Litigation Cases After Post-Bariatric Surgery: Lesson from the Past.

BACKGROUND: Due to the high demand of post-bariatric surgeries, the number of litigation cases is rapidly growing. Even if surgical mistakes still represent one of the main causes of medico-legal issues, many disputes depend on what happens in the post-operative course. In this article we analyzed the litigation cases that occurred in our Plastic Surgery Department, the current literature about medico-legal disputes and the importance of the doctor-patient relationship. PATIENTS AND METHODS: The medical records of 788 post-bariatric surgeries, the post-operative complications and the related litigation cases from January 2015 to December 2019 were collected, analyzed and compared. RESULTS: We performed 380 abdominoplasties, 28 torsoplasties, 65 breast reductions, 99 mastopexies, 94 brachioplasties, 52 thighplasties, 65 liposuctions and 5 facelifts between 2015 and 2019. Eight patients complained of medical issues and claimed for litigation. Despite in all cases the judges highlighted the risk of consent misinterpretation, the payout was granted only in one case. CONCLUSION: Post-bariatric patients often mistake their preoperative condition and consider body contouring procedures as an aesthetic surgery treatment. Patients should be therefore clearly informed about the complexity of body contouring procedures after massive weight loss, which should never be compared to aesthetic surgery. Surgeons should always promote the communication with their patients and build a strong and trustworthy relationship. This attitude will allow to deal more easily with complications and, in the worst situations, with medico-legal litigations. LEVEL OF EVIDENCE IV: 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 .

Naming the Barriers between Anti-CCR5 Therapy, Breast Cancer and Its Microenvironment.

Breast cancer represents the most common malignancy among women in the world. Although immuno-, chemo- and radiation therapy are widely recognized as the therapeutic trifecta, new strategies in the fight against breast cancer are continually explored. The local microenvironment around the tumor plays a great role in cancer progression and invasion, representing a promising therapeutic target. CCL5 is a potent chemokine with a physiological role of immune cell attraction and has gained particular attention in R&D for breast cancer treatment. Its receptor, CCR5, is a well-known co-factor for HIV entry through the cell membrane. Interestingly, biology research is unusually unified in describing CCL5 as a pro-oncogenic factor, especially in breast cancer. In silico, in vitro and in vivo studies blocking the CCL5/CCR5 axis show cancer cells become less invasive and less malignant, and the extracellular matrices produced are less oncogenic. At present, CCR5 blocking is a mainstay of HIV treatment, but despite its promising role in cancer treatment, CCR5 blocking in breast cancer remains unperformed. This review presents the role of the CCL5/CCR5 axis and its effector mechanisms, and names the most prominent hurdles for the clinical adoption of anti-CCR5 drugs in cancer.

Irradiated Triple-Negative Breast Cancer Co-Culture Produces a Less Oncogenic Extracellular Matrix.

Triple-negative breast cancer is the most common and most deadly cancer among women. Radiation is a mainstay of treatment, administered after surgery, and used in the hope that any remaining cancer cells will be destroyed. While the cancer cell response is normally the focus of radiation therapy, little is known about the tumor microenvironment response after irradiation. It is widely reported that increased collagen expression and deposition are associated with cancer progression and poor prognosis in breast cancer patients. Aside from the classical fibrotic response, ratios of collagen isoforms have not been studied in a radiated tumor microenvironment. Here, we created one healthy co-culture of stromal fibroblasts and adipose-derived stem cells, and one triple-negative breast cancer co-culture, made of stromal fibroblasts, adipose derived stem cells, and triple-negative breast cancer cells. After irradiation, growth and decellularization of co-cultures, we reseeded the breast cancer cells for 24 h and analyzed the samples using mass spectrometry. Proteomic analysis revealed that collagen VI, a highly oncogenic collagen isoform linked to breast cancer, was decreased in the irradiated cancer co-culture. This indicates that the anti-cancer impact of radiation may be not only cell ablative, but also influential in creating a less oncogenic microenvironment.

The Role of Portable Incisional Negative Pressure Wound Therapy (piNPWT) in Reducing Local Complications of Post-bariatric Brachioplasty: A Case-Control Study.

BACKGROUND: Due to the great impact of bariatric surgery on the overweight epidemic, the number of post-bariatric body-contouring procedures is constantly increasing worldwide. The portable incisional negative pressure wound therapy (piNPWT) is a promising medical device for accelerating wounds closure and controlling post-operative complication, which have been shown promising results in post-bariatric population. We aimed to evaluate the role of piNPWT in optimizing wound healing and controlling post-operative complications after a post-bariatric brachioplasty. PATIENTS AND METHODS: 26 post-bariatric female patients who underwent a brachioplasty followed by either a piNPWT (14 cases) or a standard wound treatment (12 controls) were analyzed. The number of post-operative dressing changes, the rate of local post-operative complications (re-operation, hematoma and serosa development, dehiscence and necrosis), the time to dry as well as the scar quality and hospitalization length were evaluated. RESULTS: None of the patients prematurely stopped treatment with piNPWT due to intolerance. The piNPWT patient group showed a significant lower healing time as well as a significant reduction of the number of post-operative dressing changes and hospital stay. Despite the scarring process was excellent from the functional point of view in the long term, we noticed a higher rate of hyperchromic scarring at 90 days after surgery. CONCLUSION: The piNPWT is a cost-effective and user-friendly medical tool that increase and promote wound healing. We suggest the use of this device in post-bariatric patients who undergo a brachioplasty, especially if there is the need to minimize the number of post-operative dressing changes. LEVEL OF EVIDENCE IV: 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 Table of Contents or the online Instructions to Authors www.springer.com/00266.

Deferiprone Stimulates Aged Dermal Fibroblasts via HIF-1α Modulation.

BACKGROUND: Hypoxia-inducible factor 1α (HIF-1α), a transcription factor responsible for tissue homeostasis and regeneration, presents reduced functionality in advanced age. In addition to absence of oxygen, sequestration of iron also stimulates HIF-1α. Therefore, we analyzed the efficacy of the iron-chelator deferiprone (DFP) at stimulating dermal fibroblasts. OBJECTIVES: The main objective of this study was to quantify the DFP concentrations capable of stimulating dermal fibroblasts in vitro and to correlate the effective DFP concentrations with the ability of DFP to penetrate the epidermis, reach the dermis, and activate HIF-1α in vivo. METHODS: We measured cell proliferation, metabolic activity, HIF-1α expression, and lactate dehydrogenase levels of both young and aged fibroblasts after a 24-hour in vitro preconditioning with DFP. In addition, we evaluated cell survival rates and morphology with different cellular stainings. Finally, we performed a transdermal permeation study with a 1% DFP topical formulation to quantify the concentration required to reach the dermis. RESULTS: In vitro administration of iron-chelation therapy (156-312.5 µg/mL DFP ) on aged fibroblasts resulted in activation of various antiaging processes. The concentration required to reach the dermis within 24 hours was 1.5% (0.15 mg/mL), which corresponds well with the effective doses of our laboratory analyses. CONCLUSIONS: The activation of HIF-1α by DFP enhances cell metabolism, proliferation, and survival of fibroblasts while reducing lactate dehydrogenase levels. Modulation of HIF-1α is linked to activation of key regeneration enzymes and proteins, and by proxy, antiaging. Therefore, the antiaging properties of DFP and its satisfactory dermal penetration make it a promising regenerative agent.

Preliminary Single-Cell RNA-Sequencing Analysis Uncovers Adipocyte Heterogeneity in Lipedema.

Background: Despite its increasing incidence and prevalence throughout Western countries, lipedema continues to be a very enigmatic disease, often misunderstood or misdiagnosed by the medical community and with an intrinsic pathology that is difficult to trace. The nature of lipedemic tissue is one of hypertrophic adipocytes and poor tissue turnover. So far, there are no identified pathways responsible, and little is known about the cell populations of lipedemic fat. Methods: Adipose tissue samples were collected from affected areas of both lipedema and healthy participants. For single-cell RNA sequencing analysis, the samples were dissociated into single-cell suspensions using enzymatic digestion and then encapsulated into nanoliter-sized droplets containing barcoded beads. Within each droplet, cellular mRNA was converted into complementary DNA. Complementary DNA molecules were then amplified for downstream analysis. Results: The single-cell RNA-sequencing analysis revealed three distinct adipocyte populations at play in lipedema. These populations have unique gene signatures which can be characterized as a lipid generating adipocyte, a disease catalyst adipocyte, and a lipedemic adipocyte. Conclusions: The single-cell RNA sequencing of lipedemic tissue samples highlights a triad of distinct adipocyte subpopulations, each characterized by unique gene signatures and functional roles. The interplay between these adipocyte subtypes offers promising insights into the complex pathophysiology of lipedema.

The Triple Adipose-Derived Stem Cell Exosome Technology as a Potential Tool for Treating Triple-Negative Breast Cancer.

BACKGROUND: Extracellular vesicles are pivotal mediators in intercellular communication, facilitating the exchange of biological information among healthy, pathological and tumor cells. Between the diverse subtypes of extracellular vesicles, exosomes have unique properties and clinical and therapeutical applications. Breast cancer ranks as one of the most prevalent malignancies across the globe. Both the tumor core and its surrounding microenvironment engage in a complex, orchestrated interaction that facilitates cancer's growth and spread. METHODS: The most significant PubMed literature about extracellular vesicles and Adipose-Derived Stem Cell Exosomes and breast cancer was selected in order to report their biological properties and potential applications, in particular in treating triple-negative breast cancer. RESULTS: Adipose-Derived Stem Cell Exosomes represent a potential tool in targeting triple-negative breast cancer cells at three main levels: the tumor core, the tumor microenvironment and surrounding tissues, including metastases. CONCLUSIONS: The possibility of impacting triple-negative breast cancer cells with engineered Adipose-Derived Stem Cell Exosomes is real. The opportunity to translate our current in vitro analyses into a future in vivo scenario is even more challenging.

A Novel Hair Restoration Technology Counteracts Androgenic Hair Loss and Promotes Hair Growth in A Blinded Clinical Trial.

Androgenic alopecia (AGA) is a genetically predetermined condition that occurs as a result of stepwise miniaturization of the dermal papilla. During this process, the hair follicle suffers from increasing malnutrition and eventually dies, causing progressive hair loss. We recently highlighted that HIF-1α modulation may counteract hair loss. Here, we aim to demonstrate the positive influence of Tomorrowlabs HIF strengthening factor [HSF] hair restoration technology on hair biology in a monocentric blinded clinical trial over a total period of 9 months. A trial with 20 subjects (4 female and 16 male) and once-daily application of [HSF] hair restoration technology to the scalp was conducted. To assess the tolerability and efficacy of [HSF], testing included dermatological assessment, determination of hair loss by counting after combing, macro images of the head and TrichoScan evaluation of hair density as well as the proportion of anagen hair versus telogen hair. The clinical data show Tomorrowlabs [HSF] hair restoration to be safe and effective to counteract AGA. The use of Tomorrowlabs [HSF] hair restoration resulted in improvements in the clinical parameters of hair quality such as thickness (+7.2%), hair density (+14.3%) and shine and elasticity (+20.3%) during the test period. The effectiveness of the test product was further determined by a significant reduction in hair loss of an average of 66.8% in treatment-responsive subjects after 6 months and an increase in hair growth reaching up to 32.5%, with an average percentage change of 8.4% in all participants and 10.8% in the responsive patients (85% of the study cohort) after 9 months on TrichoScan evaluation. The hair growth cycle was harmonized with the result of an average anagen hair percentage increase of +8.0% and telogen hair percentage reduction of -14.0% shown in the test area. Applicable for both sexes in an alcohol-free formulation, beneficial to scalp health and free of complications or side effects, this novel product provides objectively measurable results counteracting hair loss paired with an improved look and feel of the hair.

Augmentation-Mastopexy: Analysis of 95 Consecutive Patients and Critical Appraisal of the Procedure.

Single-stage mastopexy-augmentation has been demonstrated to be a safe procedure. However, revisions may still be necessary. We evaluate 95 consecutive patients undergoing mastopexy-augmentation and introduce a new surgical technique for the procedure: the modified dual plane technique. In this retrospective study, 95 patients (mean age 34 ± 11 years) underwent mastopexy-augmentation between 2009 and 2019. The procedures were classified as subglandular, dual plane, or modified dual plane technique. The outcome measures included major and minor complications. A total of 19 patients underwent a subglandular procedure, 32 patients a dual plane procedure, and 44 patients a modified dual plane procedure. We observed a high overall complication rate in the subglandular group (n = 12, 63%), dual plane group (n = 15, 47%), and modified dual plane group (n = 10, 23%). Complications leading to implant loss/change occurred in seven patients in the subglandular group (37%), six patients in the dual plane group (19%), and no patient in the modified dual plane group. While we observed a high complication rate in patients undergoing mastopexy-augmentations, the modified dual plane technique was associated with a lower complication rate.

A Forgotten Entity following Breast Implant Contracture: Does Baker Need a Change?

Although capsular contracture represents one of the most important complications after breast augmentation, local inflammation and fibrosis can lead, in very rare cases, to capsular calcification, an often-forgotten radiological sign of capsular contracture. In this article, the authors present a clinical case of breast implant calcification in an 81-year-old patient. Although this complication has been rarely described, the literature was reviewed to clarify the role of the local microenvironment in capsular contracture and calcification. At present, capsular contracture patients are classified using the conventional Baker score and the histological Wilflingseder classification. As it was not possible to consider capsular calcification when classifying our patient using the traditional scores, the authors propose an updated version of the current scale.

Retrospective analysis of the predictive factors associated with good surgical outcome in brachioplasty in massive weight loss patients.

BACKGROUND: Upper arm lift is a widespread body contouring procedure, but no globally accepted guidelines exist in selecting patients and, due to comorbidity and heterogeneity of them, it is difficult to identify predictive factors of good surgical outcome. The authors review the team's experience of 56 brachioplasty performed in massive weighs loss patients. METHODS: Data of 56 consecutive arm lifts were reviewed for preoperative, perioperative and postoperative variables and outcomes (complications, scarring, wound healing, revision surgery, need for blood transfusion, satisfaction, etc.). Surgical technique and postoperative care are described. A statistical analysis was performed to identify relationship between possible predictive factors and outcomes. Furthermore, an evaluation of different employed wound management devices was conducted. RESULTS: Follow-up ranged from 6 to 36 months (mean 20.1 months). Outcomes summary is reported (overall complication rate 50%, poor scarring rate 25%, delayed wound healing rate 26.8%, revision surgery rate 37.5%, need for blood transfusion rate 8.9%, satisfaction rate 71.4%) and statistical investigation evidenced the role of prior plastic surgery BMI and the associated change in BMI before and after weight loss, just prior brachioplasty, and the modality of weight loss. CONCLUSION: The authors' technique resulted in positive outcomes overall, considering the difficulty in dealing with the problems of MWL patients. Based on our results, we aim to suggest to perform brachioplasty in patient with the lower achievable BMI (preferably <30kg/m2) to reduce the negative effect of unmodifiable factors as diabetes, modality of weight loss, a wide ΔBMI, and other well-known negative predictive factors.

New perspectives in regenerative medicine and surgery: the bioactive composite therapies (BACTs).

Regenerative medicine and surgery is a rapidly expanding branch of translational research in tissue engineering, cellular and molecular biology. To date, the methods to improve cell intake, survival, and isolation need to comply with a complex and still unclear regulatory frame, becoming everyday more restrictive and often limiting the effectiveness and outcome of the therapeutic choices. Thus, the authors developed a novel 360° regenerative strategy based on the synergic action of several new components called the bioactive composite therapies (BACTs) to improve grafted cells intake, and survival in total compliance with the legal and ethical limits of the current regulatory frame. The rationale at the origin of this new technology is based on the evidence that cells need supportive substrate to survive in vitro and this observation, applying the concept of translational medicine, is true also in vivo. Bioactive composite mixtures (BACMs) are tailor-made bioactive mixtures containing several bioactive components that support cells' survival and induce a regenerative response in vivo by stimulating the recipient site to act as an in situ real bioreactor. Many different tissues have been used in the past for the isolation of cells, molecules, and growth factors, but the adipose tissue and its stromal vascular fraction (SVF) remains the most valuable, abundant, safe, and reliable source of regenerative components and particularly of adipose-derived stems cells (ADSCs). The role of plastic surgeons as the historical experts in all the most advanced techniques for harvesting, manipulating, and grafting adipose tissue is fundamental in this constant process of expansion of regenerative procedures. In this article, we analyze the main causes of cell death and the strategies for preventing it, and we present all the technical steps for preparing the main components of BACMs and the different mixing modalities to obtain the most efficient regenerative action on different clinical and pathological conditions. The second section of this work is dedicated to the logical and sequential evolution from simple bioactive composite grafts (BACGs) that distinguished our initial approach to regenerative medicine, to BACTs where many other fundamental technical steps are analyzed and integrated for supporting and enhancing the most efficient regenerative activity. Level of Evidence: Not gradable.

The Posterior Arm Flap for Reshaping the Postbariatric Breast.

Postbariatric surgery, either by itself or in association with other procedures, tries to correct physical defects and body deformities. Because of the intrinsic complexity of massive weight loss (MWL) patients, more than a single procedure is, most of the time, required. We report a combined surgical method able to improve arms' and breasts' contour that aims to obtain a satisfying functional and aesthetic result by reducing surgical times and costs. METHODS: A female MWL patient with proper body mass index was clinically evaluated and considered suitable for surgery. While authors performed a modified Pascal-Le Louarn brachioplasty for the upper arm, a standard McKissock mastopexy followed by a Wise pattern skin closure was selected to obtain the breast lift. By sparing the proximal pedicle, the fasciocutaneous flaps were harvested on both posteromedial sides of the arms. The posterior arm flaps (PAF) were tunneled and transposed below the subcutaneous skin bridge across the axilla and finally used to increase the breast mound. RESULTS: In the immediate postoperative follow-up, no complications were reported. After the 6-month and 1-year follow-up, both arms' silhouette was documented as healthy and symmetric. Breasts were soft, without any signs of ptosis and/or contracture. No skin disorders or scar hypertrophy or lymphedema were reported. CONCLUSIONS: PAF in breast contouring procedures is an interesting surgical option, but more patients need to be treated to validate the effectiveness of the procedure. This technique should be considered when there is a need for simultaneously improving arm's contour and breast's volume and shape.

Inguinocrural dermolipectomy A retrospective study.

INTRODUCTION AND AIM: Inguinocrural dermolipectomy is a constantly increasing surgical procedure, especially for postbariatric patients with significant weight loss. The "crescent medial" and "vertical medial" thigh lifting techniques (CMTL/VMTL) are the most effective type of surgery to treat laxity and excess of skin and soft tissues in the medial region of the thighs Aim of this article is to suggest which patients may be eligible for a surgical thighplasty with an acceptable risk of postoperative complications. MATERIALS AND METHODS: We performed a retrospective study with 30 female patients who underwent a surgical thighplasty between 2018 and 2008. Several parameters were evaluated such as age, patient weight and BMI before weight loss and before plastic surgery, the mode of weight loss (surgical vs. non-surgical), the type of technique performed ("crescent medial" vs. "vertical medial"), the association with other surgical procedures of size reduction plastic operation (ICD10 Procedure Code 8683), smoking at the time of the intervention. The correlations between these preoperative parameters and the development of postoperative complications were taken into consideration and different outcomes were evaluated, of which the modification of the size of the trousers after the thigh lifting operation, the days of hospitalization, the maintenance time drainage, the time needed to return to normal daily activities and improvement in the same, in walking and in physical activity after the execution of the procedure and the satisfaction in general of the patients. RESULTS: The association with other excisional surgeries such as brachioplasty, abdominoplasty or mastopexy, the BMI before thighplasty and weight loss modality condition significantly influence patient's post-operative outcomes. However, there is no clear correlation with age, smoking, the type of plastic surgery performed and its possible association with liposuction, and a drastic "drop" of BMI. DISCUSSION: In our opinion, even more than a single parameter predicts patients' post-operative complications. Acting on the significant findings of our investigation, surgeons could minimize post-operative risks as well as surgical minor complications. CONCLUSIONS: Therefore we advise to evaluate these factors before the intervention in order to select the patients more accurately and define the ideal candidate patient for inguinocrural dermolipectomy, so as obtain a reduction in postoperative complications. KEY WORDS: Body contouring, Massive weight loss, Thigh lift.

Skin Rejuvenation through HIF-1α Modulation.

The constant intrinsic and extrinsic stress the skin is exposed to leads to significant impairments of the regenerative capacity of aging skin. Current skin rejuvenation approaches lack the ability to holistically support the biological processes that exhaust during aging skin degeneration, such as collagen production, cell migration and proliferation, and new vessel formation. Similar to chronic wounds, aged skin is characterized by dysfunction of key cellular regulatory pathways impairing regeneration. Recent evidence suggests that the same mechanisms hindering a physiologic healing response in chronic wounds are the basis of impaired tissue homeostasis in aged skin. Dysfunction of a main response-to-injury pathway, the hypoxia-inducible factor (HIF)-1α regulatory pathway, has been identified as pivotal both in chronic wounds and in aging skin degeneration. HIF-1α signaling is significantly involved in tissue homeostasis and neovascularization, resulting in the production of new collagen, elastin, and nourishing blood vessels. Modulating the functionality of this pathway has been demonstrated to significantly enhance tissue regeneration. In this review, we present an overview of the regenerative effects linked to the up-regulation of HIF-1α functionality, potentially resulting in skin rejuvenation on both the cellular level and the tissue level.

Aquatic habitat modifications in La Plata River basin, Patagonia and associated marine areas.

This paper describes the environmental characteristics and situation of aquatic habitats and communities in southern continental and maritime areas of southeastern South America (Patagonian Shelf GIWA Subregion), resulting from an overall assessment carried out within the framework of a GIWA project, mostly on the basis of publicly available data. The main focus of the analysis was on the current situation of transboundary water resources and anthropogenic impacts. In the inland waters, habitat and community modifications result, principally, from dams and reservoirs built in the main watercourses for hydroelectric power generation and other uses. The transformation of lotic environments into lentic ones have affected habitats and altered biotic communities. In the La Plata River basin, invasive exotic species have displaced native ones. Habitats in the ocean have been degraded, as their biodiversity becomes affected by overfishing and pollution. This article includes a discussion on the causal chain and the policy options elaborated for the Coastal Ecosystem of Buenos Aires province and the Argentinean-Uruguayan Common Fishing Zone, where fishing resources are shared by both countries.