Meconium aspiration syndrome: from pathophysiology to treatment.

Meconium aspiration syndrome (MAS) is a clinical condition characterized by respiratory distress in neonates born through meconium-stained amniotic fluid (MSAF). Despite advances in obstetric practices and perinatal care, MAS remains an important cause of morbidity and mortality in term and post-term newborns. Since the 1960s, there have been significant changes in the perinatal and postnatal management of infants born through MSAF. Routine endotracheal suctioning is no longer recommended in both vigorous and non-vigorous neonates with MSAF. Supportive care along with new treatments such as surfactant, inhaled nitric oxide, and high-frequency ventilation has significantly improved the outcome of MAS patients. However, determining the most appropriate approach for this condition continues to be a topic of debate. This review offers an updated overview of the epidemiology, etiopathogenesis, diagnosis, management, and prognosis of infants with MAS.

Less Invasive Surfactant Administration (LISA) Versus INSURE Method in Preterm Infants: a Retrospective Study.

Background: Respiratory distress syndrome (RDS) is a major cause of morbidity and mortality in preterm infants. Early nasal CPAP and selective administration of surfactant via the endotracheal tube are widely used in the treatment of RDS in preterm infants. Objective: The aim of this study was to compare the need for intubation and mechanical ventilation after surfactant delivery between LISA-treated and INSURE-treated premature infants with respiratory distress syndrome (RDS). Methods: Retrospective registry-based cohort study enrolled 36 newborns admitted to the neonatal intensive care unit of the "Santa Maria" Hospital of Terni between 2016 and 2023. As a primary outcome, we followed the need for intubation and mechanical ventilation within 72 hours of life, while the secondary outcomes were major neonatal morbidities and death before discharge. Results: The LISA group and the INSURE group included 13 and 23 newborns respectively. Demographic features showed no significant differences between the two groups. The need for mechanical ventilation in the first 72 hours of life was similar in both groups (p >0.99). There were no significant differences in morbidities. Conclusion: LISA and INSURE are equally effective modalities for surfactant administration for the treatment of RDS in preterm infants.

A Cheek Nodule in a Child: Be Aware of Idiopathic Facial Aseptic Granuloma and Its Differential Diagnosis.

Background: Idiopathic facial aseptic granuloma (IFAG) is a rare skin disease that typically presents in children with one or more nontender, erythematous to violaceous nodules located on the cheeks or eyelids. Lesions are not accompanied by other skin abnormalities. IFAG remains a diagnostic challenge in pediatric dermatology, because several diseases may present with similar signs. Case presentation: A three-year-old girl with a previous negative clinical history was referred to our hospital for the evaluation of some asymptomatic nodules on the convexity of the left cheek. The nodules had appeared two months before, and had gradually increased in size. Her mother denied any association with trauma or insect bites. The nodules had a hard-elastic consistency, were moderately firm, and were not fluctuant. No associated lymphadenopathy was observed. The girl was afebrile and in good general condition. A histologic evaluation of a biopsy specimen revealed an inflammatory, granulomatous-diffuse infiltrate in the superficial and deep dermis consisting of giant cells, histiocytes, lymphocytes, neutrophils, eosinophils, and plasma cells. The Ziehl-Neelsen stains, Gram-stains, and cultures were negative. Suspecting an IFAG, treatment with topical fusidic acid and oral clarithromycin for 14 days was started. After two months, the lesion resolved and did not recur. Conclusion: This case shows how to differentiate IFAG from other dermatologic diseases associated with a negative evolution. Treatment with oral clarithromycin was effective in our patient. However, more scientific evidence is needed to evaluate the most suitable antibiotic therapy. Further studies are also needed to establish whether antibiotics actually impact IFAG prognosis.

What is the role of Ewingella americana in humans? A case report in a healthy 4-year-old girl.

BACKGROUND: Ewingella americana (Ea) is a Gram-negative, lactose-fermenting, oxidase-negative and catalase-positive bacterium that was first described in 1983 as a new genus and species in the family Enterobacteriaceae. It is not known whether Ea is a true pathogen or simply an opportunistic infectious agent, as most of the cases have been described in patients at risk. CASE PRESENTATION: A 4-year-old girl described here was hospitalized due to a productive cough over the previous 3 weeks and a fever > 38 °C associated with tachypnea over the previous 2 days. Her familial and personal medical histories were negative for relevant diseases, including respiratory infections. At admission, she was febrile (axillary temperature 39.2 °C) and had dyspnea with retractions, grunting and nasal flaring. A chest examination revealed fine crackling rales in the left upper field associated with bilateral wheezing. A chest X-ray revealed segmental consolidation of the lingula of the left lung. Laboratory tests revealed leukocytosis (15.,800 white blood cells/mm3 with 50.3% neutrophils), a slight increase in serum C-reactive protein (11.9 mg/L) and normal procalcitonin values (< 0.12 ng/mL). A nasopharyngeal swab culture did not reveal viral or bacterial respiratory pathogens, including atypical bacteria. A blood culture revealed the presence of a Gram-negative, lactose-fermenting rod that was oxidase negative and catalase positive. The isolate was identified by means of the VITEK®2 identification system (bioMérieux, Firenze, Italy) as Ea. This identification was confirmed by sequencing the 16 s ribosomal deoxyribonucleic acid (rDNA). The pathogen was sensitive to aminoglycoside, fluoroquinolones, carbapenems, cefotaxime, and ceftazidime but was intermediate against sulfametoxazole/trimethoprim and resistant to amoxicillin-clavulanic acid, fosfomycin, and oxacillin. The child was immediately treated orally with amoxicillin-clavulanic acid and erythromycin. Based on the results of a blood culture and sensitivity tests, the amoxicillin-clavulanic acid medication was stopped after 3 days. Erythromycin was continued for a total of 10 days, and the child was discharged after 3 days in the hospital. Follow-up visit 1 month later did not reveal any respiratory problems. CONCLUSION: This case shows that Ea infections in healthy subjects are mild even in pediatric age, and the need for antibiotic therapy is debated. Cases occurring in subjects with underlying chronic disease can be significantly more complicated and require appropriate antibiotic therapy.

Targetoid Skin Lesions in a Child: Acute Hemorrhagic Oedema of Infancy and Its Differential Diagnosis.

Acute hemorrhagic oedema of infancy (AHEI) is a cutaneous leukocytoclastic small-vessel vasculitis presenting with localized purpuric large skin plaques that are frequently associated with fever and oedema. It must be promptly differentiated from a number of diseases with similar dermatologic manifestations with potentially severe clinical courses that require adequate monitoring and prompt therapy to avoid the risk of a negative evolution. A 15-month-old girl with a negative personal medical clinical history was admitted for the sudden appearance of petechiae on the soft palate. The patient was moderately febrile during the following two days, with a maximum ear temperature of 38.3 °C. The fever disappeared on the third day, whereas the hemorrhagic rash progressively increased and extended to the limbs, face and auricles associated with a strong oedematous component. Moreover, on the second day of hospitalization, bilateral oedema of the metacarpophalangeal joints with joint pain appeared. The blood and serological tests showed an increase in C-reactive protein concentration (3.58 mg/dL) in the absence of leukocytosis and with a normal platelet count (180,000/mm³). The examination of the peripheral smear showed the presence of some large mononuclear elements with hyperbasophile cytoplasm. No alterations in platelet morphology were evidenced. The skin manifestations progressively diminished and disappeared spontaneously within 3 weeks, leaving no sequelae. Conclusion: This case shows the classic skin lesions of AHEI that require differentiation from those of more severe diseases that need prompt recognition and therapy. In this case, the age of the patient, the lack of systemic involvement and the favorable clinical course without therapy were typical. However, as these patients may present to the emergency department with an impressive clinical picture, the condition must be promptly diagnosed to avoid unnecessary diagnostic procedures and to reassure parents.

An Association of PTPN11 and SHOX Mutations in a Male Presenting With Syndromic Growth Failure.

In children with genetic syndromes, short stature is frequently a characteristic feature that, when associated with other specific manifestations, significantly aids in clinical diagnosis. In this report, an atypical case of Noonan syndrome (NS) in a 5.5-year-old child with mesomelic short stature is described. Genetic tests revealed two different mutations in this child. As expected in an NS case, a mutation in PTPN11 gene related to the RAS/MAPK signal transduction pathway was identified. Moreover, a mutation in the SHOX gene that was able to cause disproportionate short stature was detected. A clinical picture of NS with mesomelic short stature makes the diagnosis even more difficult as haploinsufficiency and complete loss of function of SHOX gene are associated with the typical differentiation and proliferation of chondrocytes, leading to mesomelic appearance. This case exemplifies the difficulties that can be encountered in achieving proper diagnoses for children with syndromic diseases and highlights the role of genetic tests in identifying final diagnoses in these patients.

Fetuin-A, adiposity-linked insulin resistance and responsiveness to an educational-based weight excess reduction program: a population-based survey in prepubertal schoolchildren.

The secreted hepatokine fetuin-A emerges as an independent predictor of type 2 diabetes in adulthood. The overall aims of this study were: (1) to investigate the associations of fetuin-A with adiposity and insulin resistance, as well as its relationship with adipokines, in prepubertal children, and, (2) to evaluate whether, in prepubertal obesity, serum fetuin-A levels may either change or predict the responsiveness to an educational-based weight excess reduction program. We studied 200 prepubertal children (boys/girls: 89/111; Tanner stage 1; age: 5-13 years), included in a cohort of 44,231 adolescents who participated in an extensive Italian school-based survey. According to Cole's criteria, 100 individuals were lean (boys/girls: 57/43) and 100 obese (boys/girls: 54/46). A subset of 53 obese individuals (boys/girls: 28/25; age: 6-12 years) were also evaluated after a weight excess reduction program. Serum fetuin-A, leptin, total and high molecular weight adiponectin levels, as well as homeostasis model assessment of insulin resistance were assessed. When compared with lean, obese children exhibited higher ( p < 0.0001) fetuin-A concentrations, without differences between sex. Fetuin-A was positively associated with adiposity, homeostasis model assessment of insulin resistance, and leptin levels. In multivariate analysis, the associations between fetuin-A and leptin or homeostasis model assessment of insulin resistance lost the significance after adjustment for BMI Z-score, which, in turn, represented an independent determinant of fetuin-A (R 2adj 0.327; p < 0.0001). Notably, after weight excess reduction program, fetuin-A levels dropped ( p < 0.0001 vs. basal). Interestingly, no significant differences of fetuin-A concentrations between responders and no responders were found. In prepubertal children, fetuin-A represents an early marker of adiposity, and its reduction after lifestyle intervention may partly contribute to the beneficial effects of weight excess reduction program.

Inflammatory adipokines, high molecular weight adiponectin, and insulin resistance: a population-based survey in prepubertal schoolchildren.

BACKGROUND: The aim of this study was to investigate sex differences and associations of high molecular weight (HMW) adiponectin, leptin and proinflammatory adipokines, individually or in combinations, with adiposity and insulin resistance (IR) measures in prepubertal childhood. METHODOLOGY: We studied 305 prepubertal children (boys/girls: 144/161; Tanner stage 1; age: 5-13 yr), included in a cohort of 44,231 adolescents who participated in an extensive Italian school-based survey. According to Cole's criteria, 105 individuals were lean (L; boys/girls: 59/46), 60 overweight (OW; boys/girls: 32/28) and 140 obese (OB; boys/girls: 70/70). Measurements comprised total and HMW adiponectin, leptin, as well as a panel of proinflammatory adipokines/chemokines associated with diabetes risk. PRINCIPAL FINDINGS: Leptin-, and the leptin-to-HMW adiponectin ratio (L/HMW)-, increased progressively (p<0.0001) from L to OW to OB boys and girls. When compared with L peers, OW and OB girls exhibited lower (p<0.001) HMW adiponectin levels, while in boys the HMW multimers did not differ significantly across the BMI-stratified groups. OB girls displayed higher (p<0.05) IL-8, IL-18, monocyte chemoattractant protein-1 (MCP-1) and soluble intercellular adhesion molecule-1 levels (sICAM-1) than L girls, whereas increased macrophage migration inhibitory factor (MIF) concentrations in OB vs OW boys were seen. HMW adiponectin (negatively), leptin or inflammatory markers (positively) correlated with adiposity and IR measures. In multivariate models, leptin represented a strong and independent determinant of HOMA-IR (R(2) 0.378; p<0.01). Adjustment for age, BMI(z-score), lipids and inflammatory mediators abolished the association between leptin and HOMA-IR in boys, while in girls leptin remained still a significant predictor of IR (R(2) 0.513; p<0.01). Finally, in both sexes, the joint effect of the L/HMW did not improve the prediction of basal IR as compared with leptin levels alone, which were mainly explained by the BMI(z-score.) CONCLUSIONS: In prepubertal children, leptin emerges as a sex-independent discrimination marker of adiposity degree and as a useful, sex-associated predictor of the systemic insulin resistance.

Retrovirus-like long-terminal repeat DQ-LTR13 and genetic susceptibility to type 1 diabetes and autoimmune Addison's disease.

Controversial data are available on the association between the retrovirus-like long-terminal repeat (LTR) DQ-LTR13 and genetic susceptibility to type 1 diabetes and other autoimmune diseases. We analyzed DNA samples from 315 type 1 diabetic patients, 166 autoimmune Addison's disease (AAD) patients, 1,054 healthy subjects, and 144 families of type 1 diabetic offspring. DQ-LTR13 was more frequent among patients than healthy subjects (P(c) < 0.0006), and a preferential transmission of DQB1*0302-LTR13(+) from parents to type 1 diabetic offspring was observed. DQ-LTR13 was in linkage disequilibrium (LD) with DQB1*0302 but not DQB1*0201. The presence of DQ-LTR13 increased the odds ratio of DQB1*0302 2.9- to 3.2-fold for type 1 diabetes and AAD. DRB1*0403 was absent in all of the 169 DRB1*04-positive patients but present in 27% (34 of 127) DRB1*04-positive healthy subjects (P(c) < 0.001). DQ-LTR13 was detected in 1 of 34 (3%) DRB1*0403-positive healthy subjects and 36 of 93 (39%) individuals carrying another DRB1*04 allele (P(c) = 0.002). Multivariate logistic regression analysis revealed that DQ-LTR13 is not independently associated with type 1 diabetes and AAD after correction for DQB1*0302 and DRB1*0403. Conversely, DQB1*0201, DQB1*0302, DRB1*0401, and DRB1*0403 were all significantly associated with disease risk also after correction for DQ-LTR13. We provide conclusive evidence that the genetic association of DQ-LTR13 with type 1 diabetes and AAD is primarily due to a LD with DQB1*0302 and DRB1*0403.

Relationships of serum leptin levels with biochemical markers of bone turnover and with growth factors in normal weight and overweight children.

OBJECTIVE: To examine the hypothesis of an influence of leptin on growth factors and on biochemical markers of bone turnover of prepubertal overweight children. DESIGN AND METHODS: 395 prepubertal children, 6-13 years of age, were selected and the relationships between circulating serum levels of leptin and insulin-like growth factor I (IGF-I), insulin growth factor binding protein-3 (IGFBP-3) and some biochemical markers of bone turnover (osteocalcin, OC; carboxyterminal propeptide of type I procollagen, PICP, and carboxyterminal propeptide of type I collagen, ICTP) were analyzed. The subjects were subdivided into normal weight (NW, n = 163) and weight excess (WE, n = 232) subjects. RESULTS AND CONCLUSIONS: Significant differences between the two groups were found for leptin (p < 0.01), IGF-I (p < 0.01) and IGFBP-3 (p < 0.01), with higher values in WEs, and for OC (p < 0.01) with higher values in NWs. A significant reduction of leptin (p < 0.01) and IGFBP-3 (p < 0.01) serum values and an increase of those of OC (p < 0.01) and PICP (p < 0.05), but not of ICTP, were registered in 103 WEs who showed a drop in weight excess during a weight-excess reduction program. No variations were observed in 26 non-responsive subjects. In a multivariate analysis in which leptin, corrected by BMI and sex, was the independent variable, a significant negative correlation was found with PICP (beta = -0.235, p < 0.01), IGF-I (beta = -0.180, p < 0.01) and height velocity (beta = -0.155, p < 0.01). There was no correlation with OC, ICTP and IGFBP-3. The results demonstrate that nutritional status and leptin levels are involved in the regulation of growth factors and biochemical markers of bone formation.