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Background In response to the COVID-19 pandemic, drastic measures for social distancing have been introduced also in Italy, likely with a substantial impact in delicate conditions like pregnancy and puerperium. The study aimed to investigate the changes in lifestyle, access to health services, and mental wellbeing during the first Italian lockdown in a sample of Italian pregnant women and new mothers. Methods We carried out a web-based survey to evaluate how pregnant women and new mothers were coping with the lockdown. We collected data about healthy habits (physical exercise and dietary habits), access to health services (care access, delivery and obstetric care, neonatal care, and breastfeeding), and mental wellbeing (psychological well-being and emotive support). Descriptive analysis was performed for both groups of participants, whereas a Poisson analysis was used to measure the association between some structural variables (age, education, socio-economic data, partner support, contact, free time, previous children, and pregnancy trimester) and anxiety or depression, difficulties in healthy eating and reduction in physical activity after lockdown started. Chi2 and Adjusted Prevalence Ratios were estimated only for pregnant women. Results We included 739 respondents (response rate 85.8 %), 600 were pregnant (81.2 %), and 139 (18.8 %) had delivered during lockdown (new mothers). We found a high score for anxiety and depression in 62.8 % of pregnant women and 61.9 % of new mothers. During the lockdown, 61.8 % of pregnant women reduced their physical exercise, and 44.3 % reported eating in a healthier way. 94.0 % of new mothers reported to have breastfed their babies during the hospital stay. Regarding the perceived impact of restrictive measures on breastfeeding, no impact was reported by 56.1 % of new mothers, whereas a negative one by 36.7 %. Conclusions The high prevalence of anxiety and depressive symptoms in pregnant women and new mothers should be a public health issue. Clinicians might also recommend and encourage “home” physical exercise. On the other hand, about half of the sample improved their approach towards healthy eating and a very high breastfeeding rate was reported soon after birth: these data are an interesting starting point to develop new strategies for public health.

The objective of this study was to identify clinical and/or metabolic predictive factors of genetic obesity. Subjects aged ≤ 18 years with obesity (BMI ≥ 97 th percentile) followed-up at the Paediatric Endocrinology Clinic of Maggiore Hospital in Novara, Italy were screened for genes associated with obesity by next-generation sequencing. Anamnestic, anthropometric, and biochemical data were collected, and parents completed two questionnaires, to screen for hyperphagia and daytime sleepiness, respectively. The study included 50 patients. Six genetic variants (6/50 patients,12%) were classified as pathogenic/likely pathogenic, three (3/50 patients,6%) as polygenic, and 16 (13/50 patients,26%) as variants of uncertain clinical significance (VUS). Eight patients carried > 1 variant. All pathogenic mutations were in genes implicated in the hypothalamic melanocortin pathway or responsible for syndromic obesity. All subjects with definitive genetic diagnosis developed obesity before five years of age. There were no statistically significant differences in auxological nor metabolic parameters between the three genetic patterns of absent genetic mutations, VUS, and pathogenic/likely pathogenic mutations. Finally, a Genetic Obesity Risk Score was developed using logistic regression analysis, selecting Hyperphagia Questionnaire score, age of onset of obesity, and family history as variables. Genetic screening of our cohort of children and adolescents with severe obesity revealed pathogenic/polygenic variants in 18% of cases, with PCSK1 the most frequently mutated gene and with a definitive genetic diagnosis in 3 patients. Identifying clinical, behavioral, and metabolic features predictive of genetic obesity would facilitate early diagnosis and tailored management.

Rates of antibiotic-resistant bacteria have increased worldwide over recent years, but the Italian Institute of Health reported a disruption to this trend in 2021 compared with 2020. Children are often recipients of unnecessary antibiotic prescriptions, especially for respiratory tract infections (RTIs). During the initial phase of the COVID-19 pandemic, common RTIs substantially decreased, so it is conceivable that antibiotic prescriptions also reduced during this time. To test this hypothesis, we retrospectively collected data on all visits to a pediatric primary care clinic in Northern Italy from February 20, 2020 to June 2, 2020 and compared data with the same period in 2019. We evaluated the antibiotic prescription rate according to the diagnosis at discharge. While the total number of visits significantly decreased (1335 in 2020 vs. 4899 in 2019), there was only a slight reduction in the antibiotic prescription rate (1039 in 2019, 21.2%, vs. 272 in 2020, 20.4%). However, this corresponded to a 73.8% decrease in the total number of antibiotic prescriptions, with antibiotics for RTI accounting for 69% of the total reduction. It is possible that, at the larger scale, reduced antibiotic prescription in pediatrics during the COVID-19 pandemic resulted in a slight reduction in antimicrobial resistance.

In our third-level Neonatal Unit in Northern Italy, we recorded a high rate of neonatal hyperbilirubinemia requiring phototherapy in March-November 2020, during the first phase of COVID-19 pandemic, compared to the previous year (198/1348, 14.2%, vs 141/1432, 9.8%, p  = 0.0004). Supposing it could be the result of neonatal polycythemia, we evaluated capillary hematocrit (Hct) and the rate of hyperbilirubinemia in all newborns ≥36 weeks gestational age born in December 2020. Out of 73 neonates, 37 had Hct ≥65% (50.7%). However, as capillary blood samples may overestimate Hct by 5-15%, even downsizing all values by 15%, Hct was still ≥65% in 9/73 neonates (12.3%), much higher than 0.4-5% prevalence of polycythemia reported in healthy newborns. All those newborns were singleton and healthy, with no clinical signs of hyperviscosity and no underlying factors predisposing to polycythemia. Out of 73 newborns, 13 (17.8%) developed hyperbilirubinemia requiring phototherapy. Their mean Hct value was 66.3 ± 8.2%. Since hyperbilirubinemia is common in the offspring of women with SARS-CoV-2 infection and we recorded increased rates of neonatal hyperbilirubinemia in the first phase of COVID-19 pandemic, it could be hypothesized that even asymptomatic Sars-CoV2 infection during pregnancy might cause placental vascular malperfusion, eliciting polycythemia in the fetus as a compensatory response, that could be the link between COVID-19 in the mothers and hyperbilirubinemia in the newborns.

The restrictive measures adopted worldwide against SARS-CoV-2 produced a drastic reduction in respiratory pathogens, including RSV, but a dramatic rebound was thereafter reported. In this multicenter retrospective observational study in 15 Pediatric Emergency Departments, all children <3 years old with RSV infection admitted between 1 September and 31 December 2021 were included and compared to those admitted in the same period of 2020 and 2019. The primary aim was to evaluate RSV epidemiology during and after the COVID-19 pandemic peak. The secondary aims were to evaluate the clinical features of children with RSV infection. Overall, 1015 children were enrolled: 100 in 2019, 3 in 2020 and 912 in 2021. In 2019, the peak was recorded in December, and in 2021, it was recorded in November. Comparing 2019 to 2021, in 2021 the median age was significantly higher and the age group 2–3 years was more affected. Admissions were significantly higher in 2021 than in 2020 and 2019, and the per-year hospitalization rate was lower in 2021 (84% vs. 93% in 2019), while the duration of admissions was similar. No difference was found in severity between 2019–2020–2021. In conclusion, after the COVID-19 pandemic, an increase in RSV cases in 2021 exceeding the median seasonal peak was detected, with the involvement of older children, while no difference was found in severity.

Background Diabetic ketoacidosis (DKA) is a frequent manifestation at the onset of type 1 diabetes mellitus in children, possibly associated with a wide range of complications, often as a consequence of wrong or delayed treatment. Due to its complex and risky management, direct exposure to real situations alone is not sufficient to achieve adequate skills in pediatric DKA for residents. Simulation could be a valuable aid, allowing to practice a standardized scenario of a complex real-world situation. We aimed to test the effectiveness of a standardized scenario of pediatric DKA in teaching its recognition and treatment. Methods We develop a standardized scenario able to guide step-by-step the learners through the flowchart of DKA management and considering alternative evolutions in the case of possible deviations from guidelines. It was a real-life simulation with the use of a high-fidelity pediatric simulator. It was played by 78 pediatrics 20 and emergency medicine residents. At the end of the simulation, a validated questionnaire was administered to collect feedback from participants regarding the impact of the simulation on learning. All materials to reproduce the DKA scenario are provided. Results Overall, the scenario was rated as realistic (mean score 4.37 ± 0.68, from 1 to 5) and relevant to professional training (4.72 ± 0.47), useful in increasing confidence in interpreting laboratory tests (3.97 ± 0.65), group organization and communication strategies (3.49 ± 0.94), and managing the treatment of DKA (3.46 ± 0.92). Conclusions The use of a standardized scenario of pediatric DKA may be a valid tool to reinforce theoretical knowledge in residents, both in pediatrics and in emergency medicine, and to directly and safely practice pediatric DKA management.

Background Celiac disease (CD) is an autoimmune disorder that primarily affects the gut of genetically predisposed individuals and is triggered by gliadin peptides (PT) produced by the digestion of gluten. Although inappropriate activation of the immune system is thought to be the main trigger of CD, the interaction between PT and intestinal epithelial cells (IECs) remains a key step. Recently, the possible involvement of ER stress in the pathogenesis of CD has been pointed out, although its role is still largely unclear. Therefore, discovering the molecular mechanism(s) activated in IECs exposed to PT represents a unique opportunity to better understand the disease and define new potential therapeutic targets. Methods In this study we used three different experimental set-ups: intestinal biopsies from CD patients and non-CD control subjects, an in vitro model, based on human CaCo-2 cells, and an ex vivo model, based on our recently described mouse gut-ex-vivo system (GEVS), with the latter two systems were studied after stimulation with gliadin peptides (PT). To understand the signaling pathways involved we monitor the expression of a number of proteins by qPCR, Western blotting, IF, ELISA or a combination of tests. Specifically, we have analyzed the level of CD, ER stress, tissue permeability, and inflammation markers. Results Indeed, our study demonstrated a prompt induction of the transcription factors ATF4, ATF6 and XBP1 in IECs upon PT exposure. Thus, the upregulation of TG2 and downregulation of CFTR were prevented by ER stress inhibition/buffering by a pharmacological chaperone, also leading to restored physiological expression of OCL, CLD-2 and CLD-15, while preventing the expression of IFNγ, IL-15 and IL-17 A. Conclusion Overall, our analysis has highlighted the key role of ER stress in the pathogenesis of CD and identified the chemical chaperones as a new potential valuable therapeutic treatment for CD patients.

Background Coeliac disease is an autoimmune disease that is primarily associated with chronic inflammation of the gut, but can also affect organs outside the gut, from the liver to the skin and CNS. The disease is triggered in predisposed individuals by a peptide mixture (PT) derived from the digestion of gliadin, a component of wheat, which is ingested with food. Although the induction of endoplasmic reticulum stress in intestinal epithelial cells (IECs) upon exposure to PT is known, the underlying molecular mechanisms remain unclear. Identifying the key players in this signaling pathway could therefore help to develop a new effective therapeutic strategy for the treatment of CD patients. Methods Two CD models were used to identify the molecular mechanism linking extracellular PT and endoplasmic reticulum (ER) stress in the IECs of predisposed individuals exposed to gliadin. These models were an in vitro model based on CaCo-2 cells and an ex vivo model based on our previously described gut ex vivo system (GEVS), both exposed to PT. Results Our results clearly show that the interaction of gliadin peptides with the transmembrane CXCR3 receptor on IECs leads to a rapid induction of PLC activity that generates IP3 molecules. This second messenger binds to the IP3R located in ER membranes, resulting in calcium efflux from the organelle. Conclusion The PT-dependent ER stress observed in the IECs of CD patients results from the excessive release of calcium from the ER. Importantly, inhibition of this signaling pathway abrogates ER stress, which in turn attenuates downstream signs of CD, such as TG2 expression and gut permeability dysregulation, as well as inhibits inflammation.

The choice of the best SARS-CoV-2 detection approach is crucial to predict which children with SARS-CoV-2 are at high risk of spreading the virus in order to manage public health measures and policies. In this prospective observational study of 35 children admitted to the Pediatric Emergency Departments of two tertiary hospitals in Northern Italy who tested positive for SARS-CoV-2 by standard RT-PCR in nasopharyngeal swab (NPS), we evaluated their presenting symptoms according to their salivary viral load (SVL) determined by droplet digital PCR (ddPCR). Despite an overall low concordance between SARS-CoV-2 detected by salivary ddPCR and NPS RT-PCR (54.3%), when only patients with nasopharyngeal symptoms were analyzed, the sensitivity of ddPCR in saliva specimens increased to 71.4%, and over half of these patients had high SVL (>105 copies/mL), which was significantly more frequent than in children without nasopharyngeal symptoms (57.1% vs. 14.3%, OR = 8, CI 95% 1.28–50.03, p = 0.03). All asymptomatic children had low SVL values. Our findings support the hypothesis that children with nasopharyngeal symptoms are at higher risk of spreading SARS-CoV-2 due to their high SVL and, conversely, asymptomatic children are unlikely to spread the virus due to their low SVL, regardless of their NPS positivity.