Clinical trials

The purpose of this non-interventional, observational study is to evaluate the clinical utility of circulating tumor DNA (ctDNA) utility-specifically how quickly tumor DNA disappears from the bloodstream (ctDNA clearance)-to help monitor and predict treatment responses in patients with breast cancer. The study focuses on patients diagnosed with Stage II to III HER2-positive or Triple-Negative Breast Cancer (TNBC) who are scheduled to receive standard neoadjuvant therapy (systemic treatment administered before surgery). Because these breast cancer subtypes involve different standard treatment regimens, the study prospectively stratifies patients into three distinct treatment cohorts (Cohorts A, B, and C) to match routine clinical practice and align blood sampling with meaningful clinical milestones.

Our study aims to investigate the safety and efficacy of high intensity focused ultrasound in the management of low back pain due to sacroiliitis. Sacroiliitis is the inflammation of a joint in the lowest part of the spin and it is one of the cause of low back; the diagnosis is essentially based on clinical examination and the confirmation of this diagnosis relies on a significant pain relief following an infiltration of local anesthetic in the joint. One of the potential treatment is to ablate the nerves which carry the painful stimuli from the joint to the central nervous system through; these nerves enter the spinal canal through the sacral foramina which are two series of four pairs of openings located on the sacrum, the triangular bone at the base of the spine. Traditionally, these nerves are ablated by the heat produced by radiofrequency or the cold produced by cryoablation; both techniques require percutaneous needle insertion in close proximity to the targeted nerves, posing potential discomfort and risk of infection for the patient. High intensity focused ultrasound delivered by the device Neurolyser XR uses ultrasounds which are converged to the targeted point thanks to a gel pad positioned on the back of the patient; this mechanism of action does not require sterile conditions as the skin is not pierced and the discomfort of patient is dramatically reduced during the procedure for there is non need to insert and move any needle to properly position it. The correct orientation of the ultrasound beam is guaranteed by the alignment of the targeting system of the device and the X-ray image. The lesion is produced only if there is a bone right under the focus of the ultrasound beam and this is a safety system which assures that no direct injuries of other structures (e.g., vessels, spinal root) can be caused. To date, Neurolyser XR has been extensively used to treat facet joint syndrome through the ablation of the medial branches. However, its application in sacroiliitis has not yet been as deeply investigated.

The aim of this observational study is to evaluate the impact of raw cornstarch supplementation on postprandial glycemic response in adult patients with Glycogen Storage Disease type I (GSD I), using continuous glucose monitoring (CGM) systems.GSD I is a rare inherited metabolic disorder characterized by impaired glucose homeostasis during fasting, leading to recurrent hypoglycemia and metabolic abnormalities. Nutritional therapy, based on frequent carbohydrate intake and raw cornstarch supplementation, represents the cornerstone of treatment. However, the optimal timing of raw cornstarch administration in relation to meals and its effect on postprandial glycemic control remain unclear.The main question this study aims to answer is: "Does raw cornstarch intake during meals affect postprandial glycemic response in adult patients with Glycogen Storage Disease type I?". Additional objectives include evaluating whether dose and timing of cornstarch intake influences glucose profile, glycemic variability, hypoglycemic events, body composition, energy expenditure, and lipid profile. Participants will include adults with genetically confirmed GSD Ia or Ib who routinely use CGM systems and regularly consume raw cornstarch as part of their dietary management. This is a real-life observational study, and participants will continue their routine clinical care without receiving additional experimental treatments. After providing informed consent, participants will undergo clinical, metabolic, and nutritional assessments, including: * anthropometric measurements; * body composition analysis by bioelectrical impedance; * indirect calorimetry for resting energy expenditure; * handgrip strength evaluation; * biochemical analyses, including fasting glucose, HbA1c, lipid profile, liver enzymes, creatinine, uric acid, and lactate. CGM-derived parameters collected during the 14 days preceding the visit will be analyzed, including Time in Range (TIR), Time Above Range (TAR), Time Below Range (TBR), coefficient of variation (CV%), Glucose Management Indicator (GMI), and frequency of hypoglycemic episodes. Participants will also complete a 7-day food diary reporting meal timing, food intake, and raw cornstarch consumption. Investigators will compare meals consumed with and without raw cornstarch supplementation and evaluate postprandial glycemic trends. Postprandial glycemic response will be assessed using dynamic indices, including glucose peak, nadir, time to peak, time to nadir, glucose excursion rates, and incremental area under the curve (iAUC). Glucose values will be analyzed every 5 minutes for up to 4 hours after meals using CGM data. Inclusion criteria include: genetically confirmed GSD Ia or Ib, age \>18 years, routine CGM use, and habitual raw cornstarch consumption.Exclusion criteria include psychiatric disorders, pregnancy, celiac disease, dialysis treatment, nocturnal enteral feeding, and severe acute or chronic illnesses. Approximately 8 adult patients are expected to be enrolled. Risks for participants are considered minimal, as all procedures are part of routine clinical follow-up. Potential benefits include improved personalization of nutritional therapy and optimization of carbohydrate and raw cornstarch administration, potentially improving glycemic control and reducing metabolic complications in patients with GSD I.

Background and Purpose: Deciding on the best treatment for HER2-negative metastatic breast cancer (MBC) is a complex process. Patients often have unique values and preferences regarding their care and quality of life. Shared Decision Making (SDM) is a communication process where doctors and patients work together to make healthcare choices. This study aims to evaluate whether providing specific SDM training to oncologists and educational materials to patients can improve the quality of these conversations and make the treatment process feel more focused on patient goals. Study Design and Procedures: This is a prospective, randomized multicenter study involving oncology centers in Italy. A total of 120 patients starting their first-line therapy for HER2-negative metastatic breast cancer will participate. Participants and their oncologists will be assigned to one of two main study arms: The SDM Trained Group: This group includes different approaches, such as formal SDM training for oncologists, providing educational materials (booklet and video) to patients, or a combination of both. The Usual Care Group: In this group, patients and oncologists follow standard care processes without specific SDM training or additional educational materials. What to Expect: Patients in all groups will be asked to complete standardized questionnaires (such as CollaboRATE, SURE, and SDM-Q-9) at two time points: on Day 1 after the first encounter with the oncologist and at a 6-month follow-up. These surveys will measure the patient's perception of the decision-making process, their satisfaction with the treatment choice, and their overall quality of life. Goal: The researchers hypothesize that educational training for patients and/or physicians will improve the quality of conversations about MBC therapy. If successful, this study may provide tools to enhance patient adherence to treatment and overall well-being.

CardioMET is an observational, multicenter, real-life registry, intending to collect data on patients with Type 2 Diabetes Mellitus, attending internal medicine and cardiology outpatient clinics. The aim of the registry is to characterize the cardiovascular risk profile and pharmacological management of Type 2 Diabetes Mellitus in Italy, in accordance with current ESC and AHA guidelines for primary and secondary prevention of CV disease.

This is a Phase IIb, multicentric, prospective, randomized (1:1 ratio), open label, and no profit study, with the aim of evaluating the efficacy of late INa current inhibition to improve coronary microcirculation in patients presenting with acute myocardial infarction and multivessel disease. All consecutive patients presenting with acute MI undergoing primary PCI (pPCI) on a major coronary artery, and with at least one remaining angiographically significant (% diameter stenosis \> 50%) non-culprit stenosis will be enrolled. The primary objective of the study is to evaluate the potential effect of Ranolazine in preserving coronary microcirculation subtended to the culprit vessel as compared with control group. Coronary microcirculation will be assessed both at the time of the culprit lesion revascularization and within 6+/-2 weeks by measuring the Index of Microcirculatory Resistance (IMR) either invasively or derived by the angiography (angioIMR). In addition, the following secondary endpoints will be assessed: 1. The prevalence of residual CMD downstream to the culprit vessel in all patients (CMDculprit). CMDculprit will be defined as the finding of an IMR/angioIMR value \> 25, assessed after successful pPCI. 2\. The prevalence of CMD downstream to the non-culprit vessel in the two group of patients (CMDnon-culprit). CMDnon-culprit will be defined as the finding of an IMRnon-culprit or an angioIMRnon-culprit value \> 25. IMRnon-culprit or angioIMRnon-culprit will be assessed at the time of staged PCI of the non-culprit stenosis. 3\. The incidence of peri-procedural CMD after staged PCI of the non-culprit stenoses, defined as a 20% increase of IMR values assessed before and after elective PCI of the non-culprit vessel (CMDprocedural). 4\. The difference between the two groups of patients, in terms of incidence of periprocedural Myocardial Infarction (PMI), eventually occurring during the staged procedure. 5\. The effects of INa current inhibition on endothelial function assessed at follow up as compared with control group. 6\. The extent of the Infarct Size, as assessed by the CMR, as compared with control group. 7\. The incidence of MACE, defined as composite of death, myocardial infarction, periprocedural MI, or any unplanned percutaneous coronary revascularization at short (42+/-7 days) term follow-up. 8\. Angina symptoms and quality of life

Proximal femoral fractures are associated with increased mortality in older adults and may contribute to loss of functional independence, resulting in a higher risk of long-term institutionalization. The SIOT 2021 guidelines emphasize that management of older patients with proximal femoral fracture (FPF) requires a multidisciplinary approach, ideally integrated across all phases of care, including rehabilitation and secondary prevention at the community level, according to a continuity-of-care model that incorporates the implementation of Fracture Liaison Services. Multiple clinical, social, and environmental factors influence fall risk. Falls are also associated with psychological consequences. Age-related reductions in muscle strength contribute to progressive functional decline, increased morbidity and mortality related to falls, reduced quality of life, depression, and hospitalization. Sarcopenia is characterized by both quantitative and qualitative reductions in muscle tissue, including progressive replacement of contractile tissue with fibrous and adipose tissue. The European Working Group on Sarcopenia in Older People (EWGSOP), in its updated consensus (EWGSOP2), identifies low muscle strength as the primary parameter of sarcopenia, accompanied by a significant and generalized reduction in muscle mass. A use-case model dedicated to patients with sarcopenia describes typical demographic and social characteristics, associated comorbidities, and specific care needs, with the aim of identifying the most appropriate management pathways. This study adopts a person-centered approach to design, validate, and implement an integrated strategy for fall prevention, taking into account the multiple determinants of fall risk and related adverse health outcomes.

Allergy prevalence is increasing steadily with some describing as the "epidemic of the twenty-first century". Maternal diet during pregnancy has been linked to offspring allergy risk, so it represents a potential target for allergy prevention. The Mediterranean Diet (MD) is considered one of the healthiest dietary models which exerts regulatory effects on immune system, due to the synergistic and interactive combinations of nutrients. We aim to study the effects of MD in pregnancy on the onset of allergic diseases at 2 years of age in the offspring.

Evaluation of adherence, persistence, and efficacy of treatment with Bempedoic acid in a real-life Italian population.

Evaluation of adherence, persistence and efficacy of treatment with alirocumab 300 mg in a real-life Italian population.

Evaluation of adherence, persistence and efficacy of treatment with Inclisiran in a real-life Italian population

Evaluation of adherence, persistence and efficacy of treatment with PCSK9 inhibitors in a real-life Italian population.

Autism spectrum disorders (ASD) are a group of severe neurodevelopmental conditions characterized by impaired communication and social interaction, as well as repetitive/stereotyped behaviors deriving from a combination of genetic and environmental factors. The ASD diagnosis rates increased dramatically over the past number of decades. The Diagnostic and Statistical Manual of Mental Disorders (DSM-5) describes a worldwide prevalence of approximately 1%. The prevalence of ASD is 1 in 59 individuals in the US reported by the Centers for Disease Control and Prevention. According to the latest data from the Italian National Observatory for ASD, the actual prevalence in Italy is about 1/77 for children aged between 7 and 9 years, with a 4.4 times higher prevalence in male. The origin of ASD is still largely undefined. It has been hypothesized a possible role for the influence of early life alteration of gut microbiome (GM). We demonstrated an imbalance in Bacteroidetes and Firmicutes phyla with a decrease in Bacteroidetes/Firmicutes ratio in the GM of pediatric patients affected by ASD. Similar data have been observed by others. Data from ASD animal model confirm the presence of GM dysbiosis with significant correlation with behavioral, gastrointestinal and immunologic alterations. Altogether these data support the hypothesis that GM dysbiosis could be involved in the ASD pathogenesis. The ASD children present an increased prevalence of functional gastrointestinal disorders (FGIDs), mainly chronic constipation, functional diarrhea, and irritable bowel syndrome (IBS). A role for GM has been suggested also for these conditions. The presence of these disorders negatively influence the disease severity and the parental quality of life of ASD children. Starting from all these considerations GM is becoming a possible target of intervention for pediatric ASD. Probiotics are one of the most investigated strategy for a beneficial modulation of GM. Probiotics are commonly defined as live microorganisms which when ingested in adequate amounts confer a beneficial effect on the host. The most used probiotics in the pediatric age are Saccharomyces and Lactobacillus strains including Lactobacillus rhamnosus GG (LGG). Data report a beneficial influence elicited by LGG on GM structure and function. This probiotic resulted also effective in treating FGIDs patients. Preliminary evidence suggest the potential efficacy of probiotics for FGIDs treatment in ASD children. Altogether these evidence strongly support the hypothesis that LGG could exert a beneficial action in ASD children. The purpose of this study is to evaluate the therapeutic efficacy of LGG on FGIDs in ASD children.

Type II diabetes mellitus (T2DM) is a chronic disease associated with a very high risk of developing cardiovascular (CV) events, especially because of its long-term effects. Glucagon-like-peptide-1 receptor agonists (GLP1-RAs) are recommended in subjects suffering from T2DM with a history or at risk for CV disease; however there is a lack of evidence on local actions of GLP1-RAs on inflammation and endothelial function. The STABLE-GLP1 study aims to evaluate, in patients with T2DM without atherosclerotic cardiovascular disease (ASCVD) or severe target-organ damage (TOD), the possible beneficial effect of semaglutide, a GLP1-AR, on clinical prognosis, inflammatory and endothelial biomarkers. The STABLE-GLP1 trial is a phase IV interventional, national, multicenter, randomized, pragmatic study, aiming at enrolling 80 patients with T2DM and no ASCVD. Participants will be randomized in 1:1 ratio to receive semaglutide in addition to standard therapy or standard therapy alone, according to body mass index (BMI) category (BMI \<30 vs. ≥30 kg/m²). All patients will perform clinical visit, ECG, echocardiography, blood sample collection for endothelial and inflammatory biomarkers dosage at baseline, at 26 weeks, and after 52 weeks of treatment. Data from CTA, performed according to clinical practice before enrollment, will be recorded and retrospectively evaluated to test secondary outcomes.

This retrospective study aims to evaluate the effectiveness and safety of Ropeginterferon Alfa-2b (BESREMI) in patients with Polycythemia Vera (PV). Eligible patients have a confirmed PV diagnosis according to current criteria, have received at least one dose of Ropeginterferon, and have complete clinical and laboratory data available. The primary objective is to analyze the time course of hematologic response (complete or partial, CHR/PR) according to ELN criteria, and to identify clinical and treatment-related factors associated with achieving and maintaining response. Secondary objectives include time to response, duration of response, progression-free survival, thromboembolic event rate, safety and tolerability, treatment discontinuation, dose modifications and adherence, normalization of hematologic parameters, and changes in JAK2 V617F allele burden. Data will be collected retrospectively from medical records at participating centers.

This prospective randomized study aims to evaluate whether the application of an intrauterine anti-adhesion gel reduces the incidence of intrauterine adhesions (IUAs) following robotic-assisted laparoscopic myomectomy. Intrauterine adhesions may develop after endometrial trauma during surgery and can negatively affect menstrual function, fertility, and future pregnancy outcomes. Robotic myomectomy offers a minimally invasive approach, but postoperative adhesion formation remains a concern. Sixty-two women undergoing myomectomy will be randomized to receive either intrauterine anti-adhesion gel (intervention group) or no adhesion-prevention method (control group). Adhesions will be assessed by ultrasound and hysteroscopy during follow-up. Secondary outcomes include reproductive results over a 24-month period, such as implantation rate, clinical pregnancy, miscarriage, live birth, pregnancy complications, and neonatal outcomes. The study seeks to determine whether combining a minimally invasive surgical approach with an intrauterine gel provides additional protection against adhesion formation and improves fertility-related outcomes.

The aim this prospective observational study is to evaluate the role of Indocyanine Green Fluorescence (ICG) in patients with achalasia underwent to Heller-Dor laparoscopic. The main gol are: * If with use of ICG iatrogenic mucosal leaks can be identified and, if necessary, improve the myotomy. * Assess the need for postoperative radiographic control using esophagogastric radiography with gastrografin. * Compare clinical characteristics, perioperative outcomes, and 12-month postoperative follow-up between the two populations.

The goal of this observational study is to explore inter- and intra-individual determinants of postprandial glucose response in patients with type 1 diabetes using continous glucose monitoring (CGM). Blood samples and anthropometrics will be collected during hospital visit. Participants will be asked to: * record a seven-day food diary * complete EPIC food frequency questionnaire * complete questionnaires on sleep hygiene * collect a stool sample

This is a controlled, open study designed to compare the effects of dual-release hydrocortisone preparations versus conventional glucocorticoid therapy on clinical, anthropometric parameters, metabolic syndrome, hormonal profile, bone status, quality of life, reproductive, sexual and psychological functions and treatment compliance in patients affected by congenital adrenal hyperplasia due to 21 OH deficiency.

Considering the compelling amount of studies focused on patients in the active phase of COVID-19 disease and the scarcity of studies focused on patient cured from disease aimed at evaluating the sequelae of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, the purpose of the study is to investigate, in patients recovered from COVID-19 disease: 1) whether SARS-CoV-2 infection has induced in male patients, a primary (testicular) and / or secondary (pituitary) damage to the hypothalamic-pituitary-testicular hormonal axis, structural and / or functional damage to the testis and penis, sexual dysfunction or fertility disorders; 2) the prevalence in male and female patients of chemosensory symptoms (olfactory dysfunction) and assess whether there is a correlation between the prevalence, severity, duration and eventual persistence of olfactory dysfunction and the severity of COVID-19 disease. Patients will be evaluated at baseline (at discharge from infectious and/or pneumology unit) and after 3- 12 months. A better definition of the prevalence and type of sequelae after recovery from COVID-19 disease could significantly improve the therapeutic management and long-term follow-up of these patients, with a relevant impact in terms of health resources and public health.

Obesity is a life-threatening disease, defined by excessive fat accumulation that increases the risk of other diseases such as cardiovascular events, hypertension, diabetes and cancer. Obesity is also a risk factor for nosocomial infections and is associated with worse COVID-19 outcomes, although anthropometric measurements are not routinely recorded during hospitalization and lack of a registry data does not allow performing retrospective studies.Obesity is closely related to chronodisruption, characterized by deregulation of physiological and behavioral central and peripheral circadian rhythms contributing to the obesity-related metabolic impairment. Eating and sleeping time schedules are relevant synchronizers of humans' biological clock. Several studies suggest a role of dietary interventions in rewiring the circadian rhythm, with Mediterranean diet (MD) regulating nutritional patterns. Moreover, considering its positive impact on sleep quality, melatonin intake was suggested as a potential regulator of circadian rhythms. The relation between chronodisruption, obesity and infections has not been investigated, and a first proof of concept (Pilot study) will aim at investigating it. Three cohorts of obese patients with different aetiology (essential obesity, obesity with type 2 diabetes, genetic forms of obesity) and a cohort of lipodystrophic patients will be enrolled in the study, which is designed as a two-phases protocol. During the first phase (0-12 weeks (w)) patients will be subjected to dietary intervention with hypocaloric MD; in a second phase (12-24w), melatonin 1mg/die before sleep will be added to the hypocaloric MD. The susceptibility to infections will be investigated through the evaluation of 1) the number of events - i.e. flu- or flulike syndromes, skin, respiratory, digestive, urinary infections-per patient of the 4 groups and the blood assays to detect the infection with Epstein-Barr, Cytomegalovirus, Varicella, Measles and SARS-CoV-2 IgG and IgM; hepatitis C and hepatitis B core antibodies and Quantiferon TB Gold, 2) the clock genes rhythm and TLRs expression in patient immune cells at baseline, 12w and 24w.The mutual relationship between biomedical values, environmental and social conditions, and lifestyle habits will be evaluated by structured questionnaires. Validation of questionnaires to explore the susceptibility to infections is another delivery planned for the current study.

Considering the compelling amount of studies focused on patients in the active phase of COVID-19 disease and the scarcity of studies focused on patient cured from disease aimed at evaluating the sequelae of SARS-CoV-2 infection, the purpose of the study is to investigate whether in patients recovered from COVID-19 disease, SARS-CoV-2 infection has induced: 1) endocrine-metabolic function damage; 2) neuro-psychiatric damage; 3) muscle damage; 4) pulmonary damage; 5) cardiological damage; 6) venous vascular damage; 7) dermatological damage. Patients will be evaluated at baseline (at discharge from infectious and/or pneumology unit) and after 3- 12 months. A better definition of the prevalence and type of sequelae after recovery from COVID-19 disease could significantly improve the therapeutic management and long-term follow-up of these patients, with a relevant impact in terms of health resources and public health.

The Registro Campania Salute Network (RCSN) is a prospective registry aimed at improving the management of essential hypertension by integrating the activity of general practitioners (GPs) with that of the hypertension specialist. It involves selected GPs homogeneously allocated in the regional area, and the Hypertension Clinic of the Federico II University in Naples, which served as co-ordinating centre. Through the RCSN system it is possible to store clinical data detected at each visit between the peripheral units and the co-ordinating centre and to support scientific analysis of the dataset.

Non-specific lipid transfer proteins (nsLTPs) are currently recognized as the most prevalent cause of primary IgE-mediated food allergy in Mediterranean populations and constitute a leading trigger of anaphylactic reactions. In Italy, the prevalence of LTP sensitization is estimated at 2-2.4% in adults and approximately 9% in children, with marked geographic variation. Specifically, higher prevalence rates are observed in central and southern regions and on the islands (21.3%-27.2%) compared to the northern regions (approximately 11%). LTPs are ubiquitous panallergens, widely expressed throughout the plant kingdom. They represent the major allergens within the Rosaceae family in individuals not sensitized to birch pollen and have also been identified and characterized in numerous plant-derived foods, including nuts, legumes, rice, maize, beer, spelt, and wheat. The clinical spectrum of LTP hypersensitivity is highly heterogeneous. While a significant proportion of sensitized individuals remain asymptomatic, others may present with localized reactions such as contact urticaria or oral allergy syndrome (OAS). More severe cases may involve gastrointestinal symptoms (e.g., vomiting, epigastric discomfort, abdominal pain), cutaneous and respiratory manifestations, and systemic responses up to anaphylactic shock. Nickel is a ubiquitous metal employed in a wide range of industrial applications and consumer products, including stainless steel, metal plating, various alloys, and inexpensive jewelry. It is also naturally present in both animal and plant-based food sources (e.g., cereals, cocoa, legumes, fresh fruits and nuts, fish). Nickel is the most common sensitizer in allergic contact dermatitis, affecting approximately 20% of the general population and around 10% of the pediatric population. Sensitization to nickel involves a delayed-type (Type IV) hypersensitivity reaction and is not IgE-mediated. Clinical manifestations range from localized allergic contact dermatitis to systemic involvement, referred to as systemic nickel allergy syndrome (SNAS), which is characterized predominantly by gastrointestinal symptoms, although respiratory and other systemic manifestations can also occur. Gastrointestinal symptoms such as gastroesophageal reflux disease (GERD), functional dyspepsia, abdominal pain, and altered bowel habits, when not associated with overt allergic signs or underlying organic disease, are typically classified as functional gastrointestinal disorders (FGIDs). Several studies report that up to 40% of adult patients with FGIDs exhibit nickel sensitization; however, data in the pediatric population remain scarce. Chelanik® is a dietary supplement designed to support individuals with nickel hypersensitivity. It contains bioactive components purported to exert immunomodulatory and anti-inflammatory effects. Nevertheless, in vitro human data directly demonstrating its activity on lymphocyte function are currently lacking. This prospective, experimental, single-center study aims to determine the prevalence of sensitization to LTP and nickel among patients presenting with functional dyspepsia or irritable bowel syndrome (IBS), and to assess in vitro the potential immunomodulatory effects of Chelanik® on peripheral blood lymphocytes from individuals with nickel allergy.

Eosinophilic esophagitis (EoE) is a chronic antigen-mediated inflammatory disease of the esophagus that affects both children and adults. The incidence and prevalence of EoE is rapidly increasing in Western countries with an estimated incidence of 6.6 per 100,000 person-years (95% CI, 3-11.7) in children and 7.7 per 100,000 person-years (95% CI, 1.8-17.8) in adults. Clinically, it is characterized by various symptoms related to esophageal dysfunction, including vomiting, regurgitation, feeding difficulties, epigastric heartburn, dysphagia, or food bolus impaction, and may cause growth retardation. Diagnosis is made on the basis of clinical symptoms and histological evidence of eosinophilic infiltration of the esophagus (at least 15 eosinophils/high power microscope field (eos /hpf), excluding other etiologies of esophageal eosinophilia (gastroesophageal reflux disease, infectious esophagitis, achalasia, celiac disease and Crohn's disease, connective tissue disorders, gra ft versus host disease, drug hypersensitivity and hypereosinophilic syndromes). EoE is primarily characterized by a T helper 2 type inflammation, but the pathogenesis and the immunopathological mechanisms underlying the pathology are not yet fully understood. Recent evidence suggests that in genetically predisposed individuals, interaction with environmental factors (e.g., dietary lifestyle) may play a role in activating several inflammatory pathways and cause EoE. Ultra-processed foods (UPFs) are food and beverage products resulting from industrial formulations, ready for consumption, typically obtained with five or more ingredients from different manufacturing processes (cooking methods, addition of additives such as stabilizers or preservatives). During the last decade, the consumption of the latter has increased significantly among the pediatric population to represent 30% of the daily caloric intake of an average child in Europe and America. Recent evidences show that UPFs favor the onset of chronic non-communicable diseases through the activation of different inflammatory pathways. The components mostly represented in UPFs are the advanced glycation end products (AGEs), a heterogeneous group of highly oxidizing compounds that are formed through non-enzymatic reactions (Maillard reaction) between reduced sugars and free amino groups of proteins, lipids, or nucleic acids. Evidence demonstrates that dietary AGEs are absorbed and contribute significantly to the total concentration of AGEs in the body. AGEs induce oxidative stress and inflammation, leading to structural and functional protein alterations, cellular apoptosis and multi-tissue/organ damage. These mechanisms are mediated at least in part by interactions with their cell-surface receptor for advanced glycation end-products (RAGE). The AGEs-RAGE interaction modulates the immune response. AGEs are able to activate le mast cells, to stimulate the release of histamine and to induce a chronic inflammatory state that promotes a T helper 2 type response.