Clinical Management of Complications Following Filler Injection.

AIM: Dermal fillers have been progressively used for cosmetic procedures. Concurrently, the rates of filler complications have also increased. The aim of this study is to describe the clinical management and treatment we performed in patients with complications occurred after filler injection. METHODS: From March 2000 to February 2020, 197 patients have been evaluated for complications due to filler injection. For each patient type of material, symptoms and signs were recorded. Ultrasound evaluation was used to obtain information about the type, amount and location of the injected material. Magnetic Resonance Imaging was performed in those patients who were candidate for surgery. Based on the clinical manifestations, we performed a targeted therapy. RESULTS: The local and systemic medical therapy allowed us a complete remission of the clinical signs and symptoms in all patients presented with edema and erythema. We obtained optimal results with surgery, where a complete removal of the injected material was possible. In all the cases in which the complete removal of the infiltrated area could have led to functional impairments, we performed partial removal with poor outcomes. CONCLUSION: We observed complex clinical manifestations in the patients subjected to permanent fillers. An accurate knowledge upon the effects of the materials on tissues, a specific instrumental evaluation and a targeted therapy are crucial. We suggest the use of absorbable fillers. Patient should be subjected to filler implant in authorized structures by an expert specialist with experience in filler injection and with a thorough knowledge of the anatomical structures. 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 .

MiR-200c-3p maintains stemness and proliferative potential in adipose-derived stem cells by counteracting senescence mechanisms.

Adipose-derived mesenchymal stem cells (ASCs) are promising therapeutic tools in regenerative medicine because they possess self-renewal, differentiation and immunomodulatory capacities. After isolation, ASCs are passaged multiple times in vitro passages to obtain a sufficient amount of cells for clinical applications. During this time-consuming procedure, ASCs become senescent and less proliferative, compromising their clinical efficacy. Here, we sought to investigate how in vitro passages impact ASC proliferation/senescence and expression of immune regulatory proteins. MicroRNAs are pivotal regulators of ASC physiology. Particularly, miR-200c is known to maintain pluripotency and targets the immune checkpoint Programmed death-ligand 1 (PD-L1). We therefore investigated its involvement in these critical characteristics of ASCs during in vitro passages. We found that when transiently expressed, miR-200c-3p promotes proliferation, maintains stemness, and contrasts senescence in late passaged ASCs. Additionally, this miRNA modulates PD-L1 and Indoleamine 2,3-Dioxygenase (IDO1) expression, thus most likely interfering with the immunoregulatory capacity of ASCs. Based on our results, we suggest that expression of miR-200c-3p may prime ASC towards a self-renewing phenotype by improving their in vitro expansion. Contrarily, its inhibition is associated with senescence, reduced proliferation and induction of immune regulators. Our data underline the potential use of miR-200c-3p as a switch for ASCs reprogramming and their clinical application.

Dual-Plane Retro-pectoral Versus Pre-pectoral DTI Breast Reconstruction: An Italian Multicenter Experience.

BACKGROUND: The use of conservative mastectomies has risen significantly during the last few years. The reconstructive choice of direct-to-implant reconstruction has become more practicable with modern mastectomy techniques. The initial trend in Italian centers was to use dual-plane hybrid reconstruction. However, a high level of complications has been registered. From 2015 onward, in our centers, a pre-pectoral approach has been adopted. The authors sought to describe the Italian trend to gradually discard the sub-pectoral technique with lower lateral pole coverage of the prosthesis using ADMs comparing it with the pre-pectoral approach with ADMs, without any muscle dissection, in terms of complication rates. MATERIALS AND METHODS: A multicenter retrospective clinical study was performed from January 2010 to June 2018. The enrolled patients were divided into two groups: Cases with an ADM-only coverage pre-pectoral reconstruction made up the first group (Group 1). Those with the retro-pectoral muscular position + ADM implant coverage comprised the second one (Group 2). Complications such as seroma, hematoma, wound dehiscence, surgical site infection, reconstruction failure, animation deformity and capsular contracture were recorded. RESULTS: We performed 716 direct-to-implant reconstructions: 509 were partially sub-pectoral and 207 were pre-pectoral. Minimum follow-up was 1 year. Incidence of complications was higher in dual-plane reconstructions. There were statistical significant differences in the rates of seroma and hematoma. CONCLUSION: Using the pre-pectoral approach, the authors have experienced favorable aesthetics and superior clinical and functional outcomes. Retro-pectoral muscular ADM implant coverage has to be considered only in specific complicated second-stage surgeries. 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 .

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.

Neuropilin 1 Mediates Keratinocyte Growth Factor Signaling in Adipose-Derived Stem Cells: Potential Involvement in Adipogenesis.

Adipogenesis is regulated by a complex network of molecules, including fibroblast growth factors. Keratinocyte growth factor (KGF) has been previously reported to promote proliferation on rat preadipocytes, although the expression of its specific receptor, FGFR2-IIIb/KGFR, is not actually detected in mesenchymal cells. Here, we demonstrate that human adipose-derived stem cells (ASCs) show increased expression of KGF during adipogenic differentiation, especially in the early steps. Moreover, KGF is able to induce transient activation of ERK and p38 MAPK pathways in these cells. Furthermore, KGF promotes ASC differentiation and supports the activation of differentiation pathways, such as those of PI3K/Akt and the retinoblastoma protein (Rb). Notably, we observed only a low amount of FGFR2-IIIb in ASCs, which seems not to be responsible for KGF activity. Here, we demonstrate for the first time that Neuropilin 1 (NRP1), a transmembrane glycoprotein expressed in ASCs acting as a coreceptor for some growth factors, is responsible for KGF-dependent pathway activation in these cells. Our study contributes to clarify the molecular bases of human adipogenesis, demonstrating a role of KGF in the early steps of this process, and points out a role of NRP1 as a previously unknown mediator of KGF action in ASCs.

Tuberous breast and predisposition to breast deformity in consanguineous.

Tuberous breast deformity is a pathologic condition of the breast consisting of a constricting ring at the breast base, reduction in the volume of the breast parenchyma, and herniation of breast tissue through the nipple-areola complex with areola enlargement. This pathology is generally congenital and has an unknown etiopathogenesis. We report the first observation of tuberous breast deformity in consanguineous. This report suggests the potential role of a genetic base in the development of this deformity. Between May 2008 and March 2011, we observed six female patients from two different families, aged between 18 and 55 years, affected by tuberous breast deformity. The breast deformity was characterized by breast asymmetry in all six cases. Four patients underwent surgery to correct the deformity. Standardized objective measurements of breast and chest were taken. A Visual Analog Scale was used to evaluate patients' and physicians' satisfaction. The first three patients were consanguineous; two were first cousins, and the third was second cousin with one of the above. The other three patients were also from the same family: two sisters and their mother. According to Von Heimburg's classification, the patients presented different degrees of breast deformity. In all operated cases, a good esthetic result with a high satisfaction (average visual analog scale score 9) was achieved. The results remained stable over time and no revisions were needed after the 1-year follow-up. The possibility of a parental consanguinity for breast deformities such tuberous breast has never been described in the literature. This report suggests the possible genetic role in the development of tuberous breast deformity. Further studies and genetic tests are required to prove this hypothesis.

Chemotherapy Extravasation Management: 21-Year Experience.

Chemotherapy extravasation may result in serious damage to patients, with irreversible local injures and disability. Evidence-based standardization on extravasation management is lacking and many institutions do not practice adequate procedures to prevent the severer damages. Our aim was to explore the prevention and treatment of extravasation injuries, proposing a standard therapeutic protocol together with a review of the literature. From January 1994 to December 2015, 545 cases were reviewed (age range, 5-87 years; 282 men and 263 women). Our therapeutic protocol consisted of local infiltration of saline solution and topical occlusive applications of corticosteroids. The infiltrations were administrated 3 to 6 times a week depending on damage severity. Our protocol allowed us to prevent ulceration in 373 cases. Only 27 patients required surgery (escarectomy, skin graft, regional, and free flap). Numerous treatments have been proposed in literature. The antidotes have been discussed controversially and are not considered standard methods for treatment, especially when polychemotherapy is administrated and the identification of the responsible drug is not possible. We proposed the use of saline solution injection to dilute rapidly the drug, thus reducing its local toxic effects. This method is easy to use and always reproducible even when the drug is not known or when it is administrated in combination with other drugs. It is possible to perform it in ambulatory regimen, and, overall, it represents a standard method.

Clinical, histological, and ultrasound follow-up of breast reconstruction with one-stage muscle-sparing "wrap" technique: A single-center experience.

BACKGROUND: Prepectoral implant placement and complete coverage with porcine acellular matrix after mastectomy is a new concept in breast surgery presented in few cases in the literature. This paper aimed to present our single-center experience in one-stage breast reconstruction muscle-sparing "wrap" technique by evaluating clinical and aesthetic outcomes, ultrasound and histological examination, and patient quality of life. METHODS: From January 2014 to January 2017, 52 patients (40 unilateral, 12 bilateral) underwent one-stage muscle-sparing breast reconstructions with Braxon® acellular dermal matrix and implant. In 3 patients, a surgical biopsy and histological examination with immunohistochemical analysis of the periprosthetic tissue were performed. All patients underwent breast ultrasound examination, and the occurrence of capsular contracture was assessed through the Baker classification and by measuring the mammary compliance scores with the Antoon Paar Mammary compliance system. Breast appearance was evaluated using a visual analogue scale (VAS) and in terms of quality of life using the EOCRT QLQ C-30 and QLQ BR-23 questionnaires. RESULTS: Early and late postoperative complications are reported. Histological and ultrasound evaluation showed a complete integration of the matrix. According to the VAS scale, the EOCRT QLQ C-30, and QLQ BR-23, patients' satisfaction resulted in a high score in terms of quality of life and aesthetic outcomes. CONCLUSION: The results of this new surgical technique in selected cases are promising in terms of effectiveness and low rate of postoperative complications, but further long-terms evaluations are required.

Improvement of Mouth Functional Disability in Systemic Sclerosis Patients over One Year in a Trial of Fat Transplantation versus Adipose-Derived Stromal Cells.

Background. Systemic sclerosis (SSc) is a multisystem disease characterized by cutaneous and visceral fibrosis. Face and mouth changes include telangiectasia, sicca syndrome, and thinning and reduction of mouth width (microcheilia) and opening (microstomia). We applied autologous fat transplantation compared with autologous adipose-derived stromal cells (ADSCs) injection to evaluate the clinical improvement of mouth opening. Methods. From February to May 2013 ten consecutive SSc patients were enrolled from the outpatient clinic of Plastic Surgery Department of Sapienza University of Rome. Patients were divided into two groups as follows: 5 patients were treated with fat transplantation and 5 patients received infiltration of ADSCs produced by cell factory of our institution. To value mouth opening, we use the Italian version of Mouth Handicap in Systemic Sclerosis Scale (IvMHISS). Mouth opening was assessed in centimetres (Maximal Mouth Opening, MMO). In order to evaluate compliance and physician and patient satisfaction, we employed a Questionnaire of Satisfaction and the Visual Analogic Scale (VAS) performed before starting study and 1 year after the last treatment. Results and Conclusion. We noticed that both procedures obtained significant results but neither one emerged as a first-choice technique. The present clinical experimentation should be regarded as a starting point for further experimental research and clinical trials.

Effect of enzymatic debridement with two different collagenases versus mechanical debridement on chronic hard-to-heal wounds.

A chronic ulcer is usually defined as an injury that does not spontaneously evolve towards healing and does not progress through normal healing stages such as inflammation, proliferation and remodelling. This study was designed in order to compare two types of collagenases with mechanical debridement alone. It was thus possible to evaluate their differences in terms of pain and debridement efficacy. Patients were divided into three groups: 30 patients were daily dressed using an ointment based on collagenase produced by Vibrio alginolyticus (B group), 30 patients were daily dressed using an ointment based on a collagenase preparation derived from Clostridium histolyticum (N group) and 30 patients underwent classical mechanical debridement (M group). Complete wound healing over a period of 8 weeks occurred in 24 patients (27%) out of 90;10 patients belonging to the B group, 8 patients to the N group and 6 patients to the M group. This study was performed in order to highlight the differences between two commercially available collagenase-based ointments in comparison with mechanical debridement alone. At the final time point of week, the difference in the percentage of debridement was not statistically significant in all groups, but at 4 weeks, the debrided area in the B group was larger with respect to the N and M groups, suggesting a more rapid wound bed cleansing process. On the basis of our experience, collagenase derived from V. alginolyticus with hyaluronic acid showed chemical and physical properties that make it a product of great manageability and ensure the protection of peri-wound skin. Moreover, less pain was experienced by the patients.

Successful Management of a Chronic Refractory Leg Ulcer in an Adolescent with Sickle Cell Anemia.

Sickle cell disease (SCD) is an inherited hemoglobinopathy characterized by a wide range of clinical manifestations. Chronic leg ulcers are a disabling complication with repercussions on the quality of life. We report the case of a 14-year-old girl with a diagnosis of SCD who developed a chronic leg ulcer that was successfully treated with a multi-disciplinary approach, including local and systemic therapies. The role of different treatments, in particular low molecular weight heparin, in the refractory chronic leg ulcer healing process will be discussed.

Clinical Examination and Treatment of a Leg Ulcer Caused by a Stingray Puncture.

The most frequent causes of leg ulcers include venous incompetency (superficial and deep), arterial insufficiency, trauma, vasculitis, and neoplasm. Leg ulcers from injury by stingrays are quite rare. In this case report, we describe a leg ulcer caused by a stingray sting complicated by infection, which healed completely without surgery. In addition, since there few cases in the literature describing such traumas, we performed a comprehensive review of the literature. Important is the fact that the wound healing was complete without resorting to surgery, but only with a correct targeted antibiotic therapy and the use of a collagenase, which has the particularity of having hyaluronic acid as a component.

Intense pulsed light in the treatment of telangiectasias: case report of Behçet's disease with superficial vascular involvement.

Behçet's disease (BD) is a chronic systemic inflammatory disorder of unknown etiology with variable clinical manifestations. HLA-B51 allele is the most strongly associated known genetic factor. The mucocutaneous lesions (oral aphthae, genital aphthae, skin lesions such as pseudofolliculitis) constitute the hallmark of the disease, but also gastrointestinal, vascular, central nervous systems, and others may be involved. We report a case of a young man affected with Behçet's disease who presented facial telangiectasias and striae rubra in the inner region of his arms and at the level of his hips, as uncommon minor superficial vascular manifestations of BD. To manage them we have subjected the patient to a cycle of Intense Pulsed Light (IPL) therapy. Our findings showed that the use of IPL is a safe and effective treatment for telangiectasias and striae rubra, also in the complex clinical condition of Behçet's disease. In fact, the treatments were well tolerated, no sign of scarring or hyper/hypopigmentation was reported and we obtained a significant improvement of the lesions in terms of color and size of them.

Co2/Erbium:YAG/Dye laser combination: an effective and successful treatment for angiofibromas in tuberous sclerosis.

BACKGROUND: Tuberous sclerosis, an autosomal dominant neurocutaneous syndrome seen in approximately 1 in 6,000 people worldwide, is characterized by the appearance of hamartomas in multiple organs. The classic clinical triad consists of angiofibromas, epilepsy, and developmental delay. Dermatologic disorder is one of the main characteristics. Angiofibromas, a common form of presentation, causes significant cosmetic and medical problems. The current treatment for skin lesions is laser therapy. The carbon dioxide (CO2) laser has been used satisfactorily in treating these lesions, but several studies have demonstrated a high percentage of recurrences. Erbium:yttrium-aluminum-garnet (YAG) laser treatment has been used to resurface skin abnormalities in patients with dermatologic conditions. The dye laser as an alternative uses the principles of selective photothermolysis and is very effective in treating the vascular component of tuberous sclerosis. The use of all these lasers to treat skin lesions in patients affected by tuberous sclerosis has never been described in the literature. METHODS: A retrospective study, conducted from 2007 to May 2013, investigated 13 patients who had tuberous sclerosis treated with an erbium:YAG/CO2/dye laser combination. RESULTS: All the patients showed great improvement of their skin lesions. The results were evident immediately after the first treatment. No patient experienced complications or recurrence. CONCLUSIONS: The combined use of the erbium:YAG/Dye/CO2 laser is a safe and effective treatment for skin lesions in patients affected by tuberous sclerosis. 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 .

Female pseudohermaphroditism: strategy and bias in a fast diagnosis. How tricky could be a diagnosis with a wrong anamnesis.

AIM: Congenital genitalia anomalies are a spectrum of malformation, difficult to classify because similar or identical phenotypes could have several different aetiology; therefore it's essential to assess an efficient diagnostic algorithm for a quick diagnosis and to develop an efficient therapeutic strategy. The aim of this study is to underline the importance of imaging in case of ambiguous genitalia due to its high sensitivity and specificity in detecting internal organs and urogenital anatomy. MATERIAL OF STUDY: We report a case of a young girl affected by a complex genitor-urinary malformation with an initial wrong anamnesis that led to a tricky diagnosis. RESULTS: Imaging techniques - especially Magnetic Resonance Imaging (MRI) - together with karyotype, hormones and physical investigations, offered complete and reliable informations for the best surgical treatment of our patient. CONCLUSION: Karyotype, hormones investigation, and radiological examinations are the main criteria considered in the diagnostic iter. Ultrasonography (US) is the primary modality for the detection of the presence or absence of gonads and müllerian derivatives, whereas Cystourethrography can define urethral and vaginal tract or the presence of fistulas. In our experience MRI, due to its multiplanar capability and superior soft tissue characterization, proved to be useful to provide detailed anatomic information.

Nonsurgical treatment of a massive substance loss.

Traumatic wounds are caused by severe trauma, resulting in lesions with extensive skin and subcutaneous tissue loss and damage to tissue viability. A "difficult wound" is a solution of continuity that does not heal spontaneously within three months. The factors that determine it may be as follows: a massive loss of substance, an infection, the presence of foreign bodies, or the clinical condition of the patient. We report a case of a 25-year-old man that presents a skin lesion on the anterior region of the left arm with extensive necrosis of skin and subcutaneous plants that involve the underlying muscle planes, caused by a trauma due to a car accident. In most of the lesions of such size and position, there is always a need for surgery. But in this case, considering the young age and the regenerative capacity of the patient, a quick and targeted antibiotic therapy was chosen, combined with debridement and worked with collagenase ointment.