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Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Stroke-like syndrome (SLS) is a rare subacute neurological complication of intrathecal or high-dose (≥500 mg) Methotrexate (MTX) administration. Its clinical features, evoking acute cerebral ischaemia with fluctuating course symptoms and a possible spontaneous resolution, have elicited interest among the scientific community. However, many issues are still open on the underlying pathogenesis, clinical, and therapeutic management and long-term outcome., Materials and Methods: We retrospectively analyzed clinical, radiological and laboratory records of all patients diagnosed with SLS between 2011 and 2021 at 4 National referral centers for Pediatric Onco-Hematology. Patients with a latency period that was longer than 3 weeks between the last MTX administration of MTX and SLS onset were excluded from the analysis, as were those with unclear etiologies. We assessed symptom severity using a dedicated arbitrary scoring system. Eleven patients were included in the study., Results: The underlying disease was acute lymphoblastic leukemia type B in 10/11 patients, while fibroblastic osteosarcoma was present in a single subject. The median age at diagnosis was 11 years (range 4-34), and 64% of the patients were women. Symptoms occurred after a mean of 9.45 days (± 0.75) since the last MTX administration and lasted between 1 and 96 h. Clinical features included hemiplegia and/or cranial nerves palsy, paraesthesia, movement or speech disorders, and seizure. All patients underwent neuroimaging studies (CT and/or MRI) and EEG. The scoring system revealed an average of 4.9 points (± 2.3), with a median of 5 points (maximum 20 points). We detected a linear correlation between the severity of the disease and age in male patients., Conclusions: SLS is a rare, well-characterized complication of MTX administration. Despite the small sample, we have been able to confirm some of the previous findings in literature. We also identified a linear correlation between age and severity of the disease, which could improve the future clinical management., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Santangelo, Bartolini, Nuzzi, Foiadelli, Michev, Mina, Trambusti, Fichera, Bonuccelli, Massimetti, Peroni, De Marco, Coccoli, Luti, Bernasconi, Nardi, Menconi, Casazza, Pruna, Mura, Marra, Zama, Striano, Cordelli, Battini and Orsini.)

Asthma is the most common chronic non-communicable disease in children, the pathogenesis of which involves several factors. The increasing burden of asthma worldwide has emphasized the need to identify the modifiable factors associated with the development of the disease. Recent research has focused on the relationship between dietary factors during the first 1000 days of life (including pregnancy)-when the immune system is particularly vulnerable to exogenous interferences-and allergic outcomes in children. Specific nutrients have been analyzed as potential targets for the prevention of childhood wheeze and asthma. Recent randomized controlled trials show that vitamin D supplementation during pregnancy, using higher doses than currently recommended, may be protective against early childhood wheezing but not school-age asthma. Omega-3 fatty acid supplementation during pregnancy and infancy may be associated with a reduced risk of childhood wheeze, although the evidence is conflicting. Data from observational studies suggest that some dietary patterns during pregnancy and infancy might also influence the risk of childhood asthma. However, the quality of the available evidence is insufficient to allow recommendations regarding dietary changes for the prevention of pediatric asthma. This review outlines the available high-quality evidence on the role of prenatal and perinatal nutritional interventions for the primary prevention of asthma in children and attempts to address unmet areas for future research in pediatric asthma prevention.

Introduction of complementary feeding, or weaning, is the period where infants are gradually introduced to solid foods, with a progressive reduction of breastfeeding or bottle-feeding. Weaning represents a crucial nutritional moment in the growth and development of infants, and it can also affect future health. Throughout the years, various weaning strategies have been proposed, ranging from classic to baby-led weaning. Recently, vegetarian-/vegan-based approaches are also being increasingly adopted by young parents. This rostrum aims to critically address the safety profiles of current weaning practices for infants and to highlight the important role of pediatricians in choosing the most advisable weaning approach for their patients., (© 2022 The Authors. Pediatric Allergy and Immunology published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Importance: Although imaging has become a standard tool of modern medicine, its widespread use has been paralleled by an increasing cumulative radiation dose to patients despite technological advancements and campaigns calling for better awareness and minimization of unnecessary exposures., Objective: To assess patients' knowledge about medical radiation and related risks., Design, Setting, and Participants: A survey study of hospitals in Italy was conducted; all patients in waiting rooms for medical imaging procedures before undergoing imaging examinations at 16 teaching and nonteaching hospitals were approached to take the survey. The survey was performed from June 1, 2019, to May 31, 2020., Main Outcomes and Measures: Survey respondents' basic knowledge of ionizing radiation levels and health risks, earlier imaging tests performed, and information and communication about radiation protection issues., Results: Among 3039 patients invited to participate, the response rate was 94.3% (n = 2866). Participants included 1531 women (53.4%); mean (SD) age was 44.9 (17.3) years. Of the 2866 participants, 1529 (53.3%) were aware of the existence of natural sources of ionizing radiation. Mammography (1101 [38.4%]) and magnetic resonance imaging (1231 [43.0%]) were categorized as radiation-based imaging modalities. More than half of the 2866 patients (1579 [55.1%]; P = .03) did not know that chest computed tomography delivers a larger dose of radiation than chest radiography, and only 1499 (52.3%) knew that radiation can be emitted after nuclear medicine examinations (P = .004). A total of 667 patients (23.3%) believed that radiation risks were unrelated to age, 1273 (44.4%) deemed their knowledge about radiation risks inadequate, and 2305 (80.4%) preferred to be informed about radiation risks by medical staff. A better knowledge of radiation issues was associated with receiving information from health care professionals (odds ratio [OR], 1.71; 95% CI, 1.43-2.03; P < .001) and having a higher educational level (intermediate vs low: OR, 1.48; 95% CI, 1.17-1.88; P < .001; high vs low: OR, 2.68; 95% CI, 2.09-3.43; P < .001)., Conclusions and Relevance: The results of this survey suggest that patients undergoing medical imaging procedures have overall limited knowledge about medical radiation. Intervention to achieve better patient awareness of radiation risks related to medical exposures may be beneficial.

Nutraceuticals, including vitamin D, vitamin A, zinc, lactoferrin, polyphenols coenzyme Q, magnesium, and selenium, are implicated in the modulation of the complex molecular pathways involved in the immune response against viral pathogens. A common element of the activity of nutraceuticals is their ability to enhance the innate immune response against pathogens by acting on the major cellular subsets and inducing the release of pro-inflammatory cytokines and antimicrobial peptides. In some cases, this action is accompanied by a direct antimicrobial effect, as evidenced in the specific case of lactoferrin. Furthermore, nutraceuticals act through complex molecular mechanisms to minimize the damage caused by the activation of the immune system against pathogens, reducing the oxidative damage, influencing the antigen presentation, enhancing the differentiation and proliferation of regulatory T cells, driving the differentiation of lymphocyte subsets, and modulating the production of pro-inflammatory cytokines. In this paper, we review the main molecular mechanisms responsible for the immunomodulatory function of nutraceuticals, focusing on the most relevant aspects for the prevention and treatment of viral infections.

Asthma and other allergic disorders, such as atopic dermatitis and food allergies, are common chronic health problems in childhood. The rapid rise in the prevalence of these conditions registered over the last few decades has stressed the need to identify the modifiable risk factors associated with the development of these diseases. Breast milk, recognized as the gold standard for healthy growth and development of the newborn, is one of the major factors associated with a lower incidence of allergic and infectious diseases in childhood and young adulthood. Although the underlying mechanisms for these effects are not well understood, breastfeeding leads to immune system maturation. In this narrative review, we summarize existing evidence on breastfeeding and human milk composition in relation to allergic disease prevention or development.

From an evolutionary and nutritional standpoint, exclusive human milk feeding for the first 6 months of life, with continued breastfeeding for 1 to 2 years of life, is recognized as the gold standard nourishment for the infant: it is a species-specific food, with a composition designed by nature to better respond to the biological and psychological needs of the newborn/infant. Human milk contains many hundreds of bioactive molecules that protect newborn against infection and inflammation and contribute to immune maturation, organ development, and healthy microbial colonization. Compared with formula feeding, breastfeeding has been associated with decreased morbidity and mortality in infants and to lower incidence of gastrointestinal infections and inflammatory, respiratory and allergic disease. Here, we briefly review the nutritional and functional composition of human milk and provide an overview of its varied bioactive factors.

Children are not small adults and this fact is particularly true when we consider the respiratory tract. The anatomic peculiarities of the upper airway make infants preferential nasal breathers between 2 and 6 months of life. The pediatric larynx has a more complex shape than previously believed, with the narrowest point located anatomically at the subglottic level and functionally at the cricoid cartilage. Alveolarization of the distal airways starts conventionally at 36-37 weeks of gestation, but occurs mainly after birth, continuing until adolescence. The pediatric chest wall has unique features that are particularly pronounced in infants. Neonates, infants, and toddlers have a higher metabolic rate, and consequently, their oxygen consumption at rest is more than double that of adults. The main anatomical and functional differences between pediatric and adult airways contribute to the understanding of various respiratory symptoms and disease conditions in childhood. Knowing the peculiarities of pediatric airways is helpful in the prevention, management, and treatment of acute and chronic diseases of the respiratory tract. Developmental modifications in the structure of the respiratory tract, in addition to immunological and neurological maturation, should be taken into consideration during childhood., (© 2020 Wiley Periodicals LLC.)

Soybean ( Glycine max ) is a species of legume native to East Asia and used in childhood diet for over 2,000 years in the East. Soy protein formulas have been available for almost a century. Nowadays, the increase in cow's milk allergy and vegetarian dietary preferences are driving consumers toward cow's milk alternatives. In this paper, we reviewed the nutritional composition of soy-based infant formula and discussed their possible use in pediatric age, mainly focusing on prevention and treatment of cow's milk allergy. Protein quality is determined by digestibility and amino acid content. Purified or concentrated vegetable proteins (e.g., soy protein and gluten) have high digestibility (>95%), similar to those of animal ones. For some intact vegetable products (e.g., whole cereals and pulses), protein digestibility is lower (80-90%). Food processing and heat treatment also influence protein digestibility. Considering these data, we tried to evaluate the possible use of soybean and derivatives in pediatric age, including the nutritional composition of soy formulas and the clinical indications for their use. Moreover, since plant-based beverages are being perceived as healthy by consumers and their use is growing on the market, we recommend that soy drink should not be used as a substitute for infant formulas or cow's milk in children younger than 24 months., (Copyright © 2020 Verduci, Di Profio, Cerrato, Nuzzi, Riva, Vizzari, D'Auria, Giannì, Zuccotti and Peroni.)

Asthma is the most frequent chronic disease in children, and its pathogenesis involves genetic, epigenetic, and environmental factors. The rapid rise in the prevalence of asthma registered over the last few decades has stressed the need to identify the environmental and modifiable factors associated with the development of the disease. In particular, there is increasing interest in the role of modifiable nutritional factors specific to both the prenatal and post-natal early life as, during this time, the immune system is particularly vulnerable to exogenous interferences. Several dietary factors, including maternal diet during pregnancy, the duration of breastfeeding, the use of special milk formulas, the timing of the introduction of complementary foods, and prenatal and early life supplementation with vitamins and probiotics/prebiotics, have been addressed as potential targets for the prevention of asthma. In this review, we outline recent findings on the potential role of prenatal and perinatal dietary and nutritional interventions for the primary prevention of pediatric asthma. Moreover, we addressed unmet needs and areas for future research in the prevention of childhood-onset asthma., (Copyright © 2020 Trambusti, Nuzzi, Costagliola, Verduci, D'Auria, Peroni and Comberiati.)

Allergic diseases, such as food allergy (FA), atopic dermatitis (AD), and asthma, are heterogeneous inflammatory immune-mediated disorders that currently constitute a public health issue in many developed countries worldwide. The significant increase in the prevalence of allergic diseases reported over the last few years has closely paralleled substantial environmental changes both on a macro and micro scale, which have led to reduced microbial exposure in early life and perturbation of the human microbiome composition. Increasing evidence shows that early life interactions between the human microbiome and the immune cells play a pivotal role in the development of the immune system. Therefore, the process of early colonization by a "healthy" microbiome is emerging as a key determinant of life-long health. In stark contrast, the perturbation of such a process, which results in changes in the host-microbiome biodiversity and metabolic activities, has been associated with greater susceptibility to immune-mediated disorders later in life, including allergic diseases. Here, we outline recent findings on the potential contribution of the microbiome in the gastrointestinal tract, skin, and airways to the development of FA, AD, and asthma. Furthermore, we address how the modulation of the microbiome composition in these different body districts could be a potential strategy for the prevention and treatment of allergic diseases., (Copyright © 2020 Peroni, Nuzzi, Trambusti, Di Cicco and Comberiati.)

Several scientific societies established that vitamin D (VD), in its metabolized form 25(OH)D, levels higher than 20 ng/mL are sufficient to ensure optimal bone health, while 25(OH)D levels higher than 30 ng/mL are needed to favor VD extraskeletal actions. However, it has been estimated that approximately 30% of children and 60% of adults worldwide are VD deficient and insufficient, respectively. This is the reason why it is important to provide a practical approach to VD supplementation for infants, children, and adolescents. It is the pediatrician's role to evaluate the modifiable lifestyle risk factors for deficiency, particularly a reduced sun exposure, following an evidence-based approach, and to suggest VD supplementation only when there is a rational reason to support its use., (© 2020 EAACI and John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: To evaluate the outcome after buckle removal in a consecutive series of treated detachments., Methods: Segmental and/or encircling buckles were removed in 46 consecutive patients operated upon for rhegmatogenous retinal detachment, showing buckle extrusion, recurrent pain, and diplopia. Patients underwent a preoperative retinal examination, and a six- months postoperative follow-up., Results: Cryopexy of retinal breaks was performed in all 46 patients during the primary surgery. At the time of buckle removal none of the patients underwent argon-laser treatment. The removed buckling material was made of MIRAGEL in 32 cases (74%), silicone sponge in 7 (17%), and silicone band in 4 (9%). The time between the first surgery and buckle removal ranged from 1 to 17 years (8 +/- 7.5, M +/- SD). Neither postoperative complications, nor recurrences of retinal detachment developed. Best corrected visual acuity remained unchanged during the follow-up. Diplopia resolved in all 4 eyes after buckle removal with no need for a strabismus operation, prismatic lenses were required in one case only., Conclusions: Although the absence of a control group, the adequately applied retinopexy during primary surgery could probably prevent the recurrence of retinal detachment.

Background: Visual reaction times (RT) have been used for the evaluation of the response to visual stimuli in amblyopic subjects in a case-control study., Materials and Methods: A Study Group, consisting in nine subjects with amblyopia and anomalous retinal correspondence, and a Control Group of nine normal subjects, were examined. In order to measure RT a test was carried out using a personal computer, for generating the visual stimuli on a special 14" monitor and for recording the response. A program was specifically created to record the dimensions of the stimuli and times of presentation in milliseconds. An electrographic tracing controlled the visual fixation. Visual stimuli of different dimensions were presented to the amblyopic eye, the dominant and non dominant eye, and in binocular vision, and RT were recorded., Results: In all cases RT represented a decreasing function of the stimulus dimension, with no statistical difference between the two groups (p=0.471). In both groups, RT values deriving from the greatest stimuli were rather inferior to those measured with smaller stimuli (p<0.001). In the Study Group the same stimulus produced longer reaction times in the amblyopic eye compared with those of the dominant eye (p<0.001), as well as those recorded during binocular vision (p<0.001)., Conclusions: RT to visual stimuli could supply objective information on uncertain or hidden amblyopia. The extension of the experimental protocol to a larger population under school age could provide a clinical application for the early diagnosis of sensory alterations.

Vitreous fluorophotometry was used to investigate the effect of Bendazac lysine on the blood retinal barrier in 12 insulin-dependent diabetics with mild background retinopathy. The study was a randomized, double blind, cross-over trial, drug versus Placebo. Each treatment period was of 4 months. The vitreous penetration coefficient was reduced by 21% (95% c.i. 12, 30; p = 0.001) by treatment with respect to Placebo.

Background: The aim of the study was to introduce a new test to detect small areas of suppression in the binocular visual field and to lower the minimum age at which a suppression test could be identified correctly. Two tests were compared: the Binocular Polaroid Test (poltest), introduced in clinical practice a few years ago and used in screening programs for vision impairment; and the Second Generation Binocular Polaroid Test (polstar), more recently designed to have simpler answers than the poltest., Methods: One hundred and eighty-two children were examined consecutively. To assess the validity of the two tests, sensitivity, specificity, predictive value, and phi coefficient were calculated. The applicability of the two tests and the speed of the responses was assessed by means of the test of probability of binomial distribution., Results: The polstar has appeared to be simpler and easier in younger patients (age range 20 to 36 months, P = 0.078), and has shown 100% of specificity with a sensitivity of 84% for the polstar 1 and of 100% for the polstar 2., Conclusion: The results appear to demonstrate that the poltest has been improved, and that the polstar may be considered an interesting investigation device for early detection of monocular visual impairment.

A test is presented for the detection of small suppression scotomas in strabismic and in anisometropic patients. Three small light-spots (the central is polarized) are viewed through Polaroid filters placed in front of the eyes. This arrangement produces the perception of the central spot only from one eye, but normal fusion provides the perception of three light-spots. Complete suppression of the central light indicates the presence of a scotoma in the binocular visual field. An inhibition scotoma in the non-dominant eye was found in all cases of small angle esotropia and of anisometropic amblyopia.

We have studied metabolic, circulatory and vascular parameters in a group of 57 diabetics (37 affected by IDDM, 20 affected by NIDDM; 35 were males, 22 were females). Goals of present study were: 1) quantitative evaluation of the blood retinal barrier; 2) influence of the metabolic state, blood pressure, sex, type and duration of the diabetes on the ocular conditions; 3) relationship between ophthalmoscopic appearance of the retina and vitreous fluorophotometric recordings. We concluded that: a) ocular alterations depend by lipidic metabolism, blood pressure, sex, type and duration of the diabetes; b) vitreous fluorophotometry has proved a good device for early detection of retinal damages in the diabetic retinopathy.

A 14-year-old white boy, the second of 5 brothers, showed a congenital deficit of ocular motility in his left eye, characterized by limited elevation, marked retraction of the globe and narrowing of the palpebral fissure during upward gaze. The ocular movements in the other directions of gaze were normal with normal binocular vision and stereopsis. The characteristics of the motility defect and the results of the forced duction test suggest the possibility of an anomaly of superior rectus scleral insertion rather than of an innervational defect or of a muscular fibrosis.

The authors have utilized a binocular flat or stereoscopic pattern (grating) to record visual evoked responses (VER) in normal and strabismic subjects. The aim was to find an electrophysiological correlate with the degree of binocular interaction in these subjects. The perception of the grating as tridimensional or flat derived from the disparity obtained with Polaroid filters placed in front of the eyes. In normal subjects, the results demonstrated a significant increase of VER amplitude during tridimensional perception of the pattern. In strabismic subjects the electrophysiological response was not correlated with the binocular conditions.

We report the results obtained with the Binocular Polaroid Test in a large population screening devised to detect vision disturbances in pre-school age children. The Binocular Polaroid Test is a new test for rapid detection of small unilateral scotoma in the binocular visual field. The test was performed on 1566 children age 3 to 6 years in a field examination. The reliability of the test was controlled in a study examination. A complete study examination was performed in 60 of the 96 subjects with a positive response to the test. One hundred subjects selected at random among those with a negative response were used as controls. The study examination disclosed vision disturbances in 41 of the 60 children with a positive response to the Binocular Polaroid Test. The remaining 19 results were normal. No vision disturbances were detected in the control group. The predictive value and the "phi" coefficient were calculated. The results indicate that the Binocular Polaroid Test appears very suitable for vision screening in pre-school age children for whom an early diagnosis is of paramount importance for treatment and prognosis of a vision alteration.