Mario Di Gioacchino

The widespread use of proton pump inhibitors (PPIs) in clinical practice has increased the number of related hypersensitivity reactions (HSRs). The active ingredient is not always responsible for the reaction. In some cases, HSRs may be related to the excipients contained in the drug. The adverse reactions to anti-SARS-CoV-2 vaccines have drawn the scientific community’s attention to the potential roles of excipients such as polyethylene glycol (PEG) and polysorbate 80. We present a case of a patient with three anaphylactic reactions following the administration of the anti-SARS-CoV-2 vaccine and a history of HSR to omeprazole. Through an in-depth medical history and allergy testing, we found that the patient was sensitized to PEG contained in the vaccine and to the omeprazole formulation used. We also conducted a mini-review of the literature, reporting all cases of reactions to PPIs, both related to the active ingredient and to excipients. Adverse reactions to PPIs are rare but still increasing. To our knowledge, this is the first reported case of anaphylaxis to PPI-related PEG. Some excipients are widely used in commonly used products, including non-pharmaceuticals. Therefore, in patients with multiple episodes of anaphylaxis, it appears necessary to exclude a possible allergy to excipients. This could ensure a greater safety and a better quality of life.

This review describes the eosinophil journey through the various physiological and pathophysiological phases, from production, maturation, and activation by chemokines and cytokines [especially eotaxin, interleukin (IL)-5, IL-3, and granulocyte-macrophage colony-stimulating factor (GM-CSF)], to interaction with the innate and adaptive immune system and tissue homing. Excessive production and activation of eosinophils lead to the release of granule proteins, such as major basic protein, eosinophil cationic protein, eosinophil peroxidase, and others, resulting in inflammation, cell cytotoxicity, and oxidative stress. The pathogenesis, clinical features, diagnostic processes, and the latest therapeutic approaches to the resulting diseases—which affect the upper and lower airways, gastrointestinal tract, skin, myocardium, and may occur systemically—are discussed.

Guidelines provide specific recommendations based on the best available medical knowledge, summarizing and balancing the advantages and disadvantages of various diagnostic and treatment options. Currently, consensus methods are the best and most common practices in creating clinical guidelines, even though these approaches have several limitations. However, the rapid pace of biomedical innovation and the growing availability of real-world data (RWD) from clinical registries (containing data like clinical outcomes, treatment variables, imaging, and laboratory results) call for a complementary paradigm in which recommendations are continuously stress-tested against high-quality, interoperable data and auditable artificial intelligence (AI) pipelines. AI, based on information retrieved from patient registries, can optimize the process of creating guidelines. In fact, AI can analyze large volumes of data, ensuring essential tasks such as correct feature identification, prediction, classification, and pattern recognition of all information. In this work, we propose a four-phase lifecycle, comprising data curation, causal analysis and estimation, objective validation, and real-time updates, complemented by governance and machine learning operations (MLOps). A comparative analysis with consensus-only methods, a pilot protocol, and a compliance checklist are provided. We believe that the use of AI will be a valuable support in drafting clinical guidelines to complement expert consensus and ensure continuous updates to standards, providing a higher level of evidence. The integration of AI with high-quality patient registries has the potential to substantially modernize guideline development, enabling continuously updated, data-driven recommendations.

Innate lymphoid cells are lymphocytes that are neither T cells nor B cells. They are relatively rare in lymphoid tissues and peripheral blood and are distinguished by their absence of an adaptive antigen receptor. In the present study, we describe the mechanisms underlying the generation of the various cell populations and highlight the functional importance of their plasticity. These cells are indeed capable of transdifferentiating from one type to another. This adds complexity to their functional program, and this feature appears to be crucial for adapting and modulating immune responses under different conditions. These lymphoid cells are of great hematological interest due to their pathophysiological and therapeutic role in many onco-hematological pathologies such as acute myeloid leukemia, multiple myeloma, and several types of lymphomas. In hematological disorders, innate lymphoid cells may exert differential effects on the pathogenesis of hematologic malignancies. Furthermore, within the same disease, certain cell populations have been shown to play a protective role in antitumor immune responses, whereas others appear to suppress these responses. This review aims to provide an integrated description of innate lymphoid cells, their alterations in hematological malignancies, and potential preventive strategies, by proposing new specific targets for correcting anomalies. We also discuss the use of innate lymphoid cells as new therapies by applying chimeric antigen receptor-modified natural killer cells. We examine the current knowledge and outline future perspectives.

Key points Allergen immunotherapy (AIT) is a disease-modifying treatment with long-term effects that persist after its discontinuation.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease that affects multiple organs and systems with a broad and heterogeneous spectrum of clinical manifestations. National disease-specific datasets and registries are crucial for clinical research since they can provide real-world and long-term data about clinical aspects, biomarkers, and treatments. Registries collect data from actual patients over time, outside the controlled environment of randomized controlled trials. This can help enhance the understanding of the natural history of a disease, provide information about how treatments work in everyday settings and elucidate potential variations in care and outcomes across different geographic areas. Here, we present a protocol for the creation of a standardized national disease-specific dataset for patients with SLE—the Systemic Lupus Erythematous Network (LUNET) Registry—which will facilitate data sharing, cross-comparison, and interoperability among centers. The LUNET registry is intended to serve as a comprehensive primary data source, capturing real-world longitudinal clinical information and the heterogeneity of patient presentations that are often underrepresented in traditional clinical trials. Ultimately, the LUNET registry will help to optimize SLE management in routine clinical practice by enabling the compilation of real-world evidence to inform clinical decision-making and health policy.

Lipid peroxidation (LPO) is a biochemical process through which lipids are subjected to a peroxidation reaction in the presence of free radicals. The process can cause alterations in biological membranes and the formation of substances harmful to the body that can form aggregates with proteins and nucleic acids. Malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) are the main products of LPO. These compounds have cytotoxic and genotoxic properties and contribute to the pathogenesis of various diseases. This research focuses on the correlation between LPO and skin diseases. For some skin diseases, such as psoriasis, vitiligo, and alopecia, LPO products have been shown to have a clear role in the pathogenesis of the disease. Lipid aldehydic products like MDA and 4-HNE can enhance inflammation by stimulating pro-inflammatory genes and producing cytokines. Furthermore, these products can stimulate cell death and increase oxidative stress. For other diseases (atopic dermatitis, urticaria, pemphigus, and melanoma), the role of LPO is unclear, even if the levels of LPO biomarkers are elevated in proportion to the severity of the disease. LPO can also be exploited to counteract the proliferation of neoplastic cells. Therefore, enhancing LPO would play an adjuvant role in the therapy of neoplastic diseases such as melanoma. In particular, the therapeutic implication resulting from the role of LPO products in the cytotoxicity induced by photodynamic therapy used for the adjuvant treatment of melanoma could be of interest in the future.

Inter-kingdom communication between human microbiota and mast cells (MCs), as sentinels of innate immunity, is crucial in determining health and disease. This complex signaling hub involves micro-organisms and, more importantly, their metabolic products. Gut microbiota is the host’s largest symbiotic ecosystem and, under physiological conditions, it plays a vital role in mediating MCs tolerogenic priming, thus ensuring immune homeostasis across organs. Conversely, intestinal dysbiosis of various etiologies promotes MC-oriented inflammation along major body axes, including gut-skin, gut-lung, gut-liver, and gut-brain. This review of international scientific literature provides a comprehensive overview of the cross-talk under investigation. This process is a key biological event involved in disease development across clinical fields, with significant prognostic and therapeutic implications for future research.

Allergic rhinitis (AR), traditionally considered as a childhood condition, is increasingly recognized among older adults, driven by rising life expectancy and environmental factors. Although allergic sensitization declines with age, AR prevalence in the elderly is underestimated, with 3–12% of geriatric patients affected. Diagnosis is challenging due to nonspecific symptoms and overlapping conditions, leading to underdiagnosis and inadequate treatment. AR significantly impacts the quality of life (QoL), often exacerbating respiratory comorbidities like asthma and COPD. Presbynasalis, encompassing age-related sinonasal changes, includes reduced allergic responses, increased chronic rhinosinusitis, altered nasal structure, and impaired mucociliary clearance. Non-allergic rhinitis, atrophic rhinitis, and overlapping rhinitis further complicate AR diagnosis in the elderly. Effective management involves personalized pharmacotherapy, allergen-specific immunotherapy (AIT), and addressing comorbidities and polypharmacy risks. Despite safety concerns, recent studies demonstrate AIT efficacy in elderly patients, reducing symptoms and medication use. Given AR’s impact on cognitive and respiratory health, accurate diagnosis and treatment can enhance QoL and mitigate health decline. Greater awareness and further research are essential to understand AR prevalence and improve outcomes for geriatric patients.