Hymenoptera venom immunotherapy: Safety and efficacy of an accelerated induction regimen with depot aluminum adsorbed extracts.

Introduction: Hymenoptera venom immunotherapy (VIT) is the only therapy that protects patients with Hymenoptera venom allergy by preventing systemic reactions after a new sting. Various extracts for VIT are available and used. VIT administration consists of an induction phase and a maintenance phase. Depot preparations of Hymenoptera VIT extracts are typically used for cluster and conventional protocols, and the maintenance phase. Many patients with Hymenoptera allergy need to achieve tolerance quickly because of the high risk of re-sting and possible anaphylaxis. Objective: Our study aimed to show the safety and efficacy of an accelerated regimen with depot preparations on aluminum hydroxide by using relatively high starting doses in a heterogeneous group of patients. Methods: The research focused on a group of patients with a history of severe systemic reactions to Hymenoptera stings, with the necessity of swift immunization due to high occupational risks. Aluminum hydroxide depot extracts either of Vepula species or Apis mellifera extracts were used. Results: The induction protocol was started with the highest concentration of depot venom extract of 100,000 standard quality unit and was well tolerated by 19 of 20 patients. Onne patient presented with a mild systemic reaction during the accelerated induction schedule, which was promptly treated with intravenous steroids and intramuscular H1 antihistamine; when switched to a conventional induction protocol, he had a similar reaction but finally reached maintenance with an H1-antagonist premedication. Conclusion: If validated, the accelerated induction protocol by using depot aluminum adsorbed extracts with the highest concentration of venom from the beginning could offer a streamlined and accessible treatment modality for patients diagnosed with anaphylaxis from bee and wasp venoms in need of rapid desensitization.

Vitamin C Supplementation in the Treatment of Autoimmune and Onco-Hematological Diseases: From Prophylaxis to Adjuvant Therapy.

Vitamin C is a water-soluble vitamin introduced through the diet with anti-inflammatory, immunoregulatory, and antioxidant activities. Today, this vitamin is integrated into the treatment of many inflammatory pathologies. However, there is increasing evidence of possible use in treating autoimmune and neoplastic diseases. We reviewed the literature to delve deeper into the rationale for using vitamin C in treating this type of pathology. There is much evidence in the literature regarding the beneficial effects of vitamin C supplementation for treating autoimmune diseases such as Systemic Lupus Erythematosus (SLE) and Rheumatoid Arthritis (RA) and neoplasms, particularly hematological neoplastic diseases. Vitamin C integration regulates the cytokines microenvironment, modulates immune response to autoantigens and cancer cells, and regulates oxidative stress. Moreover, integration therapy has an enhanced effect on chemotherapies, ionizing radiation, and target therapy used in treating hematological neoplasm. In the future, integrative therapy will have an increasingly important role in preventing pathologies and as an adjuvant to standard treatments.

Pomegranate (Punica granatum L.) Extract Effects on Inflammaging.

Pomegranate is a notable source of nutrients, containing a considerable proportion of organic acids, polysaccharides, vitamins, fatty acids, and polyphenols such as flavonoids, phenolic acids, and tannins. It is also rich in nutritionally important minerals and chemical elements such as K, P, Na, Ca, Mg, and N. The presence of several bioactive compounds and metabolites in pomegranate has led to its incorporation into the functional food category, where it is used for its numerous therapeutic properties. Pomegranate's bioactive compounds have shown antioxidant, anti-inflammatory, and anticancer effects. Aging is a process characterized by the chronic accumulation of damages, progressively compromising cells, tissues, and organs over time. Inflammaging is a chronic, subclinical, low-grade inflammation that occurs during the aging process and is linked to many age-related diseases. This review aims to summarize and discuss the evidence of the benefits of pomegranate extract and its compounds to slow the aging processes by intervening in the mechanisms underlying inflammaging. These studies mainly concern neurodegenerative and skin diseases, while studies in other fields of application need to be more practical. Furthermore, no human studies have demonstrated the anti-inflammaging effects of pomegranate. In the future, supplementation with pomegranate extracts, polyphenols, or urolithins could represent a valuable low-risk complementary therapy for patients with difficult-to-manage diseases, as well as a valid therapeutic alternative for the topical or systemic treatment of skin pathologies.

Alarmins and MicroRNAs, a New Axis in the Genesis of Respiratory Diseases: Possible Therapeutic Implications.

It is well ascertained that airway inflammation has a key role in the genesis of numerous respiratory pathologies, including asthma, chronic obstructive pulmonary disease, and acute respiratory distress syndrome. Pulmonary tissue inflammation and anti-inflammatory responses implicate an intricate relationship between local and infiltrating immune cells and structural pulmonary cells. Alarmins are endogenic proteins discharged after cell injury in the extracellular microenvironment. The purpose of our review is to highlight the alterations in respiratory diseases involving some alarmins, such as high mobility group box 1 (HMGB1) and interleukin (IL)-33, and their inter-relationships and relationships with genetic non-coding material, such as microRNAs. The role played by these alarmins in some pathophysiological processes confirms the existence of an axis composed of HMGB1 and IL-33. These alarmins have been implicated in ferroptosis, the onset of type 2 inflammation and airway alterations. Moreover, both factors can act on non-coding genetic material capable of modifying respiratory function. Finally, we present an outline of alarmins and RNA-based therapeutics that have been proposed to treat respiratory pathologies.

Antituberculosis drug-induced non-blistering systemic severe reactions: A 10-year (2012-2022) literature review.

Drug reaction with eosinophilia and systemic symptoms (DRESS) and drug-induced liver injury (DILI) can hamper therapeutic strategy, contribute to multiple drug resistance and serious public health burden. Diagnosis (including allergy assessment) and management of these two severe hypersensitivity reactions in clinical practice are somewhat difficult and published scientific evidence is rather weak and limited. The first step is always represented by stopping all anti-tuberculosis (TB) drugs, treating reaction with systemic corticosteroids, and identifying the offending drug, even if it is often complicated by the patient's simultaneous intake of antibiotics. Patch tests and in vitro tests, such as lymphocyte transformation test, could bridge this diagnostic gap, but the available data are scarce and their sensitivity low. The re-challenge test is often necessary but places patients at risk for serious adverse reactions. The desensitization protocols are quite varied and not universally accepted. In this narrative review, we provide an update to the literature data on the management of DRESS and DILI with particular attention to the allergological work-up in the last decade.

IL-33 and the Cytokine Storm in COVID-19: From a Potential Immunological Relationship towards Precision Medicine.

Coronavirus SARS-CoV-2 has represented, and still represents, a real challenge from a clinical, diagnostic and therapeutic point of view. During acute infection, the increased levels of pro-inflammatory cytokines, which are involved in the pathology of disease and the development of SARS-CoV-2-induced acute respiratory disease syndrome, the life-threatening form of this infection, are correlated with patient survival and disease severity. IL-33, a key cytokine involved in both innate and adaptive immune responses in mucosal organs, can increase airway inflammation, mucus secretion and Th2 cytokine synthesis in the lungs, following respiratory infections. Similar to cases of exposure to known respiratory virus infections, exposure to SARS-CoV-2 induces the expression of IL-33, correlating with T-cell activation and lung disease severity. In this work, we analyse current evidence regarding the immunological role of IL-33 in patients affected by COVID-19, to evaluate not only the clinical impact correlated to its production but also to identify possible future immunological therapies that can block the most expressed inflammatory molecules, preventing worsening of the disease and saving patient lives.

A spotlight on lime: a review about adverse reactions and clinical manifestations due to Citrus aurantiifolia.

Lime (Citrus aurantiifolia) is a plant belonging to the family of Rutaceae and to the genus Citrus. The fruit is widely used in the United States, Mexico, Southeast Asia, Latin America, but is increasingly widespread all over the world. It is used as a fresh fruit, in the preparation of foods, sweets and drinks and its oils are used in the cosmetic and pharmaceutical industry. The main adverse reactions to lime seem to be represented by contact dermatitis, allergic and phototoxic type. In the context of allergic forms, several allergens have been identified in the citrus family, the main one being limonene, but no noteworthy cross-reactivity has been identified. However, a case of fruit protein contact dermatitis has been described, showing sensitization to other fruits, such as kiwi, avocado, pineapple and apple. There are several molecules responsible for phototoxic reactions and mainly belonging to the coumarin and furocoumarins families. Reactions related to ingesting the fruit or inhaling pollen from the tree appear to be rare, as there are no known cases reported in the literature. The increasing diffusion of lime in Europe must pay attention to possible adverse reactions due to contact with this fruit, which seem destined to increase in future years. Further importance must be placed on patch tests and on the possibility of using alternative extracts to classic fragrance mixes.

Asian herbal medicine and chronic urticaria: which are the therapeutic perspectives?

Chronic urticaria (CU) is a pathologic condition marked by the emergence of wheals, angioedema, or both for more than six weeks. The improper activation and degranulation of mast cells is the triggering event, which results in the production of various mediators such as histamine, leukotrienes, PAF, chemokines, and cytokines. Antihistamines are currently the most common pharmacological treatment for urticaria, but corticosteroids and monoclonal antibodies can also be employed. Patients who have been taking antihistamines for a long time are often looking for alternatives. Whole plants, portions of plants, or single extracted active compounds are all used in phytomedicine. Plant elements are frequently combined to create formulations that can be utilized to treat a variety of pathological disorders. Anti-inflammatory and/or anti-allergic properties are found in several herbs regularly used in herbal formulations. Antioxidant properties are also present in some of the constituents. Exogenous antioxidants have been shown to improve the progression of autoimmune disorders in numerous studies. The aim of this review is to identify the most common herbs used to treat chronic urticaria, and to characterize their efficacy, mechanisms of action, and risk/benefit ratio in comparison to western treatment, and also to find less often used formulations and assess their therapeutic efficacy, safety profile, and potential for wider use.[Figure: see text].

Machine learning application in autoimmune diseases: State of art and future prospectives.

Autoimmune diseases are a group of disorders resulting from an alteration of immune tolerance, characterized by the formation of autoantibodies and the consequent development of heterogeneous clinical manifestations. Diagnosing autoimmune diseases is often complicated, and the available prognostic tools are limited. Machine learning allows us to analyze large amounts of data and carry out complex calculations quickly and with minimal effort. In this work, we examine the literature focusing on the use of machine learning in the field of the main systemic (systemic lupus erythematosus and rheumatoid arthritis) and organ-specific autoimmune diseases (type 1 diabetes mellitus, autoimmune thyroid, gastrointestinal, and skin diseases). From our analysis, interesting applications of machine learning emerged for developing algorithms useful in the early diagnosis of disease or prognostic models (risk of complications, therapeutic response). Subsequent studies and the creation of increasingly rich databases to be supplied to the algorithms will eventually guide the clinician in the diagnosis, allowing intervention when the pathology is still in an early stage and immediately directing towards a correct therapeutic approach.

The Emerging Role of Innate Lymphoid Cells (ILCs) and Alarmins in Celiac Disease: An Update on Pathophysiological Insights, Potential Use as Disease Biomarkers, and Therapeutic Implications.

Celiac disease (CD) is an intestinal disease that develops in genetically predisposed individuals and is triggered by the ingestion of gluten. CD was considered a Th1-disease. Today, the role of Th17, IL-21, and IL-17A lymphocytes is well known. Inflammation is regulated by the activity of gluten-specific CD4+ T lymphocytes that produce pro-inflammatory cytokines, including IFN-γ, TNF-α, and IL-21, perpetuating the Th1 response. These cytokines determine an inflammatory state of the small intestine, with consequent epithelial infiltration of lymphocytes and an alteration of the architecture of the duodenal mucosa. B cells produce antibodies against tissue transglutaminase and against deamidated gliadin. Although the role of the adaptive immune response is currently known, the evidence about the role of innate immunity cells is still poorly understood. Epithelial damage determines the release of damage-associated molecular patterns (DAMPs), also known as alarmins. Together with the intestinal epithelial cells and the type 1 innate lymphoid cells (ILC1s), alarmins like TSLP, IL-33, and HMGB1 could have a fundamental role in the genesis and maintenance of inflammation. Our study aims to evaluate the evidence in the literature about the role of ILCs and alarmins in celiac disease, evaluating the possible future diagnostic and therapeutic implications.

Emerging Role of Alarmins in Food Allergy: An Update on Pathophysiological Insights, Potential Use as Disease Biomarkers, and Therapeutic Implications.

Food allergies are immuno-mediated adverse reactions to ingestion or contact with foods, representing a widespread health problem. The immune response can be IgE-mediated, non-IgE-mediated, or with a mixed mechanism. The role of innate immunity and alarmins in the pathogenesis of diseases such as asthma and atopic dermatitis is well known. Some authors have investigated the correlation between alarmins and food allergies, often obtaining interesting results. We analyzed articles published in English from the last 22 years present on PubMed concerning the role of alarmins in the pathogenesis of food allergies and their potential use as disease biomarkers, response biomarkers to therapy, or potential therapeutic targets. Nuclear alarmins (TSLP, IL-33, IL-25) appear to have a critical role in IgE-mediated allergies but are also implicated in entities such as eosinophilic esophagitis. Calprotectin and defensins may play a role as disease biomarkers and could help predict response to therapy, although results in the literature are often conflicting. Despite the promising results, more studies on humans still need to be conducted. Deepening our knowledge regarding alarmins and their involvement in food allergies could lead to the development of new biological therapies, significantly impacting patients' quality of life.

Therapeutic Strategies to Prevent the Recurrence of Nasal Polyps after Surgical Treatment: An Update and In Vitro Study on Growth Inhibition of Fibroblasts.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is the most bothersome phenotype of chronic rhinosinusitis, which is typically characterized by a Type 2 inflammatory reaction, comorbidities and high rates of nasal polyp recurrence, causing severe impact on quality of life. Nasal polyp recurrence rates, defined as the number of patients undergoing revision endoscopic sinus surgery, are 20% within a 5 year period after surgery. The cornerstone of CRSwNP management consists of anti-inflammatory treatment with local corticosteroids. We performed a literature review regarding the therapeutic strategies used to prevent nasal polyp recurrence after surgical treatment. Finally, we report an in vitro study evaluating the efficacy of lysine-acetylsalicylic acid and other non-steroidal anti-inflammatory drugs (ketoprofen and diclofenac) on the proliferation of fibroblasts, obtained from nasal polyp tissue samples. Our study demonstrates that diclofenac, even more so than lysine-acetylsalicylic acid, significantly inhibits fibroblast proliferation and could be considered a valid therapeutic strategy in preventing CRSwNP recurrence.