding values for complex traits. Although GP can significantly enhance predictive accuracy, it can be expensive and difficult to implement. To help design optimum breeding programs and experiments, including genome-wide association studies and genomic selection experiments, we have developed SeqBreed, a generic and flexible forward simulator programmed in python3. Results: SeqBreed accommodates sex and mitochondrion chromosomes as well as autopolyploidy. It can simulate any number of complex phenotypes that are determined by any number of causal loci. SeqBreed implements several GP methods, including genomic best linear unbiased prediction (GBLUP), single-step GBLUP, pedigree-based BLUP, and mass selection. We illustrate its functionality with Drosophila genome reference panel (DGRP) sequence data and with tetraploid potato genotype data. Conclusions: SeqBreed is a flexible and easy to use tool that can be used to optimize GP or genome-wide association studies. It incorporates some of the most popular GP methods and includes several visualization tools. Code is open and can be freely modified. Software, documentation, and examples are available at https://github.com/miguelperezenciso/SeqBreed

The Impact of COVID-19 on Plastic Surgery Residency Training

Abstract: Nowadays didactic and surgical activities for residents in the surgery field are less and less due to an increasing burden of documentation and \u201cnon-educational work.\u201d Considering the current lockdown due to the COVID-19 pandemic, it has never been so important to find different ways to allow residents to improve their knowledge. We asked all plastic and esthetic surgery residents in our country to fill out a questionnaire to investigate changes in their didactical activity and analyze problems about their professional growth in the last few months. From the results of such questionnaires, we found that most of the residents feel the decrease in surgical activities during this time is a detrimental factor for their training and that even if all the schools have changed their didactical activities no school has introduced the use of virtual simulators to compensate for the decrease in surgical practice. Actually, the majority of residents use webinars to keep updated, stating that such technologies are useful but not sufficient to analyze plastic surgery topics in depth during COVID-19 lockdown. Virtual interactive tools are well known in different clinical and surgical specialties, and they are considered as a valid support, but it seems that in plastic surgery they are not so used. According to the most recent studies about residents\u2019 didactical program, we have investigated the potential of Anatomage Table in combination with Touch Surgery application as physical and mental aids to bypass the decreased number and kind of surgical interventions performed in this particular time. Anatomage is an academic user-friendly touch screen table; it is used by both medical students and residents to learn human anatomy and to master surgical anatomy. Touch Surgery is an application available on smartphones and tablets that gives the possibility to watch real and virtually designed surgical videos, accompanied by explanatory comments on the surgical phases; they are interactive and give the possibility to check what you have learned through tests administered after virtual classes. In our opinion, these tools represent reliable solutions to improve plastic residents\u2019 training, mostly during the COVID-19 pandemic. Level of Evidence V: 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

Human Adipose-Derived Stem Cells in Madelung's Disease: Morphological and Functional Characterization

Madelung Disease (MD) is a syndrome characterized by the accumulation of aberrant symmetric adipose tissue deposits. The etiology of this disease is yet to be elucidated, even though the presence of comorbidities, either genetic or environmental, has been reported. For this reason, establishing an in vitro model for MD is considered crucial to get insights into its physiopathology. We previously established a protocol for isolation and culture of stem cells from diseased tissues. Therefore, we isolated human adipose-derived stem cells (ASC) from MD patients and compared these cells with those isolated from healthy subjects in terms of surface phenotype, growth kinetic, adipogenic differentiation potential, and molecular alterations. Moreover, we evaluated the ability of the MD-ASC secretome to affect healthy ASC. The results reported a difference in the growth kinetic and surface markers of MD-ASC compared to healthy ASC but not in adipogenic differentiation. The most commonly described mitochondrial mutations were not observed. Still, MD-ASC secretome was able to shift the healthy ASC phenotype to an MD phenotype. This work provides evidence of the possibility of exploiting a patient-based in vitro model for better understanding MD pathophysiology, possibly favoring the development of novel target therapies

Pre-pectoral Breast Reconstruction: Surgical and Patient-Reported Outcomes of Two-Stages vs Single-Stage Implant-Based Breast Reconstruction

Background: Two-stages pre-pectoral breast reconstruction may confer advantages over direct to implant (DTI) and subpectoral reconstruction in selected patients who have no indication for autologous reconstruction. The primary endpoint of the study was to evaluate and compare the incidence of capsular contracture in the pre-pectoral two-stages technique versus the direct to implant technique. Complications related to the two surgical techniques and patient satisfaction were also evaluated. Methods: A retrospective review of 45 two stages and 45 Direct-to-implant, DTI patients was completed. Acellular dermal matrix was used in all patients. An evaluation of anthropometric and clinical parameters, surgical procedures and complications was conducted. Minimum follow-up was 12 months after placement of the definitive implant. Results: There was no statistically significant difference in the rate of capsular contracture in the two groups. Rippling occurred more in DTI reconstruction. In the two-stages reconstruction, lipofilling was applied more often and there was a higher incidence of seroma. Patient satisfaction extrapolated from the Breast Q questionnaire was better for patients submitted to two-stage implant-based breast reconstruction. Conclusion: Dual-stage pre-pectoral reconstruction with acellular dermal matrix appears to be a good reconstructive solution in patients with relative contraindications for one-stage heterologous reconstruction with definitive prosthesis and no desire for autologous reconstruction

A Multicentre Study: The Use of Micrografts in the Reconstruction of Full-Thickness Posttraumatic Skin Defects of the Limbs - A Whole Innovative Concept in Regenerative Surgery

The skin graft is a surgical technique commonly used in the reconstructive surgery of the limbs, in order to repair skin loss, as well as to repair the donor area of the flaps and cover the dermal substitutes after engraftment. The unavoidable side effect of this technique consists of unaesthetic scars. In order to achieve the healing of posttraumatic ulcers by means of tissue regeneration and to avoid excessive scarring, a new innovative technology based on the application of autologous micrografts, obtained by Rigenera technology, was reported. This technology was able to induce tissue repair by highly viable skin micrografts of 80 micron size achieved by a mechanical disaggregation method. The specific cell population of these micrografts includes progenitor cells, which in association with the fragment of the Extracellular Matrix (ECM) and growth factors derived by patients' own tissue initiate biological processes of regeneration enhancing the wound healing process. We have used this technique in 70 cases of traumatic wounds of the lower and upper limbs, characterized by extensive loss of skin substance and soft tissue. In all cases, we have applied the Rigenera protocol using skin micrografts, achieving in 69 cases the complete healing of wounds in a period between 35 and 84 days. For each patient, the reconstructive outcome was evaluated weekly to assess the efficacy of this technique and any arising complication. A visual analogue scale (VAS) was administered to assess the amount of pain felt after the micrografts' application, whereas we evaluated the scars according to the Vancouver scale and the wound prognosis according to Wound Bed Score. We have thus been able to demonstrate that Rigenera procedure is very effective in stimulating skin regeneration, while reducing the outcome scar

Expression of Human α2-Adrenergic Receptors in Adipose Tissue of β3-Adrenergic Receptor-deficient Mice Promotes Diet-induced Obesity

Catecholamines play an important role in controlling white adipose tissue function and development. β- and α2-adrenergic receptors (ARs) couple positively and negatively, respectively, to adenylyl cyclase and are co-expressed in human adipocytes. Previous studies have demonstrated increased adipocyte α2/β-AR balance in obesity, and it has been proposed that increased α2-ARs in adipose tissue with or without decreased β-ARs may contribute mechanistically to the development of increased fat mass. To critically test this hypothesis, adipocyte α2/β-AR balance was genetically manipulated in mice. Human α2A-ARs were transgenically expressed in the adipose tissue of mice that were either homozygous (−/−) or heterozygous (+/−) for a disrupted β3-AR allele. Mice expressing α2-ARs in fat, in the absence of β3-ARs (β3-AR −/− background), developed high fat diet-induced obesity. Strikingly, this effect was due entirely to adipocyte hyperplasia and required the presence of α2-ARs, the absence of β3-ARs, and a high fat diet. Of note, obese α2-transgenic, β3 −/− mice failed to develop insulin resistance, which may reflect the fact that expanded fat mass was due to adipocyte hyperplasia and not adipocyte hypertrophy. In summary, we have demonstrated that increased α2/β-AR balance in adipocytes promotes obesity by stimulating adipocyte hyperplasia. This study also demonstrates one way in which two genes (α2 and β3-AR) and diet interact to influence fat mass

Outcomes in Hybrid Breast Reconstruction: A Systematic Review

Background and Objectives: Lipofilling is a commonly performed procedure worldwide for breast augmentation and correction of breast contour deformities. In breast reconstruction, fat grafting has been used as a single reconstructive technique, as well as in combination with other procedures. The aim of the present study is to systematically review available studies in the literature describing the combination of implant-based breast reconstruction and fat grafting, focusing on safety, complications rate, surgical sessions needed to reach a satisfying reconstruction, and patient-reported outcomes. Materials and Methods: We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) throughout the whole review protocol. A systematic review of the literature up to April 2022 was performed using Medline, Embase, and Cochrane Library databases. Only studies dealing with implant-based breast reconstruction combined with fat grafting were included. Results: We screened 292 articles by title and abstract. Only 48 articles were assessed for full-text eligibility, and among those, 12 studies were eventually selected. We included a total of 753 breast reconstructions in 585 patients undergoing mastectomy or demolitive breast surgeries other than mastectomy (quadrantectomy, segmentectomy, or lumpectomy) due to breast cancer or genetic predisposition to breast cancer. Overall, the number of complications was 60 (7.9%). The mean volume of fat grafting per breast per session ranged from 59 to 313 mL. The mean number of lipofilling sessions per breast ranged from 1.3 to 3.2. Conclusions: Hybrid breast reconstruction shows similar short-term complications to standard implant-based reconstruction but with the potential to significantly decrease the risk of long-term complications. Moreover, patient satisfaction was achieved with a reasonably low number of lipofilling sessions (1.7 on average)