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Alopecia areata (AA) is a non-scarring autoimmune disease requiring long-term treatments. Topical, intralesional or systemic corticosteroids are the first option. However, considering the risk of skin atrophy and the possible lack of clinical response, new treatment options are urgently needed. A fractional carbon dioxide laser (FCL) has been proven to be effective alone or in combination with other drugs. However, no study has ever evaluated the association between FCL and topical tacrolimus. We report three cases of AA resistant to corticosteroids for at least 12 months, treated with topical tacrolimus 0.1% ointment and FCL on some patches. After 16 weeks from the beginning of treatment, all patients showed improvement in clinical and trichoscopic parameters in the areas treated in combination. FCL and tacrolimus may represent a new therapeutic option, but further studies are needed for confirmation. [ABSTRACT FROM AUTHOR]

Simple Summary: Multiple myeloma (MM) represents the second most common hematological malignancy, but its diagnosis can be significantly delayed since symptoms are not specific and, mainly in the older population, alternate diagnoses can mimic MM. Bone marrow biopsy (evaluating the amount of proliferating myeloma cells) remains an essential procedure, but several imaging methods such as whole-body low-dose computed tomography, positron emission tomography or whole-body magnetic resonance have become crucial for the diagnosis and staging of MM, and are also taking on a prognostic role. MM is a clinically and biologically heterogeneous disease; therefore, with the aim to identify patients with different outcomes, some risk models such as ISS, R-ISS or R2-ISS have been proposed over time. However, the most recent attempts have been to establish individualized patient risk, integrating clinical, genomic and therapeutic data in order to personalize treatment and avoid overtreatment and toxicities. The outcome of multiple myeloma (MM) has significantly improved in the last few decades due to several factors such as new biological discoveries allowing to better stratify disease risk, development of more effective therapies and better management of side effects related to them. However, handling all these aspects requires an interdisciplinary approach involving multiple knowledge and collaboration of different specialists. The hematologist, faced with a patient with MM, must not only choose a treatment according to patient and disease characteristics but must also know when therapy needs to be started and how to monitor it during and after treatment. Moreover, he must deal not only with organ issues related to MM such as bone disease, renal failure or neurological disease but also with adverse events, often very serious, related to novel therapies, particularly new generation immunotherapies such as CAR T cell therapy and bispecific antibodies. In this review, we provide an overview on the newer MM diagnostic and monitoring strategies and on the main side effects of MM therapies, focusing on adverse events occurring during treatment with CAR T cells and bispecific antibodies. [ABSTRACT FROM AUTHOR]

This document is an editorial from the International Journal of Molecular Sciences titled "Skin, Autoimmunity and Inflammation: A Comprehensive Exploration through Scientific Research." The editorial discusses various skin diseases characterized by inflammatory and autoimmune mechanisms, such as psoriasis, hidradenitis suppurativa, vitiligo, systemic sclerosis, lichen sclerosus, hyper-IgE syndrome, keloids, granuloma annulare, and pyoderma. The authors highlight the importance of understanding the molecular and immunological aspects of these diseases to develop precise and effective treatments. They also mention the neurological and psychiatric manifestations that often accompany these skin conditions. The editorial emphasizes the need for further research and interdisciplinary collaboration to improve the diagnosis and management of these diseases. [Extracted from the article]

In multiple myeloma impressive outcomes have improved with the introduction of new therapeutic approaches, mainly those including naked monoclonal antibodies such as daratumumab and isatuximab. However, moving to earlier lines of therapy with effective anti-myeloma drugs led to an increase in the number of patients who developed multi-refractoriness to them early on. Currently, triple- or multi-refractory MM represents an unmet medical need, and their management remains a complicated challenge. The recent approval of new immunotherapeutic approaches such as conjugated monoclonal antibodies, bispecific antibodies, and CAR T cells could be a turning point for these heavily pretreated patients. Nevertheless, several issues regarding their use are unsolved, such as how to select patients for each strategy or how to sequence these therapies within the MM therapeutic landscape. Here we provide an overview of the most recent data about approved conjugated monoclonal antibody belantamab, mafodotin, bispecific antibody teclistamab, and other promising compounds under development, mainly focusing on the ongoing clinical trials with monoclonal antibody combination approaches in advanced and earlier phases of MM treatment. [ABSTRACT FROM AUTHOR]

Background and Objectives: Recently published articles reported an association between psoriasis and interstitial lung diseases (ILDs). The aim of this study is to evaluate the differences in ILD computed tomography (CT) patterns between smoker and never smoker plaque psoriasis (PP) patients under topical treatment without psoriatic arthritis (PA), inflammatory bowel disease (IBD) or connective tissue diseases (CTDs). Matherials and Methods: Two radiologists evaluated chest CT examinations of 65 patients (33 smokers, 32 never smokers) with PP. Results: Usual interstitial pneumonia (UIP) pattern was diagnosed in 36 patients, nonspecific interstitial pneumonia pattern in 19, hypersensitivity pneumonitis in 7 and pleuropulmonary fibroelastosis (PPFE) in 3 patients. UIP pattern showed a statistically significant higher frequency in smoker patients (p = 0.0351). Respiratory symptoms were reported in 80% of patients. Conclusions: ILDs seems to represent a new comorbidity associated with psoriasis. Moreover, a statistically significant association between smokers and UIP pattern in PP patients is found. Respiratory symptoms should be evaluated in PP patients, in collaboration with a radiologist and a pneumologist. However, further studies are required to better understand the epidemiology of ILDs in PP patients. [ABSTRACT FROM AUTHOR]

Pembrolizumab has been shown to increase survival in patients with metastatic melanoma. Considering the numerous oncoming studies, we decided to conduct a narrative review of the latest efficacy evidence regarding the use of pembrolizumab, alone or in combination, in patients with metastatic melanoma. A search was conducted in PubMed using "pembrolizumab," and "metastatic melanoma" as keywords, considering studies from 2022 onward. We reviewed pembrolizumab and associations, cost-effectiveness, virus, advanced acral melanoma, long-term outcomes, real-life data, biomarkers, obesity, and vaccines. In conclusion, pembrolizumab is a fundamental option in the therapy of metastatic melanoma. However, a certain group of patients do not respond and, therefore, new combination options need to be evaluated. In particular, the use of vaccines tailored to tumor epitopes could represent a breakthrough in the treatment of resistant forms. Further studies with larger sample numbers are needed to confirm the preliminary results. [ABSTRACT FROM AUTHOR]

Simple Summary: This paper deals with Belantamab mafodotin, a novel anti-BCMA antibody-drug conjugate licensed by regulatory agencies for the treatment of anti-CD38-refractory multiple myeloma patients. In addition to describing the mechanism of action and general information about the drug, this review mostly focuses on real-life data from American, Asian and European experiences on it. The aim of this overview is to picture an updated scenario on Belantamab mafodotin in different completed or ongoing clinical trials, studying it in different settings. Furthermore, this paper would like to provide precise data collection about the efficacy and safety of Belantamab mafodotin real-world data, showing the reproducibility of randomized clinical trial data that is also in real-life settings. Despite the recent approval of novel immunotherapies, such as immunomodulatory drugs, proteasome inhibitors and anti-CD38 monoclonal antibodies, Multiple Myeloma (MM) remains incurable, and the acquisition of triple-refractoriness leads to really dismal outcomes in even earlier lines of therapy. More recently, innovative therapeutic strategies targeting B cell maturation antigen (BCMA), highly expressed on the plasma cell surface, are drawing different future landscapes in terms of effectiveness and outcomes. Belantamab Mafodotin, a first-in-class anti-BCMA antibody–drug conjugate, demonstrated good efficacy and safety profile in triple-refractory patients in the phase 2 DREAMM-2 trial, and it was approved for the treatment of MM triple-exposed patients with >4 prior lines of therapy. Here, starting from Belantamab Mafodotin clinical trials and also exploring combination studies and different schedules in order to improve its efficacy and toxicity, we focused on real-life experiences all over the world, which have confirmed clinical trial data and encourage further Belantamab Mafodotin investigations. [ABSTRACT FROM AUTHOR]

Hidradenitis suppurativa (HS) is a chronic, recurrent, and inflammatory skin disease characterized by painful, deep-seated, nodules, abscesses, and sinus tracts in sensitive areas of the body, including axillary, inguinal, and anogenital regions. Antibiotics represent the first-line pharmacological treatment of HS because of their anti-inflammatory properties and antimicrobial effects. This narrative review summarizes the most significant current issues on the role of systemic antibiotics in the management of HS, critically analyzing the main limits of their use (antibiotic resistance and toxicity). Although, in the last decades, several cytokines have been implicated in the pathomechanism of HS and the research on the use of novel biologic agents in HS has been intensified, antibiotics remain a valid therapeutic approach. Future challenges regarding antibiotic therapy in HS comprise their use in association with biologics in the management of acute flare or as a bridge therapy to surgery. [ABSTRACT FROM AUTHOR]

Micro RNAs (miRNAs) are a type of non-coding RNA (ncRNA) and typically interact with specific target mRNAs through complementary base pairing, affecting their translation and/or stability. MiRNAs regulate nearly all cellular functions, including the cell fate of mesenchymal stromal cells (MSCs). It is now accepted that various pathologies arise at the stem level, and, in this scenario, the role played by miRNAs in the fate of MSCs becomes of primary concern. Here we have considered the existing literature in the field of miRNAs, MSCs and skin diseases, classified as inflammatory (such as psoriasis and atopic dermatitis-AD) and neoplastic (melanoma and non-melanoma-skin-cancer including squamous cell and basal cell carcinoma) diseases. In this scoping review article, the evidence recovered indicates that this topic has attracted attention, but it is still a matter of opinion. A protocol for this review was registered in PROSPERO with the registration number "CRD42023420245". According to the different skin disorders and to the specific cellular mechanisms considered (cancer stem cells, extracellular vesicles, inflammation), miRNAs may play a pro- or anti-inflammatory, as well as a tumor suppressive, or supporting, role, indicating a complex regulation of their function. It is evident that the mode of action of miRNAs is more than a switch on–off, and all the observed effects of their dysregulated expression must be checked in a detailed analysis of the targeted proteins. The involvement of miRNAs has been studied mainly for squamous cell carcinoma and melanoma, and much less in psoriasis and AD; different mechanisms have been considered, such as miRNAs included in extracellular vesicles derived both from MSCs or tumor cells, miRNAs involved in cancer stem cells formation, up to miRNAs as candidates to be new therapeutic tools. [ABSTRACT FROM AUTHOR]

Hidradenitis suppurativa (HS) is an immune-mediated inflammatory disorder characterized by deep-seated nodules, abscesses, sinus tracts and scars localized in the intertriginous areas. It is accompanied by pain, malodourous secretion and a dramatically decreased quality of life. Although the pathogenesis has not been entirely elucidated, the primary event is follicular hyperkeratosis of the pilosebaceous apocrine unit. Since the registration of the tumor necrosis factor-alpha inhibitor Adalimumab in 2015, several cytokines have been implicated in the pathomechanism of HS and the research of novel therapeutic targets has been intensified. We provide an update on the inflammatory cytokines with a central role in HS pathogenesis and the most promising target molecules of future HS management. [ABSTRACT FROM AUTHOR]

Simple Summary: In newly diagnosed multiple myeloma patients (NDMM) the introduction of three-drug, and recently, four-drug combinations allowed to reach response rates never seen before, leading to significantly improved PFS and OS. Long-term therapies play a key role in delaying or preventing relapses, but they are expensive and may cause significant toxicities. As a result, several ongoing trials are evaluating the possibility to intensify or de-intensify treatment based on minimal residual disease status, assessed by highly sensitive molecular or immunophenotypic methods. In relapsed/refractory patients (RRMM), especially those with advanced disease who become refractory to all available agents, new generation immunotherapies, such as conjugated monoclonal antibodies (mAbs), bispecific antibodies and CAR-T cells showed relevant results. In patients with high-risk cytogenetics, outcome remains poor and results from risk-adapted strategies are not yet available. Here we discuss the most recent issues regarding the management of MM, reporting the most up-to-date modalities of treatment and monitoring under evaluation. Multiple Myeloma (MM) remains a difficult to treat disease mainly due to its biological heterogeneity, of which we are more and more knowledgeable thanks to the development of increasingly sensitive molecular methods that allow us to build better prognostication models. The biological diversity translates into a wide range of clinical outcomes from long-lasting remission in some patients to very early relapse in others. In NDMM transplant eligible (TE) patients, the incorporation of mAb as daratumumab in the induction regimens, followed by autologous stem cell transplantation (ASCT) and consolidation/maintenance therapy, has led to a significant improvement of PFS and OS.; however, this outcome remains poor in ultra-high risk MM or in those who did not achieve a minimal residual disease (MRD) negativity. Several trials are exploring cytogenetic risk-adapted and MRD-driven therapies in these patients. Similarly, quadruplets-containing daratumumab, particularly when administered as continuous therapies, have improved outcome of patients not eligible for autologous transplant (NTE). Patients who become refractory to conventional therapies have noticeably poor outcomes, making their treatment a difficult challenge in need of novel strategies. In this review, we will focus on the main points regarding risk stratification, treatment and monitoring of MM, highlighting the most recent evidence that could modify the management of this still incurable disease. [ABSTRACT FROM AUTHOR]

Psoriasis is an immune-mediated inflammatory systemic disease with skin tropism and chronic relapsing course; it is associated with an increased cardiovascular risk and with many metabolic comorbidities, emerging during childhood in 22–33% of cases. Diet influences the presentation and the clinical course of inflammatory diseases, including psoriasis; in particular, it was shown that a Mediterranean, gluten-free, or low-calorie diet may positively affect disease control in adult patients with psoriasis and adequate pharmacological therapy. These three dietary regimens may play a role also in children with psoriasis. It has been demonstrated that pediatric psoriasis is associated with psychological stress, celiac disease, and obesity, which may be positively influenced by these dietary regimens, respectively. Therefore, the expertise of multiple health figures (gastroenterologists, nutritionists, pediatricians, dermatologists) is required to plan a tailor-made dietary strategy, ensuring good growth, through an adequate intake of essential micro- and macronutrients and, at the same time, impacting the pro-inflammatory biochemical profile and on the associated cardiovascular risk of psoriasis disease. [ABSTRACT FROM AUTHOR]

Vitiligo is an acquired hypopigmentation of the skin due to a progressive selective loss of melanocytes; it has a prevalence of 1–2% and appears as rounded, well-demarcated white macules. The etiopathology of the disease has not been well defined, but multiple factors contribute to melanocyte loss: metabolic abnormalities, oxidative stress, inflammation, and autoimmunity. Therefore, a convergence theory was proposed that combines all existing theories into a comprehensive one in which several mechanisms contribute to the reduction of melanocyte viability. In addition, increasingly in-depth knowledge about the disease's pathogenetic processes has enabled the development of increasingly targeted therapeutic strategies with high efficacy and fewer side effects. The aim of this paper is, by conducting a narrative review of the literature, to analyze the pathogenesis of vitiligo and the most recent treatments available for this condition. [ABSTRACT FROM AUTHOR]

Botulinum toxin type B (BoNT-B), known as Myobloc® in the United States and as Neurobloc® in Europe, is a new therapeutically available serotype among the botulinum toxin family. During the last years several data have been reported in literature investigating its efficacy and safety, as well as defining the dosing and application regiments of BoNT-B in the treatment of hyperhidrosis. Moreover, recent studies have been examining its safety profile, which may be different from those known about BoNT-A. The aim of this review is to provide information about what is currently known about BoNT-B in regards to the treatment of focal hyperhidrosis. [ABSTRACT FROM AUTHOR]

Accumulating evidence considers psoriasis a systemic inflammatory disorder that is associated with comorbidities such as psoriatic arthritis, cardiovascular disease, and metabolic syndrome. Although the precise pathogenetic links between psoriasis and atherosclerosis warrants further investigation, it is believed that chronic systemic inflammation along with the T helper (Th)-1 and Th17 polarization are associated with endothelial dysfunction and subsequent acceleration of atherosclerosis. Considering the above, several studies have evaluated if optimal control of the inflammation in psoriasis by inhibiting interleukins targeting the Interleukin (IL)-23/Th17 axis could subsequently reduce the atherosclerotic process during anti-psoriatic treatment by using a variety of surrogate markers of subclinical atherosclerosis. This systematic review summarizes current knowledge on the pathogenetic mechanisms and diagnostic evaluation of atherosclerosis in the context of psoriasis and provides a systematic review of the literature on the impact of treatment with biologics targeting the IL-23/Th17 axis on subclinical atherosclerosis in patients with plaque psoriasis and/or psoriatic arthritis. [ABSTRACT FROM AUTHOR]

Cutaneous melanoma is a severe neoplasm that shows early invasiveness of the lymph nodes draining the primary site, with increased risk of distant metastases and recurrence. The tissue biomarker identification could be a new frontier to predict the risk of early lymph node invasiveness, especially in cases considered by current guidelines to be at low risk of lymph node involvement and not requiring evaluation of the sentinel lymph node (SLN). For this reason, we present a narrative review of the literature, seeking to provide an overview of current tissue biomarkers, particularly vascular endothelium growth factors (VEGF), Tetraspanin CD9, lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1), D2-40, and gene expression profile test (31-GEP). Among these, 31-GEP seems to be able to provide a distinction between low or high risk for positive SLN classes. VEGF receptor-3 and CD9 expression may be independent predictors of positive SLN. Lastly, LYVE-1 and D2-40 allow an easier assessment of lymph vascular invasion, which can be considered a good predictor of SLN status. In conclusion, biomarkers to assess the lymph node status of cutaneous melanoma patients may play an important role in those cases where the clinician is in doubt whether or not to perform SLN biopsy. [ABSTRACT FROM AUTHOR]

Antibiotic resistance is rapidly increasing, and new anti-infective therapies are urgently needed. In this regard, antimicrobial peptides (AMPs) may represent potential candidates for the treatment of infections caused by multiresistant microorganisms. In this narrative review, we reported the experience of our research group over 20 years. We described the AMPs we evaluated against Gram-positive, Gram-negative, and fungi. In conclusion, our experience shows that AMPs can be a key option for treating multiresistant infections and overcoming resistance mechanisms. The combination of AMPs allows antibiotics and antifungals that are no longer effective to exploit the synergistic effect by restoring their efficacy. A current limitation includes poor data on human patients, the cost of some AMPs, and their safety, which is why studies on humans are needed as soon as possible. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is an itchy dermatitis with multifactorial aetiology, chronic-recurrent course, and typical distribution of lesions according to the age, affecting the 10–20% of pediatric population. Patients with AD, including children, suffer from many metabolic comorbidities, including metabolic syndrome, being overweight, obesity, dyslipidaemia, and arterial hypertension, all of which had a prevalence that was demonstrated to be higher than in healthy patients. The association between AD and metabolic comorbidities is multifactorial and involves the deregulation of immune system. In fact, hypertrophic adipose tissue produces soluble adipokines involved in inflammation and immunity, which stimulate the production of pro-inflammatory cytokines, responsible for a chronic low-grade inflammatory state and a higher predisposition to hypersensitivity reactions. Especially in pediatric population with AD, these metabolic disorders are usually underestimated and are associated with long term sequelae and an increased risk of a cardiovascular event, which may also occur later in adult age. Therefore, metabolic comorbidities should be carefully evaluated and early treated in children with AD, to minimize the long-term risk of cardiovascular events. [ABSTRACT FROM AUTHOR]

Mesenchymal Stem Cells (MSCs) are multipotent non-hematopoietic stromal cells found in different body tissues such as bone marrow, adipose tissue, periosteum, Wharton's jelly, umbilical cord, blood, placenta, amniotic fluid, and skin. The biological behavior of MSCs depends mainly on their interaction with the microenvironment in which they are found, whose quality deeply influences the regenerative and immunomodulatory properties of these cells. Several studies confirm the interaction between MSCs and inflammatory microenvironment in the pathogenesis of psoriasis, designating MSCs as an important factor driving psoriasis development. This review aims to describe the most recent evidence on how the inflammatory microenvironment that characterizes psoriasis influences the homeostasis of MSCs and how they can be used to treat the disease. [ABSTRACT FROM AUTHOR]

(1) Background: In their 60-year history, dimethyl fumarate and other salts of fumaric acid have been used for the treatment of psoriasis and other immune-mediated diseases for their immune-modulating properties. Over the years, new mechanisms of action have been discovered for this evergreen drug that remains a first-line treatment for several different inflammatory diseases. Due to its pleiotropic effects, this molecule is still of great interest in varied conditions, not exclusively inflammatory diseases. (2) Methods: The PubMed database was searched using combinations of the following keywords: dimethyl fumarate, pharmacokinetics, pharmacodynamics, adverse effects, psoriasis, multiple sclerosis, and clinical indications. This article reviews and updates the pharmacokinetics, mechanisms of action, and clinical indications of dimethyl fumarate. (3) Conclusions: The pharmacology of dimethyl fumarate is complex, fascinating, and not fully known. Progressive insights into the molecule's mechanisms of action will make it possible to maximize its clinical efficacy, reduce concerns about adverse effects, and find other possible areas of application. [ABSTRACT FROM AUTHOR]

Psoriatic patients present various infectious risk factors, but there are few studies in the literature evaluating the actual impact of psoriasis in severe staphylococcal skin infections. Our narrative review of the literature suggests that psoriatic patients are at increased risk of both colonization and severe infection, during hospitalization, by S. aureus. The latter also appears to play a role in the pathogenesis of psoriasis through the production of exotoxins. Hospitalized psoriatic patients are also at increased risk of MRSA skin infections. For this reason, new molecules are needed that could both overcome bacterial resistance and inhibit exotoxin production. In our opinion, in the near future, topical quorum sensing inhibitors in combination with current anti-MRSA therapies will be able to overcome the increasing resistance and block exotoxin production. Supplementation with Vitamin E (VE) or derivatives could also enhance the effect of anti-MRSA antibiotics, considering that psoriatic patients with metabolic comorbidities show a low intake of VE and low serum levels, making VE supplementation an interesting new perspective. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a common chronic inflammatory and immune-mediated skin disease with a complex pathophysiology and still represents a therapeutic challenge, owing to limited responses to available treatments. However, recent advances in the understanding of AD pathophysiology have led to the discovery of several new potential therapeutic targets, and research in the field of new molecules with therapeutic perspectives is boiling, with more than 70 new promising drugs in development. The aim of this systematic review is to provide the state of the art on the current knowledge concerning the pathophysiology of the disease and on novel agents currently being investigated for AD, and to highlight which type of evolution is going to take place in therapeutic approaches of atopic dermatitis in the coming years. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic systemic inflammatory disease that primarily affects the skin and is associated with multiple comorbidities with a considerable reduction in quality of life of affected patients. One-third of psoriasis cases begin in childhood and are associated with significant medical comorbidities such as obesity, metabolic syndrome, arthritis, and psychiatric disorders. In addition, because of its chronic nature and frequent relapses, psoriasis tends to require long-term treatment. Treatment of pediatric psoriasis usually involves the same methods used for adults. However, most treatments for pediatric psoriasis are used off-label, and research in this regard is still lacking. Targeted therapies involving the use of newly developed biologic drugs are also increasingly being applied to childhood psoriasis. This review summarizes the clinical features of pediatric psoriasis and focuses mainly on the updated concepts of pathogenesis and biological treatments of pediatric psoriasis. [ABSTRACT FROM AUTHOR]

This study aimed to compare adalimumab originator vs. biosimilar in HS patients, and to evaluate the effect of a switch to a biosimilar, or a switch back to the originator, in terms of treatment ineffectiveness. Patients with a diagnosis of HS were enrolled from 14 Italian sites. Treatment ineffectiveness was measured using Hurley score. The major analyses were 1) comparison between the two treatment groups (non-switcher analysis), and 2) the cross-over trend of Hurley score between treatment switchers (switcher analysis). Cox and Poisson regression models were used to compare the treatment ineffectiveness between groups. A total of 326 patients were divided into four groups: 171 (52.5%) taking originator; 61 (18.7%) patients taking biosimilar; 66 (20.2%) switchers; 28 (8.6%) switchers from originator to biosimilar and switched. A greater loss of efficacy was observed in the group allocated to the biosimilar than the originator group. The switcher analysis showed an effectiveness loss in the biosimilar compared to the originator. These results seem to indicate that a switch from one drug to the other may lead to a greater risk of inefficacy. A return to the previous treatment also does not ensure efficaciousness. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is an inflammatory disease that typically begins in childhood and may persist into adulthood, becoming a lifelong condition. The major inflammatory mediators of AD are known to be interleukin IL4 and IL13, so Dupilumab, which is able to inhibit both interleukins by blocking the shared IL4Rα subunit, has become an attractive option for treating AD. Mesenchymal stem cells (MSCs) are involved in the onset and development of AD by secreting specific interleukins. The aim of this study was to isolate MSCs from healthy controls (C-MSCs) and patients with AD before (AD-MSCs T0) and after 16 weeks of treatment with Dupilumab (AD-MSCs T16); to evaluate the expression mainly of IL4 and IL13 and of other inflammatory cytokines in C-MSCs, AD-MSCs at T0 and at T16; and to evaluate the efficacy of Dupilumab on MSCs immunobiology. C- and AD-MSCs (T0, T16) were isolated from skin specimens and characterized; the expression/secretion of IL4 and IL13 was evaluated using immuno-cytochemistry (ICC), indirect immune-fluorescence (IIF) and an ELISA test; secretion of IL2, IL4, IL5, IL6, IL10, IL12, IL13, IL17A, Interferon gamma (IFNγ), Tumor necrosis factor alpha (TNFα), Granulocyte Colony-Stimulating Factor (G-CSF), and Transforming Growth Factor beta1 (TGFβ1) were measured with ELISA. IL13 and IL6 were over-expressed, while IL4 was down-regulated in AD-MSCs at T0 compared to C-MSCs. IL6 and IL13 expression was restored after 16 weeks of Dupilumab treatment, while no significant effects on IL4 expression were noted. Finally, IL2, IL5, IL10, IL12, IL17A, INFγ, TNFα, G-CSF, and TGFβ1 were similarly secreted by C- and AD-MSCs. Although Dupilumab blocks the IL4Rα subunit shared by IL4 and IL13, it is evident that its real target is IL13, and its ability to target IL13 in MSCs reinforces the evidence, already known in differentiated cells, of the central role IL13 rather than IL4 in the development of AD. The inflammatory cascade in AD begins at the mesenchymal level, so an upstream therapeutic intervention, able to modify the immunobiology of atopic MSCs, could potentially change the natural history of the disease. [ABSTRACT FROM AUTHOR]

Daptomycin is active against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and the on-label indications for its use include complicated skin and skin structure infections (cSSSI). We performed a narrative review of the literature with the aim to evaluate the role of daptomycin in the skin wound healing process, proposing our point of view on the possible association with other molecules that could improve the skin healing process. Daptomycin may improve wound healing in MRSA-infected burns, surgical wounds, and diabetic feet, but further studies in humans with histological examination are needed. In the future, the combination of daptomycin with other molecules with synergistic action, such as vitamin E and derivates, IB-367, RNA III-inhibiting peptide (RIP), and palladium nanoflowers, may help to improve wound healing and overcome forms of antibiotic resistance. [ABSTRACT FROM AUTHOR]

Psoriasis vulgaris is a common inflammatory, immune mediated, chronic recurrent dermatosis. Psoriasis is also a systemic inflammatory disease, associated with numerous comorbidities, particularly metabolic ones. Here, we summarize and discuss, in a narrative review, the current knowledge about the metabolic comorbidities in psoriatic children. Obesity, insulin resistance, diabetes, cardiovascular disease, and dyslipidemia are identified as the main comorbidities in psoriatic children. In conclusion, dermatologists should be aware of the metabolic comorbidities in children with psoriasis, modulating the therapeutic approach according to the patient's clinical condition. [ABSTRACT FROM AUTHOR]

Among the forms of idiopathic hyperhidrosis, those involving the forehead have the greatest impact on patients' quality of life, as symptoms are not very controllable and are difficult to mask for patients. Although the local injection therapy with Incobotulinum toxin type A (IncoBTX-A therapy) can be considered a rational treatment, data from the literature describing both efficacy and safety of the treatment over the long term are poor. The aim of this report is to describe the single-center experience of five patients seeking treatment, for forehead hyperhidrosis with IncoBTX-A. To evaluate the benefits, safety profile and duration of anhidrosis, patients were treated following a standardized procedure and then followed until clinical relapse. The amount of sweating was measured by gravimetric testing, the extension of hyperhidrosis area was measured through Minor's iodine starch test, and response to the treatment was evaluated using the Hyperhidrosis Disease Severity Scale (HDSS) and the Dermatology Life Quality Index (DLQI). In all treated patients, a significant anhidrotic effect was observed 4 weeks after the treatment and lasted for approximately 36 weeks. The reduction in sweat production was associated with significant amelioration of symptoms and quality of life for all treated patients. No serious side effects occurred; one patient complained of a mild transient bilateral ptosis. Although further wider studies are required, our preliminary results seem to encourage the use of IncoBTX-A in forehead hyperhidrosis. [ABSTRACT FROM AUTHOR]

The interest in and need for carbon-free fuels that do not rely on fossil fuels are constantly growing from both environmental and energetic perspectives. Green hydrogen production is at the core of the transition away from conventional fuels. Along with popularly investigated pathways for hydrogen production, thermochemical water splitting using redox materials is an interesting option for utilizing thermal energy, as this approach makes use of temperature looping over the material to produce hydrogen from water. Herein, two-step thermochemical water splitting processes are discussed and the key aspects are analyzed using the most relevant information present in the literature. Redox materials and their compositions, which have been proven to be efficient for this reaction, are reported. Attention is focused on non-volatile redox oxides, as the quenching step required for volatile redox materials is unnecessary. Reactors that could be used to conduct the reduction and oxidation reaction are discussed. The most promising materials are compared to each other using a multi-criteria analysis, providing a direction for future research. As evident, ferrite supported on yttrium-stabilized zirconia, ceria doped with zirconia or samarium and ferrite doped with nickel as the core and an yttrium (III) oxide shell are promising choices. Isothermal cycling and lowering of the reduction temperature are outlined as future directions towards increasing hydrogen yields and improving the cyclability. [ABSTRACT FROM AUTHOR]

The tetraspanin CD9 is considered a metastasis suppressor in many cancers, however its role is highly debated. Currently, little is known about CD9 prognostic value in cutaneous melanoma. Our aim was to analyse CD9 expression in melanocytic nevi and primary cutaneous melanomas through immunohistochemistry and immunofluorescence approaches to determine its correlation with invasiveness and metastatic potential. CD9 displayed homogeneous staining in all melanocytic nevi. In contrast, it showed a complete loss of reactivity in all thin melanomas. Interestingly, CD9 was re-expressed in 46% of intermediate and thick melanomas in small tumor clusters predominantly located at sites of invasion near or inside the blood or lymphatic vessels. The most notable finding is that all CD9 stained melanomas presented sentinel node positivity. Additionally, a direct association between CD9 expression and presence of distant metastasis was reported. Finally, we confirm that CD9 expression is consistent with an early protective role against tumorigenesis, however, our data endorse in melanoma a specific function of CD9 in vascular dissemination during late tumor progression. The presence of CD9 hotspots could be essential for melanoma cell invasion in lymphatic and endothelial vessels. CD9 could be a valid prognostic factor for lymph node metastasis risk. [ABSTRACT FROM AUTHOR]

Skin is the widest and most accessible organ of the human body, and among its functions, the immunological one has been one of the most intriguing and investigated during the last 10 years; so, inflammatory and immune-mediated skin diseases (s-IMID) are considered as useful models to understand which physiopathological pathways are implicated in Th1, Th2, Th17, and Th22 inflammatory diseases. Furthermore, within each single category of disease attributable to s-IMID, each patient can be considered a "per-se" expression of disease, for disease phenotype, site of involvement, related symptoms, comorbidities, and ability to respond/tolerate to current treatments. Finally, the appearance of paradoxical skin reactions in patients with inflammatory skin diseases and undergoing molecular-targeted therapies, which can potentially complicate the patient's therapeutic process, represents an emerging clinical challenge. Basic research has increasingly clarified the complexity of the immunological mechanisms that guide the manifestations of inflammatory skin diseases including psoriasis (PsO), hidradenitis suppurativa (HS), vulvar lichen sclerosus (VLS), chronic lupus erythematosus (CLE), atopic dermatitis (AD), chronic spontaneous urticaria (CSU), and cutaneous systemic sclerosis (SSc). [Extracted from the article]

Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, clinicians have been overwhelmed by questions beyond the SARS-CoV-2 infection itself. In dermatology practice, clinicians have been facing difficulties concerning therapeutic management of chronic immune-mediated skin disease, above all psoriasis. Major challenges arisen were to understand the role of immunosuppression or immunomodulation on COVID-19 evolution, the benefit/risk ratio related to discontinuation or modification of ongoing treatment, and the appropriateness of initiating new treatments, the optimization of timing in vaccination administration to patients under immunomodulatory treatments, and finally how to find new strategy of patients' management through remote assistance. In this comprehensive review, we present the current evidence about the course and management of psoriasis during the COVID-19 pandemic. The general message from dermatologists was that data did not suggest that having PSO or its treatment significantly increased risk of SARS-CoV-2 infection or more severe COVID-19 course, the vaccination is highly recommended in all psoriatic patients, beyond ongoing treatment, and that the telehealth experience was a success overall. [ABSTRACT FROM AUTHOR]

The skin is constantly exposed to exogenous and endogenous sources of reactive oxygen species (ROS). An adequate balance between ROS levels and antioxidant defenses is necessary for the optimal cell and tissue functions, especially for the skin, since it must face additional ROS sources that do not affect other tissues, including UV radiation. Melanocytes are more exposed to oxidative stress than other cells, also due to the melanin production process, which itself contributes to generating ROS. There is an increasing amount of evidence that oxidative stress may play a role in many skin diseases, including melanoma, being the primary cause or being a cofactor that aggravates the primary condition. Indeed, oxidative stress is emerging as another major force involved in all the phases of melanoma development, not only in the arising of the malignancy but also in the progression toward the metastatic phenotype. Furthermore, oxidative stress seems to play a role also in chemoresistance and thus has become a target for therapy. In this review, we discuss the existing knowledge on oxidative stress in the skin, examining sources and defenses, giving particular consideration to melanocytes. Therefore, we focus on the significance of oxidative stress in melanoma, thus analyzing the possibility to exploit the induction of oxidative stress as a therapeutic strategy to improve the effectiveness of therapeutic management of melanoma. [ABSTRACT FROM AUTHOR]

Primary dermal melanoma (PDM) is a rare distinct variant of cutaneous melanoma, predominantly occurring on the extremities of young or middle-aged adults. In comparison to conventional melanoma, PDM is characterized by unexpectedly prolonged survival and long-term survival. Thus, correct identification of this variant is crucial to avoid potential misdiagnosis and establish correct treatment and follow-up. In addition, no consensus and specific guidelines exist on the management of this peculiar subtype of cutaneous melanoma. [ABSTRACT FROM AUTHOR]

The introduction of high-dose therapy in the 1990s as well as the development of drugs such as thalidomide, lenalidomide, and bortezomib in the 2000s led to an impressive improvement in outcome of patients with multiple myeloma (MM) eligible for autologous stem cell transplantation (ASCT). Clinical trials conducted in the first ten years of the twenty-first century established as standard therapy for these patients a therapeutic approach including induction, single or double ASCT, consolidation, and maintenance therapy. More recently, incorporating second-generation proteasome inhibitors carfilzomib and monoclonal antibody daratumumab into each phase of treatment significantly improved the efficacy of ASCT in terms of measurable residual disease (MRD) negativity, Progression Free Survival (PFS), and Overall Survival (OS). The availability of techniques such as multiparameter flow cytometry (MFC) and next-generation sequencing (NGS) for MRD assessment allowed the design of MRD-based response-adjusted trials that will define, in particular, the role of consolidation and maintenance therapies. In this review, we will provide an overview of the most recent evidence and the future prospects of ASCT in MM patients. [ABSTRACT FROM AUTHOR]

Immune-mediated inflammatory skin diseases are characterized by a complex multifactorial etiology, in which genetic and environmental factors interact both in genesis and development of the disease. Nutrition is a complex and fascinating scenario, whose pivotal role in induction, exacerbation, or amelioration of several human diseases has already been well documented. However, owing to the complexity of immune-mediated skin disease clinical course and breadth and variability of human nutrition, their correlation still remains an open debate in literature. It is therefore important for dermatologists to be aware about the scientific basis linking nutrition to inflammatory skin diseases such as psoriasis, atopic dermatitis, hidradenitis suppurativa, bullous diseases, vitiligo, and alopecia areata, and whether changes in diet can influence the clinical course of these diseases. The purpose of this narrative review is to address the role of nutrition in immune-mediated inflammatory skin diseases, in light of the most recent and validate knowledge on this topic. Moreover, whether specific dietary modifications could provide meaningful implementation in planning a therapeutic strategy for patients is evaluated, in accordance with regenerative medicine precepts, a healing-oriented medicine that considers the whole person, including all aspects of the lifestyle. [ABSTRACT FROM AUTHOR]

We investigated the efficacy of tigecycline and FS8, alone or combined, in preventing prosthesis biofilm in a rat model of staphylococcal vascular graft infection. Graft infections were established in the back subcutaneous tissue of adult male Wistar rats by implantation of Dacron prostheses followed by topical inoculation with 2 X 107 colony-forming units of Staphylococcus aureus, strain Smith diffuse. The study included a control group, a contaminated group that did not receive any antibiotic prophylaxis, and three contaminated groups that received: (i) intraperitoneal tigecycline, (ii) FS8-soaked graft, and (iii) tigecycline plus FS8-soaked graft, respectively. Each group included 15 animals. The infection burden was evaluated by using sonication and quantitative agar culture. Moreover, an in vitro binding-study was performed to quantify the how much FS8 was coated to the surface of the prosthesis. Tigecycline, combined with FS8, against the adherent bacteria showed MICs (2.00 mg/L) and MBCs (4.00 mg/L) four-fold lower with respect to tigecycline alone in in vitro studies. The rat groups treated with tigecycline showed the lowest bacterial numbers (4.4 X 104 ± 1.2 X 104 CFU/mL). The FS8-treated group showed a good activity and significant differences compared to control group with bacterial numbers of 6.8 X 104 ± 2.0 X 104 CFU/mL. A stronger inhibition of bacterial growth was observed in rats treated with a combined FS8 and tigecycline therapy than in those that were singly treated with bacterial numbers of 10¹ CFU/mL graft. In conclusion, the ability to affect biofilm formation as well, its property to be an antibiotic enhancer suggests FS8 as alternative or additional agent to use in conjunction with conventional antimicrobial for prevention of staphylococcal biofilm related infection. [ABSTRACT FROM AUTHOR]

Psoriasis is an immune-mediated inflammatory disease, with a chronic relapsing-remitting course, which affects 2–3% of the worldwide population. The progressive acquisitions of the inflammatory pathways involved in the development of psoriasis have led to the identification of the key molecules of the psoriatic inflammatory cascade. At the same time, psoriasis therapy has radically evolved with the introduction of target molecules able to modify the natural history of the disease, acting specifically on these inflammatory pathways. For these reasons, biologics have been demonstrated to be drugs able to change the disease's natural history, as they reduce the inflammatory background to avoid irreversible organ damage and prevent systemic complications. However, several issues related to the use of biologics in patients with systemic comorbidities, remain open. All these data reflect the extraordinary potentiality of biologics, but also the unmet medical need to improve our knowledge on the long-term risk related to continuous use of these drugs, and their administration in special populations. This narrative review aims to highlight both the efficacy and safety profile of biologics in psoriasis, starting from pathophysiology and moving towards their clinical application. [ABSTRACT FROM AUTHOR]

The head and neck tumors (HNT) are a heterogeneous group of diseases ranging from benign to malignant lesions, with distinctive molecular and clinical behaviors. Several studies have highlighted the presence of an altered metabolic phenotype in HNT, such as the upregulation of nicotinamide N-methyltransferase (NNMT). However, its biological effects have not been completely disclosed and the role of NNMT in cancer cell metabolism remains unclear. Therefore, this comprehensive review aims to evaluate the available literature regarding the biological, diagnostic, and prognostic role of NNMT in HNT. NNMT was shown to be significantly overexpressed in all of the evaluated HNT types. Moreover, its upregulation has been correlated with cancer cell migration and adverse clinical outcomes, such as high-pathological stage, lymph node metastasis, and locoregional recurrences. However, in oral squamous cell carcinoma (OSCC) these associations are still debated, and several studies have failed to demonstrate the prognostic significance of NNMT. The shRNA-mediated gene silencing efficiently suppressed the NNMT gene expression and exhibited a clear inhibitory effect on cell proliferation, promoting the expression of apoptosis-related proteins and modulating the cell cycle. NNMT could represent a new molecular biomarker and a new target of molecular-based therapy, although further studies on larger patient cohorts are needed to explore its biological role in HNT. [ABSTRACT FROM AUTHOR]

Among the most common complications of both chronic wound and surgical sites are staphylococcal skin infections, which slow down the wound healing process due to various virulence factors, including the ability to produce biofilms. Furthermore, staphylococcal skin infections are often caused by methicillin-resistant Staphylococcus aureus (MRSA) and become a therapeutic challenge. The aim of this narrative review is to collect the latest evidence on old and new anti-staphylococcal therapies, assessing their anti-biofilm properties and their effect on skin wound healing. We considered antibiotics, quorum sensing inhibitors, antimicrobial peptides, topical dressings, and antimicrobial photo-dynamic therapy. According to our review of the literature, targeting of biofilm is an important therapeutic choice in acute and chronic infected skin wounds both to overcome antibiotic resistance and to achieve better wound healing. [ABSTRACT FROM AUTHOR]

Background: Atopic dermatitis (AD) is an inflammatory skin disease characterized by a wide phenotypic variety with a very complex pathophysiological mechanism that has led to the identification of new therapeutic targets, such as janus kinasis (JAK) inhibitors. Objectives: To evaluate the efficacy and safety of baricitinib, the first JAK 1 and 2 inhibitor approved in Europe for the treatment of adult patients with moderate-to-severe AD. Methods: The efficacy and safety data available from the Phase III studies belonging to the BREEZE AD program are presented. Results: Results from BREEZE-AD1, AD2, AD4, and AD7 showed the efficacy of Baricitib 4 mg, administered orally, once daily, as monotherapy or in combination with topical corticosteroid (TCS), with a significant proportion of patients achieving primary endpoints IGA 0–1 (16.4% vs. 4.8%; 13.8% vs. 4.5%; 21.7% vs. 9.7%; 30.6% vs. 14.7%) and EASI75 (24.8% vs. 8.8%; 21.1% vs. 6.1%; 31.5% vs. 17.2%; 47.7% vs. 22.9%) at week 16 (W16) compared to placebo, respectively. Baricitinib showed rapid improvement in symptoms, starting from week 1 of treatment at 4 mg dosage, with a good safety profile. Nasopharyngitis, upper respiratory tract infections (URIs), creatine phosphokinase (CPK) elevations, and headache were the most frequently reported adverse events. Conclusions: Following the efficacy and safety data on W 16 from the phase III BREEZE-AD studies, baricitinib has recently been approved in Europe for the treatment of moderate to severe AD in adult patients. Further data to evaluate long-term efficacy and safety in a real-life setting are needed. [ABSTRACT FROM AUTHOR]

Background: LL-37 is the only human antimicrobial peptide that belongs to the cathelicidins. The aim of the study was to evaluate the efficacy of LL-37 in the management of MRSA-infected surgical wounds in mice. Methods: A wound on the back of adult male BALB/c mice was made and inoculated with Staphylococcus aureus. Two control groups were formed (uninfected and not treated, C0; infected and not treated, C1) and six contaminated groups were treated, respectively, with: teicoplanin, LL-37, given topically and /or systemically. Histological examination of VEGF expression and micro-vessel density, and bacterial cultures of wound tissues, were performed. Results: Histological examination of wounds in the group treated with topical and intraperitoneal LL-37 showed increased re-epithelialization, formation of the granulation tissue, collagen organization, and angiogenesis. Conclusions: Based on the mode of action, LL-37 has a potential future role in the management of infected wounds. [ABSTRACT FROM AUTHOR]

Simple Summary: Skin cancers (SC) are a frequent type of malignancy in white populations and include malignant melanoma and non-melanoma skin cancer. Due to their increasing incidence rate worldwide, aggressive behavior, and usually late diagnosis, they represent an important challenge for health care systems. Therefore, identifying new biomarkers suitable for diagnosis, as well as for prognosis and targeted therapy is mandatory. Nicotinamide N-methyltransferase (NNMT) is an enzyme that plays a key role in the progression of several malignancies. There is increasing evidence that NNMT is also involved in the malignant behavior of SC. Therefore, this review aims to summarize the current state of the art regarding NNMT role in SC and to support future studies focused on exploring the diagnostic and prognostic potential of NNMT in skin malignancies, as well as its suitability for targeted therapy. Skin cancers (SC) collectively represent the most common type of malignancy in white populations. SC includes two main forms: malignant melanoma and non-melanoma skin cancer (NMSC). NMSC includes different subtypes, namely, basal cell carcinoma (BCC), squamous cell carcinoma (SCC), Merkel cell carcinoma (MCC), and keratoacanthoma (KA), together with the two pre-neoplastic conditions Bowen disease (BD) and actinic keratosis (AK). Both malignant melanoma and NMSC are showing an increasing incidence rate worldwide, thus representing an important challenge for health care systems, also because, with some exceptions, SC are generally characterized by an aggressive behavior and are often diagnosed late. Thus, identifying new biomarkers suitable for diagnosis, as well as for prognosis and targeted therapy is mandatory. Nicotinamide N-methyltransferase (NNMT) is an enzyme that is emerging as a crucial player in the progression of several malignancies, while its substrate, nicotinamide, is known to exert chemopreventive effects. Since there is increasing evidence regarding the involvement of this enzyme in the malignant behavior of SC, the current review aims to summarize the state of the art as concerns NNMT role in SC and to support future studies focused on exploring the diagnostic and prognostic potential of NNMT in skin malignancies and its suitability for targeted therapy. [ABSTRACT FROM AUTHOR]

Background: Ceftaroline represents a novel fifth-generation cephalosporin to treat infections caused by methicillin-resistant Staphylococcus aureus (MRSA). Methods: Ceftaroline susceptibility of 239 MRSA isolates was assessed by disk diffusion and a MIC test strip following both EUCAST and CLSI guidelines. Non-susceptible isolates were epidemiologically characterized by pulsed-field gel electrophoresis, spa typing, and multilocus sequence typing, and further investigated by PCR and whole genome sequencing to detect penicillin-binding protein (PBP) mutations as well as antibiotic resistance and virulence genes. Results: Fourteen isolates out of two hundred and thirty-nine (5.8%) were non-susceptible to ceftaroline (MIC > 1 mg/L), with differences between the EUCAST and CLSI interpretations. The characterized isolates belonged to seven different pulsotypes and three different clones (ST228/CC5-t041-SCCmecI, ST22/CC22-t18014-SCCmecIV, and ST22/CC22-t022-SCCmecIV), confirming a clonal diffusion of ceftaroline non-susceptible strains. Mutations in PBPs involved PBP2a for ST228-t041-SCCmecI strains and all the other PBPs for ST22-t18014-SCCmecIV and ST22-t022-SCCmecIV clones. All isolates harbored antibiotic resistance and virulence genes with a clonal distribution. Conclusion: Our study demonstrated that ceftaroline non-susceptibile isolates belonged not only to ST228 strains (the most widespread clone in Italy) but also to ST22, confirming the increasing role of these clones in hospital infections. [ABSTRACT FROM AUTHOR]

Saliva is easy to access, non-invasive and a useful source of information useful for the diagnosis of serval inflammatory and immune-mediated diseases. Following the advent of genomic technologies and -omic research, studies based on saliva testing have rapidly increased and human salivary proteome has been partially characterized. As a proteomic protocol to analyze the whole saliva proteome is not currently available, the most common aim of the proteomic analysis is to discriminate between physiological and pathological conditions. The salivary proteome has been initially investigated in several diseases: oral squamous cell carcinoma and oral leukoplakia, chronic graft-versus-host disease, and Sjögren's syndrome. Otherwise, salivary proteomics studies in the dermatological field are still in the initial phase, thus the aim of this review is to collect the best research evidence on the role of saliva proteomics analysis in immune-mediated skin diseases to understand the direction of research in this field. The results of PRISMA analysis reported herein suggest that human saliva analysis could provide significant data for the diagnosis and prognosis of several immune-mediated and inflammatory skin diseases in the next future. [ABSTRACT FROM AUTHOR]

Background: previous studies reported the involvement of reactive oxygen species (ROS) and lipid peroxidation in the pathogenesis of inflammatory skin diseases. The aim of our study was to investigate the relationship between oxidative stress and inflammation in children affected by atopic dermatitis (AD), a chronic relapsing inflammatory skin disease. Methods: levels of lipid hydroperoxides, total antioxidant capacity, and activities of the enzymes myeloperoxidase (MPO), PON1, and PON2/3 were investigated in 56 atopic pediatric patients, and compared with 48 sex-/age-matched healthy controls. Results: significantly higher levels of lipid hydroperoxides and lower values of total antioxidant potential were observed in the serum of AD children compared to that of the controls. Significant lower PON1 activities, and a significant increase in levels of MPO were observed in serum of patients, with a higher serum MPO level/PON1 paraoxonase activity ratio in patients compared to that in the controls. Significantly lower lactonase activity of PON enzymes was observed in polymorphonuclear cells isolated from AD patients. Statistically negative correlation was established between the activity of intracellular PON2/3 activity and ROS levels. Conclusions: our data confirmed that AD is associated with higher oxidative damage and a decrease in antioxidant defense. Moreover, alterations of extracellular and intracellular PON activity can promote lipoprotein dysfunction in AD patients. [ABSTRACT FROM AUTHOR]

The BNT162b2 and mRNA-1273 vaccines, consisting of mRNA, have recently become available. The absolute novelty of these vaccines introduces questions about their safety and efficacy, especially in patients who are treated with biological drugs in dermatology. The aim of our review was to provide a broad overview of the current use of all available vaccinations in concomitance with biological therapy and to suggest indications for the new mRNA Covid-19 vaccines. We conducted a narrative review of the literature regarding the indications and safety of the various types of vaccines currently available in dermatological patients treated with biological therapy. The safety and efficacy of administering inactivated vaccines in patients undergoing biological therapy with inhibitors of TNF-α, IL-17, IL-12/23, and IL-4/13 was confirmed. Inactivated vaccines can be administered during therapy with inhibitors of IL-23 and IgE, taking into account that the level of evidence is lower due to the lack of specific studies. Live attenuated vaccines were contraindicated in concomitance with all biological therapies considered, except omalizumab. According to this evidence, we assume that there are currently no contraindications to the administration of the new Covid-19 BNT162b2 and mRNA-1273 vaccines during biological therapy with inhibitors of TNF-α, IL-17, IL-12/23, IL-23, and IL-4/13, since these vaccines are comparable to inactivated ones. For patients with chronic urticaria or allergic asthma treated with omalizumab, we currently recommend caution in using the mRNA Covid-19 vaccines (30 min observation). The only contraindications were a previous history of hypersensitivity to the Covid-19 vaccines themself or to their excipients. In conclusion, further randomized clinical trials are needed to evaluate the efficacy of the antibody response in these patients. [ABSTRACT FROM AUTHOR]