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To highlight the most recent insights on cow's milk allergy (CMA), its treatment, and management.CMA is one of the most common food allergies among children. Burdened by the risk for fatal reaction, CMA may imply also a severe impairment of health-related quality of life at individual and family level as well as well as individual and societal costs. The updated Diagnosis and Rationale for Action against Cow's Milk Allergy series is going to provide a series of manuscripts that will offer a comprehensive state-of-the-art specifically on CMA, including international evidence-based recommendations. The current results from randomized clinical trials highlight that oral immunotherapy may be effective by itself in providing desensitization. Preliminary data suggest that biologicals such as omalizumab may be able to increase the threshold of reactivity to milk or several foods (if multiple food allergies) without requiring allergen exposure. Breastfeeding is the first choice for infants with CMA. Extensively hydrolyzed formula and amino-acid formula are valid alternatives and may be particularly helpful when eliminating multiple foods, with severe complex gastrointestinal food allergies, eosinophilic esophagitis, severe eczema, or symptoms while exclusively breastfeeding. Heed is needed to ensure the formula is nutritionally sufficient. Due to a high degree of cross-reactivity with cow's milk proteins and risk for allergic reactions, goats' milk or other mammals' milk should not be used.The adoption and implementation of evidence-based recommendations may guide a proper diagnostics and management and awaited advances in knowledge will allow the development of a personalized treatment tailored on the specific CMA patient's profile.

Objective Approximately 25% of ovarian cancer (OC) cases are related to an inherited predisposition. Genetic mutations for the oncosuppressor genes BRCA1 and 2 have the best-known linkage to a higher incidence of OC and breast cancer, in approximately 70% to 80% of hereditary OC cases. To provide the first comprehensive clinical description of screen-detected (SD) OCs during a 6-years surveillance of a cohort of young BRCA carriers and carriers who refuse risk-reducing salpingo-oophorectomy. Methods A prospective cohort study in a university hospital describing 191 women with BRCA1 and 2 mutations adhering continuously to our surveillance between 2015 and 2020, including a 6-monthly evaluation of cancer antigen 125 (CA 125) with concomitant transvaginal ultrasound (TVUS) performed by a dedicated specialist. Main outcomes were tumor's laterality, CA 125 at diagnosis, TVUS and computed tomography (CT) findings. Results Risk-reducing salpingo-oophorectomy was performed in 58/191 (30.4%) of mutation carriers during the study period (one OC case identified). Nine SD-OCs and no interval OCs were found in the remaining 133 women. OCs (FIGO stage I or II: 88.9%) occur mainly in BRCA 1 (77.8%), being bilateral in 85.7% BRCA 1 and unilateral in 100% BRCA 2. No lesions involved only the tubes: left ovaries/tubes were more frequently involved. We have described three new possible scenarios regarding imaging: 1) Evident cases (33.3%, TVUS and CT obvious for OC, CA 125 sensitivity: 100%), 2) Possible cases (55.6%, TVUS and CT are in general accordance, documenting new TVUS signs: increased solid pattern of the ovary with peripheral cortical small cysts, hypoechoic circular mass near the ovary, intraparenchymal small hyperechoic foci), and 3) Hidden cases (11.1%, the smallest lesion but the highest stage (IIIA2), with CA 125 44.2 U/mL and concomitant endometrial hyperplasia). Conclusions Different diagnostic tools must integrate to ensure early diagnosis of OC in BRCA mutation carriers adhering to a follow-up program.

Purpose of review To provide the most recent insights in the use of biologicals in the treatment of patients with anaphylaxis. Recent findings There is evidence that biologics such as omalizumab may be safe and effective in preventing anaphylactic reactions in patients at high risk mainly because of severe food allergy or desensitization procedures to food, airborne allergen, drugs, or hymenoptera venom. Summary Further knowledge will guide the adoption and implementation of any new therapy including biologics for anaphylaxis according to the stratification of risk/benefits.

Purpose of review To perform a nonsystematic review of the literature on the possible role of probiotics for food allergy (FA). Recent findings Animal model and in vitro evidence suggest that the gut microbiome could protect against FA and that probiotics could be a valid instrument. There is no consistent evidence in identifying the specific species, the dosage, and the optimal duration to obtain the correct immunomodulation. Early life supplementation with specific 'missing' immunomodulatory microbes - derived from machine learning approach to birth cohort studies - might represent a novel approach to the primary prevention of multiple human atopic diseases. However, further studies are needed. Summary Currently, there is no positive recommendation from the main scientific societies to use probiotics neither for the treatment nor for the prevention of FA.

PURPOSE OF REVIEW To perform a nonsystematic review of the literature on the microbiota in the different types of non-IgE-mediated food allergy. RECENT FINDINGS The commonest non-IgE-mediated disorders managed by allergists include: eosinophilic esophagitis, food protein-induced enteropathy, food protein-induced enterocolitis syndrome, and food protein-induced allergic proctocolitis. The review of the literature describes how at phylum level we observe an increase of Proteobacteria in eosinophilic esophagitis esophageal microbiota and in food protein-induced enterocolitis syndrome, and food protein-induced allergic proctocolitis gut microbiota, while we observe an increase of Bacteroidetes in healthy controls. Several studies endorse the concept that a bloom of Proteobacteria in the gut reflects dysbiosis or an unstable gut microbial community structure. In several studies, the type of diet, the use of probiotics and in a single experience the use of fecal microbiota transplantation has produced significant variations of the microbiota. SUMMARY Genetic factors alone cannot account for the rapid rise in food allergy prevalence and the microbiome might be contributing to allergy risk. Our review showed that common features of the pathological microbiota among different types of non-IgE-mediated food allergy can be identified. These evidences suggest a possible role of the microbiota in the pathogenesis and non-IgE-mediated food allergies and the need to understand the effects of its modulation on the disorders themselves.

BACKGROUND Postoperative pulmonary complications are associated with increased morbidity. Identifying patients at higher risk for such complications may allow preemptive treatment. METHODS Patients with an American Society of Anesthesiologists (ASA) score >1 and who were scheduled for major surgery of >2 hours were enrolled in a single-center prospective study. After extubation, lung ultrasound was performed after a median time of 60 minutes by 2 certified anesthesiologists in the postanesthesia care unit after a standardized tracheal extubation. Postoperative pulmonary complications occurring within 8 postoperative days were recorded. The association between lung ultrasound findings and postoperative pulmonary complications was analyzed using logistic regression models. RESULTS Among the 327 patients included, 69 (19%) developed postoperative pulmonary complications. The lung ultrasound score was higher in the patients who developed postoperative pulmonary complications (12 [7-18] vs 8 [4-12]; P < .001). The odds ratio for pulmonary complications in patients who had a pleural effusion detected by lung ultrasound was 3.7 (95% confidence interval, 1.2-11.7). The hospital death rate was also higher in patients with pleural effusions (22% vs 1.3%; P < .001). Patients with pulmonary consolidations on lung ultrasound had a higher risk of postoperative mechanical ventilation (17% vs 5.1%; P = .001). In all patients, the area under the curve for predicting postoperative pulmonary complications was 0.64 (95% confidence interval, 0.57-0.71). CONCLUSIONS When lung ultrasound is performed precociously

Introduction: Transcatheter aortic valve replacement (TAVR) is currently the mainstay of treatment of severe aortic stenosis (AS). We aim to investigate the evolution of transaortic mean gradients in surgical aortic valve replacement (SAVR) patients before and after the Food and Drug Administration (FDA) approval of TAVR. Hypothesis: We assessed the hypothesis that mean gradients across the aortic valve were higher in 2011-2012 before FDA approval of TAVR. Methods: Patients who underwent SAVR in 2011-2012 (n=138) and 2019-2020 (n=134) at the University of Minnesota Medical Center were included. Those with implanted mechanical valves (n=602) were excluded. Valve size and mean aortic gradients were compared between the 2 study groups. Results: Out of 272 patients included in this study, 65.8% were males. Patients underwent SAVR at an older age in 2011-2012 (median 74, IQR 65-82) compared to 2019-2020 (median 67, IQR 60-73). The mean aortic valve gradient post-SAVR was higher in 2011-2012 (median 12, IQR 8-18 vs. median 10, IQR 7-13 in 2019-2020, p=0.016). The median valve size was smaller in 2011-2012 (21 mm vs. 23 mm, p(table) . Conclusion: Patients who underwent SAVR in 2011-2012 were older, more likely to receive smaller valve sizes, and had higher mean aortic valve gradients after SAVR.

To critically appraise the recent most relevant studies in the rapidly advancing field of food oral and sublingual immunotherapy.Food allergen-specific immunotherapy via oral (OIT) and sublingual route (SLIT) increases the threshold of reactivity to peanut, cow's milk, egg, wheat, and many other foods in the majority of the treated individuals. This desensitized state is contingent upon the continued ingestion of the maintenance doses of the food. Permanent oral tolerance is achievable in a smaller subset of the treated individuals. The optimal duration of therapy has not been firmly established but is likely dependent on the phenotype (severity and persistence). Efficacy of food-OIT is superior compared with SLIT, whereas the safety of OIT is less favorable. Standardization of treatment protocols, maintenance dosing, duration of therapy, target populations and harmonization of the outcomes are top priorities at this stage.OIT and SLIT represent two different routes of food allergen-specific immunotherapy. Although significant progress has been made in the last decade, both treatment modalities are still in the very early stages of development and further investigations are necessary to optimize the protocols and improve safety while maximizing efficacy.

To provide an update of the studies concerning the diagnosis and management of food additives allergy.Additives improve specific characteristics of food products, but they may induce allergic even life-threatening reactions. Physical examination and medical history are basic to assess specific in-vivo and in-vitro tests. The only treatment for allergic patients consists in avoiding the food containing culprit additives. High-risk patients should be able to recognize severe reactions and self-manage them.The prevalence of adverse reactions to food additives is low, and it may depend on comorbidities, like asthma or chronic idiopathic urticaria. Food labels may help the correct identification of ingredients. Natural additives like spices should cause immediate reactions because of a pollen-sensitization or panallargen proteins presence. Additive-free diets may help the patient care, but the authors suggest assessing an oral food challenge with the culprit substance if there are no contraindications.

Purpose of review Allergic diseases are increasing worldwide and are considered an important public health problem causing severe and even life-threatening reactions. The creation of guidelines aims to help clinicians improving the quality of diagnosis and management of such diseases. Clinical practice guidelines alone are not sufficient and there is a need for implementation strategies for their introduction into daily practice. We report here the main international allergy guidelines with a more focused look on the Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) guidelines and their effect on clinical practice. Recent findings DRACMA guidelines have clearly modified the approach to cow's milk allergy (CMA) from its diagnosis to treatment tailoring the choices for each patient. Although they strongly recommend oral food challenge for diagnosing CMA, they also indicate that it may not be necessary in many cases with the introduction of the pretest probability of CMA. Studies on the implementation of DRACMA guidelines show how they influenced the formula market, making appropriate treatments more affordable. Summary DRACMA reconciled international differences in the diagnosis and management of CMA. They introduced the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology in the field of food allergy and highlighted the importance for meta-analyses to be able to adapt recommendations to the local context.

To familiarize the reader with the concept of precision medicine in food allergy through the most recent insights in the diagnosis, prognosis, and management of the disease.With the advent of omics sciences, a new era is commencing. Food protein allergens characterization and quantification together with the immunoglobulin E epitope mapping will contribute to the diagnosis/prognosis of food allergy and will lead to a better safety assessment of foods. The characterization of biomarkers able to identify specific phenotypes and endotypes will improve the diagnostic accuracy. This together with a better understanding of mechanisms of action of the different therapeutic options will allow the accurate selection of the appropriate patient.In the near future, advances in technologies and data interpretation will allow a better understanding of the pathogenesis of food allergy and the development of a personalized treatment tailored on the specific patient' profile.

The epidemiology of food allergy did inspire theories on the reasons for the recent surge of the disease. We offer here a reasoned review on the relationships between the trajectories of human development and the trend of the food allergy epidemics.The exponential trend of the frequency of food allergy paralleled the explosive acceleration of the human development over the last few decades. Dietary factors have been indicated as responsible for these trends and targeted for potential preventive strategies. Other socio-economic factors have been related to this evolution: solar exposure, climate changes, structure of societies, reproductive choices and societal inequalities.The epidemiologic associations of food allergy suggest different causal theories. Future prevention strategies may be predicated not only on dietary interventions, but on wider programmes aimed to restore a human ecology promoting food tolerance.

Severe cases of food allergy account for the majority of the burden in terms of risks, quality of life, and resource expenditure. The traditional approach to these forms has been strict avoidance. More recently, Oral ImmunoTherapy (OIT) has gained a role in their management. However, in severe food allergies OIT is often infeasible.Case reports, observational, and prospective studies have recently proposed different approaches to severe food allergy. The majority of them include the use of biologics. Omalizumab has been the most studied drug for severe food allergies, and its role as adjuvant treatment to OIT is well established. Interest has been raised on other biologics, as dupilumab, reslizumab, and mepolizumab. Toll-like receptor agonists, and gene therapy using adeno-associated virus coding for Omalizumab are promising alternatives.The recent studies are deeply influencing the clinical practice. We review the modifications of the clinical approach to severe food allergies so far available. We indicate the possible evolutions of treatment with biologics in severe food allergies.

INTRODUCTION AND OBJECTIVES:Prediction of the presence of extracapsular extension (ECE) of prostate cancer (PCa) before surgery is of paramount importance to tailor the amount of nerve-sparing during radical prostatectomy (RP). A novel nomogram to predict ECE has been recently developed with the integration of a multiparametric magnetic resonance imaging (mpMRI) derived variable (Martini et al, BJUI 2018, 1-9). Authors defined the “presence of ECE” as the loss or irregularity of the capsule, whereas contact, bulge or abutment are considered as negative for ECE.We aimed to externally validate this nomogram on 137 prostatic lobes from 106 patients undergoing mpMRI-targeted biopsy plus saturation sampling.METHODS:We applied the model from Martini to the most recent cases of PCa patients (n=106) with a positive mpMRI submitted to RP. PCa was diagnosed in all cases by mpMRI-targeted plus systematic saturation biopsy. According to Martini′s model, we considered only lobes with a positive biopsy (137). The prima...

Purpose of review To investigate the functional role of gut microbiota in diet-modulated diseases, evaluating probiotic administration effects by systems biology-driven approaches. Understanding the role of host-gut microbial and gut microbe-microbe interactions in either allergic and healthy children may assist in selecting effective and targeted probiotics for personalized therapies. Recent findings Food allergy shows a significant increase, especially in Western countries where growing epidemiological data indicate prevalence of small family groups, limited rate of infections in childhood compared with low-income countries, high consumption of sterile foods, hence stimulating a poor trigger of the gut immune system. Therefore, new therapeutic strategies to treat food allergy consist of probiotic administration since early life, thus modulating gut microbiota through immune system stimulation at the mucosal level. Summary Currently, new insights for probiotic selection should take into consideration both phenotyping and genotyping bacterial features and host-microbial cross-talk at gut level, by employing multicomponent systems biology approaches to unveil gut ecosystem dynamics in terms of bacteria phylotypes and their metabolic activities. Moreover, new food processes need to be considered to assess the actual performance of probiotic strains administered to allergic patients. The advent of high-performance platforms employing genomic-and mass spectrometry-based techniques has opened new perspectives on the gut microbiota field, and may now serve as advanced tool to dynamically investigate the interplay between probiotics and gut microbiota ecology under allergic conditions.

AIMS The aim of the present study is to determine pregnancy outcome with regard to the risk class and the modality way of referral to our joint Cardiac Obstetric Clinic. METHODS This is a prospective observational study. Patients referred to our clinic between 2011 and 2014 were included. Reason and timing for referral were recorded. Two groups were identified: women who were known to have cardiac disease before referral (group I) and women who were not (group II). Pregnancies were managed as recommended by the ESC Guidelines. Cardiac events were defined as death, heart failure requiring treatment, documented tachyarrhythmias, thromboembolic events and need for urgent endovascular procedures or surgery. RESULTS Of the 110 pregnancies, 51 (47%) were in group I and 57 (53%) in group II. Congenital (44%) and valvular (27%) diseases were the most frequent diagnosis. Thirty-two percent of patients were in WHO risk classes III-IV. Thirty percent were referred for symptoms, 70% for risk assessment. Women in group II were evaluated later in pregnancy than those in group I (25.6 ± 9 vs. 21.4 ± 9; P < 0.01). Cardiovascular events occurred in 15 (13.6%) pregnancies and were more common in WHO risk classes III-IV (11, P < 0.001), in group II (12, P= 0.02) and in patients referred for symptoms (11, P < 0.001). Stillbirths occurred only in classes III-IV (three pregnant, 2.7%). CONCLUSION There was no maternal or neonatal mortality and an overall acceptable incidence of cardiovascular events but a relevant percentage of pregnant were first referred late and/or for the onset of symptoms. Events were more frequent in these patients. Further efforts are needed to optimize referral to specialized centers.