Procalcitonin and Presepsin as Markers of Infectious Respiratory Diseases in Children: A Scoping Review of the Literature.

INTRODUCTION: Procalcitonin and presepsin have been suggested to be able to discriminate bacterial and viral infections, also in children. This scoping review aims to better explore the available evidence around the potential role of these biomarkers in the subgroup of children with respiratory infectious diseases. METHODS: We performed a systematic scoping review of studies published until March 2023 in the following bibliographic databases: PubMed, EMBASE, Cochrane and SCOPUS. RESULTS: In children with bacterial infection, procalcitonin values ranged from 0.5 ng/mL to 8.31 ng/dL, while in those hospitalized in an intensive care unit ranged from 0.6 ng/dL to 452.8 ng/dL with PCR from 2 ng/dL to 51.7 ng/dL. In children with viral infections, procalcitonin value values ranged from 0.2 ng/dL to 0.84 ng/dL, while in those hospitalized in an intensive care unit ranged from 0.61 ng/dL to 46.6 ng/dL. No studies on presepsin in children with respiratory infections were retrieved. CONCLUSIONS: Although the available literature is highly heterogeneous, evidence does not suggest a role of procalcitonin in accurately differentiating bacterial and viral infections in children with respiratory infections. In future, new approaches based on multiple markers may better help determine which febrile children require antibiotics.

Predictors of Gastrointestinal Involvement in Children with IgA Vasculitis: Results from a Single-Center Cohort Observational Study.

Background and objective: IgA vasculitis (IgAV), a predominantly pediatric leukocytoclastic disease, has an unpredictable, though largely benign, evolution. The aim of this study was to retrospectively investigate any potential clinical or laboratory predictors of gastrointestinal involvement in a single-center cohort of children with IgAV. Patients and methods: A total of 195 children with a history of IgAV, regularly followed-up for an average period of 1 ± 2.6 years via outpatients clinics of the pediatric rheumatology unit in our University, were assessed, analyzing their clinical and laboratory variables in relationship with their disease evolution and outcome. Results: Univariate analysis showed that a higher neutrophil granulocyte count and lower lymphocyte count (expressed as a percentage of the total white blood cells) were significantly associated with the presence of gastrointestinal involvement at the first examination (65.2 ± 13% versus 58.8 ± 12%, p = 0.02, and 26.4 ± 11% versus 32.1 ± 11%, p = 0.02, respectively). A positive pharyngeal swab for Streptococcus pyogenes, a deficiency of 25-hydroxyvitamin D, a persistence of purpuric rash for more than 1 month, and purpuric lesions in the genital area were also associated with gastrointestinal involvement (p = 0.0001, p = 0.0001, p = 0.007 and p = 0.001, respectively). However, multiple logistic regressions with correction for the patients' sex and age showed that lower 25-hydroxyvitamin D levels, persistent rash, and genital lesions were independently and significantly associated with signs of gastrointestinal involvement. We then performed a secondary analysis (both univariate and multivariate) to investigate whether vitamin D deficiency was associated with other IgAV manifestations: we found that only 25-hydroxyvitamin D deficiency remained significantly associated with gastrointestinal involvement in IgAV. Conclusions: Patients with IgAV and vitamin D deficiency might be more prone to developing gastrointestinal manifestations of variable severity.

Bone mineral density and body mass composition measurements in premenopausal anorexic patients: the impact of lean body mass.

INTRODUCTION: Evaluating bone density and body composition by dual-energy x-ray absorptiometry (DXA) and analyzing their relationships among young anorexic women in comparison with normal-lean matched controls. MATERIALS AND METHODS: In this observational cohort study, 98 normal-underweight young females were enrolled (aged more than 16 and less than 24 years). The study group included 68 anorexic patients and 30 healthy age-matched controls. The patients underwent a DXA examination to evaluate bone mineral density and body composition. Several indexes of body composition were used: the FMI (Fat Mass Index), the TLMI (Total Lean Mass Index) and the SMI (Skeletal Muscle mass Index) the last one as a marker of sarcopenia. RESULTS: According to the ISCD (International Society for Clinical Densitometry) criteria, a significantly higher percentage of anorexic patients were found to be below the expected range for age as compared to controls (P < 0.01). According to WHO criteria, 20% of the anorexic patients presented an osteoporotic T-score index at the lumbar level and 18% presented an osteoporotic T-score at the femoral level. As regards the lean body characteristics, the SMI and TLMI were significantly lower in the anorexic population (P < 0.01 and P < 0.001, respectively) and 24% of the anorexic patients presented SMI values that are indicative of pre-sarcopenia. In addition, only the SMI significantly correlated with both the lumbar and the femoral BMD values. CONCLUSION: Anorexic patients have a very high risk of osteoporosis and fractures. Bone density is influenced by fat body mass and also significantly by lean body mass. Special consideration should be given to the sarcopenic condition since it is a worsening factor of bone health.

Characteristics of Children and Adolescents with Hyperinsulinemia Undergoing Oral Glucose Tolerance Test: A Single-Center Retrospective Observational Study.

The aim of this study was to evaluate a potential correlation between results of the oral glucose tolerance test (OGTT) and the auxological/metabolic parameters in a cohort of overweight patients assessed for suspicion of hyperinsulinism. We analyzed 206 patients, comparing those with insulin peak below (nonhyperinsulinemic) and over 100 uIU/mL (hyperinsulinemic) at the OGTT. We found a significant difference in weight (p = 0.037), body mass index (BMI, p < 0.001) and BMI standard deviations (SD, p < 0.001), waist circumference (p = 0.001), hip circumference (p = 0.001), and waist-to-height ratio (WHtR, p = 0.016) between the two groups. Analyzing the median insulin value during OGTT in the whole population, a weakly positive correlation emerged with weight SD (p < 0.001; rho = 0.292) and a moderate positive correlation with BMI SD (p < 0.001; rho = 0.323). We also found a weakly positive correlation with waist circumference (p = 0.001; rho = 0.214), hip circumference (p = 0.001; rho = 0.217), and WHTR (p = 0.016; rho = 0.209) and a moderate positive correlation with the HOMA index (p < 0.001; rho = 0.683). The median insulin value correlates with high triglyceride (p < 0.001; rho = 0.266) and triiodothyronine values (p = 0.003; rho = 0.193) and with low HDL values (p < 0.001; rho = -0.272). In clinical practice the interpretation of laboratory and anthropometric parameters could predict the level of insulin, highlighting also a possible underlying diagnosis of insulin resistance and/or hyperinsulinemia without performing an OGTT.

Metabolic Profile of Patients with Smith-Magenis Syndrome: An Observational Study with Literature Review.

Background: Smith-Magenis syndrome (SMS) is caused by either interstitial deletions in the 17p11.2 region or pathogenic variants in the RAI1 gene and is marked by a distinct set of physical, developmental, neurological, and behavioral features. Hypercholesterolemia has been described in SMS, and obesity is also commonly found. Aim: To describe and characterize the metabolic phenotype of a cohort of SMS patients with an age range of 2.9-32.4 years and to evaluate any correlations between their body mass index and serum lipids, glycated hemoglobin (HbA1c), and basal insulin levels. Results: Seven/thirty-five patients had high values of both total cholesterol and low-density lipoprotein cholesterol; 3/35 had high values of triglycerides; none of the patients with RAI1 variants presented dyslipidemia. No patients had abnormal fasting glucose levels. Three/thirty-five patients had HbA1c in the prediabetes range. Ten/twenty-two patients with 17p11.2 deletion and 2/3 with RAI1 variants had increased insulin basal levels. Three/twenty-three patients with the 17p11.2 deletion had prediabetes. Conclusion: Our investigation suggests that SMS 'deleted' patients may show a dyslipidemic pattern, while SMS 'mutated' patients are more likely to develop early-onset obesity along with hyperinsulinism.

Auxological and Metabolic Parameters of Children Undergoing the Gonadotropin-Releasing Hormone Stimulation Test: Correlations with the Final Diagnosis of Central Precocious Puberty in a Single-Center Study.

Background-Central precocious puberty (CPP) is characterized by clinical, biochemical, and radiological features similar to those of normal puberty, but CPP occurs before the age of eight in girls and before the age of nine in boys, subsequently leading to a reduction in the final body height in adulthood due to premature fusion of growth plates. The diagnosis of CPP is confirmed with a gonadotropin-releasing hormone (GnRH) stimulation test, which can lead to different interpretations because the diagnostic peak levels of luteinizing hormone (LH) can vary. Patients and methods-This was a single-center, retrospective observational study investigating the possible correlation between gonadotropin peaks on the GnRH test and auxological, metabolic, and radiological parameters of patients evaluated for CPP. We collected and analyzed data from the medical records of children with suspected CPP over a period from January 2019 to July 2022 who underwent a GnRH test at the Fondazione Policlinico Universitario Agostino Gemelli in Rome, Italy. Results-Our correlation analysis revealed no statistically significant differences in any auxological and radiological parameters. Among laboratory parameters, baseline levels of LH, follicle-stimulating hormone, sex hormone-binding globulin, and 17-beta estradiol were higher in children with a definitive diagnosis of CPP than in those with a negative GnRH test. In particular, the levels of LH at baseline and after the GnRH test were statistically significant in the group of CPP patients, consistent with the interpretation of the test. In the multivariate analysis, using a cut-off value of 4.1 IU/L, LH peaks showed both very high sensitivity (94%) and very high specificity (95%); all other variables showed high specificity (90%) but unsatisfactory sensitivity. Conclusion-Basal hormone dosages and, especially, basal levels of LH should be considered before performing a GnRH test as they might anticipate the final diagnosis of CPP.

Efficacy and safety of growth hormone therapy in children with Noonan syndrome.

Patients with Noonan syndrome typically have a target height <2 standard deviations compared to the general population, and half of the affected adults remain permanently below the 3rd centile for height, though their short stature might result from a multifactorial etiology, not-yet fully understood. The secretion of growth hormone (GH) following the classic GH stimulation tests is often normal, with baseline insulin-like growth factor-1 (IGF-1) levels at the lower normal limits, but patients with Noonan syndrome have also a possible moderate response to GH therapy, leading to a final increased height and substantial improvement in growth rate. Aim of this review was to evaluate both safety and efficacy of GH therapy in children and adolescents with Noonan syndrome, also evaluating as a secondary aim the possible correlations between the underlying genetic mutations and GH responses.

The impact of glucocorticoids on bone health and growth: endocrine and non-endocrine effects in children and young patients.

Glucocorticoids have numerous applications in short and/or long-term therapy both in pediatric and young adults, based on their significant anti-inflammatory and immunosuppressive effects. Different routes of administration can be provided including topical, inhalatory and oral. Topical treatments are the first choice for many dermatologic conditions. The inhalatory form is widely used in asthma management while systemic pathologies often require oral administration. The risks for adverse effects are related to the dose and duration of therapy as well as the specific agent used. Therefore, long-term treatment has a negative impact on different metabolic systems and can lead to hypertension, dyslipidemia and insulin resistance. In particular, many studies emphasize the direct and indirect effects of glucocorticoids on bone health. Glucocorticoids are the most common iatrogenic cause of osteoporosis and can alter bone development in young adults. These side effects are due to an early and transient increase in bone resorption and a decrease in bone formation. Glucocorticoid-induced changes can act on the bone multicellular unit, bone cells and intracellular signaling pathways. Chronic use can also modify bone mass though indirect endocrine and non-endocrine effects by reducing the anabolic function of sex steroids and GH/IGF-1 axis, interfere with calcium metabolism, as well as muscle atrophy and central fat accumulation. The aim of our review was to revise the available evidence on the impact of glucocorticoid treatment on bone health related to endocrine and non-endocrine effects in Young patients.

Growth hormone responses during arginine and clonidine stimulation test: Correlations with patients' auxological and metabolic parameters in a single centre study.

BACKGROUND: Children with auxological parameters defining a 'short stature' is routinely subjected to various blood tests and, if necessary, to growth hormone stimulation test (GHST) for differentiating GH deficiency (GHD) and other causes of stunted growth. AIM: This retrospective monocentric study aimed to evaluate any correlations between GH peaks during GHST in children assessed for short stature and their auxological/metabolic parameters, highlighting differences between GHD and idiopathic short stature. PATIENTS AND METHODS: We reviewed the medical records of 74 children with short stature (height lower than the third percentile according to standardized growth curves for the Italian population) managed at the Pediatric Day Hospital of our Department of Life Sciences and Public Health in Università Cattolica Sacro Cuore, Rome, who performed at least two GHSTs, using arginine and clonidine as stimulants, for assessment of GH secretion. The results of a total number of 161 GHSTs, performed in 42 children diagnosed with GHD and in 32 children with other causes of short stature, were analyzed. RESULTS: We found significantly lower serum levels of insulin growth factor-1 (IGF-1) and increased levels of thyroid-stimulating hormone (TSH) in children with GHD, without other metabolic differences in comparison to children with other causes of short stature. There was also a correlation between triglycerides and GH peak during arginine test, while fT4 and LDL concentrations correlated with GH peak during the third test, if performed. Pre-test BMI (rho -0.274, p = 0.01) and weight (rho -0.251, p = 0.03) have influenced GH peak during clonidine stimulation test. Metabolic and auxological parameters could influence GH peak during clonidine and arginine stimulation tests and must be taken into account when interpreting GHST results.

Predictors of Urinary Abnormalities in Children Hospitalised for Their First Urinary Tract Infection.

We aimed to investigate if children with their first UTI and a concomitant positive blood culture have a higher risk of abnormalities. We performed a retrospective study of children younger than 18 years of age with their first UTI. Multivariate logistic regression and receiver operating characteristic (ROC) curves were used to evaluate if positive blood cultures are associated with urinary abnormalities. After the screening process, we considered the enrolled 161 children with UTIs. The median age was three months, and 83 were females (43.2%). In multivariate analysis, age (p = 0.001, 95% CI 1.005-1.020), the presence of Pseudomonas aeruginosa or unusual germs in urine cultures (p = 0.002, 95% CI 2.18-30.36) and the positivity of blood cultures (p = 0.001, 95% CI 2.23-18.98) were significantly associated with urinary abnormalities. A model based on these parameters has an AUC of 0.7168 to predict urinary malformations (p = 0.0315). Conclusions include how greater age, a positive blood culture and the presence of Pseudomonas aeruginosa or unusual germs in urine culture in children hospitalised for their first episode of a UTI are factors associated with a significantly higher risk of urinary abnormalities. These data can guide the implementation of more personalized strategies to screen for urinary abnormalities that may be included in future guidelines.

Comparison between Short Therapy and Standard Therapy in Pediatric Patients Hospitalized with Urinary Tract Infection: A Single Center Retrospective Analysis.

Introduction: There is marked heterogeneity in clinicians' choice of antibiotic duration for pediatric urinary tract infections (UTIs). Most patients with bacterial UTIs still receive between 7 and 10 days of antibiotics. Prolonged antibiotic exposure drives the emergence of resistance and increases the occurrence of adverse effects. There is increasing evidence that shorter antibiotic regimens may be equally effective compared with longer ones. However, studies evaluating shorter therapies in children hospitalized with urinary tract infections have not yet been performed. Methods: We performed a retrospective study comparing children hospitalized with UTIs treated with a short antibiotic (<7 days) or standard antibiotic treatment. The primary aim of our study was to assess the efficacy of a shorter antibiotic therapy for children with UTIs, compared with an historical group of children treated with a standard 7−14 days course. Results: 112 patients, 46 of which were females (41.1%) with a median age 6 months were enrolled. A total of 33 patients (29.5%) underwent a short therapy. All patients were successfully discharged from the acute episode, independently from antibiotic duration. Short therapy was associated with a lower risk of urinary tract relapse (22 relapses (95.6%) in the standard group, 1 (4.4%) in the short group; OR 0.081; 95%CI 0.01−0.63). Conclusions: Short antibiotic therapy was equivalent to standard duration therapy for the cure of UTIs in hospitalized children and was also associated with a lower rate of recurrences. This study provides the basis for a larger prospective randomized study to address the role of short antibiotic therapies in children with UTIs requiring hospitalization

Adherence to dietary prescriptions in patients with acute food protein-induced enterocolitis syndrome.

Food protein-induced enterocolitis syndrome (FPIES) is a non-Immunoglobulin (non-IgE)-mediated food allergy. The elimination diet is the only therapy, the culprit food will be reintroduced if tolerance is acquired. However, it is possible that patients do not follow the recommendations given by the healthcare professional. We investigated if our advice to avoid the trigger food in patients with active FPIES and to reintroduce it in the diet in patients who achieved tolerance had been implemented. We interviewed by telephone the parents of children who were diagnosed with acute FPIES. About 23.2% of our patients disregarded our dietary recommendations: 6/42 (14.3%) of patients who passed a tolerance oral food challenge (OFC) did not eat the trigger food, 4/22 (18.2%) of patients who failed OFC ate the trigger food, and 9/18 (50.0%) of patients who did not perform a tolerance OFC ate the trigger food. We have analyzed some possible influencing factors and no difference was found to be statistically significant. Our results are in line with those reported for IgE-mediated food allergies. As has already been proposed by others, we suggest reassessing food consumption in all patients after a food challenge.

Central precocious puberty in children after COVID-19 outbreak: a single-center retrospective study.

BACKGROUND: Central precocious puberty (CPP) was an unexplored issue during COVID-19 pandemic and an important disease in the adolescence life. Our aim was to evaluate the incidence of the new cases of central precocious puberty (CPP) during COVID-19 pandemic, comparing these results with the data for the same period over the previous three years. The secondary objective was to analyze the rate of pubertal progression in children during COVID-19 outbreak. METHODS: We performed a retrospective study of all children presented at our hospital for suspected CPP during COVID-19 outbreak, comparing their clinical and endocrinological data to the same over the previous three years. Secondary, endocrinological data of some patients in follow-up, with at least two visits 6 months apart during the COVID-19 period, are compared to evaluate the rate of pubertal progression. RESULTS: We enrolled 90 suspected enrolled CPP cases, 26 (28.9%) referred to our hospital during the COVID-19 outbreak and 64 (71.1%) in the previous 3 years. During COVID-19 outbreak 12 girls (42.9%) were at stage T3 compared to 14 (23%) of the 3 previous years (p=0.01). New CPP diagnosis were found in 11 (39.3%) children during pandemic, while 15 (24.2%) in the previous 3 years. A accelerated pubertal progression rate was observed in 22/45 (48.9%) patients, with a greater number of children at stages T3 and T4-5. CONCLUSIONS: Our data showed a progressive increase of newly diagnosed CPP and a significantly accelerated rate of pubertal progression in children during COVID-19 outbreak. We hypothesize that the increase in the weight and BMI during the lockdown and the psychological effects of the COVID-19 outbreak were involved in triggering and progression of puberty.

Growth hormone replacement therapy in pediatric brain tumor survivors.

Brain tumors are the most frequent type of solid neoplasms in children with a recognized 5-year survival rate between 57% and 65%. The survival rate progressively increased in the last few years, due to the improvements in their treatment based on chemotherapy, radiotherapy, and surgery. At the same time, at long term follow-up, clinicians should carefully evaluate comorbidities and long-term sequelae secondary to the disease and its treatment. Growth hormone deficiency (GHD) is an endocrinopathy commonly found among pediatric cancer survivors, with a negative effect on the child's final height and entire metabolism. GH replacement therapy (GHRT), with a synthetic hormone analog, may improve the growth rate and finally adult height, ameliorating the quality of life after cancer treatment. However, in clinical practice, GHRT is adopted with caution for fear of cancer recurrence or the onset of second malignancies. In our review, we perform a focus on the GH structure and function, comparing benefits and risks of GHRT, derived from the analysis of the data currently available in the literature.

GH Therapy in children and adolescents with Growth Hormone Deficiency during the first phase of COVID-19 lockdown: a survey in an Italian center.

BACKGROUND: Coronavirus Disease - 19 (COVID-19) had a profound impact on mental health of people and can influence the quality of life of children who need chronic therapies, affecting daily adherence to drug therapy and altering long-term outcomes. In Growth Hormone Deficiency (GHD) regular drug intake guarantees height improvement and, consequently, self-esteem of children. We conducted a survey to evaluate adherence to daily therapy and changes of height standard deviations in children with GHD during a pandemic-associated lockdown. METHODS: 30 children (17 boys and 13 girls) with aged between 7 and 18 years were examined during the observational period. Adherence to therapy (self-reported and also confirmed with a standardized questionnaire), height and growth velocity during treatment were analyzed. RESULTS: All of our patients reported a moderate to high level of adherence during the period of sanitary emergency (N=2 Morisky 7; N=28 Morisky 8). Adherence assessed by the Morisky Scale was in agreement in all cases with the self-reported one. Analysis of our data confirmed an improvement of the patients' height standard deviations, which could be related to the good adherence to growth hormone therapy during lockdown. CONCLUSIONS: We can hypothesize that limitations during the lockdown period have positively influenced adherence to therapy and, consequently, height standard deviations of children with GHD in substitution therapy. The evaluation of adherence carried out by our interview showed an increased regularity in hormonal administration due to various factors, such as the greatest amount of time spent indoors. The increased adherence is coherent with the results of our auxological evaluations, which showed an increase in percentiles and standard deviations of height, compared to chronological age.

Transcript host-RNA signatures to discriminate bacterial and viral infections in febrile children.

Traditional laboratory markers, such as white blood cell count, C-reactive protein, and procalcitonin, failed to discriminate viral and bacterial infections in children. The lack of an accurate diagnostic test has a negative impact on child's care, limiting the ability of early diagnosis and appropriate management of children. This, on the one hand, may lead to delayed recognition of sepsis and severe bacterial infections, which still represent the leading causes of child morbidity and mortality. On the other hand, this may lead to overuse of empiric antibiotic therapies, particularly for specific subgroups of patients, such as infants younger than 90 days of life or neutropenic patients. This approach has an adverse effect on costs, antibiotic resistance, and pediatric microbiota. Transcript host-RNA signatures are a new tool used to differentiate viral from bacterial infections by analyzing the transcriptional biosignatures of RNA in host leukocytes. In this systematic review, we evaluate the efficacy and the possible application of this new diagnostic method in febrile children, along with challenges in its implementation. Our review support the growing evidence that the application of these new tools can improve the characterization of the spectrum of bacterial and viral infections and optimize the use of antibiotics in children. IMPACT: Transcript host RNA signatures may allow to better characterize the spectrum of viral, bacterial, and inflammatory illnesses in febrile children and can be used with traditional diagnostic methods to determine if and when to start antibiotic therapy. This is the first review on the use of transcript RNA signatures in febrile children to distinguish viral from bacterial infections. Our review identified a wide variability of target populations and gold standards used to define sepsis and SBIs, limiting the generalization of our findings.

The Relationship between COVID-19 and Innate Immunity in Children: A Review.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus responsible for the pandemic viral pneumonia that was first identified in Wuhan, China, in December 2019, and has since rapidly spread around the world. The number of COVID-19 cases recorded in pediatric age is around 1% of the total. The immunological mechanisms that lead to a lower susceptibility or severity of pediatric patients are not entirely clear. At the same time, the immune dysregulation found in those children who developed the multisystem inflammatory syndrome (MIC-S) is not yet fully understood. The aim of this review is to analyze the possible influence of children's innate immune systems, considering the risk of contracting the virus, spreading it, and developing symptomatic disease or complications related to infection.