Multidisciplinary Treatment in Toxic Epidermal Necrolysis.

Toxic epidermal necrolysis, Leyll's syndrome (TEN), is a rare mucocutaneous blistering disease burdened with high mortality rates. The diagnosis of TEN is based on clinical symptoms and histopathological findings. In approximately 90% of cases, it is a severe adverse reaction to drugs. In TEN, not only is the skin affected, but also mucosa and organs' epithelium. There are no unequivocal recommendations in regard to systemic and topical treatment of the patients. The aim of this paper is to review available literature and propose unified protocols to be discussed. Early management and multidisciplinary treatment are necessary to improve patients' outcome. Treatment of patients with TEN suspicions should be initiated with early drug withdrawal. TEN patients, like patients with burns, require intensive care and multidisciplinary management. Each patient with TEN should be provided with adequate fluid resuscitation, respiratory support, nutritional treatment, pain control, infection prophylaxis, anticoagulant therapy, and gastric ulcer prophylaxis. The key to local treatment of patients with TEN is the use of nonadherent dressings that do not damage the epidermis during the change. The aim of the systemic treatment is purification of the blood stream from the causative agent. The most efficient way to clarify serum of TEN patients' is the combination of plasmapheresis and IVIG. Immunomodulatory therapy can reduce the mortality five times in comparison with the patients with immunosuppression or lack of full protocol.

Alloplastic Epidermal Skin Substitute in the Treatment of Burns.

The goal of burn wound treatment is to ensure rapid epithelialization in superficial burns and the process of rebuilding the lost skin in deep burns. Topical treatment plays an important role. One of the innovations in the field of synthetic materials dedicated to the treatment of burns is epidermal skin substitutes. Since the introduction of Suprathel®, the alloplastic epidermal substitute, many research results have been published in which the authors investigated the properties and use of this substitute in the treatment of wounds of various origins, including burn wounds. Burn wounds cause both physical and psychological discomfort, which is why ensuring comfort during treatment is extremely important. Alloplastic epidermal substitute, due to its biodegradability, plasticity, no need to remove the dressing until healing, and the associated reduction in pain, is an alternative for treating burns, especially in children.

Mesenchymal Stem Cells in Burn Wound Management.

Mesenchymal stem cells have a known regenerative potential and are used in many indications. They secrete many growth factors, including for fibroblasts (FGF), endothelium (VEGF), as well as 14 anti-inflammatory cytokines, and they stimulate tissue regeneration, promoting the secretion of proteins and glycosaminoglycans of extracellular matrices, such as collagen I, II, III, and V, elastin, and also metalloproteinases. They secrete exosomes that contain proteins, nucleic acids, lipids, and enzymes. In addition, they show the activity of inactivating free radicals. The aim of this study was an attempt to collect the existing literature on the use of stem cells in the treatment of a burn wound. There were 81 studies included in the analysis. The studies differed in terms of the design, burn wound model, source of stem cells, and methods of cellular therapy application. No major side effects were reported, and cellular therapy reduced the healing time of the burn wound. Few case reports on human models did not report any serious adverse events. However, due to the heterogeneity of the evidence, cellular therapy in burn wound treatment remains an experimental method.

Microbiome in Hidradenitis Suppurativa-What We Know and Where We Are Heading.

Recently, interest in the microbiome of cutaneous diseases has increased tremendously. Of particular interest is the gut-brain-skin axis proposed by Stokes and Pillsbury in 1930. The microbiome has been suggested in the pathogenesis of hidradenitis suppurativa, however the link between the commensals and the host is yet to be established. Across all studies, the increased abundance of Porphyromonas, Peptoniphilus, and Prevotella spp., and a loss of skin commensal species, such as Cutibacterium in HS lesions, is a consistent finding. The role of gut and blood microbiome in hidradenitis suppurativa has not been fully elucidated. According to studies, the main link with the intestine is based on the increased risk of developing Crohn's disease and ulcerative colitis, however, further research is highly needed in this area. Lifestyle, dietary approaches, and probiotics all seem to influence the microbiome, hence being a promising modality as adjuvant therapy. The aim of this review was to present the latest reports in the field of research on skin, blood, and gut microbiome in terms of hidradenitis suppurativa.

Accuracy of SCORTEN in predicting mortality in toxic epidermal necrolysis.

BACKGROUND: Toxic epidermal necrolysis (TEN) patients require multi-directional and multi-disciplinary treatment. In most cases, they are hospitalised at intensive care units and require multi-directional, burn-complication preventive care. Choosing the most appropriate treatment option might be troublesome even when predicting scores are used. SCORTEN is the most renowned prognostic score for TEN patients, however, there are some data indicating that the accuracy of this test may be limited. The credibility of not just the predicted mortality risk, but also componential laboratory results and clinical features subject to debate. The aim of this study was to evaluate the efficacy and credibility of SCORTEN in clinical practice, on proprietary material. METHODS: A retrospective analysis of 35 patients with diagnosed in histopathology TEN was performed. The inclusion criteria were as follows: day of submission before 5th day from the onset of the symptoms, full protocol of plasmaphereses and IVIGs according to our scheme. Our protocol includes cycle of plasmapheresis with frozen fresh plasma twice daily for the first 2 days following admission, and once daily for the subsequent 5 to 7 days. IVIGs were administered after the first two sessions of plasmapheresis, for 4 to 7 days. The dosage was calculated according to body weight, at 0.4 to 0.5 g/kg per dose. RESULTS: The sensitivity of SCORTEN for the analysed cohort was 100%, with a specificity of 24%. The estimated death was 41,9%, while the actual death rates were 12,5%. Our protocol improved the survival, OR = 26,57, RR = 6,34, p = 0,022. Decrease in mortality was caused by a combined treatment protocol we use- plasmaphereses with IVIGs. No independent risk factor was significant in death evaluation. CONCLUSION: Our data suggest that the scoring system for predicting death among TEN patients are reliable when they are high. New prognostic factors should be found to improve the evaluation of patients with low SCORTEN.

Combined therapies in scar treatment-The role of autologous derived agents in scar remodeling: A series of cases.

Comprehensive scar treatment usually requires a combination of several methods. The selection of methods should depend on the appearance and biology of the scar. The aim of this study was to determine the safety and efficiency of combined methods with the use of autologous derived agents in the treatment of scars, based on the available literature and own experience. The study consists of a description of three cases treated with autologous derived agents: platelet-rich plasma (PRP), lipofilling or stromal vascular fraction (SVF) in combination with radiofrequency, CO2 laser, or cutting threads. No adverse events were reported. Improvement in scar quality and function was observed in all cases. Combination of autologous derived injectables with medical devices is safe and accelerates both cosmetic and functional results.

Immunomodulatory Drugs in the Treatment of Hidradenitis Suppurativa-Possibilities and Limitations.

Hidradenitis suppurativa, also known as acne inversa, is a chronic, progressive, debilitating, recurrent inflammatory skin disease characterized by the occurrence of very severe, persistent, painful nodules, abscesses, and fistulas, most commonly found in the skin folds of the axilla, groin, gluteal, and perianal areas. Treatment is rather difficult and typically requires the use of multiple modalities. Regardless of the presence of several therapeutic options, treatment often turns out to be ineffective or poorly selected concerning the clinical picture of the disease. Thus, the search for new biologics and other target treatments of hidradenitis suppurativa is ongoing. The safety and efficacy of adalimumab, still the only U.S. Food and Drug Administration approved biologic in the hidradenitis suppurativa treatment, paved the way for new drugs to be compared with it. Several more drugs with new immunological targets are currently under investigation for the treatment of acne inversa. The aim of the article was to present the current and future targets of acne inversa treatment, simultaneously providing insights into the molecular pathomechanisms of the disease.

Preliminary Single-Center Experience of Bromelain-Based Eschar Removal in Children with Mixed Deep Dermal and Full Thickness Burns.

INTRODUCTION: Early eschar removal is the standard management of burns. The goal is to remove all of the necrotic tissue and render the wound suitable for healing or skin grafting. The enzymatic debridement of burn wounds allows for minimally invasive removal of burn eschar. The aim of the study was to describe and compare the demographic characteristics, surgical treatment and outcomes of patients treated with Nexobrid® with patients who had standard surgical excision. MATERIAL AND METHODS: A retrospective review was conducted on children who underwent enzymatic debridement. The study group was compared with children treated with the standard of care (SoC). RESULTS: Twelve children (mean age 8 years, range 3 to 15 years) with mixed deep dermal and full thickness burn wounds were treated with Nexobrid®. The mean size of the burns was 29% TBSA. The median percentage TBSA debrided using Nexobrid® was 15% (range 2-27%). In a clinical assessment, enzymatic debridement was effective in removing dead tissue in a single application. No adverse reaction to Nexobrid® and serious complications after enzymatic procedure were recorded in the study group. The estimated relative risk of the need for reconstructive procedures decreases 3.5 times for the study group (RR 3.5, 95%CI 0.9-13.5, p = 0.089). CONCLUSION: The bromelain-based enzymatic method offers a good and safe debridement option to improve the treatment and life quality of children with severe burns. The main outcome of interest was the number of reconstructive procedures due to scar contractures, which was reduced in the group treated enzymatically compared to the SoC-treated children.

Immunomodulatory Treatment of Lyell's Syndrome: A Simultaneous Plasmapheresis and Intravenous Immunoglobulins Therapy.

Lyell's syndrome, or toxic epidermal necrolysis (TEN) is a rare but life-threatening condition. It manifests with blistering of skin and mucous due to subepidermal bullae and keratinocyte necrosis. In most cases, it is an immune response to drugs or their metabolites. The mortality in TEN is high despite optimal infection and wound control. There are no unequivocal treatment guidelines in TEN. Immunosuppressive treatment may increase the wound infection risk and mortality. The aim of the study was to evaluate a 10-year experience with immunomodulatory therapy in TEN. We perform a combination of plasmapheresis and intravenous immunoglobulins to control the disease. There were 35 patients in the group and we performed a post hoc evaluation. Twenty-eight patients received the full protocol and there were seven patients who did not complete the treatment (single therapy group). The mortality in the test group was 14.29%, and the difference reached statistical significance in comparison with the single therapy group (P < .05). Our protocol reduced the mortality risk five times. Our study proved that simultaneous plasmaphereses with intravenous immunoglobulins administration were safe and improved patients' outcome in TEN.

Hydrogels in Burn Wound Management-A Review.

Inert hydrogels are of a great importance in burn first aid. Hydrogel dressings may be an alternative to cooling burn wounds with streaming water, especially in cases of mass casualty events, lack of clean water, hypothermia, or large extent of burns. Hydrogels that contain mostly water evacuate the heat cumulating in the skin by evaporation. They not only cool the burn wound, but also reduce pain and protect the wound area from contamination and further injuries. Hydrogels are ideally used during the first hours after injury, but as they do not have antimicrobial properties per se, they might not prevent wound infection. The hydrogel matrix enables incorporating active substances into the dressing. The active forms may contain ammonium salts, nanocrystal silver, zinc, growth factor, cytokines, or cells, as well as natural agents, such as honey or herbs. Active dressings may have antimicrobial activity or stimulate wound healing. Numerous experiments on animal models proved their safety and efficiency. Hydrogels are a new dressing type that are still in development.

Innate Immune System Response to Burn Damage-Focus on Cytokine Alteration.

In the literature, burns are understood as traumatic events accompanied by increased morbidity and mortality among affected patients. Their characteristic feature is the formation of swelling and redness at the site of the burn, which indicates the development of inflammation. This reaction is not only important in the healing process of wounds but is also responsible for stimulating the patient's innate immune system. As a result of the loss of the protective ability of the epidermis, microbes which include bacteria, fungi, and viruses have easier access to the system, which can result in infections. However, the patient is still able to overcome the infections that occur through a cascade of cytokines and growth factors stimulated by inflammation. Long-term inflammation also has negative consequences for the body, which may result in multi-organ failure or lead to fibrosis and scarring of the skin. The innate immune response to burns is not only immediate, but also severe and prolonged, and some people with burn shock may also experience immunosuppression accompanied by an increased susceptibility to fatal infections. This immunosuppression includes apoptosis-induced lymphopenia, decreased interleukin 2 (IL-2) secretion, neutrophil storm, impaired phagocytosis, and decreased monocyte human leukocyte antigen-DR. This is why it is important to understand how the immune system works in people with burns and during infections of wounds by microorganisms. The aim of this study was to characterize the molecular pathways of cell signaling of the immune system of people affected by burns, taking into account the role of microbial infections.

Adipose-Derived Stem Cells for Facial Rejuvenation.

The interest in regenerative medicine is increasing, and it is a dynamically developing branch of aesthetic surgery. Biocompatible and autologous-derived products such as platelet-rich plasma or adult mesenchymal stem cells are often used for aesthetic purposes. Their application originates from wound healing and orthopaedics. Adipose-derived stem cells are a powerful agent in skin rejuvenation. They secrete growth factors and anti-inflammatory cytokines, stimulate tissue regeneration by promoting the secretion of extracellular proteins and secrete antioxidants that neutralize free radicals. In an office procedure, without cell incubation and counting, the obtained product is stromal vascular fraction, which consists of not only stem cells but also other numerous active cells such as pericytes, preadipocytes, immune cells, and extra-cellular matrix. Adipose-derived stem cells, when injected into dermis, improved skin density and overall skin appearance, and increased skin hydration and number of capillary vessels. The main limitation of mesenchymal stem cell transfers is the survival of the graft. The final outcomes are dependent on many factors, including the age of the patient, technique of fat tissue harvesting, technique of lipoaspirate preparation, and technique of fat graft injection. It is very difficult to compare available studies because of the differences and multitude of techniques used. Fat harvesting is associated with potentially life-threatening complications, such as massive bleeding, embolism, or clots. However, most of the side effects are mild and transient: primarily hematomas, oedema, and mild pain. Mesenchymal stem cells that do not proliferate when injected into dermis promote neoangiogenesis, that is why respectful caution should be taken in the case of oncologic patients. A longer clinical observation on a higher number of participants should be performed to develop reliable indications and guidelines for transferring ADSCs.

A Questionnaire-Based Study to Obtain a Consensus from 5 Polish Burns Centers on Eschar Removal by Bromelain-Based Enzymatic Debridement (Nexobrid®) in Burns Following the 2020 Updated European Consensus Guidelines.

BACKGROUND The supplementary treatment of burns with enzymatic debridement with Nexobrid® was approved in Europe in 2013. The 2017 European consensus guidelines on the removal of eschar in burns by bromelain-based enzymatic debridement were updated in 2020. This questionnaire-based study aimed to obtain a consensus from 5 Polish burns centers on eschar removal by Nexobrid® in burns following the 2020 updated European consensus guidelines. MATERIAL AND METHODS A panel of 5 experts representing the leading burn treatment centers in Poland (Cracow, Gryfice, Siemanowice Slaskie, Poznan, and Leczna) was convened. A modified Delphi process was implemented with panel member selection, literature review, 2 rounds of voting in which panelists were asked to evaluate the European consensus and Polish consensus building by data analysis, statements preparation, final voting, and manuscript drafting. RESULTS The knowledge and experience of experts from Poland's leading burn centers resulted in the development of guidelines, formulated as 24 statements representing the following areas: indications and usage, pain management, application principles, post-enzymatic debridement wound dressing, and early and long-term outcomes. An analysis of the 7-point Likert scale polls revealed that 23 of the 24 statements achieved 100% consensus. CONCLUSIONS The findings from this survey from 5 major centers in Poland supported the main recommendations from the 2020 updated European consensus guidelines on the removal of eschar in burns by Nexobrid® and may serve as a practical guide for surgeons who care for patients with burns in this country.

Correction: Surowiecka et al. Hydrogels in Burn Wound Management-A Review. Gels 2022, 8, 122.

In the original publication, there was a mistake in Table 2 as published [...].

Stromal vascular fraction and emulsified fat as regenerative tools in rejuvenation of the lower eyelid area.

In the lower eyelid area, dermal melanocytosis, fine lines, skin atrophy, dryness, and loss of subcutaneous fat tissue represent the initial signs of aging. Beside the addition of volume, adipose tissue injections can also improve pigmentation and skin texture. Clinical studies of simultaneous stromal vascular fraction (SVF) and emulsified fat transfers have not been reported so far. Our aim was to investigate the clinical results of transferring SVF and emulsified fat into the lower eyelid area. A total of 16 patients underwent tumescent liposuction and injection of SVF and emulsified fat into the lower eyelid area. For preparation of SVF and emulsified fat, ACP double syringes with 2.4, 1.4, and 1.2 mm connectors, and a swing-out rotor centrifuge, were used. At follow-up, improvements on before and after pictures were rated by the treating physician and two independent physicians, using the global aesthetic improvement scale (GAIS). Clinical outcomes were rated as exceptional, very improved, or improved in all patients, with an average GAIS score of 1.6. No serious adverse events occurred. Our initial results suggest that SVF and emulsified fat are safe and effective tools for skin rejuvenation and correction of volume deficiencies in the lower eyelid area. More studies need to be conducted to corroborate these encouraging findings.

Role of Magnetic Resonance Spectroscopy in Evaluation of Cerebral Metabolic Status Before and After Carotid Endarterectomy/Thromboendarterectomy and Carotid Artery Stenting in Patients with Asymptomatic Critical Internal Carotid Artery Stenosis.

BACKGROUND The relative efficacy of carotid endarterectomy (CEA)/thromboendarterectomy (TEA) and carotid artery stenting (CAS) already has been compared in randomized controlled trials and a meta-analysis, but only limited data exist describing the status of cerebral metabolism before and after these interventions. The aim of the present study was to compare metabolic changes before and after treatment of carotid stenosis and assess their potential clinical implications.   MATERIAL AND METHODS Patients with asymptomatic unilateral critical internal CAS were imaged with proton 3T magnetic resonance spectroscopy (H-MRS) because the technique is more sensitive than regular magnetic resonance imaging for detection of the early signs of ischemic events. Abnormal metabolite ratios detected with H-MRS may precede actual morphological changes associated with hypoperfusion as well as reperfusion changes. Ipsilateral and contralateral middle cerebral artery vascular territories were both evaluated before and after vascular intervention. H-MRS was performed within 24 h before and after surgery. Correlations in the metabolic data from H-MRS for N-acetylaspartic acid (NAA)+N-acetylaspartylglutamate, creatinine (Cr)+phosphocreatinine, and phosphocholine+glycerophosphocholine (Cho) were sought. RESULTS H-MRS voxels from 11 subjects were analyzed. Values for dCho/CrI, dCho/CrC and Cho/Naal (P<0.001) were significantly higher ipsilaterally than contralaterally. Ratios for dNaa/ChoC and Cho/NaaC were significantly higher on the non-operated side (P<0.001). CONCLUSIONS H-MRS may be helpful for assessment of patients with CAS, particularly because unlike other modalities, it reveals postoperative changes in metabolic brain status. Initial results indicate the important role of perioperative neuroprotective treatment.

Normal Pancreas Graft Appearance in Magnetic Resonance Diffusion Tensor Imaging (DTI).

BACKGROUND The main purpose of diagnostic imaging after pancreas transplantation is to exclude potential complications. As long as standard anatomical imaging such as sonography, contrast-enhanced computed tomography, and magnetic resonance imaging (MRI) are sufficient to display macroscopic vasculature, early changes within the graft caused by insufficient microperfusion will not be displayed for evaluation. MATERIAL AND METHODS Patients with pancreas allograft function in good condition were included in the study. No specific preparation was demanded before the MRI examination. The results of MRI were correlated with Igls criteria. It was a preliminary study to examine diffusion tensor imaging (DTI) value and safety in pancreas transplantation. RESULTS Our results indicated that higher fractional anisotropy (FA) values of the graft's head were associated with delayed graft function and insulin intake. We also compared grafts' images in early and late periods and found differences in T1 signal intensity values. DTI is a reliable noninvasive tool, requiring no contrast agent, to assess graft microstructure in correlation with its function, with FA values showing the most consistent results. By Igls criteria, no graft failure, 76% had optimal function, 10% had good function, and 14% had marginal function. CONCLUSIONS Our results suggest that DTI can be safely used in patients after pancreas transplantation and is advantageous in detecting early as well as late postoperative complications such as intra-abdominal fluid collection, malperfusion, and ischemia of the graft. Our findings correspond with clinical condition and Igls criteria. DTI is free of ionizing agents and is safe for kidney grafts.

Can hydrogel dressings reduce patients' discomfort and side effects of facial platelet-rich plasma injections?

The literature shows that facial injection of platelet-rich plasma (PRP) is a safe and effective treatment modality. Serious adverse effects have not been reported so far. Nevertheless, side effects such as redness, edema, bruising, pain, pruritus, and heat sensation have been reported. Our goal was to assess the potential effects of hydrogel dressing after injection of PRP. PRP was prepared using an ACP double-syringe system and applied on face by intradermal microdeposit injections. One half of the face was covered with a cooled (20°C) hydrogel dressing for 20 minutes before and after PRP injection. Patients rated the levels of pain separately for both sides. Physician and patient rated the overall appearance of the skin, redness, swelling, bruising, and number of bruises straight after the procedure. At 6-month follow-up, the physician rated the global aesthetic outcome. Needle prick-induced pain and edema were rated less on the hydrogel side. Our results demonstrate a significant reduction of patient's discomfort and side effects through application of hydrogel dressings. Recovery has been accelerated and the overall appearance of the skin straight after the procedure has been rated significantly better than without dressing application. At 6-month follow-up, the global aesthetic improvement was rated equally on both sides.