Human milk is widely recognised as the optimal source of nutrition for newborns and infants, providing not only an ideal macronutrient composition but also a range of bioactive components that exert important non-nutritional functions, and as such it represents the first functional food consumed in early life. Among these bioactive components, the human milk oligosaccharides (HMOs)—a structurally diverse family of glycans present in human milk at concentrations 100- to 1000-fold higher than in the milk of other mammalian species—have emerged as multifunctional contributors to the establishment of the intestinal microbiome, immune development, anti-infective defence, and epithelial barrier integrity during a developmental window characterised by immune immaturity. The aim of the present narrative review is to synthesise current evidence on the anti-infective properties of HMOs in infancy and to integrate, within a single framework, five interconnected mechanisms through which HMOs protect the infant against infection: glycan-mimicry-based competitive inhibition of pathogen adhesion, direct antimicrobial and antibiofilm activity, selective prebiotic shaping of the gut microbiome, modulation of innate and adaptive immune responses, and reinforcement of mucosal barrier integrity in the gut and lungs. Breastfeeding constitutes a natural strategy for anti-infective protection in early childhood, while infant formulas supplemented with biotechnologically produced HMOs that are structurally identical to those in human milk provide measurable benefits for non-breastfed infants.

Hypophosphatasia (HPP) encompasses a group of inherited metabolic bone disorders characterized by defective skeletal mineralization and variable clinical severity in childhood. Substantial allelic heterogeneity contributes to a broad pediatric clinical spectrum, ranging from life-threatening perinatal disease to milder phenotypes characterized by chronic functional impairment. Historically, management relied primarily on supportive interventions aimed at sustaining survival, without modifying the underlying enzymatic defect. The introduction of enzyme replacement therapy (ERT) with asfotase alfa has fundamentally altered the natural history of pediatric HPP by supplementing deficient alkaline phosphatase activity at sites of active mineralization, thereby improving skeletal integrity, enhancing survival in severe forms, and supporting long-term functional gains. This therapeutic shift has redirected clinical priorities from survival alone toward sustained functional development and health-related quality of life. Nevertheless, variability in disease expression and therapeutic response persists, reflecting both diagnostic timing and the molecular heterogeneity of ALPL variants, whose phenotypic consequences cannot be predicted with complete certainty. Growing recognition of the importance of early diagnosis has prompted exploratory efforts toward systematic identification strategies, including neonatal screening initiatives reported in selected populations, which suggest the potential for earlier therapeutic intervention during active skeletal development. Together, these considerations highlight pediatric HPP as a model of precision-oriented management in rare metabolic bone disease, where timely diagnosis and targeted enzyme replacement must be aligned with long-term, multidisciplinary care to optimize outcomes.

Background: Vitamin D deficiency affects an estimated 40-60% of pregnant women worldwide and is associated with adverse obstetric and neonatal outcomes. Childhood asthma, the most prevalent chronic paediatric disease, has emerged as a plausible programming target, since vitamin D regulates foetal lung branching morphogenesis, calibrates the developing immune system, and modulates decidual and placental function in early gestation. Two landmark randomised trials, VDAART (intervention from weeks 10-18) and COPSAC2010 (from week 24), each reported a 20-25% reduction in offspring asthma or recurrent wheeze at age 3, yet neither reached significance in primary analysis, and the protective signal attenuated by school age. Post hoc stratification by baseline maternal 25-hydroxyvitamin D [25(OH)D] and 17q21 genotype recovered significant effects, raising the possibility that population-average nulls conceal a real but modifier-conditional benefit. Aim: This narrative review re-examines the evidence through a developmental-timing lens, arguing that the periconceptional and first-trimester window, rather than mid-gestation, is the biologically relevant interval for any protective effect. Methods: The review utilises a narrative synthesis of randomised trials, birth-cohort studies, mechanistic investigations, and recent meta-analyses (PubMed, Embase, Cochrane Library to April 2026) relevant to maternal vitamin D, placental biology, and offspring asthma. Findings: The periconceptional weeks coincide with implantation, decidualisation, the embryonic and pseudoglandular phases of airway morphogenesis, and the onset of epigenetic programming, while decidual CYP27B1 expression is prominent in the first trimester. Both trials initiated supplementation after branching morphogenesis was largely complete. Effect modifiers, including baseline 25(OH)D, vitamin D-binding protein, and maternal 17q21 genotype, indicate substantial inter-individual heterogeneity masked in unselected populations. Conclusions: Repositioning preventive supplementation toward the preconceptional and first-trimester window, stratified by baseline status, offers a biologically coherent strategy that existing mid-pregnancy trials have not tested. Adequately powered preconceptional trials with serial biomarker measurement and objective respiratory phenotyping are the priority.

Lower respiratory tract infections (LRTIs) are the most common cause for going to the doctor's at pediatric age. Respiratory infections are still of interest because they are widespread, significantly impact public health by potentially leading to pandemics, drive antimicrobial resistance through antibiotic misuse, more often spread globally due to traveling, and benefit from ongoing advancements in diagnostics and research for better management. This paper's main aim was to offer a systematic review of the literature published over the last 10 years on the etiology of LRTIs. The search strategy was based on reviewing original articles, systematic reviews, position papers, and guidelines published in MEDLINE, EMBASE, Cochrane Library, and PubMed. The review was previously registered with PROSPERO. The final review included 27 articles that met the eligibility criteria (studies identifying the etiology of inferior respiratory infections in children, according to the WHO definition, published in the last 10 years). Statistical analysis was performed using Microsoft Excel Version 2406 (Microsoft Corporation, Redmond, Washington, USA) and SPSS Statistics V.23 (IBM Corp., Armonk, New York, USA). The total number of patients was 2,193,978. Eight articles focused on children younger than five years, and two included children under the age of two. The results revealed that Mycoplasma pneumoniae and respiratory syncytial virus (RSV) are significant respiratory pathogens with seasonal peaks and age-specific prevalence and that nasopharyngeal aspirates (NPAs) are more reliable than throat swabs for confirming infections due to their higher positive predictive value (PPV). The impact of COVID-19 interventions led to reduced infections from RSV, adenovirus, and influenza viruses, but an increase in rhinovirus post-reopening, with high co-infection rates. Co-infections are common, particularly with pathogens like human bocavirus (HBoV) and RSV, underscoring the need for comprehensive diagnostic approaches. The impact of non-pharmaceutical interventions during the COVID-19 pandemic significantly reduced the prevalence of many respiratory pathogens, except for rhinovirus, which increased post-reopening. Understanding these dynamics is crucial for managing respiratory infections, especially in pediatric populations.

Background Lower respiratory tract infections (LRTIs) remain a significant concern in pediatrics due to their substantial burden among childhood diseases. Romania has recently attained the status of a high-income country. Even though the mortality rate from respiratory diseases has significantly declined from 24.1 per 100,000 individuals in 2000 to 5.3 per 100,000 in 2022, the rate remains notably higher than the European average. Diagnosing LRTI is challenging due to its clinical similarity to noninfectious respiratory illness and frequent false-positive results or incidental findings on microbiologic tests. This often leads to antimicrobial overuse and adverse outcomes. Additionally, antibiotic resistance poses a significant global public health threat. Patients and method We conducted a retrospective analysis of pediatric LRTI cases at a tertiary pediatric center in Romania to evaluate diagnostic testing, imaging use, etiology identification, and treatment approaches. Children under 18, admitted to the Emergency Clinical Hospital for Children in Cluj-Napoca during an eight-month peak respiratory season, were included. Data from electronic medical records were analyzed for demographics, symptoms, physical exams, laboratory data, presence of fever, etiology, treatment, and outcomes. Results In total, 222 children were included in this study, with a median age of 29 months. Among the participants, 58% were male. The average hospital stay was 11 days. The total number of cases was almost equally split between bronchiolitis and pneumonia, with lobar pneumonia accounting for 12% of the included patients. We found two statistically significant correlations between the presence of fever, intercostal retracting, and the subtype of LRTI. An inflammatory response defined as an elevated leucocyte count and elevated Creactive protein (CRP) was more likely to appear in pneumonia cases than bronchiolitis. From a therapeutic point of view, the prescription of hydrocortisone was statistically linked to bronchiolitis, but its use did not shorten hospitalization time. Conclusion Policy interventions and targeted treatments can reduce LRTI incidence and improve outcomes. Based on our correlations between specific clinical traits and subtypes of LRTIs, the use of assessment scores in children helps predict severe illness and the need for hospitalization. Promoting hygiene, social distancing, and addressing socioeconomic factors are crucial. Larger sample sizes and advanced diagnostics are needed to refine treatment strategies further. Early antibiotic use in children has long-term health implications, including a higher risk of respiratory-caused premature death in adulthood. This emphasizes the need for improved diagnostic processes and specific etiological identification, with metagenomics showing promise in this area.

Objective: COVID-19, caused by the SARS-CoV-2 virus, has had far-reaching consequences globally, affecting people of all ages. While children generally experience mild or no symptoms, they can still be affected by the disease, in particular with oral manifestations. The understanding of oral manifestations related to COVID-19 is still limited and inconsistent. This review aims to gather and analyze data on the prevalence and clinical presentations of oral lesions in pediatric patients with SARS-CoV-2 infection, contributing to a better understanding of their relationship and classification within different forms of COVID-19. Material and Methods: A comprehensive search of medical databases was conducted to identify relevant articles published up to June 2023 searched using electronic databases such as PubMed, Medline, and Web of Science. Results: This review encompasses a systematic analysis of 33 relevant articles, with a focused examination of seven studies that specifically address the subject matter. The inclusion criteria involved thorough evaluation, with 15 articles read in their entirety and additional references searched manually for supplementary information. Discussions: Research on oral lesions in pediatric population affected by SARS-CoV-2 infection is limited, leading to potential underestimation or misdiagnosis. Oral mucosa lesions occur in 2-20% of cases, often alongside skin lesions. The most common oral lesions are erosions, ulcers, maculae, petechiae, and changes in the tongue, lips, and gingiva. Oral manifestations are also observed in Multisystem inflammatory syndrome in children (MIS-C) and Kawasaki disease associated with SARS-CoV-2. Dental care providers can play a role in identifying and monitoring MIS-C, but accurate diagnosis is crucial to prevent complications. Conclusions: Pediatric patients diagnosed with COVID-19 may not frequently exhibit recognized oral signs and symptoms, necessitating thorough evaluation and consideration of differential diagnoses. Oral healthcare professionals should assess and classify oral manifestations to prevent underestimation and misdiagnosis.

Quality of life is a widely used concept that tends to become an important part of clinical management. The present study performs an analysis of the impact of suppurative chronic otitis media with and without cholesteatoma on quality of life, using the COMQ-12 questionnaire. It was applied to a group of 40 healthy people and to 40 patients before surgery, and the answers to the questions were analyzed and correlated with socioeconomic factors. After the confirmation of the diagnosis based on clinical and imaging information, the patients completed the COMQ-12 questionnaire. It was observed that the chronic ear problems had negative impacts of varying degrees on daily and long-term activities. The evaluation and analysis of information can be used in setting therapeutic targets.

Background and aim: Multisystemic inflammatory syndrome in children (MIS-C) is a rare and severe condition associated with Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) infection in children with onset approximately 4–6 weeks after infection. To date, the precise mechanism that causes MIS-C is not known and there are many questions related to the etiology, risk factors, and evolution of this syndrome. We aimed to describe the clinical manifestations, treatment methods, and disease evolution and analyze the main risk factors for MIS-C in children hospitalized in our clinic. Material and methods: We performed a retrospective study including children with MIS-C followed-up in the 2nd Pediatric Clinic of the Emergency Clinical Hospital for Children Cluj-Napoca, Romania, for 13 months (November 2020–December 2021). Results: We included in our cohort 34 children (mean age 6.8 ± 4.6 years) who met MIS-C criteria: high and prolonged fever associated with organ dysfunction (heart, lungs, kidneys, brain, skin, eyes, bone marrow or gastrointestinal organs), and autoantibodies and/or polymerase chain reaction positives for SARS-CoV-2. Nineteen patients (55.88%) had a severe form of the disease, with multiorgan failure and shock, and myocardial or respiratory failure. The number of organs affected in the severe forms was significantly higher (more than 6 in 73.70%) than in mild forms (2–3 in 60%). Cardiac dysfunction, hypoalbuminemia, hypertriglyceridemia and hyponatremia were more important in severe forms of MIS-C. These patients required respiratory support, resuscitation with fluid boluses, vasoactive drugs, or aggressive therapy. All patients with mild forms had fully recovered compared to 63.16% in severe forms. The others with severe forms developed long-term complications (dilation of the coronary arteries, premature ventricular contraction, or myocardial fibrosis). Two patients had an extremely severe evolution. One is still waiting for a heart transplant, and the other died (hemophagocytic lymphohistiocytosis syndrome with multiorgan failure). Conclusions: From mild to severe forms with multiorgan failure, shock, and many other complications, MIS-C represents a difficult challenge for pediatricians, who must be aware of the correct diagnosis and unpredictable, possibly severe evolution.

The application of artificial intelligence for the development of recognition models for food and beverages differentiation has benefited from increasing attention in recent years. For this scope, different machine learning (ML) algorithms were used in order to find the most suitable model for a certain purpose. In the present work, three ML algorithms, namely artificial neural networks (ANN), support vector machines (SVM) and k-nearest neighbors (KNN), were applied for constructing honey geographical classification models, and their performance was assessed and compared. A preprocessing step consisting of either a component reduction method or a supervised feature selection technique was applied prior to model development. The most efficient geographical differentiation models were obtained based on ANN, when a subset of features corresponding to the markers having the highest discrimination potential was used as input data. Therefore, when the samples aimed to be classified at an intercountry level, an accuracy of 95% was achieved; namely, 99% of the Romanian samples and 73% of the ones originating from other countries were correctly predicted. Promising results were also obtained for the intracountry honey discrimination; namely, the model built for classifying the Transylvanian samples from the ones produced in other Romanian regions had an 85% accuracy.

Food authenticity control represents a constant concern nowadays, and against this background, new means of food fraud detection are developed by research and control laboratories. Among the most accessible analytical methods in this regard, attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy proved to be an effective tool, being rapid, cost-effective, and not requiring solvent use. However, the generated experimental data need to be further processed in an efficient manner in order to be able to accurately assess the authenticity of a certain product. The temptation to pass some more available honey varieties as rarer ones might exist and in order to detect these types of miss labeling, we proposed in this study the development of new recognition models based on supervised chemometric models and artificial intelligence. In this way a comparison between the models' capabilities constructed based on the association between ATR-IR spectroscopy with partial least squares discriminant analysis (PLS-DA) and support vector machines (SVM), respectively, was performed. The most efficient models for the individual botanical differentiation were developed by applying SVM on the significant spectral markers, determined through a supervised method.

The coronavirus 2019 (COVID-19) disease has long-term effects, known as post-COVID conditions (PCC) or long-COVID. Post-COVID-19 syndrome is defined by signs and symptoms that occur during or after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection which persist for more than 12 weeks and cannot be supported by an alternative diagnosis. The cardiovascular damage caused by COVID-19 in the severe forms of the disease is induced by severe systemic inflammation, considered to be one of the causes of myocardial lesions, with increased levels of circulating cytokines and toxic response mediators. We have focused on conditions that can induce long-COVID-19, or multisystem inflammatory syndrome in adults or children (MIS-C/MIS-A), with an emphasis on endocrinological and metabolic disorders. Although described less frequently in children than in adults, long-COVID syndrome should not be confused with MIS-C, which is an acute condition characterized by multisystem involvement and paraclinical evidence of inflammation in a pediatric patient who tested positive for SARS-CoV-2. At the same time, we mention that the MIS-A symptoms remit within a few weeks, while the duration of long-COVID is measured in months. Long-COVID syndrome, along with its complications, MIS-A and MIS-C, represents an important challenge in the medical community. Underlying comorbidities can expose both COVID-19 adult and pediatric patients to a higher risk of negative outcomes not only during, but in the aftermath of the SARS-CoV-2 infection as well.

The use of intravenous immunoglobulins in medical prac­tice started in the early ’50’s. Today, there are more than 80 therapeutic indications of immunoglobulins. In addition to the already “classical” substitution for hu­mo­ral immunodeficiencies, or the administration for im­mu­no­mo­du­latory purposes in the immune throm­bo­cy­to­penic purpura (ITP), their effectiveness has been also de­mon­stra­ted in systemic autoimmune diseases, acquired immunodeficiencies, sepsis etc.

Lactose intolerance is a non-immune food adverse reaction due to a deficiency in lactase, an enzyme secreted by the intestinal epithelium. There are genetic and acquired forms. The congenital form of infantile type with birth on­set is rarisime. The genetic form of adult-type lactase de­fi­cien­cy, or the primary lactase deficiency, is attributable to relative or absolute absence of lactase that develops in childhood at various ages in different racial groups and is the most common cause of lactose intolerance. In pe­dia­trics, the most commonly diagnosed lactase deficiency is secondary to inflammatory, allergic, autoimmune or in­fec­tious diseases that affect intestinal mucosal integrity. The correct differential diagnosis of malabsorption syn­drome avoids the unnecessary explorations, inap­pro­priate hospitalizations and restrictive regimens.

Kawasaki disease is an acute systemic vasculitis, sometimes still perceived as an exotic disease, consequently its diag­nostic is overlooked or delayed. Although the first des­crip­tion of the disease was made in Japan 50 years ago, the diagnosis remains based on clinical crite­ria. The etio­lo­gy is unknown, but the current ac­cep­ted theory is that an infectious trigger initiates a par­ti­cular immune res­ponse in children with a genetic predisposition for this disease. The main complication of Kawasaki disease is coro­nary aneurysm. The prompt administration of high doses of im­mu­no­glo­bu­lins is essential to reduce the cardiovascular com­pli­cations.

Growth is a very reliable index of health assessment, both in children and teenagers. Growth is often affected (slowed or arrested) in children who suffer from chronic diseases, including the gastrointestinal disorders. Since the use of the serologic markers and small intestinal biopsy as diagnostic tools, it has become evident that the clinical presentation is highly variable in patients with celiac disease. Some patients present the classic symptoms of the celiac disease (diarrhea, malnutrition and growth failure), while others, unveil their disorder at puberty when growth failure and delayed puberty seem to be the only symptoms of the disease. We present the clinical case of a 16 years old girl, referred to our endocrine unit for short stature, failure to thrive and lack of menarche.

Introduction Ascariasis is the most common helminthic infection due to infestation by the roundworm Ascaris lumbricoides. It is prevalent mainly among female children, aged 2–10 years. In humans, the parasite is found mostly in the small bowel. Hepatobiliary and pancreatic ascariasis can occur due to migration of the adult, leading to serious complications like acute cholangitis or pancreatitis and hepatic abscess, intrahepatic duct calculi due to recurrent biliary invasion. Case-report We describe the case of a 3-year-old girl who, during a period of two years, suffered from three episodes of cholestatic hepatitis and acute pancreatitis due to obstruction of the biliary and pancreatic ducts. The symptoms were similar each time: anorexia, abdominal distension and upper abdominal tenderness, intermittent acholic stools and jaundice, urticaria on the lower limbs. Extensive work-up for infections and autoimmune hepatitis was unremarkable. During her first hospitalisation, the abdominal ultrasonography (US) and magnetic resonance cholangiopancreatography (MRCP) showed marked dilatation of the extrahepatic biliary duct, echogenic sludge within the gallbladder, pancreas enlargement and a dilated pancreatic duct. She was known to have had recent parasitosis. Due to treatment with albendazole, she eliminated Ascaris lumbricoides worms. Biliary sphincterotomy via endoscopic retrograde cholangiopancreatography (ERCP) was performed, evacuating the sludge and calculi most probably of parasitic origin. On her third admission, there was no history of recent parasitic infection. The MRCP findings were similar to the first, but also detected a 5 mm filling defect at the distal common bile duct (CBD). Her condition slowly ameliorated, but after 6 days ERCP was performed revealing no lacunar areas, only a dilated CBD. Thus, the highest probability is that the obstruction was due to parasitic remnants being spontaneously eliminated. Conclusions Parasitic diseases can be a diagnostic challenge and sometimes may not be included in the initial differential diagnosis. Because they can imitate infections by other agents or neoplastic processes, they can be mistaken as such. Treatment options include conservative treatment, usually effective, ERCP and surgery. Maintaining a high level of suspicion to diagnose biliary ascariasis is paramount for proper management and avoiding long-term complications.

The prevalence of coeliac disease (CD) in systemic lupus erythematosus (SLE) is unclear since evidence of this co -association is scarce. Furthermore, CD -specific antibodies have been described in patients with SLE without biopsy -confirmed CD. Here we describe the diagnostic challenges of CD in a patient suffering from SLE and secondary antiphospholipid syndrome, with transient positive serum levels of CD -specific antibodies, with an increased genetic risk for CD, demonstrated by HLA-DQ2 positivity. Guidance is still needed for the CD diagnosis in some atypical conditions.

BACKGROUND:Our aim was to investigate the prevalence and clinical relevance of inherited complement and antibody deficiency states in a large series of patients with various autoimmune rheumatologic diseases (ARD) with juvenile onset.METHODS:A total number of 117 consecutive patients from 2 tertiary referral hospitals were included in the study. All patients underwent genetic screening for type I C2 deficiency and C4 allotyping. Serum levels of immunoglobulin classes measured systematically throughout their regular medical care were recorded retrospectively.RESULTS:Our cohort of patients included 84 with juvenile idiopathic arthritis (JIA), 21 with systemic lupus erythematosus (SLE), 6 with systemic vasculitis, 2 with juvenile scleroderma, 2 with idiopathic uveitis, 1 with mixed connective tissue disease and 1 with SLE/scleroderma overlap syndrome. We have found 16 patients with evidence of primary immunodeficiency in our series (13.7%), including 7 with C4 deficiency, 5 with selective IgA deficiency, 3 with C2 deficiency and 2 with unclassified hypogammaglobulinemia (one also presented C4D). Of the 84 patients with JIA, 4 (4.8%) had a complement deficiency, which was less prevalent than in the SLE cohort (23.8%), but all of them have exhibited an aggressive disease. Most of our patients with primary antibody deficiencies showed a more complicated and severe disease course and even the co-occurrence of two associated autoimmune diseases (SLE/scleroderma overlap syndrome and SLE/autoimmune hepatitis type 1 overlap).CONCLUSIONS:Our findings among others demonstrate that complement and immunoglobulin immunodeficiencies need careful consideration in patients with ARD, as they are common and might contribute to a more severe clinical course of the disease.