A child with polyarthritis and chronic lung disease: a case report of ataxia-telangiectasia.

BACKGROUND: Ataxia-telangiectasia (A-T) is a rare autosomal recessive DNA repair disorder, characterized by progressive cerebellar degeneration, telangiectasia, immunodeficiency, recurrent sinopulmonary infections, radiation sensitivity, premature aging and predisposition to cancer. Although the association with autoimmune and chronic inflammatory conditions such as vitiligo, thrombocytopenia and arthritis has occasionally been reported, an onset with articular involvement at presentation is rare. CASE PRESENTATION: We herein report the case of a 7-year-old Caucasian girl who was admitted to the Rheumatology Department with a history of febrile chough and polyarthritis which led initially to the suspicion of an autoinflammatory disease. She had overt polyarthritis with knees deformities and presented with severe pneumonia. A chest Computed Tomography (CT) scan showed bilateral bronchiectasis, parenchymal consolidation and interstitial lung disease; rheumatoid factor and type I interferon signature resulted negative, therefore excluding COatomer Protein subunit Alpha (COPA) syndrome. A diagnosis of sarcoidosis had been suspected based on histological evidence of granulomatous liver inflammation, but ruled out after detecting normal angiotensin converting enzyme and chitotriosidase blood levels. Based on her past medical history characterized by at least six episodes of pneumonia in the previous 4 years, immunological phenotyping was performed. This showed complete IgA and IgE deficiency with defective antigen-specific antibodies to Pneumococcal, Tetanus toxin and Hemophilus Influenzae B vaccines. Additionally, low numbers of B cells and recent thymic emigrants (RTE) were found (CD4Ra 1.4%), along with a low CD4+/CD8 + T cells ratio (< 1). Finally, based on gait disturbances (wobbly wide-based walking), serum alfa-fetoprotein was dosed, which resulted increased at 276 ng/ml (normal value < 7 ng/ml). A diagnosis of Ataxia-Telangiectasia was made, strengthened by the presence of bulbar telangiectasia, and then confirmed by Whole Exome Sequencing (WES). CONCLUSIONS: Although rare, A-T should always be ruled out in case of pulmonary bronchiectasis and gait disturbances even in the absence of bulbar or skin telangiectasia. Autoimmune and granulomatous disorders must to be considered as differential diagnosis.

Parenteral Nutrition in the Pediatric Oncologic Population: Are There Any Sex Differences?

Gender-based medicine is attracting increasing interest every day, but studies on pediatric populations are still limited. In this setting, sex differences among patients undergoing total parenteral nutrition (TPN) have not been previously reported. This study investigated the presence of sex differences in parenteral nutrition composition and outcomes among a cohort of pediatric patients admitted at the Oncohematology and Bone Marrow Transplant Unit of the Institute for Maternal and Child Health "Burlo Garofolo" of Trieste, Italy. For all 145 recruited patients (87 males, 58 females), the following data were collected: age, sex, volume and duration of TPN, macro- and micronutrient composition of TPN bags, electrolytic or blood gases imbalance, glycolipid alterations, liver damage during TPN, and the incidence of sepsis and thrombosis. The analysis showed that females required higher daily phosphate intake (p = 0.054) and essential amino acid supplementation (p = 0.07), while males had a higher incidence of hypertriglyceridemia (p < 0.05) and cholestasis. A higher incidence of sepsis was found in the non-transplanted male population (p < 0.05). No significant differences were appreciable in other analyzed variables. This study aims to create a basis for future gender-based nutritional recommendations in the pediatric field.

A "SURFin' Leukemia": Acute Lymphoblastic Leukemia Masquerading as a Syndrome of Undifferentiated Recurrent Fever.

Periodic fever is not uncommon in childhood and is often ascribed to autoinflammatory conditions; however, it may be present also in children with cancer. We here describe the case of a 3-year-old boy with acute lymphoblastic leukemia who initially presented with a 4-month history of recurrent, stereotyped episodes of fever and localized joint pain, separated by completely symptom-free intervals. These symptoms were initially interpreted as a possible syndrome of undifferentiated recurrent fever until more signs of leukemia became apparent. Our report confirms that acute lymphoblastic leukemia can rarely present with periodic fever, thus possibly leading to diagnostic errors unless a high index of suspicion is maintained.

Drowning in Children and Predictive Parameters: A 15-Year Multicenter Retrospective Analysis.

BACKGROUND: Drowning is a serious and underestimated public health problem, with the highest morbidity and mortality reported among children. Data regarding pediatric outcomes of drowning are often inadequate, and data collection is poorly standardized among centers. This study aims to provide an overview of a drowning pediatric population in pediatric emergency department, focusing on its main characteristics and management and evaluating prognostic factors. METHODS: This is a retrospective multicenter study involving eight Italian Pediatric Emergency Departments. Data about patients between 0 to 16 years of age who drowned between 2006 and 2021 were collected and analyzed according to the Utstein-style guidelines for drowning. RESULTS: One hundred thirty-five patients (60.9% males, median age at the event 5; interquartile range, 3-10) were recruited and only those with known outcome were retained for the analysis (133). Nearly 10% had a preexisting medical conditions with epilepsy being the most common comorbidity. One third were hospitalized in the intensive care unit (ICU) and younger males had a higher rate of ICU admission than female peers. Thirty-five patients (26.3%) were hospitalized in a medical ward while 19 (14.3%) were discharged from the emergency department and 11 (8.3%) were discharged after a brief medical observation less than 24 hours. Six patients died (4.5%). Medium stay in the ED was approximately 40 hours. No difference in terms of ICU admission was found between cardiopulmonary resuscitation performed by bystanders or trained medical personnel ( P = 0.388 vs 0.390). CONCLUSIONS: This study offers several perspectives on ED victims who drowned. One of the major finding is that no difference in outcomes was seen in patients who received cardiopulmonary resuscitation performed by bystanders or medical services, highlighting the importance of a prompt intervention.

Type I interferon signature as a possible new marker for stratification of patients with juvenile idiopathic arthritis.

OBJECTIVES: The interferon score (IS) quantifies the expression of interferon-stimulated genes in peripheral blood, providing an indirect estimate of interferon-mediated inflammation in rheumatological disorders. This study explores the clinical significance of IS among a cohort of patients affected by juvenile idiopathic arthritis (JIA) and its relevance to disease stratification and prognosis. METHODS: All patients referred to the Rheumatology Service of the Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste, Italy, with a diagnosis of JIA (2001 ILAR criteria) were consecutively recruited. Systemic JIA was excluded. Demographic, clinical and laboratory data were collected for each patient in a structured database. Categorical variables were expressed as numbers (%) and compared by the χ2 test or Fisher's exact test. Principal Component Analysis (PCA) was performed with clinical and laboratory data. RESULTS: Forty-four patients were recruited (35 F, 9 M): 19 polyarticular, 13 oligoarticular, 6 oligoarticular-extended, 5 psoriatic and 1 enthesitis-related arthritis. Sixteen had a positive IS (≥3). Increased IS correlated with a higher number of involved joints ≥5 (p=0.013), increased erythrocyte sedimentation rate (ESR) (p=0.026) and hypergammaglobulinaemia (p=0.003). PCA highlighted a subgroup of patients who shared high levels of IS, ESR, C-reactive protein, hypergammaglobulinaemia, JADAS-27, polyarticular involvement and family history of autoimmunity. CONCLUSIONS: Although based on a small case series, our results may support the role of IS in better defining a subgroup of JIA subjects with stronger autoimmune features. The possible relevance of these results for therapeutic stratification remains to be explored.

Oral ibuprofen versus oral ketorolac for children with moderate and severe acute traumatic pain: a randomized comparative study.

This study is to compare ibuprofen and ketorolac for children with trauma-related acute pain. We conducted a multicentre randomized, double-blind, controlled trial in the Paediatric Emergency Department setting. We enrolled patients aged 8 to 17 who accessed the emergency department for pain related to a limb trauma that occurred in the previous 48 h. At the admission, patients were classified based on numeric rating scale-11 (NRS-11) in moderate (NRS 4-6) and severe (NRS 7-10) pain groups. Each patient was randomized to receive either ibuprofen (10 mg/kg) or ketorolac (0.5 mg/kg) and the placebo of the not given drug in a double dummies design. NRS-11 was asked every 30 min until 2 h after drug and placebo administration. The primary outcome was NRS-11 reduction at 60 min. Among 125 patients with severe pain, NRS-11 reduction after 60 min from drug administration was 2.0 (IQR 1.0-4.0) for ibuprofen and 1.0 (IQR 1.0-3.0) for ketorolac (p = 0.36). Ibuprofen was significantly better, considering secondary outcomes, at 90 min with a lower median of NRS-11 (p 0.008), more patients with NRS-11 less than 4 (p 0.01) and a reduction of pain score of more than 3 NRS-11 points (p 0.01). Among 87 patients with moderate pain, the NRS-11 reduction after 60 min from drug administration was 1.63 (± 1.8) for ibuprofen and 1.8 (± 1.6) for ketorolac, with no statistically significant difference.Conclusions: Oral ibuprofen and ketorolac are similarly effective in children and adolescents with acute traumatic musculoskeletal pain.Trial registration: ClinicalTrial.gov registration number: NCT04133623.

Approach to the child with fatigue: A focus for the general pediatrician.

Background: Fatigue is a common, nonspecific complaint commonly used to describe various conditions, ranging from a vague, subjective sense of weariness to muscular weakness, fatigability, exercise intolerance or excessive daytime somnolence. Despite its high frequency in the general population, literature addressing the approach to the child with fatigue from a general pediatrician perspective is poor. We herein propose a review of the available evidence on the topic, providing a practical framework to assist physicians in dealing with the issue. Methods: Data were identified by searches of MEDLINE, UpToDate, Google Scholar and references from relevant articles. Articles published between 1990 and 2021 were considered, prioritizing systematic reviews and meta-analyses. Then, an empirically-based model of approaching the tired child was proposed according to our center experience. Results: To correctly characterize the meaning of fatigue reporting, specific clues from history and physical examination should be emphasized. Duration, severity, and the age at onset are to be considered. Then, specific queries about everyday activities, sleep hygiene and social domain could be useful in reaching a specific diagnosis and offering an appropriate treatment. Conclusions: We suggest a pragmatic approach to fatigue in children based on age assessment, targeted questions, physical examination clues, and some laboratory first-level tests. This could provide pediatricians with a useful tool to discriminate the broad etiology of such a complaint, disentangling between psychological and organic causes. Further studies are needed to investigate the predictive value, specificity and sensitivity of this diagnostic workflow in managing the child with fatigue.

Impact of the first COVID-19 lockdown on the relationship with parents and peers in a cohort of adolescents with somatic symptom disorder.

To investigate the coping strategies of a group of adolescents with somatic symptom disorder compared to non-somatic symptom disorder peers during the COVID-19 related lockdown.This cross-sectional study is the second part of a previously published study showing an improved trend in depression and anxiety in a group of patients with somatic symptom disorder compared to non-somatic symptom disorder peers. An anonymous semi-structured survey was distributed to two groups of Italian adolescents to measure the impact of quarantine on their daily life and coping strategies.We recruited 115 adolescents, 58 (50.4%) mean age 15.3, with a recent diagnosis of somatic symptom disorder and 57 (49.6%) mean age 15.8, control peers.The aim of this study was to detect differences in coping strategies and relationships with parents and peers, during the lockdown period in a group of adolescents with somatic symptom disorder and low disease burden when compared with a non-somatic symptom disorder group.The relationship with parents significantly worsened in 4 (6.9%) of adolescents with somatic symptom disorder compared to 12 (21.1%) adolescents in the non-somatic symptom disorder group (p = 0.048). The relationship with peers significantly improved in 13 (22.4%) of adolescents with symptom disorder versus 3 (5.3%) of peers of the non- somatic symptom disorder group (p = 0.013).Adolescents with somatic symptom disorder with a low burden of physical symptoms experienced less deterioration in their relationships with parents and peers than the non-somatic symptom disorder group.

Pediatric males receiving hematopoietic stem cell transplant lose their male disadvantage in disease risk after the procedure: A retrospective observational study.

Sex differences play a relevant role in cancer susceptibility, incidence and survival. Exploring such differences is difficult because of the close interplay of genetic, epigenetic and hormonal factors. However, a better understanding of the role of such disparities in cancer mechanisms could improve its prevention and therapy. Our study explores how sex differences in pediatric outcomes vary after undergoing first and advanced-line therapy for hematological malignancies. The primary goal was to evaluate if sex differences in pediatric outcomes after first-line therapy persist after allogeneic hematopoietic stem cell transplantation (HSCT). The secondary goal was to analyze sex differences in disease risk at onset and pediatric outcomes after first-line therapy to compare our results with the literature's reported results. Among a total of 485 patients (280 males, 205 females) admitted for hematological malignancies, disease risk at the onset was significantly higher in males (P < .05). One hundred and seventy-four patients (111 males and 63 females) had a high-risk disease requiring HSCT. Before HSCT, all patients underwent myeloablative conditioning, which substantially impaired gonadal function. Although the number of boys undergoing HSCT was almost double that of girls, there were no sex-related differences in overall survival, cancer relapse and complications after HSCT exposure (P > .05). These findings suggest that the existing sex differences in cancer risk ab initio can be somehow flattened by a conditioning regimen, shedding new light on the role of hormonal factors in cancer mechanism and management.

The first winter of social distancing improved most of the health indexes in a paediatric emergency department.

AIM: We compared visits to a tertiary level paediatric emergency department (PED) in Italy, during winter 2020-2021, when COVID-19 social distancing measures were in place, with winter 2019-2020. METHODS: This was a retrospective analysis of an electronic database. We obtained the number of visits and the ages, main complaints, triage codes, discharge diagnoses and outcomes of patients who accessed the PED from the 1 October 2020 to 28 February 2021. These were compared to the same period in 2019-2021. RESULTS: Visits fell by 52%, from 10982 in 2019-2020 to 5317 in 2020-2021 (p < 0.0001). The reductions were 52% in neonates, 58% in infants, 53% in toddlers, 61% in preschool children, 48% in school children and 46% in adolescents. Non-urgent and urgent triage codes declined. Respiratory and gastrointestinal infections fell by 72% and 71% respectively. Injuries declined by 42%, mainly among adolescents. Accidental intoxication, psychiatric symptoms and substance or alcohol abuse declined by 24%, 33% and 64%. Hospital admissions reduced by 8% and admissions to intensive care fell by 29%. CONCLUSION: During the first winter of pandemic social distancing visits to an Italian PED fell by 52%, with higher reductions in younger children and infants, and hospital admissions fell by 8%.

Cardio-pulmonary function among children with mild or asymptomatic COVID-19 infection needing certification for return-to-play.

AIM: To explore the cardio-pulmonary function of children returning to play sports after mild or asymptomatic SARS-CoV-2 infection. METHODS: This is a consecutive case series conducted at the Institute for Maternal and Child Health, Trieste, Italy. Paediatric patients who accessed the Institute for cardiologic and pneumological evaluation before the return-to-play competitive sports were recruited, according to the Italian Sports Medical Federation recommendations. Echocardiogram, electrocardiogram, treadmill ECG test and pulmonary function tests were performed. RESULTS: One hundred and thirty-two patients (aged 8-17 years old, mean age 12.8 ± 2.5) were recruited. Among these, 127 children were considered for the final analysis (49.6% females). Out of 127, 84 (66.1%) had a mild symptomatic form of SARS-CoV-2 infection, while 43 (33.9%) were asymptomatic. The main referred symptoms were fever (n = 37, 44%), asthenia (n = 14, 16.7%), rhinitis (n = 16, 19%), ageusia (n = 19, 22.6%), anosmia (n = 24, 28.6%), sore throat (n = 3, 3.6%), cough (n = 9, 10.7%), arthralgia-myalgia (n = 11, 13.1%), headache (n = 23, 27.4%) and gastrointestinal symptoms (n = 7, 8.3%). No child presented evidence of cardio-pulmonary function impairment after an average time of 77.3 days (SD 35) from SARS-CoV-2 swab positivity and a median of 68 days (IQ1 52, IQ3 92.5). CONCLUSION: This preliminary study suggests that, in the absence of specific symptoms, the diagnostic yield of cardio-pulmonary tests before returning to play sports may be very low.

Young boy with a long history of splenomegaly and cytopenia.

A 15-year-old boy was admitted with a history of cytopenia (white blood cell count 3.170/µm, platelets 90.000/µm) associated with splenomegaly, found during investigations for recurrent mild jaundice due to Gilbert's syndrome.He was in good general health, without systemic symptoms; therefore, the leading causes of asymptomatic splenomegaly were excluded. Coagulation, liver tests and abdomen ultrasound (US) were normal, showing a hepatopetal portal flow to the colour-Doppler. There was no sign of haemolysis on haematology investigations. The C reactive protein, immune globulins levels and erythrocyte sedimentation rate were normal, excluding both an infective and an immune regulation disorder. We excluded the haematological malignancy and lymphoproliferative disorders through a peripheral blood smear and a bone marrow biopsy.His history was remarkable for neonatal sepsis, which required umbilical venous catheter during hospitalisation in a neonatal intensive care unit (NICU). The patient follow-up was interrupted for a while, probably due to his good health condition.At age 17 years, the child accessed our emergency department. for a minor trauma to the limbs, and his physical examination was unremarkable, except for the splenomegaly. We repeated the abdomen US, with colour flow Doppler (figure 1).

Topical Clobetasol: An Overlooked Cause of Cushing Syndrome.

BACKGROUND: We describe the case of an 11-year-old boy affected by chronic granulomatous disease complicated by a Crohn's like colitis needing prolonged treatment with oral corticosteroids. CASE PRESENTATION: His therapy for the control of severe oral mucositis was based on topical clobetasol, which did not decrease once the steroids were discontinued. Two years after the oral interruption of the steroids, cushingoid characteristics persisted, the cause of which, after a thorough investigation, was found to be the persistence of the topical clobetasol oral gel. CONCLUSION: Several studies investigated the efficacy of topical clobetasol for immuno-related mucositis, but little is known about its pharmacokinetics and side effects. In this report, we have reviewed the literature, defining a maximum putative dose of clobetasol mucosal gel to avoid Cushing syndrome.

Could the MED13 mutations manifest as a Kabuki-like syndrome?

MED13-related disorder is a new neurodevelopmental disorder recently described in literature, which belongs to the group of CDK8-kinase module genes-associated conditions. It is characterized by variable intellectual disability and/or developmental delays, especially in language. Autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), eye or vision problems, hypotonia, mild congenital hearth abnormalities and dysmorphisms have been described among individuals with MED13 mutations. We report the case of a 13-year-old girl who received a previous clinical diagnosis of Kabuki syndrome (KS) without mutations in classic KS genes. After a whole exome sequencing (WES) analysis a de novo missense mutation in MED13 (c.C979T; p.Pro327Ser) was found. This variant has been once described in literature as accountable for a novel neurodevelopmental disorder. The aim of this report is to improve clinical delineation of MED13-related condition and to explore differences and similarities between KS spectrum and MED13-related disorders.

Involvement of DAT1 Gene on Internet Addiction: Cross-Correlations of Methylation Levels in 5'-UTR and 3'-UTR Genotypes, Interact with Impulsivity and Attachment-Driven Quality of Relationships.

Internet influences our communication, social and work interactions, entertainment, and many other aspects of life. Even if the original purpose was to simplify our lives, an excessive and/or maladaptive use of it may have negative consequences. The dopamine transporter (DAT1) gene was studied in relation to addictions, including excessive use of the Internet. The crucial role of DAT1 was previously underlined in modulating emotional aspects, such as affiliative behaviors. The present research follows a new approach based on cross-correlation between (de)methylation levels in couples of CpG loci, as previously shown. We investigated the possible relationships between Internet addiction, impulsivity, quality of attachment, DAT1 genotypes (from the 3'-untranslated region (UTR) variable number of tandem repeats (VNTR) poly-morphism), and the dynamics of methylation within the 5'-UTR of the DAT1 gene. From a normative sample of 79 youths, we extrapolated three subgroups a posteriori, i.e., one "vulnerable" with high Internet Addiction Test (IAT) scores (and high Barrat Impulsivity Scale (BIS) scores; n = 9) and two "controls'' with low BIS scores and 10/10 vs. 9/x genotype (n = 12 each). Controls also had a "secure" attachment pattern, while genotypes and attachment styles were undistinguished in the vulnerable subgroup (none showed overt Internet addiction). We found a strongly positive correlation in all groups between CpG2 and CpG3. An unsuspected relationship between the 3'-UTR genotype and a 5'-UTR intra-motif link was revealed by CpG5-CpG6 comparison. The negative correlation between the CpG3-CpG5 positions was quite significant in the control groups (both with genotype 10/10 and with genotype 9/x), whereas a tendency toward positive correlation emerged within the high IAT group. In conclusion, future attention shall be focused on the intra- and inter-motif interactions of methylation on the CpG island at the 5'-UTR of DAT1.

Body size and tube voltage dependent corrections for Hounsfield Unit in medical X-ray computed tomography: theory and experiments.

The purpose of this work is to present a body size and tube voltage dependent correction scheme for the Hounsfield Unit, HU, in medical X-ray Computed Tomography imaging. Boltzmann photon transport equation was employed to study X-ray interaction with bulk water in CT imaging. Experimentally measured X-ray output in body of phantoms and attenuation cross sections of water were employed in the derivation of beam intensity in X-ray imaging. A Somatom Emotion CT scanner from Siemens and electron density phantoms from CIRS were employed to acquire CT images of different body sizes and different tissue materials located at different depths from body's surface. Tube voltage and depth dependent effective attenuation of bulk water was found from theoretical analysis in agreement with measured size-specific correction factors for CTDIvol under different tube voltages. A size and tube voltage dependent correction scheme for the Hounsfield Unit is established. For the same tissue material, body size has much larger impact on the CT number variations than that of depth from the body surface in phantom measurements. Good results were achieved by applying the established correction scheme on the experimentally measured CT number variations under different tube voltages and body sizes.