Perception, knowledge and attitude towards childhood fever: A survey among final-year medical students.

AIMS: Undue concerns about the consequences of fever and its inappropriate management have been documented worldwide among physicians. However, no data exist on medical students. We investigated the perception, knowledge and attitude towards childhood fever among final-year medical students. METHODS: Between June and September 2021, final-year medical students of six Italian universities were invited to complete an online survey on their conceptions and attitude towards pharmacological and non-pharmacological management of childhood fever. History of relevant personal or second-hand experience with childhood fever was also addressed. Both quantitative and qualitative approaches were used. RESULTS: Of 1095 (69%) final-year medical students, 756 completed the survey. Many students believe that high fever might cause brain damage, would recommend physical methods and alternate two drugs for fever. Most students do not think that fever has mainly beneficial effects. In Northern Italy, students are less likely to believe that fever might lead to brain damage (OR 0.55, 95% CI 0.33-0.94), and in Southern Italy students are more likely to advise physical methods (OR 1.77, 95% CI 1.22-2.57) and less likely to believe that fever has mainly beneficial effects (OR 0.55, 95% CI 0.39-0.77). History of a relevant personal episode of fever during childhood was not associated with these outcomes. CONCLUSIONS: Misconceptions about fever are common among final-year medical students in Italy. Cultural factors rather than individually learned traits might underlie these beliefs. Medical students are a promising target for educational interventions to improve childhood fever management.

IL-17 serum level in patients with chronic mucocutaneous candidiasis disease.

BACKGROUND: Chronic mucocutaneous candidiasis (CMC) is defined by recurrent or persistent superficial infections involving nails, skin, and/or oral and genital mucosae. IL-17 promotes the recruitment, chemotaxis, and expansion of neutrophils and acts directly on keratinocytes and epithelial cells, driving the production of antimicrobial peptides, essential for the immune response against Candida. AIM: To evaluate the serum level of IL-17 in a family affected by CMC restricted to the nails of the hands and feet. METHODS: Serum IL-17 was assayed on 16 patients (aged 21 ± 3.1 years) suffering from persistent onychomycosis caused by Candida and 18 healthy controls (aged 19 ± 2.7 years). Comparisons between groups were performed by Student's unpaired t-test. The level of significance was set at 0.05. RESULTS: The mean serum IL-17 level in patients was 74 ± 1.42 pg/ml, whereas the control group showed a significantly lower level of 25.6 ± 6.7 pg/ml (p < 0.05). CONCLUSIONS: We showed a potential defect in the IL-17 signaling pathway in a family affected by CMC restricted to the nails of the hands and feet. Further research is needed to clarify the immunological mechanisms and the genetic etiology at the basis of the unusual clinical presentation in this family.

Fabry disease and kidney involvement: starting from childhood to understand the future.

The accumulation of globotriaosylceramide (Gb-3) in multiple organs, such as the heart, kidney, and nervous system, due to mutations in the galactosidase alpha (GLA) gene, represents the key point of Fabry disease (FD). The common symptoms appear in childhood or adolescence, including neuropathic pain, angiokeratoma, acroparesthesia, and corneal opacities. A multi-organ involvement induces a significant deterioration in the quality of life with high mortality in adulthood. The accumulation of Gb-3 involves all types of kidney cells beginning at fetal development, many years before clinical manifestations. A decline in the glomerular filtration rate is rare in children, but it can occur during adolescence. Pediatric patients rarely undergo kidney biopsy that could assess the efficacy of enzyme replacement therapy (ERT) behind its diagnostic role. To date, diagnosis is achieved by detecting reduced α-Gal-A activity in leukocytes and plasma, allowing for the early start of ERT. This review focuses on pediatric kidney involvement in FD, analyzing in depth its diagnostic processes and treatment options.

Febrile Urinary Tract Infections in Children: The Role of High Mobility Group Box-1.

BACKGROUND: Differentiating between febrile lower urinary tract infection (LUTI) and acute pyelonephritis (APN) is crucial for prompt clinical management. We investigated whether the high mobility group box-1 (HMGB1) could be a useful biomarker in differentiating between LUTI or APN. METHODS: We enrolled seventy-four pediatric patients with suspected LUTI/APN, according to the positive or negative renal scintigraphy (DMSA) scan. If the first DMSA findings were abnormal, a second DMSA was performed after six months. Voiding cystourethrography ruled out vesicoureteral reflux (VUR). RESULTS: Higher serum (s) HMGB1 levels characterized the APN group when compared to LUTI patients (13.3 (11.8-14.3) versus 5.9 (5.2-6.8) ng/mL, p: 0.02), whereas there were no differences according to urine (u) HMGB1 values. sHMGB1 correlated with C-reactive protein (CRP) levels (ß = 0.47; p: 0.02). Receiver operating characteristic curves identified the best diagnostic profile for detecting APN. sHMGB1 area under the curve was different from CRP (p: 0.01) and white blood cells (p: 0.003). After multivariate analyses, VUR (HR:4.81) and sHMGB1 (HR 1.16; p: 0.006) were independently associated with the risk of renal scarring development. CONCLUSIONS: sHMGB1 could represent a marker to differentiate APN from LUTI. Measurement of sHMGB1 could select children for early intervention or long-term follow-up.

Update on the Classification and Pathophysiological Mechanisms of Pediatric Cardiorenal Syndromes.

Cardiorenal syndrome (CRS) is defined as a disorder resulting from the abnormal interaction between the heart and kidney, in which acute or chronic dysfunction of one organ may lead to acute and/or chronic dysfunction of the other. The functional interplay between the heart and kidney is characterized by a complex bidirectional symbiotic interaction, regulated by a wide array of both genetic and environmental mechanisms. There are at least five known subtypes of CRS, based on the severity of clinical features and the degree of heart/renal failure. The fourth subtype (cardiorenal syndrome type 4 (CRS4)) is characterized by a primary chronic kidney disease (CKD), which in turn leads to a decreased cardiac function. Impairment of renal function is among the most important pathophysiological factors contributing to heart failure (HF) in the pediatric age group, and cardiovascular complications could be one of the most important causes of mortality in pediatric patients with advanced CKD. In this context, a loss of glomerular filtration rate directly correlates with both the progression of cardiovascular complications in CRS and the risk of HF. This review describes the interaction pathways between the heart and kidney and the recently identified pathophysiological mechanisms underlying pediatric CRS, with a special focus on CRS4, which encompasses both primary CKD and cardiovascular disease (CVD).

Biallelic Variants in KIF17 Associated with Microphthalmia and Coloboma Spectrum.

Microphthalmia, anophthalmia, and coloboma (MAC) are a group of congenital eye anomalies that can affect one or both eyes. Patients can present one or a combination of these ocular abnormalities in the so called "MAC spectrum". The KIF17 gene encodes the kinesin-like protein Kif17, a microtubule-based, ATP-dependent, motor protein that is pivotal for outer segment development and disc morphogenesis in different animal models, including mice and zebrafish. In this report, we describe a Sicilian family with two siblings affected with congenital coloboma, microphthalmia, and a mild delay of motor developmental milestones. Genomic DNA from the siblings and their unaffected parents was sequenced with a clinical exome that revealed compound heterozygous variants in the KIF17 gene (NM_020816.4: c.1255C > T (p.Arg419Trp); c.2554C > T (p.Arg852Cys)) segregating with the MAC spectrum phenotype of the two affected siblings. Variants were inherited from the healthy mother and father, are present at a very low-frequency in genomic population databases, and are predicted to be deleterious in silico. Our report indicates the potential co-segregation of these biallelic KIF17 variants with microphthalmia and coloboma, highlighting a potential conserved role of this gene in eye development across different species.

HMGB1: A pleiotropic activity.

High-mobility group box 1 (HMGB1) is a nuclear protein involved in DNA replication, transcription, recombination, and repair. In the extracellular space, the HMGB1 plays an essential role in the onset and perpetuation of inflammation, belonging to the group of damage-associated molecular pattern (DAMP) molecules, also called alarmins. For this, HMGB1 has been studied in several acute and chronic inflammatory diseases as an early biomarker of inflammation. An increased concentration of HMGB1 has been detected in serum, as the expression of systemic inflammation, and in specific samples (such as stool, synovial fluid, nasal lavage fluid, sputum, and cerebrospinal fluid), as the expression of local production, in several infectious and/or inflammatory diseases. These data are particularly important because they open new futuristic possibilities for target therapies, potentially also for the COVID-19 treatment.

Respiratory syncytial virus seropositivity at birth is associated with adverse neonatal respiratory outcomes.

BACKGROUND: More than 60 years since the discovery of the respiratory syncytial virus (RSV), the effects of prenatal exposure to this virus remain largely unknown. In this investigation, we sought to find evidence of RSV seroconversion in cord blood and explore its clinical implications for the newborn. METHODS: Offspring from 22 pregnant women with a history of viral respiratory infection during the third trimester of pregnancy (respiratory viral illness [RVI] group) and 40 controls were enrolled in this study between 1 September 2016 and 31 March 2019. Cord blood sera were tested for anti-RSV antibodies by indirect fluorescent antibody assay. RSV seropositivity was defined as the presence of anti-RSV immunoglobulin M (IgM) or immunoglobulin A (IgA), in addition to IgG in cord blood serum at ≥1:20 dilution. RESULTS: Anti-RSV IgG was present in all cord blood serum samples from infants born to RVI mothers (95% confidence interval [CI] = 82%-100%), with 16 samples also having elevated titers for either anti-RSV IgA or IgM (73%; 95% CI = 52%-87%). No controls had evidence of anti-RSV antibodies. Eight (50%) seropositive newborns developed at least one respiratory tract finding, including respiratory distress syndrome (N = 8), respiratory failure (N = 3), and pneumonia (N = 1). RSV seropositive newborns also required more days on oxygen, had leukocytosis and elevated C-reactive protein (P = .025, P = .047, and P < .001, respectively). CONCLUSION: This study provides evidence of acute seropositivity against RSV in cord blood of newborns delivered from mothers with a history of upper respiratory tract illness in the third trimester. Cord blood seropositivity for anti-RSV IgA or IgM was associated with adverse clinical and laboratory outcomes in newborns.

Behavioral issues and quality of life in children with eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) is a chronic disease characterized by symptoms related to esophageal dysfunction and eosinophil-predominant inflammation (≥15 eosinophils/high power field). In the last ten years, several epidemiological studies showed a significant increase in the incidence and prevalence of EoE, especially in children in Western Countries. Although EoE often presents with gastrointestinal symptoms, adults and children may develop extraintestinal symptoms and behavioral issues. Also, the chronic nature of the disease, long-term therapies, and strict follow-up may impair the quality of life of patients and their family. This review summarizes current knowledge on the behavioral and psychosocial issues and quality of life of children and adolescents with EoE and their caregivers.

Recurrent respiratory infections between immunity and atopy.

Recurrent respiratory infections (RRIs) are frequent in children and are characterized by more than 6 airway infections in 1 year or more than 1 upper airway infection per month in the period between September and April or more than 3 lower airway infections in 1 year. Often pediatric RRIs are related to predisposing factors, such as reduced airway size, poor tussive reflex, and immaturity of the immune system. RRIs due to immature immune system are a transient condition, with spontaneous resolution in the school age. However, some RRIs are expression of more complex diseases. Red flags are the onset of symptoms in the first year of life, the involvement of other systems, unusual pathogens, slowing of growth, severe infections of the lower airways, and recurrence of the infection site. To help the pediatrician in the RRI differential diagnosis, we have created a roadmap based on scientific literature data and clinical practice that identifies 6 macro areas: immunodeficiencies, simple minimal genetic immunodeficiency, atopy, obesity, nutritional deficiencies, autoinflammatory diseases, and complex diseases.

Novel therapeutic targets for allergic airway disease in children.

The aim of precision medicine is setting up targeted therapies for selected patients that would ideally have high effectiveness and few side effects. This is made possible by targeted therapy drugs that selectively act on a specific pathway. Precision medicine is spreading to many medical specialties, and there is increasing interest in the context of allergic airway diseases, such as allergic rhinitis, chronic rhinosinusitis, and asthma. This review is an update of new targets in the treatment of childhood allergic upper airway diseases and asthma, including the most recent biologic drugs that have already been licensed or are in the pipeline to be tested with children.

Antihistamines: Recommended Dosage - Divergence between Clinical Practice and Guideline Recommendations.

The updosing of second-generation antihistamines for chronic urticaria is based on inconsistent findings. Herein, we report data on the treatment of children with chronic spontaneous urticaria (CSU) unresponsive to single doses of second-generation H(1)-antihistamines in whom an increase in antihistamine was performed without improvement and with a high prevalence of adverse events. Thus, it appears that well-controlled, well-designed clinical trials are needed to clarify which nonsedating antihistamines should be used, in what dose, and for how long in patients not responding to the standard treatment, despite the improvement in health care that guidelines help to incorporate. Furthermore, a critical use of such guidelines should be done to improve the knowledge in CSU, especially in the pediatric population.

Omalizumab treatment in a 12 year-old girl with chronic spontaneous urticaria.

Background: Omalizumab is a recombinant humanized IgG monoclonal antibody, which binds the Fc region of free IgE prevent its binding to its high-affinity receptor (FcεR1) on mast cells and basophils. Omalizumab was approved as add-on therapy for moderate-to-severe persistent allergic asthma and for patients with chronic spontaneous urticaria resistant to antihistamine treatment. Patient and results: This article reports effective and safe treatment of a 12 years old girl with add-on omalizumab. On an initial dose of omalizumab of 300 mg once every 4 weeks, the patient experienced resolution of symptoms to a degree that exceeded the effect of previous treatments. Conclusion: Convincing evidence in support of the efficacy and safety of Omalizumab in the treatment of CSU in adolescent has accumulated over the past few years.

Minor pulmonary malformations in a child.

Can you diagnose this child with minor pulmonary malformations and recurrent pulmonary symptoms? http://ow.ly/6zQB30jHZAP.

Caudal Regression and Encephalocele: Rare Manifestations of Expanded Goldenhar Complex.

Oculoauriculovertebral spectrum, or Goldenhar Syndrome, is a condition characterized by variable degrees of uni- or bilateral involvement of craniofacial structures, ocular anomalies, and vertebral defects. Its expressivity is variable; therefore, the term "expanded Goldenhar complex" has been coined. The Goldenhar Syndrome usually involves anomalies in craniofacial structures, but it is known that nervous system anomalies, including encephalocele or caudal regression, may, rarely, occur in this condition. We report two rare cases of infants affected by Goldenhar Syndrome, associated with neural tube defects, specifically caudal regression syndrome and nasal encephaloceles, to underline the extremely complex and heterogeneous clinical features of this oculoauriculovertebral spectrum. These additional particular cases could increase the number of new variable spectrums to be included in the "expanded Goldenhar complex."

Association between Allergies and Hypercholesterolemia: A Systematic Review.

BACKGROUND: There is controversy in the literature regarding the potential relationship between atopic predisposition (AP) and serum cholesterol levels. To this purpose, we reviewed human studies that investigated this possible link. METHODS: Following PRISMA guidelines, a literature search of PubMed and Science Direct for peer-reviewed journal articles in English from January 2003, with updates through to August 2016, was conducted. Relevant publications were reviewed that included pediatric and adult populations. Information on the study design, sample, intervention, comparators, outcome, time frame, and risk of bias were abstracted for each article. RESULTS: Of 601 reviewed reports, 18 were included in this systematic review. Fifteen studies assessed the relationship between AP and serum cholesterol levels. Due to the lack both of observational and cross-sectional studies from the literature search at this time (only 8 studies also analyzed confounding factors) there is a high possibility of confounding variables (familial and genetic predisposition, age, gender, BMI, comorbidity, and medication status) that could not be ruled out. CONCLUSION: Existing studies are heterogeneous, making it difficult to draw broad conclusions. Future studies and more detailed analyses, considering confounding variables and including a larger and homogeneous population, are needed to strengthen the argument for a link between lipid metabolism and atopy.

Filaggrin mutations and Molluscum contagiosum skin infection in patients with atopic dermatitis.

BACKGROUND: Although mutations in the filaggrin (FLG) gene have been reported to predispose patients with atopic dermatitis (AD) skin infection susceptibility, to date, the data reported in the literature are still controversial. OBJECTIVE: To evaluate the role of FLG polymorphisms expression and risk of developing a concomitant Molluscum contagiosum sustained skin infection in the pediatric population with AD. METHODS: A total of 100 children with AD and 97 healthy children were enrolled. AD was diagnosed and assessed according to the validated European Task Force on Atopic Dermatitis. DNA samples of patients were analyzed for allelic variants in the promoter and coding exon of FLG. Genotyping was performed with polymerase chain reaction amplification and direct sequencing. RESULTS: Sixteen FLG variants have been detected in 29% of patients with AD: 2 synonymous (rs79808464 and rs116222149), 12 missense (rs11584340, rs113136594, rs145828067, rs374910442, rs747005144, rs145627745, rs144209313, rs74129443, rs192455877, rs150957860, rs138055273, rs147472105), 1 stop gained (rs183942200), and 1 frameshift (rs 558269137). In contrast, only 13% of the control group reported FLG mutations (22 heterozygous variants). In addition, the age at disease onset correlated significantly with FLG variants (P < .001). In addition, the AD with FLG gene variants (rs145627745, rs79808464, rs150957860, rs145828067, rs747005144, rs374910442, rs138055273, rs183942200, rs11584340, and rs113136594) reported moderate to severe Scoring Atopic Dermatitis scores. Finally, the AD group and the AD plus M contagiosum skin infection group had a significant association with FLG mutations when compared with the control group (P < .01). CONCLUSION: FLG mutations are associated with early onset of AD, more severe clinical course of disease, and a significantly increased risk of M contagiosum sustained skin infection.

HMGB1 values and response to HBV vaccine in children with celiac disease.

OBJECTIVES: In addition to its wide clinical variability, celiac disease (CD) can also cause a lower response to the hepatitis B virus (HBV) than healthy individuals. The aim of this study was to examine high mobility group box 1 (HMGB1) as a new potential marker of an inadequate response to HBV vaccine in children with CD at diagnosis before starting a gluten-free diet. METHODS: We recruited 49 children with CD who were tested at admission for immunization against HBV. Serum HMGB1 levels were measured by an enzyme-linked immunosorbent assay test. RESULTS: Serum HMGB1 levels were significantly higher in nonresponders than in responders (P < 0.05). In the responders group in particular, with reference to the titer of vaccine response, we found a significantly higher serum HMGB1 level in the low responders (P < 0.001). We detected statistically significant higher values of HMGB1 in the typical form of disease presentation than in the atypical or silent form (P < 0.05). In the typical form, we showed even significantly higher HMGB1 values in low responders than in high responders (P < 0.001). With regard to the HLA haplotype and serum HMGB1 levels, any statistically significant difference was detected (P > 0.05). CONCLUSIONS: In patients with CD, HMGB1 could represent a new marker that is able to reflect the immune impairment that results in failure of the HBV vaccination.

Detection of respiratory syncytial virus (RSV) at birth in a newborn with respiratory distress.

Respiratory syncytial virus (RSV) is the most common respiratory pathogen in infants and young children. From the nasopharyngeal or conjunctival mucosa of infected individuals, RSV spreads to the lower respiratory tract causing acute bronchiolitis and pneumonia after an incubation period of 4-6 days. In addition to its well-documented tropism for the airway epithelium, it has been shown previously that RSV can also spread hematogenously and efficiently infect extrapulmonary tissues of human hosts. Furthermore, it has been shown in animal models that RSV can spread transplacentally from the respiratory tract of a pregnant mother to the lungs of the fetus. This report describes a documented case of neonatal RSV infection strongly suggestive of prenatal transmission of this infection in humans from an infected mother to her offspring.