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Background: Bacterial meningitis (BM) in infants is a serious condition that can lead to significant complications. Lumbar puncture (LP) is essential to provide diagnoses, however false negatives may result if LP is performed after the starting of antibiotic therapy. Methods: We conducted a retrospective analysis of infants of any gestational age with BM within their first 90 days of life and admitted to the Neonatal Intensive Care Unit of Modena Policlinico between 1 January 2011, and 31 December 2023. Results: A total of 44 episodes of meningitis were confirmed in 40 infants, diagnosed by positive cerebrospinal fluid cultures (n = 37), polymerase chain reaction testing (n = 4), or both methods (n = 3). Three out of forty infants (8%) experienced a relapse of meningitis. Most episodes (31/44, 70%) occurred in preterm infants. The incidence of early-onset meningitis was lower than that of late-onset (0.18 vs. 0.94 cases per 1000 births, respectively), with Gram-positive accounting for most cases (27/44, 61%). LP was performed prior to antibiotic administration in most episodes (30/44, 68%). Two preterm infants (5%) died from meningitis-related complications. Forty-two episodes occurred among thirty-eight surviving infants; brain lesions were detected through brain ultrasound or MRI in nine out of forty-two episodes (21%). Conclusions: Preterm infants have higher rates of BM, brain lesions or case fatalities. Early diagnosis and prompt antibiotic treatment are critical to improve outcomes. [ABSTRACT FROM AUTHOR]

Background: Umbilical venous catheters (UVCs) are the standard of care in neonatal intensive care units (NICUs) to administer fluids, parenteral nutrition and medications, although complications may occur, including central line-associated blood stream infections (CLABSIs). However, the dwell time to reduce CLABSI risk remains an open issue. Methods: We performed a single-center retrospective study of newborns hospitalized in the Modena NICU with at least one UVC inserted over a 6-year period (period 1: January 2011–December 2013; period 2: January 2019–December 2021). We selected a non-consecutive 6-year period to emphasize the differences in UVC management practices that have occurred over time in our NICU. The UVC dwell time and catheter-related complications during the first 4 weeks of life were examined. Results: The UVC dwell time was shorter in period 2 (median 4 days vs. 5 days, p < 0.00001). Between the two periods, the incidence of CLABSIs remained unchanged (p = 0.5425). However, in period 2, there was an increased need for peripherally inserted central catheters (PICCs) after UVC removal, with a rise in PICC infections after UVC removal (p = 0.0239). Conclusions: In our NICU, shortening UVC dwell time from 5 to 4 days did not decrease the UVC-related complications. Instead, the earlier removal of UVCs led to a higher number of PICCs inserted, possibly increasing the overall infectious risk. [ABSTRACT FROM AUTHOR]

Thyroid function is closely linked to nutrition through the diet–gut–thyroid axis. This narrative review highlights the influence of nutritional components and micronutrients on thyroid development and function, as well as on the gut microbiota. Micronutrients such as iodine, selenium, iron, zinc, copper, magnesium, vitamin A, and vitamin B12 influence thyroid hormone synthesis and regulation throughout life. Dietary changes can alter the gut microbiota, leading not just to dysbiosis and micronutrient deficiency but also to changes in thyroid function through immunological regulation, nutrient absorption, and epigenetic changes. Nutritional imbalance can lead to thyroid dysfunction and/or disorders, such as hypothyroidism and hyperthyroidism, and possibly contribute to autoimmune thyroid diseases and thyroid cancer, yet controversial issues. Understanding these relationships is important to rationalize a balanced diet rich in essential micronutrients for maintaining thyroid health and preventing thyroid-related diseases. The synthetic comprehensive overview of current knowledge shows the importance of micronutrients and gut microbiota for thyroid function and uncovers potential gaps that require further investigation. [ABSTRACT FROM AUTHOR]

The advancement of genetic knowledge and the discovery of an increasing number of genetic disorders has made the role of the geneticist progressively more complex and fundamental. However, most genetic disorders present during childhood; thus, their early recognition is a challenge for the pediatrician, who will be also involved in the follow-up of these children, often establishing a close relationship with them and their families and becoming a referral figure. In this review, we aim to provide the pediatrician with a general knowledge of the approach to treating a child with a genetic syndrome associated with dysmorphic features. We will discuss the red flags, the most common manifestations, the analytic collection of the family and personal medical history, and the signs that should alert the pediatrician during the physical examination. We will offer an overview of the physical malformations most commonly associated with genetic defects and the way to describe dysmorphic facial features. We will provide hints about some tools that can support the pediatrician in clinical practice and that also represent a useful educational resource, either online or through apps downloaded on a smartphone. Eventually, we will offer an overview of genetic testing, the ethical considerations, the consequences of incidental findings, and the main indications and limitations of the principal technologies. [ABSTRACT FROM AUTHOR]

A healthy and balanced diet is crucial for children's well-being and aids in preventing diet-related illnesses. Furthermore, unhealthy dietary habits indirectly impact children's health, as the food industry stands as one of the primary drivers of climate change. Evidence shows the Mediterranean diet is sustainable for both children's and the planet's health. The aim of this cross-sectional study was to evaluate the eating habits of children aged between 6 months and 3 years, in the province of Modena and Reggio Emilia, in Italy, along with their adherence to the guidelines for a healthy diet, and examine the role of pediatricians in promoting knowledge about nutrition and sustainability. In our sample (218 children), most children exceeded the recommended meat and cheese intake, while consuming insufficient amounts of vegetables, fruit, and legumes. Vegetable and fruit consumption declined with the increase in age category while eating sweets, soft drinks, and processed food increased. Incorporating school meals' data into this analysis, we observed a modification in dietary compliance, characterized by an increase in meat and cheese consumption, alongside improvements in the intake of vegetables, fruits, fish, eggs, and legumes. This study suggests that supporting an integrated approach that combines social and educational initiatives is crucial. Future research should prioritize fostering sustainable eating habits within communities to facilitate dietary habits' transformation and encourage healthier lifestyles. [ABSTRACT FROM AUTHOR]

Therapeutic hypothermia (TH) is the standard of care for newborns with moderate to severe hypoxic–ischemic encephalopathy (HIE). Discomfort and pain during treatment are common and may affect the therapeutic efficacy of TH. Opioid sedation and analgesia (SA) are generally used in clinical practice, and fentanyl is one of the most frequently administered drugs. However, although fentanyl's pharmacokinetics (PKs) may be altered by hypothermic treatment, the PK behavior of this opioid drug in cooled newborns with HIE has been poorly investigated. The aim of this phase 1 study protocol (Trial ID: FentanylTH; EUDRACT number: 2020-000836-23) is to evaluate the fentanyl time-concentration profiles of full-term newborns with HIE who have been treated with TH. Newborns undergoing TH receive a standard fentanyl regimen (2 mcg/Kg of fentanyl as a loading dose, followed by a continuous infusion—1 mcg/kg/h—during the 72 h of TH and subsequent rewarming). Fentanyl plasma concentrations before bolus administration, at the end of the loading dose, and 24-48-72-96 h after infusion are measured. The median, maximum, and minimum plasma concentrations, together with drug clearance, are determined. This study will explore the fentanyl time-concentration profiles of cooled, full-term newborns with HIE, thereby helping to optimize the fentanyl SA dosing regimen during TH. [ABSTRACT FROM AUTHOR]

In 1990, Gorlin et al. described four types of craniofacial duplications: (1) single mouth with duplication of the maxillary arch; (2) supernumerary mouth laterally placed with rudimentary segments; (3) single mouth with replication of the mandibular segments; and (4) true facial duplication, namely diprosopus. We describe a newborn born with wide-spaced eyes, a very broad nose, and two separate mouths. Workup revealed the absence of the corpus callosum and the presence of a brain midline lipoma, wide sutures, and a Chiari I malformation with cerebellar herniation. We conducted a systematic review of the literature and compared all the cases described as diprosopus. In 96% of these, the central nervous system is affected, with anencephaly being the most commonly associated abnormality. Other associated anomalies include cardiac malformations (86%), cleft palate (63%), diaphragmatic hernia (13%), and disorder of sex development (DSD) (13%). Although the facial features are those that first strike the eye, the almost obligate presence of cerebral malformations suggests a disruptive event in the cephalic pole of the forming embryo. No major monogenic contribution has been recognized today for this type of malformation. [ABSTRACT FROM AUTHOR]

Detection and treatment of patients with familial hypercholesterolemia (FH) starting from childhood is fundamental to reduce morbidity and mortality. The activity of National realities such as the LIPIGEN (LIpid transPort disorders Italian GEnetic Network) Paediatric Group, founded in 2018, is a milestone in this context. The aim of this exploratory survey, conducted in October 2021 among Italian lipid clinics included in the LIPIGEN Paediatric Group, was to investigate the current clinical approach in the management and treatment of paediatric patients with suspected FH. A digital questionnaire composed of 20 questions investigating nutritional treatment and nutraceutical and pharmacological therapy for children and adolescents with FH was proposed to the principal investigators of 30 LIPIGEN centres. Twenty-four centres responded to the section referring to children aged < 10 years and 30 to that referring to adolescents. Overall, 66.7% of children and 73.3% of adolescents were given lipid-lowering nutritional treatment as the first intervention level for at least 3–4 months (29.2% and 23.3%) or 6–12 months (58.3% and 53.3%). Nutraceuticals were considered in 41.7% (regarding children) and 50.0% (regarding adolescents) of the centres as a supplementary approach to diet. Lipid-lowering drug therapy initiation was mainly recommended (91.7% and 80.0%). In 83.3% of children and 96.7% of adolescents, statins were the most frequently prescribed drug. We highlighted several differences in the treatment of paediatric patients with suspected FH among Italian centres; however, the overall approach is in line with the European Atherosclerosis Society (EAS) recommendations for FH children and adolescents. We consider this survey as a starting point to reinforce collaboration between LIPIGEN centres and to elaborate in the near future a consensus document on the management of paediatric patients with suspected FH so as to improve and uniform detection, management, and treatment of these patients in our country. [ABSTRACT FROM AUTHOR]

Pediatric sarcomas are rare malignancies accounting for about 10% of solid tumors in childhood. Sarcomas represent a heterogeneous group of malignancies, especially they include Rhabdomyosarcoma (RMS) and Non-Rhabdomyosarcoma Type Sarcomas (STSNR). Therapeutic management of pediatric sarcomas is challenging. Multidisciplinary approach including chemotherapy, surgery and radiotherapy is the treatment of choice. The correct management of affected patients can be demanding, especially in terms of preserving a good quality of life (QoL). In the present study we described our experience with a series of patients diagnosed with head and neck non-metastatic sarcoma between January 1995 and December 2020, referred to Pediatric Oncology or to Maxillo-Facial Surgery of University Hospital of Modena and Reggio Emilia.The survivors were asked to complete questionnaires on health-related quality of life (HRQoL; PedsQL and EORTC QLQ-H&N 43). We found satisfactory results in terms of global HRQoL; although outstanding issues persist, such as deterioration in masticatory function, and speech. Long-term sequelae of multimodality treatment may lead to both significant aesthetic-functional and psychosocial implications that need to be further investigate during the whole the care pathway. [ABSTRACT FROM AUTHOR]

In the frame of metabolic syndrome, type 2 diabetes emerges along a continuum of the risk from the clustering of all its components, namely visceral obesity, high blood pressure and lipids, and impaired glucose homeostasis. Insulin resistance is the hallmark common to all the components and, in theory, is a reversible condition. Nevertheless, the load that this condition can exert on the β-cell function at the pubertal transition is such as to determine its rapid and irreversible deterioration leading to plain diabetes. The aim of this review is to highlight, in the context of metabolic syndrome, age-specific risk factors that lead to type 2 diabetes onset in youth; resume age specific screening and diagnostic criteria; and anticipate potential for treatment. Visceral obesity and altered lipid metabolism are robust grounds for the development of the disease. Genetic differences in susceptibility to hampered β-cell function in the setting of obesity and insulin resistance largely explain why some adolescents with obesity do develop diabetes at a young age and some others do not. Lifestyle intervention with a healthy diet and physical activity remains the pillar of the type 2 diabetes treatment in youth. As to the pharmacological management, metformin and insulin have failed to rescue β-cell function and to ensure long-lasting glycemic control in youth. A new era might start with the approval for use in pediatric age of drugs largely prescribed in adults, such as dipeptidyl peptidase-4 and sodium-dependent glucose transport inhibitors, and of new weight-lowering drugs in the pipeline such as single and multiple agonists of the glucagon-like peptide 1 receptor. The latter drugs can have tremendous impact on the natural history of the disease. By treating diabetes, they will reduce the burden of all the metabolic abnormalities belonging to the syndrome while causing a tremendous weight loss hitherto never seen before. [ABSTRACT FROM AUTHOR]

Central nervous system (CNS) neoplasms are the most common solid tumors diagnosed in children. CNS tumors represent the leading cause of cancer death and cancer-related morbidity for children less than 20 years of age, although there has been a moderate increase in survival rates over the past several decades. The average survival at 5 years now nearly reaches 75%, and for some, non-malignant histology approximates 97% at 20 years from diagnosis. Neurological, cognitive, and neuropsychological deficits are the most disabling long-term effects of brain tumors in children. Childhood is a time of extreme brain sensitivity and the time of life in which most brain development occurs. Thus, the long-term toxicities that children treated for CNS tumors experience can affect multiple developmental domains and day-to-day functioning, ultimately leading to a poor quality of survival (QoS). We reviewed literature focusing on the risk factors for cognitive and neuropsychological impairment in pediatric patients treated for brain tumors with the aim of better understanding who is at major risk and what the best strategies for monitoring these patients are. [ABSTRACT FROM AUTHOR]

The use of umbilical venous catheters (UVCs) has become the standard of care in the neonatal intensive care unit (NICU) to administer fluids, medications and parenteral nutrition. However, it is well known that UVCs can lead to some serious complications, both mechanical and infective, including CLABSI (Central Line-Associated Bloodstream Infections). Most authors recommend removing UVC within a maximum of 14 days from its placement. However, the last Infusion Therapy Standards of Practice (INS) guidelines recommends limiting the UVC dwell time to 7 to 10 days, to reduce risks of infectious and thrombotic complications. These guidelines also suggest as an infection prevention strategy to remove UVC after 4 days, followed by the insertion of a PICC if a central line is still needed. Nevertheless, the maximum UVC dwell time to reduce the risk of CLABSI is still controversial, as well as the time of its replacement with a PICC. In this study we reviewed a total of 177 articles, found by using the PubMed database with the following search strings: "UVC AND neonates", "(neonate* OR newborn*) AND (UVC OR central catheter*) AND (infection*)". We also analyze the INS guidelines to provide the reader an updated overview on this topic. The purpose of this review is to give updated information on CVCs infectious risks by examining the literature in this field. These data could help clinicians in deciding the best time to remove or to replace the UVC with a PICC, to reduce CLABSIs risk. Despite the lack of strong evidence, the risk of CLABSI seems to be minimized when UVC is removed/replaced within 7 days from insertion and this indication is emerging from more recent and larger studies. [ABSTRACT FROM AUTHOR]

Background: Environmental factors seem to influence clinical manifestations of sickle cell disease (SCD), but few studies have shown consistent findings. We conducted a retrospective multicentric observational study to investigate the influence of environmental parameters on hospitalization for vaso-occlusive crises (VOC) or acute chest syndrome (ACS) in children with SCD. Methods: Hospital admissions were correlated with daily meteorological and air-quality data obtained from Environmental Regional Agencies in the period 2011–2015. The effect of different parameters was assessed on the day preceding the crisis up to ten days before. Statistical analysis was performed using a quasi-likelihood Poisson regression in a generalized linear model. Results: The risk of hospitalization was increased for low maximum temperature, low minimum relative humidity, and low atmospheric pressure and weakly for mean wind speed. The diurnal temperature range and temperature difference between two consecutive days were determined to be important causes of hospitalization. For air quality parameters, we found a correlation only for high levels of ozone and for low values at the tail corresponding to the lowest concentration of this pollutant. Conclusions: Temperature, atmospheric pressure, humidity and ozone levels influence acute complications of SCD. Patients' education and the knowledge of the modes of actions of these factors could reduce hospitalizations. [ABSTRACT FROM AUTHOR]

Urinary tract infection (UTI) is one of the most common infectious diseases in the pediatric population and represents a major cause of antibiotic consumption and hospitalization in children. Considering the ongoing controversies on the management of pediatric UTI and the challenges due to increasing antimicrobial resistance, the aim of the present study was to evaluate the level of agreement on UTI management in pediatric age in Emilia-Romagna Region, Italy, and to assess on the basis of recent studies whether there is the need to change current recommendations used by primary care pediatricians, hospital pediatricians, and pediatric surgeons in everyday clinical practice to possibly improve outcomes. This consensus provides clear and shared indications on UTI management in pediatric age, based on the most updated literature. This work represents, in our opinion, the most complete and up-to-date collection of statements on procedures to follow for pediatric UTI, in order to guide physicians in the management of the patient, standardize approaches, and avoid abuse and misuse of antibiotics. Undoubtedly, more randomized and controlled trials are needed in the pediatric population to better define the best therapeutic management in cases with antimicrobial resistance and real usefulness of long-term antibiotic prophylaxis. [ABSTRACT FROM AUTHOR]

Background: Neonatal encephalopathy due to perinatal asphyxia is one of the leading causes of neonatal death and morbidity worldwide. The neurodevelopmental outcomes of asphyxiated neonates have considerably improved after therapeutic hypothermia (TH). The current challenge is to identify all newborns with encephalopathy at risk of cerebral lesions and subsequent disability within 6 h of life and who may be within the window period for treatment with TH. This study evaluated the neurodevelopmental outcomes in surviving asphyxiated neonates who did and did not receive TH, based on clinical and polygraphic electroencephalographic (p-EEG) criteria. Methods: The study included 139 asphyxiated newborns divided into two groups: 82 who received TH and 57 who were not cooled. TH was administered to asphyxiated newborns (gestational age ≥ 35 weeks, birth weight ≥ 1800 g) with encephalopathy of any grade and moderate-to-severe p-EEG abnormalities or seizures. Neurodevelopmental outcomes between the groups at 24 months of life and the risk factors for severe outcomes were assessed. Results: Severe neurodevelopmental impairment occurred in 10 (7.2%) out of the 139 enrolled neonates. Nine out of the 82 cooled neonates (11.0%) had severe neurodevelopmental impairment. All but one neonate (98.2%) who did not receive TH had normal outcomes. The multivariate logistic regression analysis showed that abnormal p-EEG patterns (OR: 27.6; IC: 2.8–267.6) and general movements (OR: 3.2; IC: 1.0–10.0) were significantly associated with severe neurodevelopmental impairment (area under ROC curve: 92.7%). Conclusion: The combination of clinical and p-EEG evaluations in hypoxic–ischemic encephalopathy contributed to a more accurate selection of patients treated with therapeutic hypothermia. When administered to infants with moderate to severe p-EEG abnormalities, TH prevents approximately 90% of severe neurodevelopmental impairment after any grade of hypoxic–ischemic encephalopathy. [ABSTRACT FROM AUTHOR]

With the spread of antibiotic resistance in pediatric urinary tract infections (UTIs), more patients are likely to be started empirically on antibiotics to which pathogens are later found to be resistant (discordant therapy). However, in-vivo effectiveness may be different from in-vitro susceptibility. Aims of this study were to describe clinical outcomes of discordant empirical treatments in pediatric UTIs and to investigate risk factors associated to treatment failure. This observational, retrospective study was conducted on children hospitalized for febrile UTIs with positive urine culture and started on discordant empirical therapy. Failure rates of discordant treatments and associated risk factors were investigated. A total of 142/1600 (8.9%) patients were treated with inadequate empirical antibiotics. Clinical failure was observed in 67/142 (47.2%) patients, with no fatal events. Higher failure rates were observed for combinations of penicillin and beta-lactamase inhibitors (57.1%). Significant risk factors for failure of discordant treatment were history of recurrent UTIs (95% CI: 1.13–9.98, OR: 3.23, p < 0.05), recent use of antibiotics (95% CI: 1.46–21.82, OR: 5.02, p < 0.01), infections caused by Pseudomonas aeruginosa (95% CI: 1.85–62.10, OR: 7.30, p < 0.05), and empirical treatment with combinations of penicillin and beta-lactamase inhibitors (95% CI: 0.94–4.03, OR: 1.94, p = 0.05). This study showed that discordant empirical treatments may still be effective in more than half of pediatric UTIs. Clinical effectiveness varies between different discordant antibiotics in pediatric UTIs, and patients presenting risk factors for treatment failure may need a differentiated empirical approach. [ABSTRACT FROM AUTHOR]

Enteroviruses (EVs) are an important source of infection in the paediatric age, with most cases concerning the neonatal age and early infancy. Molecular epidemiology is crucial to understand the circulation of main serotypes in a specific area and period due to their extreme epidemiological variability. The diagnosis of EVs infection currently relies on the detection of EVs RNA in biological samples (usually cerebrospinal fluid and plasma, but also throat swabs and feces) through a polymerase chain reaction assay. Although EVs infections usually have a benign course, they sometimes become life threatening, especially when symptoms develop in the first few days of life. Mortality is primarily associated with myocarditis, acute hepatitis, and multi-organ failure. Neurodevelopmental sequelae have been reported following severe infections with central nervous system involvement. Unfortunately, at present, the treatment of EVs infections is mainly supportive. The use of specific antiviral agents in severe neonatal infections has been reported in single cases or studies including few neonates. Therefore, further studies are needed to confirm the efficacy of these drugs in clinical practice. [ABSTRACT FROM AUTHOR]

Background: Prolonged mechanical ventilation in preterm infants may cause complications. We aimed to analyze the variables affecting extubation outcomes in preterm infants at high risk of extubation failure. Methods: This was a single-center, observational, retrospective study. Extubation failure was defined as survival with the need for reintubation within 72 h. Successfully extubated neonates (group 1) were compared to those with failed extubation (group 2). Multivariate logistic regression analysis evaluated factors that predicted extubation outcomes. Results: Eighty infants with a birth weight under 1000 g and/or gestational age (GA) under 28 weeks were included. Extubation failure occurred in 29 (36.2%) and success in 51 (63.8%) neonates. Most failures (75.9%) occurred within 24 h. Pre-extubation inspired oxygen fraction (FiO2) of 27% had a sensitivity of 58.6% and specificity of 64.7% for extubation failure. Post-extubation FiO2 of 32% had a sensitivity of 65.5% and specificity of 62.8% for failure. Prolonged membrane rupture (PROM) and high GA were associated with extubation success in multivariate logistic regression analysis. Conclusions: High GA and PROM were associated with extubation success. Pre- and post-extubation FiO2 values were not significantly predictive of extubation failure. Further studies should evaluate if overall assessment, including ventilatory parameters and clinical factors, can predict extubation success in neonates. [ABSTRACT FROM AUTHOR]

(1) Background: Changes in the clinical presentation of celiac disease (CD) in children have been reported. The guidelines of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) allow esophagogastroduodenoscopy (EGD) with biopsies to be avoided under specific circumstances. We aimed to assess the clinical picture of pediatric CD patients at diagnosis and to validate ESPGHAN non-biopsy criteria. (2) Methods: Patients with suspected CD or undergoing screening from 2004 to 2014 at the University Hospital in Modena, Italy were enrolled. The accuracy of ESPGHAN non-biopsy criteria and modified versions were assessed. (3) Results: In total, 410 patients were enrolled, of whom 403 were considered for analysis. Of the patients considered, 45 were asymptomatic and diagnosed with CD (11.2%) while 358 patients (88.2%) were symptomatic, of whom 295 were diagnosed with CD. Among symptomatic CD patients, 57 (19.3%) had gastrointestinal symptoms, 98 (33%) had atypical symptoms and 140 (47.4%) had both. No difference was found for the presence of gastrointestinal symptoms at different ages. The non-biopsy ESPGHAN criteria yielded an accuracy of 59.4% with a positive predictive value (PPV) of 100%; 173 out of 308 EGD (56.2%) could have been avoided. The modified 7× and 5× upper limit of normal cut-offs for IgA anti tissue-transglutaminase reached 60.7% and 64.3% of EGD avoided, respectively. (4) Conclusions: Over 10 years, late age at diagnosis and increased rates of atypical CD presentation were found. ESPGHAN non-biopsy criteria are accurate for CD diagnosis and allow half of unneeded EGD to be avoided. Modified versions allowed sparing a greater number of EGD. [ABSTRACT FROM AUTHOR]

The development and spread of antibiotic resistance is an increasingly important global public health problem, even in paediatric urinary tract infection (UTI). In light of the variability in the data, it is necessary to conduct surveillance studies to determine the prevalence of antibiotic resistance in specific geographical areas to optimize therapeutic management. In this observational, retrospective, multicentre study, the medical records of 1801 paediatric patients who were hospitalised for UTI between 1 January 2012, and 30 June 2020, in Emilia-Romagna, Italy, were analysed. Escherichia coli was the most frequently detected pathogen (75.6%), followed by Klebsiella pneumoniae (6.9%) and Pseudomonas aeruginosa (2.5%). Overall, 840 cases (46.7%) were due to antimicrobial-resistant uropathogens: 83 (4.7%) extended spectrum beta-lactamase (ESBL)-producing, 119 (6.7%) multidrug resistant (MDR) and 4 (0.2%) extensively drug resistant (XDR) bacteria. Empirical antibiotic therapy failed in 172 cases (9.6%). Having ESBL or MDR/XDR uropathogens, a history of recurrent UTI, antibiotic therapy in the preceding 30 days, and empirical treatment with amoxicillin or amoxicillin/clavulanate were significantly associated with treatment failure, whereas first-line therapy with third-generation cephalosporins was associated with protection against negative outcomes. In conclusion, the increase in the resistance of uropathogens to commonly used antibiotics requires continuous monitoring, and recommendations for antibiotic choice need updating. In our epidemiological context, amoxicillin/clavulanate no longer seems to be the appropriate first-line therapy for children hospitalised for UTI, whereas third-generation cephalosporins continue to be useful. To further limit the emergence of resistance, every effort to reduce and rationalise antibiotic consumption must be implemented. [ABSTRACT FROM AUTHOR]

Prader–Willi syndrome (PWS) is a rare disease determined by the loss of the paternal copy of the 15q11-q13 region, and it is characterized by hypotonia, hyperphagia, obesity, short stature, hypogonadism, craniofacial dysmorphisms, and cognitive and behavioral disturbances. The aims of this retrospective study were to analyze interictal EEG findings in a group of PWS patients and to correlate them with genetic, clinical, and neuroimaging data. The demographic, clinical, genetic, EEG, and neuroimaging data of seventy-four patients were collected. Associations among the presence of paroxysmal EEG abnormalities, genotype, and clinical and neuroimaging features were investigated. Four patients (5.4%) presented drug-sensitive epilepsy. Interictal paroxysmal EEG abnormalities—focal or multifocal—were present in 25.7% of the cases, and the normalization of the EEG occurred in about 25% of the cases. In 63.2% of the cases, the paroxysmal abnormalities were bilaterally localized over the middle–posterior regions. Brain magnetic resonance imaging (MRI) was performed on 39 patients (abnormal in 59%). No relevant associations were found between paroxysmal EEG abnormalities and all of the other variables considered. Interictal paroxysmal EEG abnormalities—in particular, with a bilateral middle–posterior localization—could represent an important neurological feature of PWS that is not associated with genotype, cognitive or behavioral endophenotypes, MRI anomalies, or prognosis. [ABSTRACT FROM AUTHOR]

Monoclonal antibodies (mAbs) that neutralize SARS-CoV-2 in infected patients are a new class of antiviral agents approved as a type of passive immunotherapy. They should be administered to adults and children (≥12 years old, weighing ≥ 40 kg) with SARS-CoV-2 positivity, and who are suffering from a chronic underlying disease and are at risk of severe COVID-19 and/or hospitalization. The aim of this manuscript is to discuss the benefit-to-risk of mAb therapy to treat COVID-19 in pediatric age, according to current reports. A problem is that the authorization for mAbs use in children was given without studies previously evaluating the efficacy, safety and tolerability of mAbs in pediatric patients. Moreover, although the total number of children with chronic severe underlying disease is not marginal, the risk of severe COVID-19 in pediatric age is significantly reduced than in adults and the role of chronic underlying disease as a risk factor of severe COVID-19 development in pediatric patients is far from being precisely defined. In addition, criteria presently suggested for use of mAbs in children and adolescents are very broad and may cause individual clinicians or institutions to recommend these agents on a case-by-case basis, with an abuse in mAbs prescriptions and an exacerbation of health inequalities while resources are scarce. Several questions need to be addressed before their routine use in clinical practice, including what is their associated benefit-to-risk ratio in children and adolescents, who are the patients that could really have benefit from their use, and if there is any interference of mAb therapy on recommended vaccines. While we wait for answers to these questions from well-conducted research, an effective and safe COVID-19 vaccine for vulnerable pediatric patients remains the best strategy to prevent COVID-19 and represents the priority for public health policies. [ABSTRACT FROM AUTHOR]

Phthalates, as other endocrine disrupting chemicals (EDCs), may alter the homeostasis and the action of hormones and signaling molecules, causing adverse health outcomes. This is true especially for infants, who are both more exposed and sensitive to their effects. Phthalates are particularly harmful when the exposure occurs during certain critical temporal windows of the development, such as the prenatal and the early postnatal phases. Phthalates may also interfere with the neuroendocrine systems (e.g., thyroid hormone signaling or metabolism), causing disruption of neuronal differentiation and maturation, increasing the risk of behavioral and cognitive disorders (ADHD and autistic behaviors, reduced mental, psychomotor, and IQ development, and emotional problems). Despite more studies being needed to better understand the role of these substances, plenty of evidence suggests the impact of phthalates on the neuroendocrine system development and function. This review aims to update the knowledge on the neuroendocrine consequences of neonatal and perinatal exposure to phthalates. [ABSTRACT FROM AUTHOR]

There is insufficient data regarding antimicrobial stewardship (AS) and outcomes of very low birth weight (VLBW) neonates after AS programs. This observational, retrospective study addressed AS and outcomes of VLBW neonates admitted to an Italian level-three center. Two periods were compared: (i) baseline, before AS (January 2011–December 2012) and (ii) intervention, after AS (January 2016–December 2017). Between these two periods, procedures were put in place to inform medical and nursing staff regarding AS. There were 111 and 119 VLBW neonates in the baseline (6744 live births) and in the intervention period (5902 live births), respectively. The number of infants exposed to antibiotics (70%) during the hospital stay did not change, but the total days of therapy (DOT, median 12 vs. 5) and DOT/1000 patient days (302 vs. 215) decreased in the intervention period (p < 0.01), as well as the median duration of first antibiotic treatment (144 vs. 48 h, p < 0.01). A re-analysis of single cases of culture-proven or culture-negative sepsis failed to demonstrate any association between deaths and a delay or insufficient antibiotic use in the intervention period. In conclusion, AS is feasible in preterm VLBW neonates and antibiotic use can be safely reduced. [ABSTRACT FROM AUTHOR]

Background: Intestinal failure (IF) is defined as reduction in functioning gut mass below the minimal amount necessary for adequate digestion and absorption. In most cases, IF results from intrinsic diseases of the gastrointestinal tract (digestive IF) (DIF); few cases arise from digestive vascular components, gut annexed (liver and pancreas) and extra-digestive organs or from systemic diseases (non-digestive IF) (NDIF). The present review revised etiology and treatments of DIF and NDIF, with special focus on the pathophysiological mechanisms, whereby NDIF develops. Methods: We performed a comprehensive search of published literature from January 2010 to the present by selecting the following search strings: "intestinal failure" OR "home parenteral nutrition" OR "short bowel syndrome" OR "chronic pseudo-obstruction" OR "chronic intestinal pseudo-obstruction" OR "autoimmune enteropathy" OR "long-term parenteral nutrition". Results: We collected overall 1656 patients with well-documented etiology of IF: 1419 with DIF (86%) and 237 with NDIF (14%), 55% males and 45% females. Among DIF cases, 66% had SBS and among NDIF cases 90% had malabsorption/maldigestion. Conclusions: The improved availability of diagnostic and therapeutic tools has increased prevalence and life expectancy of rare and severe diseases responsible for IF. The present review greatly expands the spectrum of knowledge on the pathophysiological mechanisms through which the diseases not strictly affecting the intestine can cause IF. In view of the rarity of the majority of pediatric IF diseases, the development of IF Registries is strongly required; in fact, through information flow within the network, the Registries could improve IF knowledge and management. [ABSTRACT FROM AUTHOR]

Type 1 diabetes (T1D) is the most common chronic metabolic disease in children and adolescents. The etiology of T1D is not fully understood but it seems multifactorial. The genetic background determines the predisposition to develop T1D, while the autoimmune process against β-cells seems to be also determined by environmental triggers, such as endocrine disrupting chemicals (EDCs). Environmental EDCs may act throughout different temporal windows as single chemical agent or as chemical mixtures. They could affect the development and the function of the immune system or of the β-cells function, promoting autoimmunity and increasing the susceptibility to autoimmune attack. Human studies evaluating the potential role of exposure to EDCs on the pathogenesis of T1D are few and demonstrated contradictory results. The aim of this narrative review is to summarize experimental and epidemiological studies on the potential role of exposure to EDCs in the development of T1D. We highlight what we know by animals about EDCs' effects on mechanisms leading to T1D development and progression. Studies evaluating the EDC levels in patients with T1D were also reported. Moreover, we discussed why further studies are needed and how they should be designed to better understand the causal mechanisms and the next prevention interventions. [ABSTRACT FROM AUTHOR]

Puberty is the process of physical changes between childhood and adulthood during which adolescents reach sexual maturity and become capable of reproduction. It is considered one of the main temporal windows of susceptibility for the influence of the endocrine-disrupting chemicals (EDCs). EDCs may act as single chemical agents or as chemical mixtures; they can be pubertal influencers, accelerating and anticipating the processing of maturation of secondary sexual characteristics. Moreover, recent studies have started to point out how exposure to EDCs during puberty may predispose to breast cancer later in life. In fact, the estrogen-mimicking endocrine disruptors (EEDs) may influence breast tissue development during puberty in two main ways: the first is the action on the proliferation of the breast stromal cells, the second concerns epigenetic mechanisms. The aim of this mini-review was to better highlight what is new and what is not completely known regarding the role of EDCs during puberty. [ABSTRACT FROM AUTHOR]

General movements (GMs) in combination with neurological examination and magnetic resonance imaging at term age can accurately determine the risk of cerebral palsy. The present study aimed to assess whether 11 motor and postural patterns concomitant with GMs were associated with cerebral palsy. Video recordings performed after birth in 79 preterm infants were reviewed retrospectively. Thirty-seven infants developed cerebral palsy at 2 years corrected age and the remaining 42 showed typical development. GMs were assessed from preterm to fidgety age and GM trajectories were defined. The 11 motor and postural patterns were evaluated at each age and longitudinally, alone and in combination with GM trajectories. A logistic regression model was used to assess the association between GMs, concomitant motor and postural patterns, and cerebral palsy. We confirmed that high-risk GM trajectories were associated with cerebral palsy (odds ratio = 44.40, 95% confidence interval = 11.74–167.85). An association between concomitant motor and postural patterns and cerebral palsy was found for some of the patterns at term age and for all of them at fidgety age. Therefore, at term age, concomitant motor and postural patterns can support GMs for the early diagnosis of cerebral palsy. [ABSTRACT FROM AUTHOR]

Wildlife has often presented and suggested the effects of endocrine disrupting chemicals (EDCs). Animal studies have given us an important opportunity to understand the mechanisms of action of many chemicals on the endocrine system and on neurodevelopment and behaviour, and to evaluate the effects of doses, time and duration of exposure. Although results are sometimes conflicting because of confounding factors, epidemiological studies in humans suggest effects of EDCs on prenatal growth, thyroid function, glucose metabolism and obesity, puberty, fertility, and on carcinogenesis mainly through epigenetic mechanisms. This manuscript reviews the reports of a multidisciplinary national meeting on this topic. [ABSTRACT FROM AUTHOR]