Seborrheic keratosis.

Seborrheic keratosis (SK) is the most common benign epidermal tumor in clinical dermatological practice. This review summarizes current knowledge about the clinical and histological appearance, epidemiology, pathogenesis, and treatment of SK. There are different subtypes of SK based on clinical presentation and histologic findings. Several factors, including age, genetic predisposition, and possibly also exposure to ultraviolet radiation, are thought to contribute to the development of SK. The lesions can occur on all areas of the body except for the palms and soles, but the most common sites are the face and upper trunk. The diagnosis is usually made clinically, and in some cases by dermatoscopy or histology. Many patients prefer to have the lesions removed for cosmetic reasons although there is no medical indication. Treatment options include surgical therapy, laser therapy, electrocautery, cryotherapy, and topical drug therapy, which is currently in development. Treatment should be individualized depending on the clinical picture and patient preference.

Acceleration of Wound Healing through Amorphous Calcium Carbonate, Stabilized with High-Energy Polyphosphate.

Amorphous calcium carbonate (ACC), precipitated in the presence of inorganic polyphosphate (polyP), has shown promise as a material for bone regeneration due to its morphogenetic and metabolic energy (ATP)-delivering properties. The latter activity of the polyP-stabilized ACC ("ACC∙PP") particles is associated with the enzymatic degradation of polyP, resulting in the transformation of ACC into crystalline polymorphs. In a novel approach, stimulated by these results, it was examined whether "ACC∙PP" also promotes the healing of skin injuries, especially chronic wounds. In in vitro experiments, "ACC∙PP" significantly stimulated the migration of endothelial cells, both in tube formation and scratch assays (by 2- to 3-fold). Support came from ex vivo experiments showing increased cell outgrowth in human skin explants. The transformation of ACC into insoluble calcite was suppressed by protein/serum being present in wound fluid. The results were confirmed in vivo in studies on normal (C57BL/6) and diabetic (db/db) mice. Topical administration of "ACC∙PP" significantly accelerated the rate of re-epithelialization, particularly in delayed healing wounds in diabetic mice (day 7: 1.5-fold; and day 13: 1.9-fold), in parallel with increased formation/maturation of granulation tissue. The results suggest that administration of "ACC∙PP" opens a new strategy to improve ATP-dependent wound healing, particularly in chronic wounds.

Electrochemotherapy for the treatment of cutaneous squamous cell carcinoma: The INSPECT experience (2008-2020).

Introduction: Cutaneous squamous cell carcinoma (cSCC) is a frequent skin cancer with a high risk of recurrence characterized by tumor infiltration and, in advanced cases, a poor prognosis. ECT (electrochemotherapy) is an alternative treatment option for locally advanced or recurrent cSCC that is unsuitable for surgical resection. In this study, we aimed to evaluate the data in the InspECT (International Network for Sharing Practice on ECT) registry of the referral centers and to clarify the indications for the use of ECT as a treatment modality for cSCC. Materials and methods: Patients with primary, recurrent or locally advanced cSCC from 18 European centers were included. They underwent at least one ECT session with bleomycin between February 2008 and November 2020, which was performed following the European Standard Operating Procedures. Results: The analysis included 162 patients (mean age of 80 years; median, 1 lesion/patient). Side effects were mainly local and mild (hyperpigmentation, 11%; ulceration, 11%; suppuration, 4%). The response to treatment per patient was 62% complete and 21% partial. In the multivariate model, intravenous drug administration and small tumor size showed a significant association with a positive outcome (objective response). One-year local progression-free survival was significantly better (p<0.001) in patients with primary tumors (80% (95% C.I. 70%-90%) than in patients with locally advanced disease (49% (95% C.I. 30%-68%). Conclusion: In the present study, ECT showed antitumor activity and a favorable safety profile in patients with complex cSCC for whom there was no widely accepted standard of care. Better results were obtained in primary and small tumors (<3 cm) using intravenous bleomycin administration.

Polyphosphate in Chronic Wound Healing: Restoration of Impaired Metabolic Energy State.

Many pathological conditions are characterized by a deficiency of metabolic energy. A prominent example is nonhealing or difficult-to-heal chronic wounds. Because of their unique ability to serve as a source of metabolic energy, inorganic polyphosphates (polyP) offer the opportunity to develop novel strategies to treat such wounds. The basis is the generation of ATP from the polymer through the joint action of two extracellular or plasma membrane-bound enzymes alkaline phosphatase and adenylate kinase, which enable the transfer of energy-rich phosphate from polyP to AMP with the formation of ADP and finally ATP. Building on these findings, it was possible to develop novel regeneratively active materials for wound therapy, which have already been successfully evaluated in first studies on patients.

Surgical Treatment in Hidradenitis Suppurativa.

Hidradenitis suppurativa (HS) is a chronic, progressive inflammatory disorder of follicular occlusion with pubertal onset that presents as painful inflammatory nodules, sinus tracts, and tunnelling in apocrine-gland-rich areas, such as the axilla, groin, lower back, and buttocks. The disease course is complicated by contractures, keloids, and immobility and is often associated with a low quality of life. It is considered a disorder of follicular occlusion with secondary inflammation, though the exact cause is not known. Management can often be unsatisfactory and challenging due to the chronic nature of the disease and its adverse impact on the quality of life. A multidisciplinary approach is key to prompt optimal disease control. The early stages can be managed with medical treatment, but the advanced stages most likely require surgical intervention. Various surgical options are available, depending upon disease severity and patient preference. In this review an evidence-based outline of surgical options for the treatment of HS are discussed. Case reports, case series, cohort studies, case-control studies, and Randomized Clinical Trials (RCT)s available in medical databases regarding surgical options used in the treatment of HS were considered for the review presented in a narrative manner in this article.

Efficacy of botulinum toxin in masseter muscle hypertrophy for lower face contouring.

BACKGROUND: Masseter muscle hypertrophy (MMH) usually presents with cosmetic concerns as it may lead to widening of the lower face. Apart from the traditional surgical approaches, botulinum toxin type A (BTA) injection is a non-invasive treatment option available. There are no standard guidelines for this procedure. OBJECTIVES: To study the efficacy of botulinumtoxin A in MMH for lower face contouring. METHODOLOGY: The Cochrane Library, PubMed/MEDLINE, Google-scholar, Science-Direct database, and ResearchGate from inception until September 2021 were searched using the keywords "botulinumtoxin type A," "masseter muscle hypertrophy," "lower face contouring," and "masseter botox." All available retrospective and prospective studies, case-series, case-reports, and expert reviews were included with an emphasis on efficacy of BTA in MMH and units injected into the muscle, points of placement, adverse events, and the duration of its effect. Reference lists of the resultant articles, as well as relevant reviews, were also searched. RESULT: 40 articles were shortlisted for the review, of which 14 studies with sample-size ≥10 in accordance with the study requirements were summarized in a tabular form for analysis and easy comparison and reference. CONCLUSION: BTA injection is a non-invasive, safe, and effective treatment for MMH. The optimum number of BTA units could not be ascertained due to wide variability in the studies as well as ethnicity of patients and extent or some measurement of MMH. The points of placement of injection should be well within the boundaries of the masseter muscle. The maximum effect of BTA after a single injection session is usually seen in ~3 months, and the duration may last for 6-12 months. Multiple injection sessions may be required to maintain a long-term effect. Injection technique and total number of injection units of neuromodulator must be individualized for each patient.

Acceleration of chronic wound healing by bio-inorganic polyphosphate: In vitro studies and first clinical applications.

The healing of chronic wounds is impaired by a lack of metabolic energy. In previous studies, we showed that physiological inorganic polyphosphate (polyP) is a generator of metabolic energy by forming ATP as a result of the enzymatic cleavage of the high-energy phosphoanhydride bonds of this polymer. Therefore, in the present study, we investigated whether the administration of polyP can substitute for the energy deficiency in chronic wound healing. Methods: PolyP was incorporated into collagen mats and applied in vitro and to patients in vivo. Results: (i) In vitro studies: Keratinocytes grown in vitro onto the polyP/collagen mats formed long microvilli to guide them to a favorable environment. HUVEC cells responded to polyP/collagen mats with an increased adhesion and migration propensity as well as penetration into the mats. (ii) In vivo - human clinical studies: In a "bench to bedside" process these promising in vitro results were translated from the laboratory into the clinic. In the proof-of-concept application, the engineered polyP/collagen mats were applied to chronic wounds in patients. Those mats impressively accelerated the re-epithelialization rate, with a reduction of the wound area to 65% after 3 weeks and to 36.6% and 22.5% after 6 and 9 weeks, respectively. Complete healing was achieved and no further treatment was necessary. Biopsy samples from the regenerating wound area showed predominantly myofibroblasts. The wound healing process was supported by the use of a polyP containing moisturizing solution. Conclusion: The results strongly recommend polyP as a beneficial component in mats for a substantial healing of chronic wounds.

The therapeutic potential of inorganic polyphosphate: A versatile physiological polymer to control coronavirus disease (COVID-19).

Rationale: The pandemic caused by the novel coronavirus SARS-CoV-2 is advancing rapidly. In particular, the number of severe courses of the disease is still dramatically high. An efficient drug therapy that helps to improve significantly the fatal combination of damages in the airway epithelia, in the extensive pulmonary microvascularization and finally multiorgan failure, is missing. The physiological, inorganic polymer, polyphosphate (polyP) is a molecule which could prevent the initial phase of the virus life cycle, the attachment of the virus to the target cells, and improve the epithelial integrity as well as the mucus barrier. Results: Surprisingly, polyP matches perfectly with the cationic groove on the RBD. Subsequent binding studies disclosed that polyP, with a physiological chain length of 40 phosphate residues, abolishes the binding propensity of the RBD to the ACE2 receptor. In addition to this first mode of action of polyP, this polymer causes in epithelial cells an increased gene expression of the major mucins in the airways, of MUC5AC and MUC1, as well as a subsequent glycoprotein production. MUC5AC forms a gel-like mucus layer trapping inhaled particles which are then transported out of the airways, while MUC1 constitutes the periciliary liquid layer and supports ciliary beating. As a third mode of action, polyP undergoes enzymatic hydrolysis of the anhydride bonds in the airway system by alkaline phosphatase, releasing metabolic energy. Conclusions: This review summarizes the state of the art of the biotherapeutic potential of the polymer polyP and the findings from basic research and outlines future biomedical applications.

The biomaterial polyphosphate blocks stoichiometric binding of the SARS-CoV-2 S-protein to the cellular ACE2 receptor.

The effect of the polyanionic polymer of inorganic polyphosphate (polyP) involved in innate immunity on the binding of the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein to the cellular ACE2 receptor was studied. The RBD surface comprises a basic amino acid stretch of four arginine residues which interact with the physiological polyP (polyP40) and polyP3. Subsequently, the interaction of RBD with ACE2 is sensitively inhibited. After the chemical modification of arginine, an increased inhibition by polyP, at a 1 : 1 molar ratio (polyP : RBP), is measured already at 0.1 µg mL-1. Heparin was ineffective. The results suggest a potential therapeutic benefit of polyP against SARS-CoV-2 infection.

Biomimetic Alginate/Gelatin Cross-Linked Hydrogels Supplemented with Polyphosphate for Wound Healing Applications.

In the present study, the fabrication of a biomimetic wound dressing that mimics the extracellular matrix, consisting of a hydrogel matrix composed of non-oxidized and periodate-oxidized marine alginate, was prepared to which gelatin was bound via Schiff base formation. Into this alginate/oxidized-alginate-gelatin hydrogel, polyP was stably but reversibly integrated by ionic cross-linking with Zn2+ ions. Thereby, a soft hybrid material is obtained, consisting of a more rigid alginate scaffold and porous structures formed by the oxidized-alginate-gelatin hydrogel with ionically cross-linked polyP. Two forms of the Zn-polyP-containing matrices were obtained based on the property of polyP to form, at neutral pH, a coacervate-the physiologically active form of the polymer. At alkaline conditions (pH 10), it will form nanoparticles, acting as a depot that is converted at pH 7 into the coacervate phase. Both polyP-containing hydrogels were biologically active and significantly enhanced cell growth/viability and attachment/spreading of human epidermal keratinocytes compared to control hydrogels without any adverse effect on reconstructed human epidermis samples in an in vitro skin irritation test system. From these data, we conclude that polyP-containing alginate/oxidized-alginate-gelatin hydrogels may provide a suitable regeneratively active matrix for wound healing for potential in vivo applications.

A physiologically active interpenetrating collagen network that supports growth and migration of epidermal keratinocytes: zinc-polyP nanoparticles integrated into compressed collagen.

The distinguished property of the physiological polymer, inorganic polyphosphate (polyP), is to act as a bio-intelligent material which releases stimulus-dependent metabolic energy to accelerate wound healing. This characteristic is based on the bio-imitating feature of polyP to be converted, upon exposure to peptide-containing body fluids, from stable amorphous nanoparticles to a physiologically active and energy-delivering coacervate phase. This property of polyP has been utilized to fabricate a wound mat consisting of compressed collagen supplemented with amorphous polyP particles, formed from the inorganic polyanion with an over-stoichiometric ratio of zinc ions. The proliferation and the migration of human skin keratinocytes in those matrices were investigated. If the cells were embedded into the mat they respond with a significantly higher motility when zinc-polyP particles are present. Interestingly, only keratinocytes that were grown in a polyP environment developed well-structured microvilli, reflecting an increased biological activity. The data show that Zn-polyP particles incorporated into wound mats are a potent cell growth and cell migration-stimulating inorganic bio-material.

Increased risk of angiosarcoma secondary to cancer radiotherapy: Case series and review of the treatment options.

Angiosarcomas (ASs) are aggressive tumors of vascular endothelial origin, occurring sporadically or in association with prior radiotherapy or chronic lymphedema. With only 1-5% of all sarcomas, the incidence seems low, but for the affected patient due to the extremely poor prognosis and the limited treatment options, the fate is often inevitable. Radiotherapy, chemotherapy, or "target therapy" have been used in the management of AS, but represent individual case decisions without lasting evidence. Over the past few years, breast-conserving surgery followed by radiation therapy, known as breast-conserving therapy (BCT), is being employed as a standard treatment for early-stage breast cancer, but there has been an increase in reports of AS following BCT. We report two cases of AS following BCT and one case of primary AS involving the lower limb.

Electrochemotherapy for advanced cutaneous angiosarcoma: A European register-based cohort study from the International Network for Sharing Practices of electrochemotherapy (InspECT).

BACKGROUND: Cutaneous angiosarcoma (cAS) is a highly aggressive malignancy that challenges the radicality of surgical treatment. Electrochemotherapy (ECT), a skin-directed treatment based on cytotoxic chemotherapy combined with local electric pulses, may be an intraoperative adjunct and a new opportunity in the therapeutic strategy. This cohort study reports the experience with ECT as an option. METHODS: Data on patients with locally-advanced/metastatic cAS who underwent ECT between October 2013 and October 2018 at eight European centres were prospectively submitted to the InspECT (International network for sharing practices of ECT) register. Patients received therapy according to the European Standard Operating Procedures of ECT (ESOPE). Treatment feasibility was assessed based on tumour coverage with electrodes and recorded tissue current; treatment toxicity and tumour response were graded according to CTCAE v5.0 and RECIST v1.1 criteria, respectively; patient-reported outcomes (PRO) were evaluated using a visual analogue score (VAS) for pain, acceptance of retreatment and the EQ-5D questionnaire. RESULTS: We enrolled 20 patients with advanced cAS in the scalp/face (n = 7), breast/trunk (n = 10) or limbs (n = 3). Target tumours (n = 51) had a median size of 2.3 cm (range, 1-20). We administered 24 ECT courses using 1-4 cm treatment safety margin around tumours. In five patients, ECT was combined/sequenced with surgery. Median tissue current was 3 A (range, 1.5-10), tumour margins coverage rate was 75% (15/20 patients). The objective response rate (ORR) was 80% (complete, 40%). Grade-3 toxicity included skin ulceration (15%) and pain (10%), with no significant change of PRO scores. Bleeding control was achieved in 13/14 patients with ulcerated tumours. With a median overall survival of 12.5 months, the local progression-free survival (LPFS) was 10.9 months. CONCLUSION: ECT produces sustained response rate with minimal side effects and should be considered an option for advanced cAS. Palliative benefits include patient tolerability, local haemostasis and durable local control. Definition of optimal timing, treatment safety margins and combination with surgery need further investigation.

Lymphedema: An early sign of rodent ulcer metastasis leads to timely intervention.

Basal cell carcinoma has a potential for early and late metastasis. Depending on the location of the primary site, the relevant lymphatic drainage routes have to be monitored. Regional lymph edema may be a first indicator for metastasizing disease.

[The "light" version of a perforator flap: significance of the Keystone Designed Perforator Flap Concept (KDPFC) in the lower extremity]. / Perforator Lappen "light" ­ der Stellenwert des Keystone Designed Perforator Flap Concept (KDPFC) an der unteren Extremität.

INTRODUCTION: Since the KDPFC was first described by Behan et al. in 2003, there have been a number of publications about this technique with case series between 1 and 300 flaps, and some have described further modifications of the design of the flap. The flap design resembles the keystone of a Roman arch and is based on the angiosome concept. The flap is a perforator flap, but does not require microsurgical dissection or preparation of the perforators. The technique is efficient and relatively simple to perform. With a few exceptions, it can be performed anywhere on the body. Although there are a large number of publications, not much data has been published on the complications, limitations and disadvantages of the technique. METHODS: This is a retrospective analysis of the outcomes of 35 patients who underwent keystone flap reconstruction for soft tissue defects over 36 months. The flap design followed the original KDPFC description. Flap selection was based on the requirements of each defect. RESULTS: Thirty-six flap procedures were performed on 35 patients. The mean defect size was 21 cm2 (range 2-100 cm2). Delayed wound healing occurred in 12 patients and flap loss was observed in 4 patients. One patient required further surgical revision. The wounds of the remaining patients healed by secondary intention. Four out of 10 patients who were on anticoagulants had delayed wound healing, compared with 12 out of 25 who were not on anticoagulants. Seven of the 16 patients with delayed wound healing, including 3 patients with flap loss, had defects reconstructed on the very distal lower leg and foot. DISCUSSION: The KDPFC is a valuable addition to the reconstructive armamentarium. Although delayed wound healing has been observed in some cases, this flap concept can replace other local or regional flaps, also in more complex situations. Care must be taken in patient selection and, in particular, in large defects and difficult topographical areas on the distal lower leg. In these situations, other reconstructive options may be more appropriate.