Novel sonic hedgehog gene variant in a patient with hyponatremia, microsomia, and midline defects; phenotype description in association with a variant of unknown significance [c.755_757del p.(Phe252del)] and an approach to salt-wasting in SHH-related adrenal disorders.

OBJECTIVES: To contribute a novel sonic hedgehog (SHH) gene variant in association with a novel-meagerly described phenotype and discuss SHH signaling pathway pathology. CASE PRESENTATION: We present a 5-year-old boy with excessive hyponatremia and natriuresis, microform holoprosencephaly and microsomia, with morphologically intact hypothalamic-pituitary-adrenal (HPA) axis, and hypoaldosteronism, yet without hyperreninemia, hyperkalemia, dehydration episodes, or glucocorticoid insufficiency. Extensive workup excluded common causes of salt-wasting and revealed a novel variant of unknown significance on the sonic hedgehog (SHH) gene; NM_000193.4:c.755_757del (p.Phe252del), in heterozygosity. CONCLUSIONS: Salt-wasting in children is predominantly caused by central nervous system lesions, renal tubular dysfunction, or adrenal insufficiency. The SHH protein is a signaling molecule, essential in embryogenesis-including HPA axis differentiation. Inactivating SHH variants disrupt the signaling pathway, leading to dysplasia or dysfunction of target organs. What's new: • We analyze the patient's phenotype in the light of this novel variant • Patient's isolated aldosterone deficiency possibly implies a selective signaling defect affecting the development of adrenal zona glomerulosa • Unexplained hyporeninemia and hypokalemia in the context of hypoaldosteronism raise questions on SHH signaling pathophysiology.

Do parental risk factors for type 2 diabetes predict offspring risk of overweight and obesity? The Feel4Diabetes study.

OBJECTIVES: The prevention of children being overweight/obese is of utmost importance. Parental characteristics play a pivotal role in shaping offspring weight status. This study aimed to examine associations between parental obesity and children's overweight/obesity status, and whether other parental type 2 diabetes (T2D) risk factors can predict children's obesity status. METHODS: Logistic regression and receiver operating characteristic (ROC) analyses were conducted, using cross-sectional data from a European cohort of 20 151 adults (10 967 mothers; 9184 fathers) and children (n = 10 967) participating in the Feel4Diabetes study. Anthropometric measurements were conducted in children, and overweight/obesity was defined according to the International Obesity Task Force criteria. Parents' T2D risk was assessed applying the Finnish Diabetes Risk Score (FINDRISC). RESULTS: After adjusting for all other FINDRISC variables, region and maternal/parental education, maternal (adjusted odds ratio [aOR]: 2.64; 95% confidence interval [CI], 2.18-3.20) and parental (aOR: 3.21; 95% CI, 2.65-3.91) obesity, maternal (aOR: 1.46; 95% CI, 1.23-1.74) and parental (aOR: 1.59; 95% CI, 1.32-1.92) high waist circumference, as well as maternal (aOR: 1.60; 95% CI, 1.27-2.01) and parental (aOR: 1.87; 95% CI, 1.58-2.21) high FINDRISC score, were associated with child overweight/obesity status. Maternal (area under the curve- ROC: 0.638; 95% CI, 0.628-0.647) and paternal body mass index (BMI; area under the curve-ROC: 0.632; 95% CI, 0.622-0.642) were the most accurate in predicting child overweight/obesity status. CONCLUSIONS: Among parental risk factors for T2D, maternal/parental overweight/obesity status, central obesity, and high FINDRISC score were the main predictors of childhood overweight/obesity status, with BMI the most accurate. Maternal or paternal BMI is simple to use, and might be useful for the early identification of children at risk of being overweight/obese rather than other T2D factors.

Obesity as a risk factor for severe influenza infection in children and adolescents: a systematic review and meta-analysis.

Obesity has been recently identified as a predisposing factor for a worse prognosis in viral illnesses such as SARS-CoV-2; however, its role in children with influenza is not yet clarified. The current systematic review and meta-analysis aims to assess whether obesity is a risk factor for either hospitalization or a worse prognosis when hospitalized among children infected by influenza. We systematically searched the following databases using a structured algorithm: MEDLINE, Clinicaltrials.gov, and Cochrane Central Register of Controlled Trials (CENTRAL). Statistical meta-analysis was performed using the "meta" package in R software, and included studies were evaluated using the Newcastle-Ottawa scale. Among children with influenza, obesity increased the odds of hospitalization with a pooled OR of 1.89 (95% CI [1.23, 2.9], I2 = 0, p = 0.003). When hospitalized, children with obesity were also more likely to have a worse outcome than their healthy-weight counterparts, with a pooled OR of 1.24 (95% Cl [1.02; 1.51], I2 = 11, p = 0.03). In an effort to lower heterogeneity, a leave-one-out meta-analysis was conducted. Publication bias was assessed with the visual inspection of funnel plots and the trim-and-fill method. Certainty assessment was evaluated using the GRADE score. CONCLUSIONS: The findings of our meta-analysis suggest that obesity in children with influenza is associated with a worse prognosis, both hospitalization and ICU admission/death. WHAT IS KNOWN: • Obesity has been identified as a risk factor for non-communicable as well as communicable diseases. • A previous meta-analysis failed to demonstrate a statistically significant association between obesity and influenza infection severity. WHAT IS NEW: • Children with high BMI and influenza infection are more likely to get hospitalized. • Pediatric inpatients with increased BMI and influenza infection may have a worse prognosis.

Insights in paediatric virology during the COVID-19 era (Review).

The present article provides an overview of the key messages of the topics discussed at the '7th Workshop on Paediatric Virology', which was organised virtually on December 20, 2021 by the Institute of Paediatric Virology, located on the Island of Euboea in Greece. The workshop's plenary lectures were on: i) viral pandemics and epidemics in the ancient Mediterranean; ii) the impact of obesity on the outcome of viral infections in children and adolescents; and iii) COVID-19 and artificial intelligence. Despite the scarcity of evidence from fossils and remnants, viruses have been recognised as significant causes of several epidemics in the ancient Mediterranean. Paediatric obesity, a modifiable critical health risk factor, has been shown to impact on the development, progression and severity of viral infections. Thus, the prevention of paediatric obesity should be included in formulating public health policies and decision-making strategies against emerging global viral threats. During the current COVID-19 pandemic, artificial intelligence has been used to facilitate the identification, monitoring and prevention of SARS-CoV-2. In the future, it will play a fundamental role in the surveillance of epidemic-prone infectious diseases, in the repurposing of older therapies and in the design of novel therapeutic agents against viral infections. The collaboration between different medical specialties and other diverse scientific fields, including archaeology, history, epidemiology, nutritional technologies, mathematics, computer technology, engineering, medical law and ethics is essential for the successful management of paediatric viral infections. The current COVID-19 pandemic has underscored this need, which should be further encouraged in modern medical education.

Clinical value of significance of Hypoxia Inducible Factor-1α, Glucose Transporter-1 and Carbonic Anhydrase IX in rectal cancer after preoperative chemoradiotherapy.

PURPOSE: The standard treatment of rectal cancer is surgery along with preoperative radiotherapy, administered alone or in combination with chemotherapy. Preoperative chemoradiotherapy (preCRT) is widely used as it allows better local control and the use of sphincter-saving surgery. Pathological response after preCRT has been shown to be a significant prognostic factor of rectal cancer recurrence and survival. In this review we will assess the value of Hypoxia Induced Factor 1α (HIF-1α), Carbonic Anhydrase IX (CA-9) and Glucose Transporter 1 (GLUT-1) genes as predictive markers of the course of local advanced rectal cancer in patients who underwent pre-CRT. METHODS: We searched studies, from Pubmed and in English language, obtained the information by using "HIF-1 alpha", "Carbonic Anhydrase IX (CA-9)", "Glucose Transporter 1 (GLUT-1)" and "rectal cancer" as key words. RESULTS: 27 relevant articles were retrieved in initial stage. After full-text review, 13 articles were selected for the final analysis. CONCLUSIONS: HIF-1α, GLUT-1 and CA-IX may be connected with tumor response to preCRT, however, there is still skepticism towards their clinical use as predictors of outcome. Therefore, there is a need to conduct larger and more extensive cohort studies in order to find whether these predictors can be used in practice.