Maria Grazia Piccioni

Background: Food allergy (FA) is an emerging problem in pediatrics, with tree nuts and peanuts being frequent causes of severe reactions. Oral food challenge (OFC) remains the gold standard for diagnosing FA. However, it is a stressful treatment and not always risk-free. Objectives: To identify potential biomarkers, using component-resolved diagnosis (CRD) associated with OFC outcome in children with tree nut (hazelnut, walnut, almond, and pistachio) and peanut allergy, who live in central and southern Italy. Methods: Eighty-eight (1–18 years) children followed at the Pediatric Allergy Clinic of Policlinico Umberto I in Rome were included in this study. All patients underwent skin prick tests (SPTs), prick-by-prick (PbP) tests, and serum-specific Immunoglobulin E (sIgE) measurement to allergenic components using CRDs. Results: In hazelnut allergy (n = 60 OFCs), OFC failure occurred in 41 children. Higher sIgE levels to Cor a 8 (OR 2.04, 95% CI 1.17–3.55), Cor a 9 (OR 2.61, 95% CI 1.37–5.00), and Cor a 14 (OR 1.65, 95% CI 1.14–2.38) were all significantly associated with an increased probability of a positive OFC outcome. In peanut allergy (n = 30 OFCs), OFC failure occurred in 16 children. Ara h 9 was the only statistically significant predictor of OFC failure, showing a very wide confidence interval (OR, 95% CI: 1.116–484). For walnut, almond, and pistachio, sample sizes were insufficient to support inferential modeling. Conclusions: CRD biomarkers can stratify the likelihood of OFC reactions in pediatric FA, enhancing clinical decision-making and reducing unnecessary challenges.

Background/Objectives: Alcohol and smoking during pregnancy may be associated with several complications, but the underlying mechanism is still unclear. The aim of this study was to evaluate the role of oxidative stress induced by smoking and alcohol during pregnancy and their effects on fetal and neonatal outcomes. Material and methods: We considered pregnant women at term. Validated questionnaires were used to investigate smoking and alcohol habits. Ultrasound was performed to evaluate fetal weight, amniotic fluid index, and maternal-fetal Doppler velocimetry. At the time of delivery, we collected a tuft of maternal hair, maternal venous blood, and cord blood. In these samplings we determined in phase I nicotine, cotinine, and ethyl glucuronide on the maternal keratin matrix with the gas chromatography-mass spectrometry technique. In phase II, the Free Oxygen Radicals Test (FORT) and Free Oxygen Radical Defense (FORD) test were used to assess circulating reactive oxygen species (ROS). Results: 119 pregnant patients were enrolled (n = 62 for smoking and n = 57 for alcohol). Twenty-six patients (42%) out of 62 were active smokers. Three patients (5%) out of 57 were alcoholic consumers. Mean neonatal weight and mean placental weight were significantly lower for active smokers (p = 0.0001). The neonatal weight was in the 1st–2nd percentile for all alcohol abusers. Considering two subgroups (n = 10 non-smokers and n = 10 smokers) for ROS determination, a statistically significant higher oxidative stress in the blood of smoking patients was evidenced (p < 0.0001). In cord blood the differences were not statistically significant (p = 0.2216). Conclusions: Fetal growth restriction was present in the group of active smokers and in patients with alcohol abuse. Oxidative stress was higher in smoking patients than in non-smokers. However, in cord blood, FORT was negative in all cases, suggesting a protective mechanism in utero. Given the limited sample size, the results obtained are preliminary and require future studies.

Background/Objectives: Endometriosis affects up to 10% of women of reproductive age and about 47% of adolescents with pelvic pain. Symptoms include dysmenorrhea, dyspareunia, and chronic pelvic pain (CPP). Adolescents often present atypical symptoms that can make endometriosis more difficult to diagnose. This study aimed to compare characteristics of pain, atypical symptoms, and the effects of hormonal treatments between adolescents and adults with endometriosis. Methods: A total of 238 women with endometriosis were included: 92 aged 12–18 (group A) and 146 over 18 (group B). Data on menarches, cycle length, comorbidities, dysmenorrhea, dyspareunia, CPP, analgesic use, pain characteristics, atypical symptoms, and endometrioma size were recorded. The efficacy, compliance, and side effects of hormonal treatments were also assessed. Quality of life (QoL) was measured using the SF-12 questionnaire at baseline and after six months of therapy. Results: Adolescents had earlier menarche (p < 0.001), longer menstrual periods (p < 0.001), and higher analgesic use (p = 0.001) compared to adults. Dysmenorrhea was more frequent (p = 0.01), lasted longer (p < 0.001), and was associated with higher pain scores (p < 0.001) in adolescents. CPP was more common in adolescents (p < 0.001), often described as “confined” (p = 0.04) and “oppressive” (p = 0.038), while adults reported it as “widespread” (p = 0.007). Headaches (p < 0.001) and nausea (p = 0.001) were also more frequent in adolescents. Both groups showed significant improvement in QoL with hormonal treatment (p < 0.001) and reported minimal side effects. Conclusions: Adolescents with endometriosis often present with earlier menarche, longer menstrual periods, more severe dysmenorrhea, and atypical symptoms. Hormonal contraceptives and dienogest are effective and safe treatments that improve pain and QoL.

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by the appearance of recurrent eczematous lesions and intense itching. The World Allergy Organization (WAO) suggested the administration of probiotics in pregnant women at high risk of allergies in their children. Objectives: Our study aims to evaluate the role of administering the Bifidobacterium bifidum strain PRL2010 during pregnancy and breastfeeding in preventing and/or reducing the severity of AD manifestations in children. Methods: It is a monocentric, randomized, double-blind, placebo-controlled trial with probiotic/placebo administration since the 36th week of gestation to mothers with atopy or a family history of atopy; the effects were evaluated over the first 12 months of the children’s lives. Results: No severe adverse effects due to probiotic intake were reported in our cohort. Although proportionally fewer children with AD were in the probiotic group, the statistical analysis showed no significant differences between the probiotic and placebo groups. However, infants who developed the most severe forms of AD in the probiotic group showed a better clinical course during follow-up compared to those in the placebo group. Conclusions: In conclusion, administering the probiotic Bifidobacterium bifidum strain PRL2010 during pregnancy and breastfeeding is safe and potentially beneficial; further large-scale studies may confirm its usefulness in improving the clinical manifestation of AD in children with a family history of atopy.

Background/Objectives : Endometriosis affects up to 10% of women of reproductive age and about 47% of adolescents with pelvic pain. Symptoms include dysmenorrhea, dyspareunia, and chronic pelvic pain (CPP). Adolescents often present atypical symptoms which can make endometriosis more difficult to diagnose. This study aimed to compare characteristics of pain, atypical symptoms, and the effects of hormonal treatments between adolescents and adults with endometriosis. Methods: A total of 238 women with endometriosis were included: 92 aged 12–18 (group A) and 146 over 18 (group B). Data on menarches, cycle length, comorbidities, dysmenorrhea, dyspareunia, CPP, analgesic use, pain characteristics, atypical symptoms, and endometrioma size were recorded. The efficacy, compliance, and side effects of hormonal treatments were also assessed. Quality of Life (QoL) was measured using the SF-12 questionnaire at baseline and after six months of therapy. Results: Adolescents had earlier menarche (p<0.001), longer menstrual periods (p<0.001), and higher analgesic use (p=0.001) compared to adults. Dysmenorrhea was more frequent (p=0.01), lasted longer (p<0.001), and was associated with higher pain scores (p<0.001) in adolescents. CPP was more common in adolescents (p<0.001), often described as "confined" (p=0.04) and "oppressive" (p=0.038), while adults reported it as "widespread" (p=0.007). Headaches (p<0.001) and nausea (p=0.001) were also more frequent in adolescents. Both groups showed significant improvement in QoL with hormonal treatment (p<0.001) and reported minimal side effects. Conclusions: Adolescents with endometriosis often present with earlier menarche, longer menstrual periods, more severe dysmenorrhea, and atypical symptoms. Hormonal contraceptives and dienogest are effective and safe treatments, that improve pain and QoL.

Alcohol is the second-most misused substance after tobacco. It has been identified as a causal factor in more than 200 diseases and 5.3% of all deaths and is associated with significant behavioral, social, and economic difficulties. As alcohol consumption may modulate the immune system’s regulatory mechanisms to avoid attacking the body’s tissues, it has been proven to play a dichotomic role in autoimmune diseases (ADs) based on the quantity of consumption. In this review, we report updated evidence on the role of alcohol in ADs, with a focus on alcohol addiction and the human biological immune system and the relationship between them, with alcohol as a risk or protective factor. Then, in this narrative review, we report the main evidence on the most studied ADs where alcohol represents a key modulator, including autoimmune thyroiditis, multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, diabetes, allergic rhinitis, and primary biliary cholangitis. Alcohol at low–moderate dosages seems mostly to have a protective role in these diseases, while at higher dosages, the collateral risks surpass possible benefits. The specific mechanisms by which low-to-moderate alcohol intake relieves AD symptoms are not yet fully understood; however, emerging studies suggest that alcohol may have a systemic immunomodulatory effect, potentially altering the balance of anti-inflammatory innate and adaptive immune cells, as well as cytokines (via the NF-κB or NLRP3 pathways). It might influence the composition of the gut microbiome (increasing amounts of beneficial gut microbes) and the production of their fatty acid metabolites, such as short-chain fatty acids (SCFAs) and polyunsaturated fatty acids (PUFAs), as well as elevated concentrations of acetate, high-density lipoprotein (HDL), and nitric oxide (NO). Unfortunately, a definite acceptable daily intake (ADI) of ethanol is complicated to establish because of the many mechanisms associated with alcohol consumption such that despite the interesting content of these findings, there is a limit to their applicability and risks should be weighed in cases of alcoholic drinking recommendations. The aim of future studies should be to modulate those beneficial pathways involved in the alcohol-protective role of ADs with various strategies to avoid the risks associated with alcohol intake.

Cow’s milk allergy (CMA) is the most common food allergy among children. An oral food challenge (OFC) remains a mainstay of the diagnosis of CMA, especially for the non-IgE-mediated type; however, this test can be risky and time-consuming. Hence, there is a need to identify biomarkers. Fecal calprotectin (FC) showed variable results, with good reliability and reproducibility in CMA patients. In this prospective study, we enrolled 76 children (aged 5–18 months) with CMA-related gastrointestinal and cutaneous symptoms following guidelines from the European Society of Pediatric Gastroenterology, Hepatology and Nutrition. Clinical assessments included history, physical examination, skin prick tests, and IgE assays. FC levels and the Cow’s Milk Related Symptom Score (CoMiSS) were measured in 51 patients pre (T1) and post-diet (T2), with a subgroup analysis of 15 patients with elevated baseline FC (>50 mg/kg). The results showed that FC levels significantly decreased after the elimination diet (median: 30 mg/kg at T1, 16 mg/kg at T2; p < 0.01). In the subgroup with higher FC levels, median values dropped from 90 mg/kg to 33 mg/kg (p < 0.01). CoMiSS also improved (median: 8.50 at T1, 3.00 at T2; p < 0.01). Linear regression analysis showed no correlation between FC values and the CoMiSS at T1 and T2. In conclusion, the reduction in FC value after an elimination diet suggests that it could be considered a possible biomarker of bowel inflammation in CMA patients. Further studies are necessary to confirm these data and to evaluate and standardize the use of FC for diagnosis and follow-up of CMA.

Alcohol consumption has been consistently linked to an increased risk of several cancers, including breast and ovarian cancer. Despite substantial evidence supporting this association, the precise mechanisms underlying alcohol’s contribution to cancer pathogenesis remain incompletely understood. This narrative review focuses on the key current literature on the biological pathways through which alcohol may influence the development of breast and ovarian cancer. Key mechanisms discussed include the modulation of estrogen levels, the generation of reactive oxygen species, the production of acetaldehyde, the promotion of chronic inflammation, and the induction of epigenetic changes. Alcohol’s impact on estrogenic signaling, particularly in the regulation of estrogen and progesterone, is explored in the context of hormone-dependent cancers. Additionally, the role of alcohol-induced DNA damage, mutagenesis, and immune system modulation in tumor initiation and progression is examined. Overall, this review emphasizes the importance of alcohol as a modifiable risk factor for breast and ovarian cancer and highlights the need for further research to clarify its role in cancer biology.

Background: Cow’s milk allergy (CMA) is the most common food allergy in the pediatric age. The oral food challenge (OFC) remains a mainstay of its diagnosis, especially for the non-IgE-mediated type; this test can be risky and time-consuming. Hence, the need to identify biomarkers. Fecal calprotectin (FC) showed variable results, with good reliability and reproducibility in CMA patients. Methods: In this prospective study we enrolled 76 children (age 5-18 months) with CMA-related gastrointestinal and cutaneous symptoms following the European Society of Pediatric Gastroenterology, Hepatology and Nutrition guidelines. Clinical assessments included history, physical examination, skin prick tests, and IgE assays. FC levels and Cow’s Milk Related Symptom Score (CoMiSS) were measured in 51 patients pre- (T1) and post-diet (T2), with a subgroup analysis of 15 patients with elevated baseline FC (>50 mg/kg). Results: FC levels significantly decreased after the elimination diet (median: 30 mg/kg at T1, 16 mg/kg at T2; p <0.01). In the subgroup with higher FC levels, median values dropped from 90 mg/kg to 33 mg/kg (p < 0.01). CoMiSS also improved (median: 8.50 at T1, 3.00 at T2; p <0.01). Linear regression analysis showed no correlation between FC values and the CoMiSS at T1 and T2. Conclusions: The reduction of FC value after an elimination diet suggests that it could be considered a possible biomarker of bowel inflammation in CMA patients. Further studies are necessary to confirm these data and to evaluate and standardize the use of FC for diagnosis and follow-up of CMA.

Food allergy (FA) affects approximately 6–8% of young children, with a peak prevalence at approximately one year of age. Tree nut and peanut allergies are among the main causes of anaphylaxis in the world. The gold standard for the diagnosis of FAs is the oral food challenge (OFC). Other diagnostic tests used in the clinical practice are skin prick tests (SPTs) and laboratory tests to measure out the presence of serum specific IgE (sIgE). In this narrative review, we collect the current evidence of the predictive value (PV) of SPTs and sIgE for the outcome of the OFCs. In literature, data are conflicting as to whether increasing sIgE concentration and wheal size in SPTs correlate with OFC outcomes. Most studies included in our review have shown that in vivo and in vitro tests may predict OFC outcomes with variable PV, but data are not conclusive; therefore, the OFC currently remains the gold standard for FA diagnosis.