Long-term cytokine profile in multisystem inflammatory disease among children.

BACKGROUND: Multisystem inflammatory disease in children (MIS-C) is a post-infectious condition following coronavirus disease-19 infection. Long-term follow-up data suggests that initial clinical severity does not necessarily correlate with long-term outcomes. The long-term immunological response in children with MIS-C remains poorly understood. We analyzed cytokine profiles at diagnosis and during follow-up, in pediatric patients with MIS-C, exploring correlations among cytokine expressions and standard biochemical and hormonal test results. METHODS: Twenty-five MIS-C patients (mean 9.4 ± 3.9) with complete test results at diagnosis and at 6- and 12-months follow-up were included in the study. Selected cytokines, such as IL-9, eotaxin, IP-10, MIP-1ß, RANTES, MCP-1(MCAF), TNF-α, PDGF-B, IL-4, and MIP-1α, were included in the analysis. RESULTS: IP-10, MCP-1 (MCAF), and MIP-1α levels normalized or nearly normalized at 6-12 months, the remaining cytokines, including IL-9, eotaxin, MIP-1ß, RANTES, TNF-α, PDGF-B, IL-4, remained higher in MIS-C than in controls at our last follow-up time. At 6 months post-diagnosis, a mild negative correlation between triglycerides and HOMA-IR with MCP-1 (MCAF), IL-4, and Eotaxin was noted. At the 12-month follow-up we found a mild positive correlation of cortisol and ACTH levels with PDGF-B, MIP-1α, and TNF-α. Conversely, a negative correlation between these cytokines with fasting glucose and HOMA-IR was observed. CONCLUSIONS: Our study findings highlight a notable cytokine-mediated inflammatory response in pediatric patients with MIS-C, characterized by sustained elevated levels over a 12-month monitoring period compared to the control group. We have identified various interrelationships among different cytokines, as well as correlations between heightened cytokine levels and metabolic and hormonal patterns. The pronounced inflammatory response underscores its involvement in acute organ damage, while its persistence suggests potential implications for long-term metabolic disorders.

Longitudinal Anthropometry and Body Composition in Children With SARS-CoV-2-Associated Multisystem Inflammatory Syndrome.

OBJECTIVES: Acute coronavirus disease 2019 infection has been shown to negatively affect body composition among adult and malnourished or obesity children. Our aim is to longitudinally evaluate body composition in children affected by the Multisystem Inflammatory Syndrome (MIS-C). METHODS: In this cohort study, we recruited 40 patients affected by MIS-C, aged 2-18 years old, who were admitted in our clinic between December 2020 and February 2021. Physical examination for each participant included weight, height, body mass index (BMI) z score, circumferences, and skinfolds assessment. The same measurements were repeated during outpatient follow-up at 10 (T2), 30 (T3), 90 (T4), and 180 (T5) days after hospital discharge. Fat mass and fat free mass were calculated according to skinfolds predictive equations for children and adolescents. A control group was randomly selected among patients attending a pediatric nutritional outpatient clinic. RESULTS: BMI z score significantly decrease between preadmission and hospital discharge. Similarly, arm circumference z score, arm muscular area z score, and arm fat area z score significantly decreased, during hospital stay. Fat mass index (FMI) significantly increased over time, peaking at T3. Fat free mass index decreased during hospitalization. CONCLUSIONS: To the best of our knowledge, this is the first study to assess body composition in a numerically large pediatric MIS-C population from acute infection to 6 months after triggering event. FMI and anthropometric parameters linked to fat deposits were significantly higher 6 months after acute event. Thus, limiting physical activity and having sedentary lifestyle may lead to an accumulation of adipose tissue even in healthy children who experienced MIS-C and long hospitalization.

Severe hypoglycemia in children treated with nadolol: A case report and FDA adverse event reporting system (FAERS) database analysis.

OBJECTIVE: We describe a case of severe hypoglycemia in a 14-month-old child as a suspected adverse drug reaction (ADR) to nadolol, and we performed an analysis of the FDA Adverse Event Reporting System (FAERS) database. Although previous reports have identified the risk of severe hypoglycemia in children during treatment with ß-blockers, little is known about hypoglycemia as an ADR in infants treated with nadolol. Moreover, the pharmacodynamic and pharmacokinetic profiles of nadolol in children aged less than 1 year old are still not fully known. MATERIALS AND METHODS: We extracted all ADR reports involving nadolol from the FAERS database; in order to reduce the risk of bias, we only considered cases that exclusively reported nadolol as the suspect drug. We then selected cases of hypoglycemia in the pediatric population and conducted a manual deduplication. RESULTS: Upon FAERS database analysis, a total of 2,674 suspected ADR reports to nadolol were found. Of these, 1,950 (73%) were solely attributed to nadolol, and 63 of them were hypoglycemic events. A total of 47 reports included the relevant pediatric age (74.6%). After deduplication, we identified 25 cases (mean age: 3.65 years old); all of these reports were categorized as serious, and hospitalization was required in 15 cases. CONCLUSION: Hypoglycemia is a reported life-threatening ADR associated with nadolol, especially in infants, in whom this drug should be used with caution.

Leveraging User-Friendly Mobile Medical Devices to Facilitate Early Hospital Discharges in a Pediatric Setting: A Randomized Trial Study Protocol.

BACKGROUND: Mobile technology is increasingly prevalent in healthcare, serving various purposes, including remote health monitoring and patient self-management, which could prove beneficial to early hospital discharges. AIMS: This study investigates the transitional care program experience facilitating early discharges in a pediatric setting through the use of an easy-to-use mobile medical device (TytoCare™, TytoCare Ltd., Natanya, Israel). OUTCOMES: This study aims to assess the effectiveness of telehomecare in achieving complete resolution of diseases without readmission, compare the length of stay between intervention and standard care groups, and gather user and professional experiences. METHODS: A randomized open-label, controlled pilot study enrolled 102 children, randomly assigned to the telehomecare (TELE) group (n = 51, adopting early hospital discharge with continued home monitoring) or the standard-of-care (STAND) group (n = 51). Primary outcomes include complete disease resolution without readmission. Secondary objectives include recording a shorter length of stay in the intervention group. Surveys on user and professional experiences were conducted. A group of 51 children declining telemedicine services (NO-TELE) was also included. RESULTS: In the TELE group, 100% of children achieved complete disease resolution without readmission, with a median duration of stay of 4 days, significantly shorter than the 7 days in the STAND group (p = 0.01). The telemedicine system demonstrated efficient performance and high satisfaction levels. The NO-TELE group showed no significant differences in demographics or digital technology competence. Perceived benefits of telemedicine included time and cost savings, reduced hospital stays, and technology utility and usability. CONCLUSIONS: This study demonstrates that user-friendly mobile medical devices effectively facilitate early hospital discharges in a pediatric setting. These devices serve as a bridge between home and hospital, optimizing care pathways.

MRSA Femoral Osteomyelitis from Superinfected Scabies Lesions: A Pediatric Case Report.

Scabies is a skin infestation from the Sarcoptes scabiei. It is considered a public health issue causing concern in developing countries and is considered a "neglected tropical disease" by the World Health Organization (WHO). Scabies skin lesions may cause severe itching and can be the portal of entry for opportunistic and pathogenic bacteria, which can cause serious systemic infections. We report the case of a 3-year-old boy with recurrent scabies infections who presented to the emergency department because of a fever and refusal to walk. Blood tests showed neutrophilic leukocytosis and significantly increased C reactive protein (CRP) and procalcitonin. Upon medical examination, his right thigh was extremely painful upon palpation, knee flexion was lost and he was unable to stand, so magnetic resonance imaging (MRI) was performed. MRI showed osteomyelitis of metaphysis and distal diaphysis of the right femur with associated subperiosteal purulent collection and concomitant pyomyositis and fasciitis of the distal right thigh. Blood cultures were positive for methicillin-resistant Staphylococcus aureus (MRSA). The patient received a long course of intravenous antibiotic therapy and his condition slowly improved. Follow-up femur X-ray showed a mixed pattern of erosion and sclerosis at the meta-diaphyseal region and periosteal reaction at the diaphyseal region. This case highlights the importance of early scabies diagnosis even in Western countries where poverty and household overcrowding are uncommon. Early diagnosis, timely initiation of proper treatment and evidence of clinical resolution are important elements to prevent recurrence of infection and serious systemic superinfections even from multi-drug resistant bacteria. Clinical consequences from unrecognized disease or inadequate eradication are preventable.

Hypercalcemia and Neurological Symptoms: A Rare Presentation of Hyperfunctioning Parathyroid Adenoma in an Adolescent.

Neuropsychiatric symptoms are rarely described as a manifestation of hyperparathyroidism, especially in children. We describe the case of an adolescent with hypercalcemia related to and hyperfunctioning parathyroid adenoma presenting with acute neuropsychiatric symptoms. A 14-year-old-girl presented into the Emergency Service Department because of an acute onset of marked asthenia, muscle weakness with difficulty in walking, and altered mental status, which included nonsensical speech. No other neurological signs were present. Abdominal, cardiac, and thoracic examination were unremarkable. There was no recent history of trauma or infection. Family history was negative for neurologic disorders. Her past medical history was unremarkable. A head CT scan showed negative results. The laboratory work-up showed elevated levels of calcium level (14.35 mg/dl; nv 9-11 mg/dl), parathyroid hormone (PTH; 184 pg/ml; nv 3.5-36.8 pg/ml), and creatinine (1.23 mg/dl; nv 0.45-0.75 mg/dl). Sodium, potassium, chloride, thyroid function, glycemia, and insulin values were normal. Neck ultrasonography showed a solid, oval, capsulated, hypoechoic neoformation, with discrete vascularization localized to the inferior pole of the right thyroid lobe, referring to parathyroid tissue. Scintigraphy revealed a hyperfunctioning parathyroid tissue at the inferior pole of the right thyroid lobe. Massive intravenous hydration and diuretic therapy were started. The signs and symptoms of hypercalcemia improved after the initiation of therapy. The patient was submitted to right cervicotomy and muscle sparing for the removal of the adenoma of the right superior parathyroid gland. After surgery, a decrease in PTH levels (<4 pg/ml) and calcium levels (9.1 mg/dl) was recorded. During follow-up, calcium values remained stable; a progressive normalization of PTH was obtained. The oral calcium therapy was suspended after 3 months from surgery. No neuropsychiatric symptoms recurred. An evaluation of the serum calcium level is mandatory in children and adolescents with unexplained neurological signs or symptoms, and a check for hyperparathyroidism should be considered.

Thyroid Function and Metabolic Syndrome in Children and Adolescents with Neuromotor Disability.

Thyroid function plays a crucial role in nervous system integrity and metabolic homeostasis. We evaluated the pattern of TSH, FT4 and FT3 release in children with neuromotor impairment (NI) in relationship with metabolic syndrome (MS). We enrolled 55 patients with NI and 30 controls. Clinical parameters, thyroid function and MS presence were recorded. Principal component analysis (PCA), cluster analysis, and logistic regression models were performed. MS was detected in 54.5% of patients. Four clusters were identified: the first one included only controls and, contrasting with cluster 4, was exclusively characterized by children with disability and MS. This latter showed increased FT4 and FT3 and decreased TSH levels. Cluster 2, characterized by disability without MS showed high FT4 and FT3, whereas cluster 3 with low FT4 and FT3 mainly included disability (90%) and showed prevalent MS (57%). The association between TSH and NI is represented by a U-shape structure. The TSH, FT3 and FT4 release patterns may reflect thyrotropic adaptation, allostatic response and compensatory mechanisms. These mechanisms, found in both MS and disability, show that the odds of having a condition of NI with or without MS increase as the TSH values deviate, in both directions, from a value of 2.5 mLU/mL.

Six-month multidisciplinary follow-up in multisystem inflammatory syndrome in children: An Italian single-center experience.

Background: A severe multisystem inflammatory syndrome in children (MIS-C) related to SARS-CoV-2 has been described after infection. A limited number of reports have analyzed the long-term complications related to pro-inflammatory status in MIS-C. We evaluated multiorgan impairment at the 6-month follow-up in MIS-C. Methods: We enrolled 33 pediatric patients consecutively hospitalized for MIS-C and monitored for almost 6 months. The inter-relationship of patient's features and disease severity at admission with long term complications was studied by multivariate analysis. Results: Endo-metabolic derangement, cardiac injury, respiratory, renal and gastrointestinal manifestations and neurological involvement are part of the initial presentation. The most abnormalities appear to resolve within the first few weeks, without significant long term dysfunction at the 6-months follow-up, except for endocrine (non-thyroidal illness syndrome in 12.1%, insulin resistance in 21.2%) and neurological system (27.3% cognitive or psychological, behavioral, adaptive difficulties). Endocrine and heart involvement at admission represent a significant factor on the long term sequelae; however no association between severity score and long-term outcome was noted. Conclusions: The severity of initial clinical presentation may be associated to organ domain, however it is not related to long term sequelae. The prevalent organ restoration supports a predominant indirect immune-mediated injury triggered by a systemic inflammatory response; however a direct damage due to the viral entry could be not excluded. Eventhought our preliminary results seem to suggest that MIS-C is not a long-term risk condition for children health, a longer follow-up is mandatory to confirm this hypothesis.

Impaired Glucose-Insulin Metabolism in Multisystem Inflammatory Syndrome Related to SARS-CoV-2 in Children.

An interaction between metabolic glucose impairment and coronavirus disease 2019 is reported. The development of a severe multisystem inflammatory syndrome in children (MIS-C) related to SARS-CoV-2 infection has been described. We evaluated the impact of MIS-C on glycemic patterns in pediatric patients. A group of 30 children and adolescents affected by MIS-C were considered; all patients were normal weight. Clinical and biochemical assessments, including surrogate markers of insulin resistance (IR) such as homeostasis model analysis-IR (HOMA-IR) and triglyceride-glucose (TyG) indexes, were recorded. Patients were also invited to undergo an intermittently scanned continuous glucose monitoring (isCGM). HOMA-IR index was calculated in 18 patients (60%), of which 17 (94%) revealed a pathological value. TyG index was computed for all patients and pathological values were detected in all cases. In 15 patients, isCGM data were recorded on average for 9 days (±3 days). Overall, average glucose was 105 mg/dL (±16 mg/dL) and average time spent in the 70-180 mg/dL range (TIR) was 93.76%, with nearly 10% of glucose readings in the 141-180 mg/dL range; glycemic fluctuations over the hyperglycemic threshold were detected in four patients. Regular glucose monitoring may be useful to prevent metabolic imbalance and obtain a better outcome.

Evaluation of rapid assay for detection of Streptococcus pneumoniae urinary antigen among infants and young children with possible invasive pneumococcal disease.

The usefulness of the rapid assay for detection of Streptococcus pneumoniae urinary antigen was evaluated in 155 children ages 1 to 60 months with suspected invasive pneumococcal disease and 200 healthy controls. Although the assay was highly sensitive in the children with invasive pneumococcal disease, it should be interpreted with caution in young patients because a positive urine test result may simply be the result of nasopharyngeal colonization.