Chilblain-like lesions in children following suspected COVID-19 infection.

During the COVID-19 pandemic, chilblain-like lesions have been reported in mildly symptomatic children and adolescents. We present four children investigated for suspected COVID-19 infection who presented with acral skin findings and mild systemic symptoms. Histology from one case showed signs of vasculitis with evident fibrin thrombus.

Epileptic Encephalopathy, Myoclonus-Dystonia, and Premature Pubarche in Siblings with a Novel C-Terminal Truncating Mutation in ATRX Gene.

The X-linked alpha thalassemia mental retardation (ATR-X) syndrome is a genetic disorder caused by X-linked recessive mutations in ATRX gene, related to a wide spectrum of clinical manifestations, such as alpha thalassemia, developmental delay, genital abnormalities, and gastrointestinal disorders. Patients with ATR-X syndrome can suffer from different types of epileptic seizures, but a severe epileptic encephalopathy pattern has not been described to date. We describe, for the first time, two brothers with genetically confirmed ATR-X syndrome who presented with drug-resistant epileptic encephalopathy, with tonic and polimorphic seizures reported in the elder brother and epileptic spasms in the younger brother. Moreover, both brothers showed a peculiar movement disorder with myoclonus-dystonia, worsened during periods of distress or pain. These cases expand the clinical spectrum of ATR-X syndrome and open new opportunities for the molecular diagnosis of ATRX mutations in male patients with severe epileptic encephalopathies and movement disorders.

HIV-1 envelope-dependent restriction of CXCR4-using viruses in child but not adult untransformed CD4+ T-lymphocyte lines.

Phytohemagglutin-stimulated child and adult leukocytes equally supported CCR5-dependent (R5) and CXCR4-dependent (X4) HIV-1 replication. In contrast, when phytohemagglutin-stimulated leukocytes from either healthy or congenitally immunodeficient children were cultured on feeder cells, they well supported R5, but not X4 HIV-1 replication, whereas both viruses equally spread in adult cells maintained in similar conditions. Both child and adult cells showed similar levels of proliferation and surface expression of CD4, CCR5, CXCR4, CD25, CD69, and HLA-DR. Lack of X4 HIV-1 replication in child versus adult cells was not caused by a differential expression of several known HIV-1 restriction factors. Similar levels of HIV DNA synthesis occurred in child cells infected with R5 and X4 viruses up to 48 hours after infection when R5 HIV-1 showed a significantly superior capacity to spread in culture than X4 virus. Cultured child cells well supported single round vescicular stomatitis virus-G pseudotyped virus replication, whereas superinfection of R5-infected cells with X4 HIV-1 (or vice versa) rescued the replication of this latter virus. Thus, child cells exposed to feeder cell culture represent a novel model system in which the superior capacity of R5 versus X4 viruses to spread can be investigated in primary, untransformed CD4(+) cells.

Using electrical impedance tomography to characterize lung impairment of children with primary ciliary dyskinesia: A pilot cross-sectional study.

BACKGROUND: In children with primary ciliary dyskinesia (PCD), measures more sensitive than spirometry are needed to characterize underlying pulmonary impairment. Electrical impedance tomography (EIT) is a promising noninvasive method for monitoring the distribution of lung ventilation, and it does not require patient collaboration. We aimed to provide an assessment of the feasibility and clinical usefulness of EIT in characterizing lung impairment in children with PCD, compared to spirometry and multiple breath nitrogen washout (MBWN2 ) test. METHODS: Children and adolescents with PCD underwent MBWN2 test as first respiratory assessment, followed by EIT monitoring and spirometry during outpatient follow-up. RESULTS: We included 12 out of 16 individuals regularly followed at our clinic. A total of 41.7% (5/12) showed abnormal forced expiratory volume in 1 s (FEV1 ), whereas 11/12 (91.7%) had abnormal ventilation inhomogeneity measured with MBWN2 test. Using EIT, the global inhomogeneity (GITOT ) index showed moderate to strong correlation with FEV1 (ρ = -0.55, 95% confidence interval [CI]: -0.87 to 0.02) and ranged from 37 to 44, with the highest inhomogeneity detected in the dorsal right quadrant. GITOT was moderately correlated with RV/TLC %predicted (ρ = 0.38, 95% CI: -0.17 to 0.74), while we detected a weak correlation between GITOT and lung clearance index (ρ = 0.29, 95% CI: -0.45 to 0.82). CONCLUSION: EIT appears promising as a noninvasive technique to characterize ventilation distribution in children with PCD, thus providing a complementary assessment to static and dynamic lung function measures of PCD disease.

Pediatric Sleep Respiratory Disorders: A Narrative Review of Epidemiology and Risk Factors.

Sleep is a fundamental biological necessity, the lack of which has severe repercussions on the mental and physical well-being in individuals of all ages. The phrase "sleep-disordered breathing (SDB)" indicates a wide array of conditions characterized by snoring and/or respiratory distress due to increased upper airway resistance and pharyngeal collapsibility; these range from primary snoring to obstructive sleep apnea (OSA) and occur in all age groups. In the general pediatric population, the prevalence of OSA varies between 2% and 5%, but in some particular clinical conditions, it can be much higher. While adenotonsillar hypertrophy ("classic phenotype") is the main cause of OSA in preschool age (3-5 years), obesity ("adult phenotype") is the most common cause in adolescence. There is also a "congenital-structural" phenotype that is characterized by a high prevalence of OSA, appearing from the earliest ages of life, supported by morpho-structural abnormalities or craniofacial changes and associated with genetic syndromes such as Pierre Robin syndrome, Prader-Willi, achondroplasia, and Down syndrome. Neuromuscular disorders and lysosomal storage disorders are also frequently accompanied by a high prevalence of OSA in all life ages. Early recognition and proper treatment are crucial to avoid major neuro-cognitive, cardiovascular, and metabolic morbidities.

Impact of COVID-19 Pandemic on Headache Evaluations in the Pediatric Emergency Department.

BACKGROUND: To evaluate the impact of COVID-19 on evaluations in the pediatric emergency department (ED) because of headache as main symptom. METHODS: Number and clinical features of patients evaluated in the pediatric ED of a single site in Milan, Italy, were collected between January 2017 and January 2022. The impact of COVID-19 on evaluation rates was quantified by using the incidence rate ratio (IRR) and 95% confidence intervals (CI) between the pandemic (March 2020 to January 2022) and the prepandemic period (January 2017 to February 2020). RESULTS: During the study period, 890 evaluations were registered: 689 over the prepandemic period and 201 over the pandemic period. Mean age at evaluation was 10 years (range: 1 to 17 years). Evaluation rates per month were 18.1 during the prepandemic period and 8.7 during COVID-19 pandemic, with peaks in autumn and winter months and considerable drops in the summer. The IRR was 0.49 (95% CI, 0.40-0.61). The reduction in evaluation rate was higher for secondary headache (IRR, 0.31; 95% CI, 0.23-0.42) when compared with primary headache (IRR, 0.56; 95% CI, 0.40-0.78). CONCLUSIONS: We found a remarkable reduction in the number of evaluations in the pediatric ED for headache during the pandemic period.

Frequency of asymptomatic carriers of SARS-CoV-2 among children and adults after school reopening.

BACKGROUND: Children often develop an asymptomatic form of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), but it is debated if children are at higher risk than adults to be asymptomatic carriers of SARS-CoV-2, especially during the school reopening. The main aim of this study was to investigate the frequency of SARS-CoV-2 asymptomatic carriers in children and adults during the reopening of the schools in Milan, Italy. METHODS: We conducted a cross-sectional study at the pediatric and adult Emergency Department (ED) of the Ca' Granda Ospedale Maggiore Policlinico (Milan) between October 1 and 31, 2020, i.e. 3 weeks after the reopening of schools. Patients admitted to the ED short stay observation and without any sign or symptom consistent with a SARS-CoV-2 were eligible. These patients underwent a nasopharyngeal swab specimen for the detection of SARS-CoV-2. The odds ratio and its 95% confidence interval (CI) was calculated to assess the risk of asymptomatically carrying the SARS-CoV-2 infection in children and adults. RESULTS: A total of 69 (27 females, median age 8.7 years) children and 251 (107 females, median age 71 years) adults were enrolled. Pediatric and adult subjects tested positive for SARS-CoV-2 with a similar frequency (1/69 [1.4%] vs 4/251 [1.6%]). Children had an odds ratio to be a carrier of 0.91 (CI 0.02- 9.38) compared to adults. CONCLUSIONS: The frequency of asymptomatic SARS-CoV-2 carriers was similar among children and adults. Considering the emerging diffusion of new SARS-CoV-2 variants, the asymptomatic spread of SARS-CoV-2 infection among children and adults should be monitored.

Early evidence of SARS-CoV-2 in Milan, Jan-Feb 2020.

BACKGROUND: A few studies have suggested that the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) was present in Northern Italy several weeks before its official detection on February 21, 2020. On the other hand, no clinical data have been provided so far to support such hypothesis. We investigated clinical-epidemiological evidence of SARS-CoV-2 infection among children and adults referring to emergency department (ED) in the main hospital of the center of Milan (Italy) before February 21, 2020. METHODS: A retrospective analysis of medical records of ED visits at the Fondazione Ca' Granda Policlinico, Milan between January 11 and February 15 in 2017, 2018, 2019 and in 2020 was performed. The number of subjects referring with fever, cough or dyspnea was compared between the studied period of 2020 and the previous 3 years, by calculating a standardized referral ratio (SRR, number of observed cases in 2020 divided by the number of expected cases according to 2017-2019) and the corresponding 95% confidence interval (CI). RESULTS: In the pediatric ED, 7709 (average 2570/year) and 2736 patients were visited during the period 2017-2019 and in the 2020, respectively. Among adults, 13,465 (average 4488/year) and 4787 were visited during the period 2017-2019 and in the 2020, respectively. The SRR was 1.16 (95% CI 1.10-1.23) in children and 1.25 (95% CI 1.16-1.35) in adults. The ratio for the two (children and adults) SRRs was 0.93 (0.84-1.02), suggesting a trend towards a higher frequency in adults compared to children. CONCLUSIONS: This study suggests that SARS-CoV-2 might have spread in Milan before February 21, 2020 with a minor trend among children.

Can Asymptomatic or Non-Severe SARS-CoV-2 Infection Cause Medium-Term Pulmonary Sequelae in Children?

Pulmonary complications in adults who recovered from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported even in minimally symptomatic patients. In this study, lung ultrasound (LUS) findings and pulmonary function of children who recovered from an asymptomatic or mildly symptomatic SARS-CoV-2 infection were evaluated. We prospectively followed up for at least 30 days patients younger than 18 years who recovered from SARS-CoV-2 infection at the Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan (Italy). All enrolled patients underwent LUS. Airway resistance measured by the interrupter technique test was assessed in subjects aged 4-6 years, whereas forced spirometry and measurement of diffusing capacity of the lungs for carbon monoxide were performed in subjects older than 6 years. To evaluate a possible correlation between pulmonary alterations and immune response to SARS-CoV-2, two semiquantitative enzyme immune assays were used. We enrolled 16 out of 23 eligible children. The median age of enrolled subjects was 7.5 (0.5-10.5) years, with a male to female ratio of 1.7. No subject presented any abnormality on LUS, airway resistance test, forced spirometry, and diffusing capacity of the lungs for carbon monoxide. On the other hand, all subjects presented Ig G against SARS-CoV-2. In contrast in adults, we did not detect any pulmonary complications in our cohort. These preliminary observations suggest that children with an asymptomatic or mildly symptomatic SARS-CoV-2 infection might be less prone to develop pulmonary complications than adults.

Hyponatremia in infants with community-acquired infections on hospital admission.

Acute moderate to severe gastroenteritis is traditionally associated with hypernatremia but recent observations suggest that hypernatremia is currently less common than hyponatremia. The latter has sometimes been documented also in children with acute community-acquired diseases, such as bronchiolitis and pyelonephritis. We investigated the prevalence of dysnatremia in children with acute moderate severe gastroenteritis, bronchiolitis and pyelonephritis. This prospective observational study included 400 consecutive previously healthy infants ≥4 weeks to ≤24 months of age (232 males and 168 females): 160 with gastroenteritis and relevant dehydration, 160 with moderate-severe bronchiolitis and 80 with pyelonephritis admitted to our emergency department between 2009 and 2017. Circulating sodium was determined by means of direct potentiometry. For analysis, the Kruskal-Wallis test and the Fisher's exact test were used. Hyponatremia was found in 214 of the 400 patients. It was common in gastroenteritis (43%) and significantly more frequent in bronchiolitis (57%) and pyelonephritis (68%). Patients with hyponatremia were significantly younger than those without hyponatremia (3.9 [1.6-13] versus 7.5 [3.4-14] months). The gender ratio was similar in children with and without hyponatremia. Hyponatremia was associated with further metabolic abnormalities (hypokalemia, hyperkalemia, metabolic acidosis or metabolic alkalosis) in gastroenteritis (71%) and pyelonephritis (54%), and always isolated in bronchiolitis. In conclusion, hyponatremia is common at presentation among previously healthy infants with gastroenteritis, bronchiolitis or pyelonephritis. These data have relevant consequences for the nutrition and rehydration management in these conditions.

Predictive value of EEG for febrile seizure recurrence.

OBJECTIVE: To define the role of the EEG in predicting recurrence of febrile seizures (FS) in children after a first FS. METHODS: Children with a first simple or complex FS who underwent EEG at our hospital were retrospectively enrolled. EEG recordings were classified in three groups: normal, abnormal (slow activity or epileptiform discharges), and pseudo-petit mal discharge (PPMD) pattern. Children were followed-up for at least three years. RESULTS: A total of 126 patients met the entry criteria, and 113 of them completed the follow-up. Risk of FS recurrence decreased linearly with increasing age (-2% per month). The risk was higher among patients with PPMD pattern (absolute risk 86%, adjusted relative risk 2.00) and abnormal EEG (epileptiform discharges: absolute risk 71%, adjusted relative risk 2.00; slow activity: absolute risk 56%, adjusted relative risk 1.44), compared with those with normal EEG (absolute risk 41%). CONCLUSIONS: PPMD and abnormal EEG should be considered as an independent risk factor for FS recurrence.

Hyponatremia in infants with new onset moderate-severe bronchiolitis: A cross-sectional study.

BACKGROUND: The reported cumulative prevalence of hyponatremia (sodium <135 mmol/L) in bronchiolitis is 28%. However, sodium level was never measured by direct potentiometry, the method recommended by the International Federation of Clinical Chemistry and Laboratory Medicine. Aim of this study was to assess the prevalence of hyponatremia, measured by direct potentiometry, in infants with moderate-severe bronchiolitis. METHODS: A prospective cross-sectional study was conducted in infants ≥1month and ≤24months of age with bronchiolitis. RESULTS: 160 consecutive infants were enrolled. Hyponatremia was observed in 91 (57%) patients and occurred more commonly in infants ≤6 months than in older infant (P < 0.005). CONCLUSION: The first study on sodium level measured by the direct potentiometry in infants with bronchiolitis points out that the prevalence of hyponatremia is two-fold higher than so far reported.

Electrical impedance tomography in children with community acquired pneumonia: preliminary data.

BACKGROUND: Electrical impedance tomography (EIT) is a noninvasive pulmonary function test that provides spatial and temporal information of changes in regional lung ventilation. We aimed to assess the feasibility of EIT as a supplementary tool in the evaluation of community acquired pneumonia in children. Furthermore, we performed a prospective evaluation of regional lung ventilation changes during a six-month follow-up period. METHODS: We enrolled otherwise healthy children aged 2-15 years with radiological diagnosis of community acquired pneumonia on admission at pediatric emergency department. Chest EIT was performed at enrollment, at three and six-months from baseline. RESULTS: Nineteen children were enrolled. A significant agreement between EIT and chest radiography in identifying the affected lung (left or right) was observed (Cohen K statistic = 0.73, 95% CI 0.5-0.98). Ventilation improvement was documented at three-month follow-up, but a full recovery only at six months. CONCLUSION: EIT reliably provides additional information on lung ventilation disorders due to CAP in children. It further allows bedside, real time and radiation free monitoring of lung functional recovery. Future studies are needed to expand the generalizability of this method and evaluate effectiveness on clinical practice.

Cytokine levels in sputum of cystic fibrosis patients before and after antibiotic therapy.

It is not known whether cytokine levels in sputum may be used as outcome measures after parenteral antibiotic therapy in cystic fibrosis (CF) patients. Here, we assessed the effects of antibiotic therapy on cytokine levels in sputum and serum obtained from young CF patients. Thirty-two CF patients (14 females; mean age, 18.6 years; range, 11.4-35.7 years), consecutively admitted at the CF Center of Milan for parenteral antibiotic therapy during pulmonary exacerbation, were enrolled in the study. Before and after 21 days (range, 5-41) of intravenous antibiotic treatment, all patients underwent routine laboratory determinations (including white blood cell (WBC) count and C-reactive protein (CRP)), a chest X-ray, pulmonary function tests (forced expiratory volume in 1 sec (FEV1) and forced vital capacity (FVC) as % predicted), and sputum cultures. Interleukin (IL)-6, IL-8, IL-10, and tumor necrosis factor (TNF)-alpha levels in serum and sputum samples were determined by means of immunometric assays. After therapy, FEV1 and FVC significantly improved (median increase of 7.5% and 8.5% predicted, respectively), while CRP and WBC count were significantly decreased (median values from 14 to 5.5 mg/dl and from 8,350 to 7,400 n/mm3, respectively). While levels of IL-6 and IL-10 in sputum were generally undetectable, IL-8 and TNF-alpha were always measurable, and IL-8 levels significantly decreased after antibiotic treatment (median values from 7,165 to 5,415 pg/ml). Following antibiotic therapy, IL-8 and TNF-alpha levels in sputum were inversely related with both FEV(1) and FVC. In conclusion, TNF-alpha and IL-8 levels in sputum of young CF patients with pulmonary exacerbation were always detectable and may be useful, noninvasive outcome measures to assess response to therapy in CF patients.

Effects of liver transplantation on the nutritional status of patients with cystic fibrosis.

The long-term effects of liver transplantation on nutritional status, body composition and pulmonary function in patients with liver disease associated with cystic fibrosis (CF) are poorly defined. We studied 15 patients with CF-associated biliary cirrhosis and severe portal hypertension. Seven underwent liver transplantation (age: 14.8 +/- 6.2 years), and eight were treated conservatively (age: 15.9 +/- 6.7 years). All patients were evaluated at baseline and thereafter yearly for a median duration of 5 years. During follow-up, transplanted patients gained weight and showed a significant increment in body mass index (P < 0.004), whereas patients without transplantation remained stable (P = 0.063). Baseline bone mineral content (dual energy X-ray absorptiometry scan) was lower than normal in all patients (more in transplanted patients) and increased in transplanted patients (P < 0.05), but not in patients without transplantation. In both groups percent body fat did not change, whereas fat free mass increased only in the transplant group (P = 0.06) (P < 0.03 versus nontransplanted patients). Only in transplanted patients' plasma concentrations of vitamin E and A increased (P < 0.05 versus nontransplanted patients). Forced espiratory volume in 1 s and forced vital capacity showed similar deterioration in transplanted and in nontransplanted patients. Liver transplantation is associated with long-term beneficial effects on the nutritional status of CF patients and seems to favor bone mineralization.