How Covid-19 changed the epidemiology of febrile urinary tract infections in children in the emergency department during the first outbreak.

BACKGROUND: The first Covid-19 pandemic affected the epidemiology of several diseases. A general reduction in the emergency department (ED) accesses was observed during this period, both in adult and pediatric contexts. METHODS: This retrospective study was conducted on the behalf of the Italian Society of Pediatric Nephrology (SINePe) in 17 Italian pediatric EDs in March and April 2020, comparing them with data from the same periods in 2018 and 2019. The total number of pediatric (age 0-18 years) ED visits, the number of febrile urinary tract infection (UTI) diagnoses, and clinical and laboratory parameters were retrospectively collected. RESULTS: The total number of febrile UTI diagnoses was 339 (73 in 2020, 140 in 2019, and 126 in 2018). During the first Covid-19 pandemic, the total number of ED visits decreased by 75.1%, the total number of febrile UTI diagnoses by 45.1%, with an increase in the UTI diagnosis rate (+ 121.7%). The data collected revealed an increased rate of patients with two or more days of fever before admission (p = 0.02), a significant increase in hospitalization rate (+ 17.5%, p = 0.008) and also in values of C reactive protein (CRP) (p = 0.006). In 2020, intravenous antibiotics use was significantly higher than in 2018 and 2019 (+ 15%, p = 0.025). Urine cultures showed higher Pseudomonas aeruginosa and Enterococcus faecalis percentages and lower rates of Escherichia coli (p = 0.02). CONCLUSIONS: The first wave of the Covid-19 pandemic had an essential impact on managing febrile UTIs in the ED, causing an absolute reduction of cases referring to the ED but with higher clinical severity. Children with febrile UTI were more severely ill than the previous two years, probably due to delayed access caused by the fear of potential hospital-acquired Sars-Cov-2 infection. The possible increase in consequent kidney scarring in this population should be considered.

A well-appearing infant with a sudden anisocoria.

Case presentationA 10-month-old boy was admitted to the emergency department due to a sudden onset of left unilateral mydriasis (figure 1). His medical history was unremarkable. A minor head trauma 2 days before was reported, without alarming signs or symptoms. His mother was putting him to sleep, after coming back from work, when she noticed a different pupil size and promptly went to the ED with her husband. The parents denied any use of medications, including nebulised therapy or direct contact with plants. The child was well appearing and his vital signs were within the standard age limits. His extraocular motility was normal as well as the rest of his neurological and physical examination. Parents' behaviour was somehow remarkable. Even though the child was not suffering, the mother seemed very worried while the father was nervous and aggressive, repeatedly asking for a discharge.

Metabolomic profile of children with recurrent respiratory infections.

Recurrent respiratory infections (RRI) represent a widespread condition which has a severe social and economic impact. Immunostimulants are used for their prevention. It is crucial to better characterize children with RRI to refine their diagnosis and identify effective personalized prevention strategies. Metabolomics is a high-dimensional biological method that can be used for hypothesis-free biomarker profiling, examining a large number of metabolites in a given sample using spectroscopic techniques. Multivariate statistical data analysis then enables us to infer which metabolic information is relevant to the biological characterization of a given physiological or pathological condition. This can lead to the emergence of new, sometimes unexpected metabolites, and hitherto unknown metabolic pathways, enabling the formulation of new pathogenetic hypotheses, and the identification of new therapeutic targets. The aim of our pilot study was to apply mass-spectrometry-based metabolomics to the analysis of urine samples from children with RRI, comparing these children's biochemical metabolic profiles with those of healthy peers. We also compared the RRI children's and healthy controls' metabolomic urinary profiles after the former had received pidotimod treatment for 3 months to see whether this immunostimulant was associated with biochemical changes in the RRI children's metabolic profile. 13 children (age range 3-6 yeas) with RRI and 15 matched per age healthy peers with no history of respiratory diseases or allergies were enrolled. Their metabolomic urine samples were compared before and after the RRI children had been treated with pidotimod for a period of 3 months. Metabolomic analyses on the urine samples were done using mass spectrometry combined with ultra-performance liquid chromatography (UPLC-MS). The resulting spectroscopic data then underwent multivariate statistical analysis and the most relevant variables characterizing the two groups were identified. Data modeling with post-transformation of PLS2-Discriminant Analysis (ptPLS2-DA) generated a robust model capable of discriminating the urine samples from children with RRI from those of healthy controls (R2=0.92,Q2CV7-fold=0.75, p-value<0.001). The dataset included 1502 time per mass variables, and 138 of them characterized the difference between the two groups. Thirty-five of these distinctive 138 variables persisted in the profiles of the children with RRI after pidotimod treatment. Metabolomics can discriminate children with RRI from healthy controls, suggesting that the former have a dysregulated metabolic profile. Among the variables characterizing children with RRI there are metabolites that may reflect the presence of a different microbiome. After pidotimod treatment, the metabolic profile of the children with RRI was no longer very different from that of the healthy controls, except for the persistence of some microbiome-related variables. We surmise that pidotimod partially "restores" the altered metabolic profile of children with RRI, without modifying the metabolites related to the composition of the gut microbiota. In the light of these results, we hypothesize a potential synergic effect of the combined use of immunostimulants and probiotics for the purpose of prevention in children with RRI.

FPIES in exclusively breastfed infants: two case reports and review of the literature.

BACKGROUND: Food Protein-Induced Enterocolitis Syndrome (FPIES) is a non IgE-mediated food allergy that generally affects children in the first year of life. Usually symptoms break out when formula milk or solid foods are introduced for the first time but they might also appear in exclusively breastfed infants, since the trigger elements, especially cow's milk proteins, can be conveyed by maternal milk as well. FPIES in exclusively breastfed babies is a very rare clinical condition and only few cases have been reported in the medical literature. CASE PRESENTATION: We describe two cases of FPIES in exclusively breastfed babies. The first one is a two-month-old infant with a brief history of vomit and diarrhea that presented to the Emergency Department in septic-like conditions. The main laboratory finding was a significant increase in methemoglobin (13%). Clinically, we noted that, when breastfeeding was suspended, diarrhea drastically improved, and vice versa when maternal milk was reintroduced. An amino acid-based formula allowed a complete normalization of the symptoms. The second one is a three-month-old infant admitted for a 3 days history of persistent vomit and diarrhea. Blood tests showed a raised level of methemoglobin (7%). An esophagogastroduodenoscopy was performed and biopsies showed an eosinophilic infiltration of the duodenal mucosa. A maternal exclusion diet and an amino acid-based formula allowed a rapid regularization of the bowel function. CONCLUSIONS: We searched all the cases of FPIES in exclusively breastfed babies reported in the medical literature, identifying eight patients, with an average age of 3 months (range 15 days - 6 months). The majority of the cases were initially diagnosed as gastroenteritis or sepsis, five cases were characterized by an acute on chronic scenario and cow's milk was the most frequently involved food. Methemoglobin was never tested. An oral food challenge test was performed in two patients. FPIES in exclusively breastfed infants is a rare condition that, in the presence of compatible history and symptoms, should be considered also in exclusively breastfed babies. The evaluation of methemoglobin can simplify the diagnostic process.

Asymmetric dimethylarginine in exhaled breath condensate and serum of children with asthma.

BACKGROUND: Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor and uncoupler of nitric oxide synthase. By promoting the formation of peroxynitrite, ADMA is believed to contribute to several aspects of asthma pathogenesis (ie, airway inflammation, oxidative stress, bronchial hyperresponsiveness, and collagen deposition). The aim of the present study was to compare this mediator in healthy children and children with asthma using the completely noninvasive exhaled breath condensate (EBC) technique. METHODS: We recruited 77 children with asthma (5-16 years of age) and 65 healthy children (5-15 years of age) who underwent EBC collection and spirometry. Serum ADMA levels and fractional exhaled nitric oxide levels were measured on the same day in a subgroup of children with asthma. EBC was collected using the Turbo-Deccs (Medivac). ADMA levels were measured using the ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) technique. RESULTS: ADMA could be detected in the EBC of 71 subjects with asthma and 64 healthy subjects. ADMA levels in the EBC of children with asthma were significantly higher than in the healthy control subjects (median, 0.12 [interquartile range, 0.05-0.3] vs 0.07 [0.05-0.12]; P = .017), whereas no difference emerged between the children with asthma who were or were not receiving inhaled steroid treatment. No correlation was found between serum and EBC ADMA levels (P > .5). CONCLUSIONS: We measured ADMA in EBC by UPLC-MS/MS, a reference analytical technique. Higher ADMA levels were found in children with asthma, supporting a role for this mediator in asthma pathogenesis. This oxidative stress-related mediator also seems to be scarcely affected by steroid therapy. We speculate that ADMA might be a target for new therapeutic strategies designed to control oxidative stress in asthma.