Plasma lipids paediatric reference intervals: Indirect estimation using a large 14-year database.

OBJECTIVES: Establishing direct reference intervals (RIs) for paediatric patients is a very challenging endeavour. Indirect RIs can address this problem, using existing clinical laboratory databases from real-world data research. Compared to the traditional direct method, the indirect approach is highly practical, widely applicable, and low-cost. Considering the relevance of dyslipidemia in the paediatric age, to provide better laboratory services to the local paediatric population, we established population-specific lipid RIs via data mining. METHODS: Our laboratory information system was searched for cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) of patients aged less than 18 years, performed from January 2009 until December 2022. RIs were estimated using RefineR algorithm. RESULTS: Values from 215,594 patients were initially collected. After refining data on the basis of specific exclusion criteria that left 17,933 patients, we determined the RIs for each analyte, including corresponding 95% confidence interval (95% CI). Age and sex partitions were required for proper stratification of the heterogenous subpopulations. Age-related variations in TC and TG values were observed mainly in children until 5 years. RIs were defined for children less than 3 years and for those of 3-18 years. In our population, the obtained RIs were comparable with those of the literature, but the upper TG limit in subjects under the age of 3 (2.03 mmol/L with 95% CI: 1.45-2.86) was lower than that previously reported. CONCLUSIONS: Our RIs, necessary for paediatric lipid monitoring, are tailored to the serviced patient population as should be done whenever possible.

Metabolomics reveals new metabolic perturbations in children with type 1 diabetes.

OBJECTIVE: Using an untargeted metabolomics approach we investigated the metabolome of children with type 1 diabetes (T1D) in comparison with healthy peers and explored the contribution of HbA1c and clinical features to the observed difference. RESEARCH DESIGN AND METHODS: We enrolled children with T1D aged 6-15 years, attending the pediatric diabetes clinic of University of Padova (Italy). Healthy controls were enrolled on voluntary basis and matched for age, sex, pubertal status, body mass index (BMI). We performed a liquid chromatography and mass spectrometry analysis (LC-MS) on fasting urinary samples of the 2 groups. RESULTS: A total of 56 patients with T1D aged (11.4 ± 2.2) years, and 30 healthy controls (10.7 ± 2.8) years were enrolled. We identified 59 urinary metabolites having a higher level in children with T1D, mainly represented by gluco- and mineralcorticoids, phenylalanine and tryptophan catabolites (kynurenine), small peptides, glycerophospholipids, fatty acids, and gut bacterial products. We did not find any association between HbA1c, pubertal status, disease duration, and metabolome profile within the case group. CONCLUSIONS: T1D profoundly disrupts the metabolome of pediatric patients. The excess of cortisol and aldosterone may contribute to the development of macrovascular complications in adulthood, while the increase of tryptophan derivates may have a role in neuronal damage associated to hyperglycemia. Determinants of such findings, other than HbA1c, should be explored.

The long-term treatment of a patient with type 1 diabetes mellitus and glutaric aciduria type 1: the effect of insulin.

UNLABELLED: The coexistence of two diseases associated with different metabolic disorders is a very rare event. Some associations, although sporadic, can be particularly challenging both in terms of diagnostic and therapeutic management and in terms of theoretical perspective. Here, we report a child affected by type 1 diabetes mellitus (T1DM) and glutaric aciduria type 1 (GA1). The child was diagnosed with classical T1DM at 15 months of age, with a tendency toward hypoglycemia. A few months later, during an acute intercurrent infective episode, the child displayed acute hypotonia of the lower limbs and limbs dystonia. A brain MRI showed bilateral striatal necrosis, suggesting GA1 diagnosis. Treatment with a low-lysine dietary regimen and carnitine supplementation was started and resulted in an improvement in metabolic control and a reduction of hypoglycemic episodes along with an increasing in insulin daily dose. After 2 years, the neurological outcome consisted of a reduction in dystonic movements and a metabolic stability of both diseases. CONCLUSION: This case provides some insight into the reciprocal interconnections between the two metabolic disorders. Similar pathogenic mechanisms responsible for the neuronal injury might have impacted each other, and a strict relationship between a specific aspect of GA1-impaired metabolism and glucose homeostasis might explain how the tailored management of GA1 was not only effective in controlling the disease, but it also resulted in an improvement in the control of the glycemic profile. What in known: • Glutaric aciduria type 1 (GA1) usually presents in childhood with severe and possibly irreversible neuronal damage, triggered by a catabolic stress • The association of GA1 with other diseases, including type 1 diabetes mellitus (T1DM), is a rare event, complicating the treatment management What is new: • Insulin treatment has a role in preventing GA1 metabolic decompensation, even in the catabolic condition of hypoglycemia • Promoting GA1 metabolic equilibrium by tailoring drug and dietary treatment in our patient affect by T1DM has a positive impact also in improving glycemic balance.

"One and a Half Years of Things We Could Have Done": Multi-Method Analysis of the Narratives of Adolescents with Type 1 Diabetes during the COVID-19 Pandemic.

BACKGROUND: Public health interventions for COVID-19 forced families to adopt changes in daily routines that affected children's and adolescents' psychological well-being. In youth with type 1 diabetes (T1D), psychological symptoms may compromise glycemic control and outcomes; however, evidence of improved glycemic control in children and adolescents with T1D emerged early during the pandemic. This qualitative study aims to provide a more in-depth understanding of how the COVID-19 pandemic affected adolescents' with T1D routines, experiences, T1D management, and psychological well-being. METHODS: 24 adolescents, aged 15-18 years, with T1D, joined focus-group discussions during the diabetes summer camp. Word frequency analysis and thematic analysis were conducted on adolescents' narratives. The average frequencies of use of words related to COVID-19 and to T1D were compared by t-test. RESULTS: Word frequency analysis identified "friends", "family", and "home" as the most recurrent terms. Seven themes were highlighted: (1) COVID-19 and T1D; (2) emotional reactions to the COVID-19 pandemic; (3) changes in daily life; (4) feelings of loss; (5) coping with the COVID-19 pandemic; (6) the COVID-19 pandemic as opportunity; (7) return to (new) normality. COVID-19 related words were on average more frequent than words referring to T1D. CONCLUSIONS: The COVID-19 pandemic may have represented a more stressful condition for adolescents with T1D, facing additional challenges compared to their healthy peers. Findings offer directions to the diabetes care team for customized interventions while the effects of the pandemic on adolescents' health continue.

Outer Retinal and Choroidal Changes in Adolescents with Long-Lasting Type 1 Diabetes.

This study aimed to assess outer retinal layer (ORL), retinal pigment epithelium (RPE), choroid (Ch) and choriocapillaris (CC) modifications in adolescents with long-lasting (>10 years) type 1 diabetes (T1D) without (noDR) or with diabetic retinopathy (DR). ORL and RPE thickness were measured at optical coherence tomography (OCT) macular scans. Vascular parameters of Ch and CC were quantified after elaboration of macular OCT-angiography (OCTA) images. Insulin dose and auxological and metabolic parameters were correlated with OCT and OCTA findings in patients. ORL thickness was higher in DR eyes than in noDR and healthy controls (HC), and RPE thickness was higher in noDR and DR eyes than in HC, with statistical significance for some sectors in noDR versus HC. No OCTA parameters of CC and Ch differed among groups, and no significant correlation was observed with auxological and metabolic parameters. In conclusion, ORL and RPE were both increased in adolescents with long-lasting T1D. Such changes were not associated with insulin dose and glycemia control, nor to any choroid or choriocapillaris flow change clinically detectable at OCTA, and they could be potential imaging biomarkers of disease progression.

Juvenile diabetes and systemic sclerosis: just a coincidence?

BACKGROUND: Limited joint mobility (LJM), previously known as cheiroarthropathy, refers to the presence of reduced extension at the finger joints in people with diabetes and may be associated with scleroderma-like syndromes such as diabetic sclerodactyly. While scleroderma-like syndromes and LJM have been observed in patients with long-term diabetes and associated complications, the coexistence of diabetes with Juvenile systemic sclerosis (jSSc) is rarely described. CASE PRESENTATION: We describe the case of a 14-year-old boy with long-lasting type 1 diabetes (T1D) and suspected LJM associated with Raynaud phenomenon, sclerodactyly and tapering of the fingertips. A comprehensive work-up showed positive autoantibodies (ANA, anti-Ro-52, anti-Mi-2b), abnormal nailfold capillaroscopy with a scleroderma pattern, interstitial lung disease and cardiac involvement. The overall clinical picture was consistent with the diagnosis of jSSc. CONCLUSIONS: LJM can be the initial sign of underlying systemic sclerosis. Nailfold capillaroscopy may help differentiate jSSc from classical LJM in pediatric patients with T1D and finger contractures or skin induration of no clear origin. This case report provides a starting point for a novel hypothesis regarding the pathogenesis of jSSc. The association between T1D and jSSc may be more than a coincidence and could suggest a relationship between glucose metabolism, fibrosis and microangiopathy.

SGLT2i Improves Glycemic Control in Patients With Congenital Severe Insulin Resistance.

Insulin-resistant diabetes in Rabson-Mendenhall syndrome (RMS) is relatively unresponsive to first-line antidiabetic treatments, including metformin and insulin. We report 2 patients with RMS treated with 2 different sodium-glucose cotransporter inhibitors 2: empagliflozin in an 11-year-old boy and dapagliflozin in a 12-year-old girl. In the first patient, we began empagliflozin at 2.5 mg/day and increased the dose to 10 mg/day over 3 months. During treatment with empagliflozin, the amount of time during which the patient maintained serum glucose in the 70 to 180 mg/dL target range increased by 2 hours per day. Hemoglobin A1C dropped from >14% to 11.9%, urinary calcium increased almost twofold, and ß-hydroxybutyrate remained <2.5 mmol/L. Because glycemic control did not further improve with dose escalation, we reverted to the 2.5 mg/day dose. We initiated dapagliflozin in a second patient at 5 mg/day and witnessed a reduction of hemoglobin A1C from 8.5% to 6.2% after 6 months and a mild increase in urinary excretion of phosphorus but not calcium. Insulin levels fell by >50%. In 2 patients with RMS, empagliflozin and dapagliflozin were well tolerated and improved glycemic control without significantly increasing ketonemia. Renal calcium excretion should be carefully monitored.

Retinal Microvascular and Neuronal Changes Are Also Present, Even If Differently, in Adolescents with Type 1 Diabetes without Clinical Diabetic Retinopathy.

The purpose of this study was to evaluate retinal changes in adolescents with childhood-onset, long-lasting type 1 diabetes mellitus (T1D). Patients and healthy controls (HC) underwent optical coherence tomography (OCT) and OCT-angiography (OCTA). Individual macular layers, peripapillary retinal nerve fiber layer (pRNFL), and vascular parameters (vessel area density (VAD), vessel length fraction (VLF) and vessel diameter index (VDI)) of macular superficial vascular (SVP), intermediate (ICP), deep (DCP) and radial peripapillary capillary plexuses (RPCP) were quantified. Thirty-nine patients (5 with (DR group) and 34 without (noDR group) diabetic retinopathy) and 20 HC were enrolled. The pRNFL and ganglion cell layer (GCL) were thicker in noDR compared to HC and DR, reaching statistically significant values versus HC for some sectors. At the macular level, VAD and VLF were reduced in DR versus HC in all plexuses, and versus noDR in SVP (p < 0.005 for all). At the RPCP level, VAD and VDI were increased in noDR versus HC, significantly for VDI (p = 0.0067). Glycemic indices correlated to retinal parameters. In conclusion, in T1D adolescents, retinal capillary and neuronal changes are present after long-lasting disease, even in the absence of clinical DR. These changes modify when clinical retinopathy develops. The precocious identification of specific OCT and OCTA changes may be a hallmark of subsequent overt retinopathy.

Health-Related Quality of Life, Family Conflicts and Fear of Injecting: Perception Differences between Preadolescents and Adolescents with Type 1 Diabetes and Their Mothers.

Good management of diabetes requires at the same time self-regulation behaviour and a balanced involvement of family components. This cross-sectional study's aims were: understanding fear of injections and perceptions of family conflicts in preadolescents and adolescents with type 1 diabetes mellitus and their mothers, comparing their perceptions, and identifying the risk factors impacting patients' quality of life. Eligibility criteria were: treatment for diabetes mellitus type I, currently aged 10-18 years, attending the hospital for annual hospital follow-ups. Exclusion criteria were: intellectual disabilities, inability to complete questionnaires alone and neuropsychiatric illness with active pharmacotherapy. The study design was cross-sectional. Participants were one hundred and two patients (Mean age = 14.6, SD = 2.4; age range = 10-19 years; Females = 52 and Males = 50) and their mothers (Mean age = 46.9, SD = 6.2, age range = 27-63 years), who filled in self and proxy-report questionnaires (N total= 204). The results showed that 20% of patients and 14.7% of their mothers reported clinical scores for fear of self-injection and blood testing. The mothers reported lower fear of injecting and higher family conflicts compared with the patients. Age, fear of injecting and family conflicts were significantly associated with patients' quality of life perceptions. Clinical considerations and recommendations are given based on the empirical results.

Anxiety, depression, and glycemic control during Covid-19 pandemic in youths with type 1 diabetes.

OBJECTIVES: Our study aims to assess the impact of lockdown during the coronavirus disease 2019 pandemic on glycemic control and psychological well-being in youths with type 1 diabetes. METHODS: We compared glycemic metrics during lockdown with the same period of 2019. The psychological impact was evaluated with the Test of Anxiety and Depression. RESULTS: We analyzed metrics of 117 adolescents (87% on Multiple Daily Injections and 100% were flash glucose monitoring/continuous glucose monitoring users). During the lockdown, we observed an increase of the percentage of time in range (TIR) (p<0.001), with a significant reduction of time in moderate (p=0.002), and severe hypoglycemia (p=0.001), as well as the percentage of time in hyperglycemia (p<0.001). Glucose variability did not differ (p=0.863). The glucose management indicator was lower (p=0.001). 7% of youths reached the threshold-score (≥115) for anxiety and 16% for depression. A higher score was associated with lower TIR [p=0.028, p=0.012]. CONCLUSIONS: Glycemic control improved during the first lockdown period with respect to the previous year. Symptoms of depression and anxiety were associated with worse glycemic control; future researches are necessary to establish if this improvement is transient and if psychological difficulties will increase during the prolonged pandemic situation.

Stress, Resilience, and Well-Being in Italian Children and Their Parents during the COVID-19 Pandemic.

The novel coronavirus (COVID-19) outbreak has forced parents and children to adopt significant changes in their daily routine, which has been a big challenge for families, with important implications for family stress. In this study, we aimed to analyze the potential risk and protective factors for parents' and children's well-being during a potentially traumatic event such as the COVID-19 quarantine. Specifically, we investigated parents' and children's well-being, parental stress, and children's resilience. The study involved 463 Italian parents of children aged 5-17. All participants completed an online survey consisting of the Psychological General Well Being Index (PGWB) to assess parental well-being, the Strengths and Difficulties Questionnaire (SDQ) to measure children's well-being, the Parent Stress Scale (PSS) to investigate parental stress, and the Child and Youth Resilience Measure (CYRM-R) to measure children's resilience. The results show that confinement measures and changes in daily routine negatively affect parents' psychological dimensions, thus exposing children to a significant risk for their well-being. Our results also detect some risk factors for psychological maladjustments, such as parental stress, lower levels of resilience in children, changes in working conditions, and parental psychological, physical, or genetic problems. In this study, we attempted to identify the personal and contextual variables involved in the psychological adjustment to the COVID-19 quarantine to identify families at risk for maladjustment and pave the way for ad hoc intervention programs intended to support them. Our data show promising results for the early detection of the determinants of families' psychological health. It is important to focus attention on the needs of families and children-including their mental health-to mitigate the health and economic implications of the COVID-19 pandemic.

Medical practitioners' attitudes towards animal assisted interventions. An Italian survey.

OBJECTIVES: The present study had a dual purpose: to obtain a comprehensive picture of the Italian medical practitioners' opinions, professional experiences, training needs and knowledge of Animal Assisted Interventions (AAI); and to provide a detailed description of the medical practitioners who are characterized by a strongly positive attitude towards AAI. METHODS: An online survey addressed to Italian medical practitioners was carried out using a 35-items structured questionnaire. Data obtained from the survey were analysed through appropriate summary statistics, analysis of variance (ANOVA) and logistic regression analysis. RESULTS: 670 medical practitioners participated in the online survey. Among them, 508 stated that they knew of AAI. 93.7% of these described themselves fully favourable towards the use of the human-animal relationship for therapeutic purposes, 84.4% defined themselves as confident and interested in studying the theme. A positive attitude towards AAI was greater in females, in people between 45 and 54 years old, in those who are pet owners and in those who believe that conferences are the most suitable tool to share information on AAI. CONCLUSIONS: The chance of having a positive attitude towards AAI is higher in respondents with specific characteristics. Data collected could be used as a starting point to promote and implement communication and training activities on AAI addressed to medical practitioners.

An Unexpected Fever Post Serogroup B Meningococcal Sepsis.

This case report describes an invasive meningococcal group B infection followed by the development of Kawasaki disease (KD) complicated by macrophage activation syndrome (MAS) in a 2-year-old child. The presented case indicates the possible etiologic relationship between meningococcal sepsis and KD as support of bacterial toxin induced theory. It's important to maintain a high grade of suspicious for KD in every relapse of fever also during convalescence phase of severe infection. Usually, initial treatment with intravenous immunoglobulin is sufficient to control the disease; but, in case of refractory KD complicated by MAS, corticosteroid therapy represents a good option inducing prompt fever resolution and clinical improvement.

Prevention and early recognition: the role of family pediatrician.

Even if it is empirically evident that pediatricians play a key role in diagnosis, treatment and prevention of FB injuries, almost all studies have focused on the subset of injured children who receive medical care in the hospital or in the Emergency Department; moreover, a lack of scientific interest to improve information about pediatric injuries in primary care seems to exist. Primary care physicians can play an important role if they promptly identify suspect unrecognized FB aspiration in children. Moreover, prevention is a cornerstone of pediatric practice, and pediatricians, as reliable sources of information, may be efficacious in promoting injury prevention message. Given the paucity of works finalized to evaluate the role of injury preventive strategies in primary care it is arduous to identify an ideal approach to implement counseling strategies. However, evidences obtained elsewhere have suggested that effective preventive strategy origins from an effective communication technique, moreover, the probability of success is greater when the attention toward the problem is greater; particularly, the postpartum period is a time of tremendous change, increased health problems, and emotional upheaval for new parents. General practitioners are in an ideal position to assist families during this period and may consider a sooner rather than later, approach to injury prevention education.