The Crossroads of the Coagulation System and the Immune System: Interactions and Connections.

The coagulation and immune systems, two vital systems in the human body, share intimate connections that fundamentally determine patient health. These systems work together through several common regulatory pathways, including the Tissue Factor (TF) Pathway. Immune cells expressing TF and producing pro-inflammatory cytokines can influence coagulation, while coagulation factors and processes reciprocally impact immune responses by activating immune cells and controlling their functions. These shared pathways contribute to maintaining health and are also involved in various pathological conditions. Dysregulated coagulation, triggered by infection, inflammation, or tissue damage, can result in conditions such as disseminated intravascular coagulation (DIC). Concurrently, immune dysregulation may lead to coagulation disorders and thrombotic complications. This review elucidates these intricate interactions, emphasizing their roles in the pathogenesis of autoimmune diseases and cancer. Understanding the complex interplay between these systems is critical for disease management and the development of effective treatments. By exploring these common regulatory mechanisms, we can uncover innovative therapeutic strategies targeting these intricate disorders. Thus, this paper presents a comprehensive overview of the mutual interaction between the coagulation and immune systems, highlighting its significance in health maintenance and disease pathology.

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.

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.

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.

Evaluation of Bromelain-Based Enzymatic Debridement Combined with Laser Doppler Imaging and Healing of Burn Wounds.

BACKGROUND Accurate estimation of burn depth is crucial for correct treatment decision making. Bromelain-based enzymatic debridement (ED) may improve clinical assessment of burn depth. Laser Doppler imaging (LDI) provides a valuable indicator of burn depth by analyzing microcirculation within tissue beds. This study aimed to evaluate bromelain-based enzymatic debridement combined with laser Doppler imaging and healing of 42 wounds in 19 patients with mixed second- and third-degree thermal burns. MATERIAL AND METHODS We included 42 wounds in 19 patients with mixed deep dermal and full-thickness thermal burns. All patients were treated with eschar-specific removal agent for ED. The perfusion of each wound after ED was assessed using LDI. Healing time was estimated by 2 experienced burn surgeons and marked by the observation of epithelization. The usefulness of the LDI performed after ED in predicting healing time was estimated. The findings were analyzed to determine a cut-off value for LDI that indicates if a burn will heal spontaneously. RESULTS We observed that burn wounds with higher mean perfusion healed faster. The analysis showed a strong relationship between perfusion after ED and healing time (Spearman rank correlation coefficient=-0.803). A mean perfusion greater than 296.89 indicated that the wound could heal spontaneously and does not require skin grafting. CONCLUSIONS LDI examination of an already debrided wound allows for a reliable assessment of perfusion at an early stage of treatment. The use of a safe and effective debridement method in conjunction with a non-invasive diagnostic tool could improve burn management.

The role of oestrogen and progesterone receptors in gigantomastia.

Introduction: Gigantomastia is a rare condition characterised by excessive breast growth. The pathophysiology of mammary enlargement varies depending on the type of gigantomastia: gestational, juvenile virginal, or idiopathic. The study aimed at examining the receptor status (oestrogen receptor α (ERα) and progesterone receptor (PR)) of breast tissue in adult women with juvenile or idiopathic gigantomastia. Material and methods: The study involved 70 women who underwent breast reduction due to juvenile or idiopathic gigantomastia. Control breast specimens were obtained from 18 female cadavers. ERα and PR expressions were detected immunohistochemically in breast gland samples. Results: Categorised and uncategorised ERα and PR expression did not differ between women with gigantomastia and control women. It was found that in both groups weak (0-30%) ERα and PR expression was the most common. Analysis of categorised data also did not reveal any significant correlations between ERα or PR and the women's age: for the whole group: p = 0.795 (ERα), p = 0.207 (PR), for women with gigantomastia: p = 0.934 (ERα), p = 0.43 (PR), and for control women: p = 0.638 (ERα), p = 0.805 (PR). Conclusions: Gigantomastia is not caused by increased expression of ERα and PR. Analysing abnormal sensitivity of these receptors to hormones may be crucial in establishing the increased risk of breast cancer in women with gigantomastia.

The Role of the Immune System in Pediatric Burns: A Systematic Review.

Burns are one of the most common causes of home injuries, characterized by serious damage to the skin and causing the death of affected tissues. In this review, we intended to collect information on the pathophysiological effects of burns in pediatric patients, with particular emphasis on local and systemic responses. A total of 92 articles were included in the review, and the time range of the searched articles was from 2000 to 2021. The occurrence of thermal injuries is a problem that requires special attention in pediatric patients who are still developing. Their exposure to various burns may cause disturbances in the immune response, not only in the area of tissue damage itself but also by disrupting the systemic immune response. The aspect of immunological mechanisms in burns requires further research, and in particular, it is important to focus on younger patients as the existence of subtle differences in wound healing between adults and children may significantly influence the treatment of pediatric patients.

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.

Genetic Factors of Idiopathic Gigantomastia: Clinical Implications of Aromatase and Progesterone Receptor Polymorphisms.

The role of estrogen, progesterone, their receptors and aromatase in the development of the breast is well documented. In this study we examined the association of genetic variants of progesterone receptor (PGR) and aromatase (CYP19A1) genes with gigantomastia risk. We conducted a case-control study among 124 women: 60 with gigantomastia and 64 controls. We examined the single nucleotide polymorphisms (SNPs) for CYP19A1 (rs749292 and rs7172156) and PGR (rs1042838). Our results showed that allele G in rs749292 (CYP19A1) increased the risk of gigantomastia, but not significantly (p = 0.09). There is a correlation between rs1042838 (PGR) and waist-to-hip ratio (WHR) in women with gigantomastia-AC genotype correlates with lower WHR and CC with higher WHR. There were no correlations between the onset of gigantomastia, the age of menarche and the length of the menstrual cycle, and rs1042838, rs749292 and rs7172156. We did not find differences in the SNP of PGR (rs1042838) between women with gigantomastia and controls. However, our findings showed more frequent G allele in CYP19A1 (rs749292) in women with gigantomastia.

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 [...].

Effectiveness of Suprathel® application in partial thickness burns, frostbites and Lyell syndrome treatment.

UNLABELLED: The skin is the largest organ of the human body consisting of several layers possessing different properties and performing different physiological functions. The loss of skin integrity caused by a trauma or disease may provoke acute physiological and immune disorders that may even be fatal. The following properties are primarily taken into account when choosing the appropriate burn wound dressing: support of the epithelialisation process, pain and patient discomfort reduction, and treatment costs. THE AIM OF THE STUDY was to assess the usefulness of Suprathel in the treatment of partial-thickness burns and frostbites and Lyell's syndrome and to determine the preferable time of Suprathel application to the wound. MATERIAL AND METHODS: At The Eastern Poland Burn Treatment and Reconstructive Surgery Centre, Suprathel was used in 21 patients: 11 men and 4 women with wound burns, 5 men with frostbites and 1 woman with Lyell's syndrome. Dressings were applied within 96 hours of injury. RESULTS: Treatment results depended on the time of Suprathel application to the wound and on the type of injury. Among 9 partial-thickness burn patients treated within 24 h of injury, the epithelialisation time was up to 14 days in 7 patients and up to 21 days in 1 patient, and skin grafting was necessary in 1 patient. In one of the 2 partial-thickness burn patients treated on the second day after injury, the epithelialisation time was 21 days, and skin grafting was necessary in the other of these 2 patients. Among 4 partial-thickness burn patients treated on the second day after the injury, the epithelialisation time was 21 days in 2 patients and skin grafting was necessary in 2 patients. Among the 5 frostbite patients, the epithelialisation time was up to 14 days in 3 patients and up to 21 days in 2 patients. In 1 patient with Lyell's syndrome, the epithelialisation time was 21 days. CONCLUSIONS: Suprathel is a good dressing that can perform the function of a temporary epidermal substitute in partial-thickness burns and frostbites and in Lyell's syndrome. The dressing should be applied within 24 hours of injury, when there is the least exudate from the wound and the wound is not infected. Therapeutic effectiveness of Suprathel decreases along with a delay of its application to the burn wound and with increasing burn depth.

[Burn shock, diagnostics, monitoring and fluid therapy of severe burns--new look]. / Wstrzas oparzeniowy, diagnostyka, monitorowanie i leczenie plynowe ciezkich oparzen--nowe spojrzenie.

Pathomechanism of burn shock is associated with an important endocrine disorder and cytokines storm. As a result of the burns are released to bloodstream kinins such as: histamine, serotonin and bradykinin and also inflammatory mediators such as: tromboxans, prostacyclins, prostaglandins and leukotrienes. Arises temporary endothelial failure. Comes to the escape of liquid blood to the tissues and a sudden decrease in the quantity of the fluid in the vessels and appear symptoms of burn shock. Offset of fluids by vascular wall to the extravascular space described mathematically with Landis-Starling law. Treatment of burn shock relies on intensive fluid therapy to fill vessels. Fluid rules are based on infusion crystalloids, colloids, hypersaline or plasma. Effect of fluid resuscitation after severe burn are edemas of whole body. Severe burn receives up to 25 000 ml of fluids intravenous in the first 48 hours after injury. The quantity of water defaulting tissue after 48 hours is even 13 000-18 500 ml which is 300-400% of the volume of blood flow. From 3rd day after burn this may produce symptoms of acute circulatory insufficiency or polycompartment syndrom. Enforces this restrictive fluid treatment and removing significant quantities of water from the bloodstream. In East Poland Burn Center and Reconstructive Surgery we remove even 300-350 ml fluid/h by ultrafiltration during CVVHD CiCa. Additional application hemodynamic monitoring such Vigileo-Flotrac has considerably reduce the amount of complications such as: intra-abdominal hypertension IAH, acute heart syndrome, cerebral edema and pulmonary edema.