Prevention of recurrent respiratory infections : Inter-society Consensus.

Recurrent respiratory infections (RRIs) are a common clinical condition in children, in fact about 25% of children under 1 year and 6% of children during the first 6 years of life have RRIs. In most cases, infections occur with mild clinical manifestations and the frequency of episodes tends to decrease over time with a complete resolution by 12 years of age. However, RRIs significantly reduce child and family quality of life and lead to significant medical and social costs.Despite the importance of this condition, there is currently no agreed definition of the term RRIs in the literature, especially concerning the frequency and type of infectious episodes to be considered. The aim of this consensus document is to propose an updated definition and provide recommendations with the intent of guiding the physician in the complex process of diagnosis, management and prevention of RRIs.

Italian consensus on the therapeutic management of uncomplicated acute hematogenous osteomyelitis in children.

BACKGROUND: Acute hematogenous osteomyelitis (AHOM) is an insidious infection of the bone that more frequently affects young males. The etiology, mainly bacterial, is often related to the patient's age, but it is frequently missed, owing to the low sensitivity of microbiological cultures. Thus, the evaluation of inflammatory biomarkers and imaging usually guide the diagnosis and follow-up of the infection. The antibiotic treatment of uncomplicated AHOM, on the other hand, heavily relies upon the clinician experience, given the current lack of national guidelines for the management of this infection. METHODS: A systematic review of the studies on the empirical treatment of uncomplicated AHOM in children published in English or Italian between January 1, 2009, and March 31, 2020, indexed on Pubmed or Embase search engines, was carried out. All guidelines and studies reporting on non-bacterial or complicated or post-traumatic osteomyelitis affecting newborns or children older than 18 years or with comorbidities were excluded from the review. All other works were included in this study. RESULTS: Out of 4576 articles, 53 were included in the study. Data on different topics was gathered and outlined: bone penetration of antibiotics; choice of intravenous antibiotic therapy according to the isolated or suspected pathogen; choice of oral antibiotic therapy; length of treatment and switch to oral therapy; surgical treatment. CONCLUSIONS: The therapeutic management of osteomyelitis is still object of controversy. This study reports the first Italian consensus on the management of uncomplicated AHOM in children of pediatric osteomyelitis, based on expert opinions and a vast literature review.

Early limb paralysis in infants: do not forget about congenital syphilis.

We describe the case of a 2-month-old baby with congenital syphilis, presenting with limb paralysis. The radiological investigations showed periosteal thickenings of the limb. Despite negative maternal serology during the first trimester of pregnancy, clinical and radiological features led to the suspicion of pseudoparalysis of Parrot, which was confirmed by blood tests. Delayed diagnoses or misdiagnoses are possible when uncommon presentations of forgotten diseases occur. The needing for a second screening for syphilis in high-risk pregnant women should be evaluated.

COVID-19 in Pregnant Women and Neonates: A Systematic Review of the Literature with Quality Assessment of the Studies.

The SARS-CoV-2 virus emerged in December 2019 and then spread globally. Little is still known about the impact of COVID-19 on pregnant women and neonates. A review of the literature was performed according to the PRISMA guideline recommendations, searching the MEDLINE and EMBASE databases. Studies' quality assessments were performed using the JBI Critical Appraisal Checklist. A total of 37 studies were included, involving 275 pregnant women with COVID-19 and 248 neonates. The majority of pregnant women presented with mild to moderate symptoms, only 10 were admitted in the ICU, and one died. Two stillbirths were reported and the incidence of prematurity was 28%. Sixteen neonates were tested positive for SARS-CoV-2 by RT-PCR, and nine of them were born from mothers infected during pregnancy. Neonatal outcomes were generally good: all the affected neonates recovered. RT-PCR for SARS-CoV-2 yielded negative results on amniotic fluid, vaginal/cervical fluids, placenta tissue, and breast milk samples. SARS-CoV-2 infection in pregnant women appeared associated with mild or moderate disease in most cases, with a low morbidity and mortality rate. The outcomes of neonates born from infected women were mainly favorable, although neonates at risk should be closely monitored. Further studies are needed to investigate the possibility of vertical transmission.

Prescribing Controversies: An Updated Review and Meta-Analysis on Combined/Alternating Use of Ibuprofen and Paracetamol in Febrile Children.

Background: Ibuprofen and paracetamol are the only antipyretics recommended in febrile children. According to international guidelines the choice of the drug should rely on the child's individual characteristics, while a controversial issue regards the combined or alternate use of the two drugs. Objective: To compare the efficacy and safety of combined or alternating use of ibuprofen and paracetamol in children. Methods: A systematic review of literature was performed on Medline and Embase databases. The included studies were randomized controlled trials analyzing the efficacy of combined or alternating therapy with antipyretics in febrile children vs. monotherapy. A meta-analysis was performed to measure the effect of treatment on child's temperature and discomfort. Adverse effects were analyzed as secondary outcome. Results: Nine studies were included, involving 2,026 children. Mean temperature was lower in the combined therapy group at 1 h (mean difference: -0.29°C; 95%CI: -0.45 to -0.13) after the initial administration of therapy. No statistical difference was found in mean temperature at 4 and 6 h from baseline. A significant difference was found in the proportion of children reaching apyrexia at 4 and 6 h with the combined treatment (RR: 0.18, 95%CI: 0.06 to 0.53, and 0.10, 95%CI: 0.01-0.71, respectively) and at 6 h with alternating treatment (RR: 0.30, 95% CI: 0.15-0.57), compared to children treated with monotherapy. The child's discomfort score was slightly lower with alternating therapy vs. monotherapy. The pooled mean difference in the number of medication doses per child used during the first 24 h was not significantly different among groups. Discussion: Combined or alternating therapy resulted more effective than monotherapy in reducing body temperature. However, the benefit appeared modest and probably not clinically relevant. The effect on child discomfort and number of doses of medication was modest as well. According to our findings, evidences are not robust enough to encourage combined or alternating paracetamol and ibuprofen instead of monotherapy to treat febrile children, reinforcing the current recommendation of most of the international guidelines.

Accuracy of presepsin in neonatal sepsis: systematic review and meta-analysis.

INTRODUCTION: Neonatal sepsis represents a major cause of morbidity and mortality in neonates. No diagnostic test has been demonstrated to be sufficiently accurate to confirm or exclude neonatal sepsis. This study aimed to evaluate the diagnostic accuracy of presepsin (P-SEP) for neonatal sepsis. Areas covered: A systematic review of literature was performed on Medline and EMBASE. A meta-analysis was performed to calculate pooled sensitivity, specificity, diagnostic odds ratio (DOR), and summary receiver operating characteristic of P-SEP for neonatal sepsis. Eight studies were included, involving 636 neonates. Pooled sensitivity and specificity were 0.90 and 0.90, respectively. The pooled DOR was 120.94, and the Area Under Curve (AUC) was 0.968, indicating a high level of diagnostic accuracy. Using cut-off values <600 ng/L, sensitivity reached 0.93, with a specificity of 0.81 and AUC 0.8195, while using a threshold >600 ng/L, sensitivity was 0.87 and specificity 0.97, with higher diagnostic accuracy (AUC 0.976). Significant heterogeneity was found between studies. Expert commentary: Diagnostic accuracy of P-SEP resulted high in detecting neonatal sepsis. Even though it cannot be recommended as a single diagnostic test, P-SEP could be a helpful and valuable biomarker in neonates with suspected sepsis.

An early diagnosis of trichorhinophalangeal syndrome type 1: a case report and a review of literature.

BACKGROUND: Trichorhinophalangeal syndrome (TRPS) is a rare autosomal dominant disorder caused by defects involving the TRPS1 gene. It exhibits distinctive craniofacial, ectodermal and skeletal abnormalities, such as sparse hair, bulbous nasal tip and short deformed fingers, with extremely variable expressivity. CASE PRESENTATION: We report the case of a 17 months old girl, who presented growth retardation and dysmorphic features. Postnatal growth was always below - 2 Standard Deviation for both weight and length and physical examination revealed relative macrocephaly, sparse hair, bulbous nasal tip, thin upper lip, protruding ears, prominent forehead, small jaw, and short hands and feet. Patient's mother shared the same facial features, and presented sparse hair and small hands. The maternal grandfather and two uncles presented short stature, bulbous nasal tip, thin hair, and premature alopecia. Molecular analysis of TRPS1 gene showed a heterozygous c.2086C > T;(p.Arg696Ter) mutation both in the patient and her mother, confirming the diagnosis of TRPS, type I. CONCLUSIONS: Clinical phenotype of TRPS can be subtle and the syndrome often remains undiagnosed. A comprehensive clinical examination and an exhaustive family history are crucial to reach the correct diagnosis, which is essential to perform adequate follow-up and timely therapeutic procedures.

Inflammatory biomarkers to guide diagnostic and therapeutic decisions in children presenting with fever without apparent source.

A systematic review of literature from 2011 to 2016 was performed, in order to evaluate the diagnostic performance of inflammatory biomarkers in children with fever without apparent source and their usefulness in clinical decision-making. Data source was the Pubmed database. Thirteen studies were included, analysing the following biomarkers: erythrocyte sedimentation rate, white blood count, absolute neutrophil count, C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6) and the Lab-score (a combination of CRP, PCT and urine dipstick). Among the available biomarkers, CRP and PCT seem to be the most useful, showing the best performance at a threshold of 20 mg/L for CRP and 0.5 ng/mL for PCT. Lab-score increases diagnostic accuracy and also health-care costs. PCT demonstrated higher specificity levels, particularly in younger children. However, CRP remains the most accessible biomarker and is also available as a validated point-of-care test.

Procalcitonin performance in detecting serious and invasive bacterial infections in children with fever without apparent source: a systematic review and meta-analysis.

INTRODUCTION: The management of children with fever without apparent sources (FWAS) is difficult. This study aimed to evaluate the diagnostic accuracy of procalcitonin (PCT) in detecting serious or invasive bacterial infection (SBI or IBI) in children with FWAS. Areas covered: A systematic review of literature from 2007 to 2017 was performed on Medline. Twelve studies were included, involving 7,260 children with FWAS and analyzing the diagnostic performance of PCT. Four meta-analyses were performed to calculate pooled sensitivity, specificity, diagnostic odds ratio, and summary receiver operating characteristic curve for PCT in detecting SBI and IBI, at two different thresholds. Considering IBI, PCT sensitivity and specificity at a threshold of 0.5 ng/mL were 0.82 and 0.86, respectively; at a threshold of 2 ng/mL sensitivity and specificity were 0.61 and 0.94, respectively. In detecting SBI, PCT performance was lower, with 55% sensitivity and 85% specificity at a threshold of 0.5 ng/mL, and 30% sensitivity and 95% specificity at a threshold of 2 ng/mL. Expert commentary: Considering IBI, results showed high diagnostic accuracy for PCT. Conversely, PCT performance in diagnosis of SBI was poor. These findings suggest that PCT level determination could be helpful in detecting meningitis, bacteremia and sepsis in children with FWAS.