Background Severe pertussis remains a major cause of morbidity and mortality in early infancy, particularly among unvaccinated and preterm infants who lack sufficient maternally derived antibody protection. This study aimed to identify clinical and laboratory predictors of severe disease and fatal outcomes in hospitalized infants and young children with PCR- or serologically confirmed pertussis. Methods We conducted a retrospective study of 107 pediatric patients hospitalized with pertussis at a tertiary care center in Serbia between 2015 and 2025. Clinical characteristics, laboratory parameters, and outcomes were analyzed. Logistic regression—including Firth’s penalized models where appropriate—was used to explore predictors of PICU admission, mechanical ventilation (MV), and mortality. Viral coinfections were assessed using multiplex PCR, and leukocyte dynamics were monitored through standardized follow-up testing. Results Thirteen children (12.1%) required PICU admission and 12 (11.2%) underwent MV. Five patients (4.7%) died; all were unvaccinated infants younger than 2 months of age. Prematurity was a strong independent predictor of PICU admission and MV. Higher absolute lymphocyte counts and an elevated neutrophil-to-lymphocyte ratio at admission were also associated with severe disease. Viral coinfection was documented in 22.4% of patients and was associated with increased mortality. In exploratory analyses, both viral coinfection and elevated N/L ratio were associated with fatal outcome; however, these findings should be interpreted with caution due to the small number of events. Conclusions Severe and fatal pertussis predominantly affected infants in the first months of life, especially those born preterm and those without maternal or postnatal vaccine-derived protection. Viral coinfection was associated with worse clinical outcomes. These findings highlight the importance of early identification of high-risk patients and support preventive strategies targeting early infancy, including maternal pertussis immunization.

Newborn screening (NBS) is a well-established public health program that enables early detection and treatment of rare disorders in newborns, preventing severe complications or death. Despite its recognized importance, the scope and implementation of NBS programs vary across Southeastern (SE) and Central Europe. This study aimed to evaluate the current status of NBS in 16 countries of SE and Central Europe and assess progress since the previous survey in 2021. A structured questionnaire was distributed to national experts between April and December 2025, collecting data on program organization, coverage, diseases included, laboratory methods, confirmatory testing, consent practices, and future expansion plans. All countries reported universal screening for congenital hypothyroidism, except Kosovo, where a national NBS is in the process of being established. Expanded NBS using tandem mass spectrometry was available in Austria, Bulgaria, Croatia, Cyprus, Greece, Hungary, North Macedonia, Romania, and Slovenia. Spinal muscular atrophy screening became universal in Austria, Croatia, Hungary, Serbia, and Slovenia. Most countries reported plans for further expansion, with congenital adrenal hyperplasia, severe combined immunodeficiency, spinal muscular atrophy, and cystic fibrosis being the most frequently targeted conditions. Although notable infrastructural progress has been achieved, financial constraints, lack of staff, and organizational barriers remain key challenges. The study’s assessment of program effectiveness was further limited by the absence of region-wide systems for capturing end-to-end performance indicators, such as the age of the infant at treatment initiation or missed cases. Regional collaboration and adoption of best practices are therefore vital to ensure equitable access and continuous advancement of NBS programs.

Pediatric-onset neuromuscular diseases (NMDs) represent a clinically and genetically heterogeneous group of rare disorders, often posing significant diagnostic challenges due to overlapping phenotypes. Next-generation sequencing (NGS), particularly whole-exome sequencing (WES), has transformed the diagnostic landscape; however, its clinical utility varies across phenotypic subgroups. We conducted a combined retrospective-prospective cohort study that included 100 pediatric patients with suspected neuromuscular disorders evaluated at a tertiary referral center between 2015 and 2025. Patients were stratified into seven clinically defined diagnostic categories prior to genetic testing. NGS-based diagnostics (primarily WES) were performed following initial clinical and targeted evaluations. Diagnostic yield and predictors of a positive genetic result were analyzed using univariate and multivariable statistical approaches. A molecular diagnosis was established in 71% of patients, including 64% with pathogenic/likely pathogenic variants and 7% with clinically consistent variants of uncertain significance. Diagnostic yield varied significantly across disease categories (p < 0.001), reaching near-complete rates in well-defined phenotypes such as congenital myasthenic syndromes, neuropathies, and metabolic myopathies, while markedly lower yield was observed in unclassified cases (38.2%). Multivariable logistic regression identified disease group as the only independent predictor of diagnostic success (B = -0.436, p = 0.001). Frequently implicated genes included DMD, RYR1, and LAMA2, reflecting a predominance of structural and excitation-contraction coupling defects. NGS demonstrates high diagnostic utility in pediatric neuromuscular disorders, particularly when applied in a phenotype-driven framework. Diagnostic performance is strongly influenced by the degree of clinical definition prior to testing, highlighting the continued importance of expert phenotyping in the genomic era.

Background/Objectives: Although SARS-CoV-2 infection is usually mild in children, some develop severe respiratory disease (RD) or multisystem inflammatory syndrome in children (MIS-C). We evaluated long-term respiratory symptoms, pulmonary function, and cardiopulmonary exercise performance in children recovering from SARS-CoV-2-related RD and MIS-C. Methods: This single-center prospective observational study included children hospitalized for SARS-CoV-2-related RD or MIS-C. Pulmonary function tests (PFTs) and cardiopulmonary exercise testing (CPET) were performed at a mean follow-up of 22.8 ± 9.8 months after hospitalization and compared between groups. Results: Forty-two children (25 RD, 17 MIS-C) were included. Persistent post-COVID symptoms were reported by 38.1% of participants and were more frequent in the RD group (56.0% vs. 11.8%; p < 0.01), with fatigue being the predominant symptom (p = 0.02). Pulmonary function and CPET parameters were comparable between groups, with no evidence of clinically significant ventilatory limitation or impaired aerobic capacity. VO2peak did not differ between groups. Multivariable regression identified the breathing reserve index and OUES normalized to body weight as strong positive predictors of aerobic capacity in both groups. Despite differences in follow-up duration, stratified analyses using a 24-month cut-off showed comparable physiological findings. Conclusions: Children demonstrated preserved pulmonary function and exercise capacity nearly two years after hospitalization for severe SARS-CoV-2-related RD or MIS-C. Despite these favorable objective findings, subjective symptoms persisted in a substantial subset of patients, particularly those recovering from RD, suggesting that symptom resolution may lag behind objective physiological recovery. OUES normalized to body weight and the breathing reserve index may serve as complementary markers of aerobic capacity.

Cystic fibrosis (CF) sputum represents a highly permissive niche for microbial colonization, yet the contribution of Candida albicans to disease progression remains insufficiently investigated despite its frequent detection in CF airways. We hypothesized that the heterogeneous nature of CF lung, reflected through the emergence of oxygen-depleted niches during disease progression, modulates C. albicans pathogenicity and antifungal susceptibility. Using complementary in vitro and in vivo approaches, we show that clinical CF isolates of C. albicans are virulent in CF-mimicking environments. Synthetic CF medium (SCFM2) supported robust filamentation, with oxygen-nutrient interplay critically shaping fungal growth and drug response. In a novel CF infection model using zebrafish morphants, we observed heightened susceptibility to C. albicans compared to wild-type embryos. Reporter strains showed elevated ECE1 expression, indicating increased candidalysin production and virulence in vivo. Our study provides compelling evidence that CF isolates of C. albicans have pathogenic potential, warranting consideration in future therapeutic strategies.

Background/Objectives: Primary malignant lung tumors in children are rare and diagnostically challenging. This study presents a single-center experience in the diagnosis and treatment of these tumors, emphasizing the role of histopathological and genetic profiling in informing individualized therapeutic strategies. Methods: We retrospectively reviewed records of seven pediatric patients (ages 2–18) treated from 2015 to 2025. Diagnostics included laboratory tests, chest CT, bronchoscopy, and histopathological/immunohistochemical analysis. Treatment primarily involved surgical resection, complemented by chemo-, radio-, or targeted therapies when indicated. Results: Inflammatory myofibroblastic tumor (IMT) represented the most commonly diagnosed entity (3/7 cases). The tumors presented with nonspecific symptoms, most frequently dry cough. Tumor type distribution was age-dependent, with aggressive forms such as pleuropulmonary blastoma predominantly affecting younger children, whereas IMT and carcinoid tumors were more common in older patients. Surgical resection remained the mainstay of treatment in the majority of cases. Bronchoscopy served as a valuable adjunct in the initial management of tumors exhibiting intraluminal growth, allowing for direct visualization, tissue sampling, and partial debulking to alleviate airway obstruction. In patients with an initially unresectable IMT harboring specific gene fusion rearrangement (e.g., TFG::ROS1), neoadjuvant targeted therapy with crizotinib enabled adequate tumor shrinkage to allow for subsequent surgical resection. Two patients in the study cohort died as a result of disease progression. Conclusions: A multidisciplinary diagnostic approach—integrating radiologic, bronchoscopic, histopathological, and genetic evaluations—ensures high diagnostic accuracy. While conventional treatments remain curative in many cases, targeted therapies directed at specific molecular alterations may offer essential therapeutic options for selected patients.

Background/Objectives: Myotonic dystrophy type 1 (DM1) is a rare neuromuscular disorder characterized by respiratory dysfunction that significantly impacts quality of life and longevity. This study aimed to explore the outcomes of pulmonary function tests and sleep-disordered breathing (SDB) workups in children with DM1 and to identify the factors contributing to SDB. Methods: A retrospective study examined patients’ medical records, including genetic analyses, clinical characteristics, and noninvasive pulmonary function testing (PFT), when possible. The Pediatric Sleep Questionnaire (PSQ), arterial blood gases, polygraphy, and overnight transcutaneous capnometry (PtcCO2) were used to assess SDB. Results: The size of CTG expansion in the DMPK gene directly correlated with the severity of respiratory complications and the need for early tracheostomy tube insertion in 7/20 (35%) patients. A total of 13/20 (65%) children were available for respiratory evaluation during spontaneous breathing. While moderate/severe obstructive sleep apnea syndrome (OSAS) and hypoventilation were confirmed in 4/13 (31%) children, none of the patients had mixed or dominantly central sleep apnea syndrome. There was no correlation between apnea–hypopnea index (AHI) or PtcCO2 and the presence of SDB-related symptoms or the PSQ score. Although a significant correlation between AHI and PtcCO2 was not confirmed (p = 0.447), the oxygen desaturation index directly correlated with PtcCO2 (p = 0.014). Conclusions: While SDB symptoms in children with DM1 may not fully correlate with observed respiratory events or impaired gas exchange during sleep, a comprehensive screening for SDB should be considered for all patients with DM1. Further research into disease-specific recommendations encompassing the standardization of PFT, as well as overnight polygraphic and capnometry recordings, could help to guide timely, personalized treatment.

Background/Aim. Prolonged ventilation is the most common indication for pediatric tracheostomy. The aim of the study was to determine the indications, possible complications, and outcomes of tracheostomy in infants, as well as the association of patient phenotype with complications following tracheostomy. Methods. This retrospective study highlights the main indications, complications, and decannulation rates in tracheostomy pediatric patients treated at the Institute of Mother and Child Health Care of Serbia "Dr. Vukan & Ccaron;upi & cacute;", Belgrade, for three years. Results. A total of 38 infants were included in our retrospective study, 31 (81%) of whom underwent elective tracheostomy, and 7 (19%) underwent urgent tracheostomy due to acute respiratory distress and difficult intubation. The mean age was 5.4 +/- 3.5 months, and the youngest participant was 36 hrs old. The primary indication for elective tracheostomy was prolonged mechanical ventilation in 13 (42%) patients, neuromuscular disorders in 5 (16%), airway obstruction in 10 (32%), craniofacial anomalies in 2 (5%), and pulmonary disease in 1 (3%) patient. Early complications (occurring within the first seven days after tracheostomy) were present in 4 (10.5%) patients, three of whom had air leaks (due to inappropriate cannula selection), whereas wound dehiscence was reported in one patient. Late complications (those occurring more than seven days after tracheostomy) were reported in 4 (10.5%) patients and they were peristomal granulations in three patients and tube obstruction in one patient. There were no deaths associated with tracheostomy, although overall mortality was 21% (8 patents). All of these patients died as a result of their primary diseases. Seventeen (44%) patients were successfully decannulated. Conclusion. Most patients required long-term treatment and tracheostomy retention due to the nature of their primary diseases, which coincided with low decannulation rates. Therefore, tracheostomies should preferentially be carried out in specialized pediatric centers with trained medical personnel ensuring adequate health care.

Escherichia coli is a Gram-negative bacterium and part of the intestinal microbiota. However, it can cause various diarrhoeal illnesses, i.e., traveller’s diarrhoea, dysentery, and extraintestinal infections when the bacteria are translocated from the intestine to other organs, such as urinary tract infections, abdominal and pelvic infections, pneumonia, bacteraemia, and meningitis. It is also an important pathogen in intensive care units where cross-infection may cause intrahospital spread with serious consequences. Within this study, four E. coli isolates from the tracheal aspirates of a tracheotomised paediatric patient on chronic respiratory support were analysed and compared for antibiotic resistance and virulence potential. Genomes of all four isolates (5381a, 5381b, 5681, 5848) were sequenced using Oxford Nanopore Technology. According to PFGE analysis, the clones of isolates 5681 and 5848 were highly similar, and differ from 5381a and 5381b which were isolated first chronologically. All four E. coli isolates belonged to an unknown sequence type, related to the E. coli ST131, a pandemic clone that is evolving rapidly with increasing levels of antimicrobial resistance. All four E. coli isolates in this study exhibited a multidrug-resistant phenotype as, according to MIC data, they were resistant to ceftriaxone, ciprofloxacin, doxycycline, minocycline, and tetracycline. In addition, principal component analyses revealed that isolates 5681 and 5848, which were recovered later than 5381a and 5381b (two weeks and three weeks, respectively) possessed more complex antibiotic resistance genes and virulence profiles, which is concerning considering the short time period during which the strains were isolated.

The pathogenic variants in the telomerase reverse transcriptase (TERT) gene have been identified in adults with idiopathic pulmonary fibrosis, while their connection to childhood diffuse lung disease has not yet been described. Within this study, we present a case of a five-month-old, previously healthy infant, with early-onset respiratory failure. The clinical suspicion of diffuse lung disease triggered by cytomegalovirus (CMV) pneumonitis was based on clinical and radiological presentation. Multiorgan involvement was not confirmed. Considering the possible connection between CMV pneumonitis and early-onset respiratory failure, clinical exome sequencing was performed and a novel variant, classified as likely pathogenic in the TERT gene (c.280A>T, p.Lys94Ter) was detected. After segregation analysis yielded negative results, the de novo status of the variant was confirmed. Respiratory support, antiviral and anti-inflammatory therapy offered modest benefits, nevertheless, eighteen months after the initial presentation of disease, an unfavourable outcome occurred. In conclusion, severe viral pneumonia has the potential to induce extremely rare early-onset diffuse lung disease accompanied by chronic respiratory insufficiency. This is linked to pathogenic variants in the TERT gene. Our comprehensive presentation of the patient contributes to valuable insights into the intricate interplay of genetic factors, clinical presentations, and therapeutic outcomes in cases of early-onset respiratory failure.

Background: Subglottic stenosis (SGS) is the most frequent type of laryngeal stenosis and a common cause of upper airway obstruction in pediatric patients. The etiology of SGS is congenital or acquired. Clinical presentation depends on the degree of the stenosis, and biphasic stridor is the most prominent sign. Objective: To determine the etiology of subglottic stenosis in children during the ten-year period, as well as the treatment modalities and outcomes. Methods: This retrospective study included patients in whom subglottic stenosis was confirmed with flexible bronchoscopy and who were treated at the Pulmonology department of the Mother and Child Healthcare Institute of Serbia from January 2013 to December 2022. The data were obtained from patients' medical history. Results: During the study period, total of 19 patients had endoscopically confirmed SGS. Among them, 68.4% had acquired and 32.6% congenital SGS. Every patient with acquired SGS had a history of endotracheal intubation, and 61.5% had gastroesophageal reflux (GER). The incidence of prematurity was 25.3%, all preterm infants were previously intubated. Majority of patients had mild SGS (36.8%), but in 26.3% tracheotomy was required due to critical SGS. Among tracheotomized patients, 80% had acquired SGS and 20% congenital. Patients with severe SGS (31.6%) were operated on, with favorable outcomes. Decannulation was done in 40%. Patients in whom decannulation was not possible had severe comorbidities. During the ten-year period, one patient died. Conclusion: SGS is an important cause of airway obstruction, acquired SGS is more prevalent than congenital. Endotracheal intubation is leading cause of acquired SGS, and GER is the most prevalent associated comorbidity.

Patients with cystic fibrosis (CF) are repeatedly exposed to antibiotics, especially during the pulmonary exacerbations of the disease. However, the available therapeutic strategies are frequently inadequate to eradicate the involved pathogens and most importantly, facilitate the development of antimicrobial resistance (AMR). The evaluation of AMR is demanding; conventional culture-based susceptibility-testing techniques cannot account for the lung microenvironment and/or the adaptive mechanisms developed by the pathogens, such as biofilm formation. Moreover, features linked to modified pharmaco-kinetics and pulmonary parenchyma penetration make the dosing of antibiotics even more challenging. In this review, we present the existing knowledge regarding AMR in CF, we shortly review the existing therapeutic strategies, and we discuss the future directions of antimicrobial stewardship. Due to the increasing difficulty in eradicating strains that develop AMR, the appropriate management should rely on targeting the underlying resistance mechanisms; thus, the interest in novel, molecular-based diagnostic tools, such as metagenomic sequencing and next-generation transcriptomics, has increased exponentially. Moreover, since the development of new antibiotics has a slow pace, the design of effective treatment strategies to eradicate persistent infections represents an urgency that requires consorted work. In this regard, both the management and monitoring of antibiotics usage are obligatory and more relevant than ever.

Background Bronchiolitis is the main acute lower respiratory tract infection in infants. Data regarding SARS-CoV-2-related bronchiolitis are limited. Objective To describe the main clinical characteristics of infants with SARS-CoV-2-related bronchiolitis in comparison with infants with bronchiolitis associated with other viruses. Setting, patients, interventions A multicentre retrospective study was conducted in 22 paediatric emergency departments (PED) in Europe and Israel. Infants diagnosed with bronchiolitis, who had a test for SARS-CoV-2 and were kept in clinical observation in the PED or admitted to hospital from 1 May 2021 to 28 February 2022 were considered eligible for participation. Demographic and clinical data, diagnostic tests, treatments and outcomes were collected. Main outcome measures The main outcome was the need for respiratory support in infants testing positive for SARS-CoV-2 compared with infants testing negative. Results 2004 infants with bronchiolitis were enrolled. Of these, 95 (4.7%) tested positive for SARS-CoV-2. Median age, gender, weight, history of prematurity and presence of comorbidities did not differ between the SARS-CoV-2-positive and SARS-CoV-2-negative infants. Human metapneumovirus and respiratory syncytial virus were the viruses most frequently detected in the group of infants negative for SARS-CoV-2. Infants testing positive for SARS-CoV-2 received oxygen supplementation less frequently compared with SARS-CoV-2-negative patients, 37 (39%) vs 1076 (56.4%), p=0.001, OR 0.49 (95% CI 0.32 to 0.75). They received less ventilatory support: 12 (12.6%) high flow nasal cannulae vs 468 (24.5%), p=0.01; 1 (1.0%) continuous positive airway pressure vs 125 (6.6%), p=0.03, OR 0.48 (95% CI 0.27 to 0.85). Conclusions SARS-CoV-2 rarely causes bronchiolitis in infants. SARS-CoV-2-related bronchiolitis mostly has a mild clinical course.

Introduction/aim: Central congenital hypoventilation syndrome (CCHS) is a rare genetic disorder characterized by autonomic dysregulation and alveolar hypoventilation with ventilatory support being the cornerstone of long-term survival. The aim was to present different ventilatory strategies in CCHS. Material and methods: The study included retrospectively analyzed medical records of five patients diagnosed with CCHS in a national pediatric center. Alveolar hypoventilation was evidenced by noninvasive continuous transcutaneous capnometry and central sleep-disordered breathing documented by polygraphy. Clinical evaluation included cardiac evaluation, rectal biopsies, and urinalysis of catecholamine levels. Life-threatening cardiac arrhythmias were indications for pacemaker implantation. Genetic analyses of alanine residues in paired-like homeobox 2B gene (PHOX2B) confirmed the diagnosis. Results: A range of pathogenic changes in the PHOX2B gene resulted in varying clinical outcomes. 3/4 (75%) of patients with an early onset were ventilated continuously through a tracheostomy tube, while one patient was successfully treated with noninvasive ventilation (NIV) as the preferred option. Additionally, NIV was applied in one child with early-onset disease after decannulation. Finally, NIV was also feasible in a case with late-onset disease presented by the time of four years with symptoms of pulmonary hypertension. There were no serious side effects of ventilation, and one patient died due to cardiac arrhythmias. Conclusion: Invasive mechanical ventilation remains the treatment of choice in most children with early-onset disease. However, the indications for NIV have been widened from overnight ventilation in the late-onset course to selected cases with early-onset disease. The timely switch from IMV to NIV has been popularized in recent years worldwide.

This retrospective study aimed to investigate the clinical features and treatment of pediatric subglottic hemangioma (SH), identify risk factors for treatment-induced adverse effects, and identify a strategy for timely therapy discontinuation in children diagnosed with SH at the national pediatric center. Medical records of patients presented with stridor from 2010 to 2020 were retrieved and assessed, the diagnosis of SH was established via flexible bronchoscopy, and the patients were treated using propranolol with a subsequent gradual dose increase to 3 mg/kg body weight daily. A two-week oral steroids trial was added for those with circumferential lesions. Early indicators of a good therapeutic response included decreased stridor and primary lesion size on follow-up bronchoscopy performed one week after propranolol commencement. Duration of therapy, tailored individually based on bronchoscopy findings, and at least twelve months of treatment were the two main criteria for deciding therapy termination. Outpatient visits were arranged at least every three months. Our results showed that SH was the third most frequent cause of stridor (15/137 patients), and biphasic stridor was uniformly present as a typical symptom. Both clinical improvement and bronchoscopy findings confirmed the efficacy of the treatment. The mean therapy duration was 17 months. The only significant adverse event observed was hypoglycemic seizures in one infant. Contributory factors were all prematurity, high propranolol dose (3 mg/kg) and poor oral intake. Collectively, defining a safe and timely protocol for therapy cessation and avoidance of risk factors for adverse effects is the mainstay of SH treatment.