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Search Results (371)

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20 pages, 1593 KB  
Article
Pediatric DOCK8 Deficiency Beyond Infections and Atopy: An Immunoactinopathy with Immune Dysregulation and Multisystem Involvement
by Figen Çelebi Çelik, Necmi Can Yüksel, Ömer Akçal, Emre Fırat, Aymen Hişmioğulları, Soner Günder, Gülçin Kaymakoğlu, Nesrin Gülez and Ferah Genel
Children 2026, 13(9), 1226; https://doi.org/10.3390/children13091226 - 10 Sep 2026
Abstract
Background/Objectives: Dedicator of cytokinesis 8 (DOCK8) deficiency is an autosomal recessive combined immunodeficiency and an actin cytoskeleton-related inborn error of immunity characterized by severe atopy, recurrent infections, and broad immune dysregulation. We aimed to describe the clinical, immunological, genetic, treatment-related, and outcome [...] Read more.
Background/Objectives: Dedicator of cytokinesis 8 (DOCK8) deficiency is an autosomal recessive combined immunodeficiency and an actin cytoskeleton-related inborn error of immunity characterized by severe atopy, recurrent infections, and broad immune dysregulation. We aimed to describe the clinical, immunological, genetic, treatment-related, and outcome features of children with genetically confirmed DOCK8 deficiency, emphasizing immune dysregulation and systemic involvement. Methods: We retrospectively reviewed 17 pediatric patients from 14 unrelated kindreds with genetically confirmed DOCK8 deficiency followed at a tertiary pediatric immunology center between 2005 and 2026. Demographic data, infectious and allergic manifestations, autoimmune and hematological findings, organ involvement, malignancy, laboratory parameters, genetic findings, hematopoietic stem cell transplantation (HSCT) status, and survival outcomes were analyzed descriptively. Results: Twelve patients were male (70.6%), and parental consanguinity was present in 13 patients (76.5%). The median age at symptom onset was 5 months (IQR, 3–10), whereas the median age at diagnosis was 44 months (IQR, 23–56). A history of eczema was documented in all patients. Recurrent skin infections occurred in 16 patients (94.1%), recurrent pneumonia in 13 (76.5%), mucocutaneous candidiasis in 10 (58.8%), and cytomegalovirus infection in four (23.5%). Confirmed autoimmune manifestations were documented in two patients, including autoimmune hepatitis and autoimmune hemolytic anemia. Malignancy occurred in two patients: gastrointestinal stromal tumor and cutaneous squamous cell carcinoma. Additional uncommon systemic manifestations included sclerosing cholangitis, giant aortic aneurysm, and chronic pancreatitis. HSCT was performed in 12 patients (70.6%); complete clinical recovery was achieved in 11, whereas one patient died after transplantation. Four of five non-transplanted patients died during follow-up. Conclusions: Pediatric DOCK8 deficiency showed an early-onset, severe, multisystem phenotype. Beyond infections and atopy, immune dysregulation-related and systemic manifestations were clinically important. Favorable HSCT outcomes were consistent with previous evidence supporting early molecular diagnosis and timely transplant evaluation. Full article
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20 pages, 10733 KB  
Review
Streptococcus pneumoniae: Perspectives of Clinicians and Microbiologists on the Underrecognized Threat of Pneumococcal Disease in India
by Balaji Veeraraghavan, Ami Varaiya, Anand Shah, Bibhudutta Rautaraya, Anusha Karunasagar, Rosemol Varghese, Chetan Trivedi, Sanjay Biswas, Anu Gupta, Dip Narayan Mukherjee, Samir Garde, Santosh Taur, Ritika Rampal and Namrata Kulkarni
Acta Microbiol. Hell. 2026, 71(3), 35; https://doi.org/10.3390/amh71030035 - 9 Sep 2026
Abstract
Background: Invasive pneumococcal disease (IPD) is predominantly caused by Streptococcus pneumoniae and is associated with high mortality. This vaccine-preventable disease has been a significant public health concern, particularly among children < 5 years and adults > 50 years in India. Pneumococcal vaccines [...] Read more.
Background: Invasive pneumococcal disease (IPD) is predominantly caused by Streptococcus pneumoniae and is associated with high mortality. This vaccine-preventable disease has been a significant public health concern, particularly among children < 5 years and adults > 50 years in India. Pneumococcal vaccines help prevent pneumococcal infections caused by certain strains of S. pneumoniae, but diagnostic challenges in India hinder disease management. Methods: The objective of this expert panel discussion is to deliberate upon the pathogenesis and epidemiology of S. pneumoniae in India, techniques for overcoming the diagnostic challenges in the isolation and detection of S. pneumoniae, and to explore opportunities for partnerships between clinicians and microbiologists to bridge gaps. A non-systematic, targeted literature search was conducted to identify studies supporting key themes of expert panel discussion. Eight microbiologists, one infectious disease, one pediatrics and neonatology, and one respiratory medicine specialist from different parts of India participated in the discussion. Results: The panelists reiterated that while culture is the gold standard, multiplex real-time polymerase chain reaction and BioFire® FilmArray® technology have been the most common diagnostic methods for the detection of S. pneumoniae in India, especially in tier 1 cities. Conclusions: This article elucidates the challenges faced by microbiologists and clinicians in isolating and detecting the pathogen, and proposes solutions to determine the true burden of pneumococcal disease in India. This information could further inform public health policy and vaccination strategies. Full article
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18 pages, 650 KB  
Systematic Review
Evidence for the Efficacy and Safety of Tigecycline for the Treatment of Ventilator-Associated Pneumonia in Preterm Infants: A Systematic Review
by Gorana Nedin Ranković, Dane Krtinić, Aleksandar Nikolić, Nada Pejčić, Nemanja Dimić, Nikola Milenković, Iva Binić and Branislava Ranković
Life 2026, 16(9), 1502; https://doi.org/10.3390/life16091502 - 8 Sep 2026
Abstract
Background: Ventilator-associated pneumonia (VAP) is a common and serious nosocomial infection in mechanically ventilated preterm infants and is increasingly caused by multidrug-resistant (MDR) and extensively drug-resistant (XDR) Gram-negative organisms. Tigecycline, a glycylcycline with broad activity against many such pathogens, is not approved below [...] Read more.
Background: Ventilator-associated pneumonia (VAP) is a common and serious nosocomial infection in mechanically ventilated preterm infants and is increasingly caused by multidrug-resistant (MDR) and extensively drug-resistant (XDR) Gram-negative organisms. Tigecycline, a glycylcycline with broad activity against many such pathogens, is not approved below 18 years of age and carries a boxed warning for excess mortality that is most pronounced in hospital-acquired and ventilator-associated pneumonia. Its role, if any, in preterm infants with VAP is undefined. Objectives: To systematically identify and appraise all human evidence on the efficacy (clinical cure, microbiological eradication, survival) and safety (adverse events, mortality) of tigecycline used to treat VAP or nosocomial pneumonia during mechanical ventilation in preterm infants and neonates. Methods: A PRISMA 2020 structured search of PubMed/MEDLINE, Cochrane CENTRAL, Scopus, trial registries, regulatory documents, Google Scholar and reference lists was designed without language or date restrictions. Eligible reports described tigecycline treatment of pneumonia/VAP in neonates or young infants; pediatric case series and syntheses were retained as contextual evidence. Because only case reports and small non-comparative series were anticipated, a narrative synthesis was pre-specified; JBI tools and GRADE were planned for appraisal and certainty. Results: No randomized controlled trial, controlled observational study, or study dedicated to tigecycline for VAP in preterm infants was identified. Direct evidence meeting the full eligibility criteria (preterm neonate, VAP specifically, separately extractable outcomes) was limited to two case reports of extremely preterm neonates with VAP successfully weaned after tigecycline-based salvage combination therapy. Six further neonatal/young-infant reports initially considered were, on full-text re-review, reclassified as contextual (not index) evidence because they described non-VAP infections (sepsis, or CNS infections such as ventriculitis/meningitis), non-preterm ages, or mixed-infection series without separable VAP data. Reported outcomes were generally favorable in published cases but are subject to severe selection and publication bias; thrombocytopenia, hypofibrinogenemia and hepatic enzyme elevation were the principal adverse signals, against a class-level mortality signal concentrated in VAP. Quantitative pooling was not appropriate. The overall certainty of evidence was very low. Conclusions: There is no direct, credible efficacy or safety evidence supporting tigecycline for VAP in preterm infants. Available data neither establish benefit nor exclude harm. Based on this very-low-certainty evidence and on regulatory/class-level safety data rather than on demonstrated efficacy, tigecycline warrants consideration only as a last-resort, combination salvage option for culture-confirmed pan- or extensively drug-resistant pathogens when no safer alternative exists, with intensive monitoring and, ideally, within a registry or trial. Adequately designed neonatal pharmacokinetic and comparative safety studies are urgently needed. Registration: PROSPERO CRD420261450972 (registered 14 July 2026). Full article
(This article belongs to the Special Issue Drug Safety)
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18 pages, 2999 KB  
Article
Etiology and Clinical Manifestations of Acute Respiratory Infections in Pediatric Patients: A Retrospective Study in Moscow, Russia
by Diana A. Grigoryan, Maria A. Gordukova, Elena V. Galeeva, Irina E. Turina, Ekaterina V. Ligskaya, Oleg B. Kovalev and Alina D. Matsvay
Diseases 2026, 14(9), 326; https://doi.org/10.3390/diseases14090326 - 6 Sep 2026
Viewed by 154
Abstract
Background/Objectives: Acute respiratory viral infections (ARVIs) are the leading cause of pediatric morbidity and exhibit considerable clinical heterogeneity. The analysis of clinical and etiological associations, as well as the identification of factors linked to severe ARVI cases, is essential for effective epidemiological surveillance. [...] Read more.
Background/Objectives: Acute respiratory viral infections (ARVIs) are the leading cause of pediatric morbidity and exhibit considerable clinical heterogeneity. The analysis of clinical and etiological associations, as well as the identification of factors linked to severe ARVI cases, is essential for effective epidemiological surveillance. Methods: A retrospective, single-center observational study was conducted including 1362 non-COVID-19 pediatric cases of acute respiratory infections (ARIs), registered between 2021 and 2024. Viral pathogens were detected using real-time PCR for broad-spectrum screening of respiratory viruses. Results: Viral etiology was established in approximately 50% of cases. The most frequently detected pathogen was Human rhinovirus (HRV) (35.6%), followed by Respiratory syncytial virus (RSV) and Human adenovirus (HAdV). Despite its predominance, HRV did not demonstrate nosological specificity. The strongest associations with lower respiratory tract infections were identified for RSV (OR = 3.2) and Human bocavirus (HBoV; OR = 2.4), predominantly within the pneumonia category. RSV was also associated with bronchitis/bronchiolitis (OR = 1.8). Significant associations with upper respiratory tract infections were established for Influenza viruses (OR = 10.4) and HAdV, including nasopharyngitis (OR = 3.88) and acute tonsillitis (OR = 3.9). HAdV additionally demonstrated an association with otitis media (OR = 5.1). Severe disease was registered in 52.3% of all clinical observations and occurred most frequently among young children, particularly in cases associated with respiratory syncytial virus (RSV >80%), as well as with human bocavirus (HBoV) and Human metapneumovirus (HMPV) (~55–59%). Co-infections were not associated with increased disease severity compared with monoinfections (OR = 1.1). Conclusions: The obtained results highlight the contribution of specific etiological agents to severe respiratory infections in children. These findings support the prioritization of such pathogens in clinical diagnostics, including the design of diagnostic algorithms and the selection of patient management strategies in pediatric populations. Full article
(This article belongs to the Section Infectious Disease)
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19 pages, 5667 KB  
Article
Diagnostic Performance of Complementary Serum and Cerebrospinal Fluid Multiplex PCR for Acute Bacterial Meningitis
by Lema Ayele, Daniel Asrat, Aminu Seman, Jemal Aman, Muluwork Tefera, Derso Wale Mesele, Ashenafi Alemu, Andargachew Mulu, Dawit Hailu Alemayehu, Adane Mihret and Getachew Tesfaye Beyene
Diagnostics 2026, 16(17), 2800; https://doi.org/10.3390/diagnostics16172800 - 31 Aug 2026
Viewed by 159
Abstract
Background: Developing molecular tools for the diagnosis of bacterial meningitis is crucial for improving the diagnosis and initiation of prompt treatment of patients. This study aimed to evaluate the diagnostic performance of cerebrospinal fluid and serum multiplex PCR compared with conventional diagnostic [...] Read more.
Background: Developing molecular tools for the diagnosis of bacterial meningitis is crucial for improving the diagnosis and initiation of prompt treatment of patients. This study aimed to evaluate the diagnostic performance of cerebrospinal fluid and serum multiplex PCR compared with conventional diagnostic methods for detecting bacterial pathogens among patients clinically suspected of bacterial meningitis. Methods: A cross-sectional study was conducted at Tikur Anbessa Specialized Hospital and Yekatit 12 Hospital Medical College from August 2023 to February 2024. A total of 202 patients who were suspected of having meningitis were included in the study. Conventional laboratory analysis, including Gram staining and bacterial culture from CSF, was performed. CSF and serum PCR for the detection of Neisseria meningitidis, Haemophilus influenzae, Streptococcus pneumoniae, Streptococcus agalactiae, Escherichia coli, Staphylococcus aureus, Listeria monocytogenes, and Klebsiella pneumoniae were performed. The agreement between tests used to detect etiologic agents of bacterial meningitis was determined by McNemar’s Test and Cohen’s kappa statistic. Results: Of the 202 study participants, 109 (54.0%) were male, and 178 (88.1%) were pediatric, with the majority being infants (mean age: 1.45 ± 0.69 years). Poor feeding was the most common clinical presentation at 151/202 (74.8%), followed by high fever at 144/202 (71.3%), and loss of consciousness at 134/202 (66.3%). Among the 202 CSF samples, nine (4.5%) and 11 (5.4%) tested positive for culture and Gram stain, respectively. Bacterial DNA was detected in 54/202 (26.7%) of the CSF samples and 93/202 (46.0%) of the serum samples. E. coli was detected in 30/54 (55.5%) of CSF samples and 57/93 (61.2%) of serum samples, followed by S. pneumoniae, which was detected in 8/54 (14.8%) of CSF samples and 27/93 (29.0%) of serum samples. The overall agreement between CSF and serum PCR is 60.9% (123/202), with a positive percent agreement of 62.96% (34/54), and a negative percent agreement of 60.14% (89/148). McNemar’s test indicated a significant difference between the two tests (p < 0.0001), and Cohen’s kappa statistic showed slight agreement (κ = 0.188, 95% CI: 0.109–0.293). Conclusions: Bacterial DNA was detected more often in serum multiplex PCR than CSF PCR or culture, suggesting its potential role as a complementary diagnostic tool for epidemiological surveillance, particularly in resource-limited settings where lumbar puncture may not always be feasible. However, serum PCR should not replace CSF analysis for definitive diagnosis; rather, it can serve as a screening or surveillance tool, with positive results requiring clinical correlation and, where possible, CSF confirmation. A relatively small sample size, reliance on conventional PCR, absence of comparison with quantitative PCR, potential blood contamination, lack of sequencing, and lack of long-term outcome data limit the generalizability of our findings. Future investigations should include a large sample size in conjunction with confirmatory culture techniques to enhance the robustness and validity of the findings. Full article
(This article belongs to the Section Diagnostic Microbiology and Infectious Disease)
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18 pages, 860 KB  
Article
Factors Associated with Acute Lower Respiratory Infections in Children Under Five at a Peruvian Emergency Hospital
by Anthony D. Mautino-Reyes, Fiorella F. Fuentes-Cosme and Miguel A. Arce-Huamani
Children 2026, 13(8), 1120; https://doi.org/10.3390/children13081120 - 21 Aug 2026
Viewed by 332
Abstract
Background/Objectives: Acute lower respiratory infections (ALRIs) are an important cause of morbidity among children under five years of age. This study aimed to identify factors associated with ALRI among children under five treated at a Peruvian emergency hospital. Methods: We conducted [...] Read more.
Background/Objectives: Acute lower respiratory infections (ALRIs) are an important cause of morbidity among children under five years of age. This study aimed to identify factors associated with ALRI among children under five treated at a Peruvian emergency hospital. Methods: We conducted an observational, analytical, retrospective cross-sectional study using medical records of children treated in the pediatric emergency department of Hospital de Emergencias José Casimiro Ulloa, Lima, Peru, between January and December 2024. ALRI was defined as a physician-recorded diagnosis of pneumonia or bronchiolitis; the comparison group comprised children with acute bronchitis or upper respiratory tract infection. Crude and adjusted prevalence ratios (PRs) with 95% confidence intervals (CIs) were estimated using Poisson regression with robust variance. Results: The final sample included 322 children, of whom 154 (47.8%) had ALRI. In the adjusted model, age 0 to <2 years (aPR = 1.27; 95% CI: 1.03–1.56), absence of exclusive breastfeeding (aPR = 1.24; 95% CI: 1.02–1.51), birth weight < 1000 g (aPR = 1.43; 95% CI: 1.09–1.87), incomplete immunizations (aPR = 1.28; 95% CI: 1.07–1.53), and passive smoking exposure (aPR = 1.38; 95% CI: 1.15–1.65) were independently associated with higher ALRI prevalence. Conclusions: ALRI accounted for nearly half of the ARI diagnoses in this pediatric emergency analytical sample. Younger age, absence of exclusive breastfeeding, extremely low birth weight, incomplete immunizations, and passive smoking exposure were independently associated with ALRI and may help identify children requiring closer clinical assessment and preventive interventions. Full article
(This article belongs to the Section Pediatric Pulmonary and Sleep Medicine)
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15 pages, 924 KB  
Article
Seroepidemiology of Enterovirus D68 in Xiamen Children: A Cross-Sectional Study in 2022
by Liting Wang, Qiguo Zhu, Yi Lu, Yuanyuan Wu, Zhifeng Ke, Qingbing Zheng, Longfa Xu, Tong Cheng, Rui Zhu and Jun Shen
Viruses 2026, 18(8), 903; https://doi.org/10.3390/v18080903 - 17 Aug 2026
Viewed by 426
Abstract
Enterovirus D68 (EV-D68) is a re-emerging pathogen associated with severe acute flaccid myelitis (AFM) and pneumonia, predominantly in children but also capable of causing severe disease in immunocompromised adults. Seroprevalence data are essential for understanding population immunity, age-specific susceptibility, and viral transmission dynamics; [...] Read more.
Enterovirus D68 (EV-D68) is a re-emerging pathogen associated with severe acute flaccid myelitis (AFM) and pneumonia, predominantly in children but also capable of causing severe disease in immunocompromised adults. Seroprevalence data are essential for understanding population immunity, age-specific susceptibility, and viral transmission dynamics; yet, such data for the period after the COVID-19 pandemic are scarce. We conducted a cross-sectional serological survey to characterize the neutralizing antibody profile of EV-D68 among children in Xiamen, China, in 2022. A total of 453 children aged 0–16 years (217 with acute respiratory tract infection [ARTI] and 236 without) were enrolled. Neutralizing antibody (NtAb) titers against the EV-D68 STL strain were measured using a microneutralization assay, seropositivity was defined as a titer ≥1:16. Multivariable regression and analysis of covariance were used to adjust for age and sex. Overall seroprevalence was 96.0% (435/453), exceeding 90.0% in every age subgroup (0–1 y: 100%; 1–3 y: 97.6%; 3–5 y: 92.6%; ≥5 y: 96.2%). The geometric mean titer (GMT) was 76.78 (95% CI: 68.32–85.24). After adjustment, ARTI status was not significantly associated with seropositivity (adjusted OR = 1.42, 95% CI: 0.46–4.41, p = 0.542). In an exploratory comparison, children with ARTI showed nominally higher antibody titers than those without (Mann–Whitney U test, p = 0.003), although the absence of EV-D68-specific PCR testing precludes etiologic attribution of respiratory symptoms to EV-D68 infection. Infants < 1 year showed the highest GMT (86.31), while children aged 1–3 years had the lowest GMT (63.52) and the largest low-titer fraction, indicating a susceptibility gap. Our study revealed EV-D68 circulated endemically in this pediatric population, establishing a high population immune baseline (>90.0%) with distinct age-dependent patterns. These findings provide key reference data for ongoing serosurveillance, outbreak risk assessment, and the evaluation of future vaccines or immunoprophylactic strategies should they become available. Full article
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30 pages, 745 KB  
Review
Biofilm-Mediated Antimicrobial Resistance in Pediatric Klebsiella pneumoniae Urinary Tract Infections: A Narrative Review of Mechanisms, Clinical Challenges, and Therapeutic Strategies
by Larisa Goroftei, Cristina-Mihaela Popescu, Irina Profir, Geanina-Adelina Jalba and Gabriela Gurau
Antibiotics 2026, 15(8), 783; https://doi.org/10.3390/antibiotics15080783 - 13 Aug 2026
Viewed by 412
Abstract
Urinary tract infections (UTIs) caused by Klebsiella pneumoniae are an increasing challenge in pediatric practice due to the combined effects of biofilm formation, multidrug resistance (MDR), and limited therapeutic options for children. Biofilm development promotes bacterial persistence by impairing antibiotic penetration, enabling metabolic [...] Read more.
Urinary tract infections (UTIs) caused by Klebsiella pneumoniae are an increasing challenge in pediatric practice due to the combined effects of biofilm formation, multidrug resistance (MDR), and limited therapeutic options for children. Biofilm development promotes bacterial persistence by impairing antibiotic penetration, enabling metabolic adaptation, promoting persister-cell formation, facilitating horizontal gene transfer (HGT), and inducing stress-induced mutagenesis, thereby reducing the effectiveness of conventional antimicrobial therapy. These mechanisms are further compounded by pediatric-specific challenges, including age-dependent pharmacokinetic variability, congenital urinary tract abnormalities, device-associated infections, and the limited availability of validated diagnostic tools for biofilm-associated infections. This narrative review integrates current knowledge of the molecular mechanisms underlying biofilm-mediated antimicrobial resistance with the unique diagnostic, pharmacological, and therapeutic challenges encountered in pediatric patients with K. pneumoniae UTIs. Emerging therapeutic strategies, such as optimized antibiotic combination therapy, bacteriophages, biofilm matrix-degrading enzymes, quorum-sensing inhibitors (QSIs), antimicrobial peptides (AMPs), and microbiome-directed approaches are critically evaluated with particular emphasis on their potential applicability in children. Although several anti-biofilm strategies have demonstrated encouraging results in experimental models, robust pediatric clinical evidence remains scarce. Current international guidelines continue to rely primarily on planktonic antimicrobial susceptibility testing without addressing biofilm-specific therapeutic considerations. In the absence of validated biofilm diagnostics, catheter stewardship and dosing optimization remain the most defensible clinical interventions available today. Broader translation of anti-biofilm strategies into pediatric practice will require dedicated pharmacokinetic studies, standardized biofilm diagnostics, and prospective clinical trials. Full article
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18 pages, 5887 KB  
Article
Analysis of CNN-Based Deep Learning Architectures and Performance Enhancement Strategies for Pneumonia Classification Using Chest X-Ray Images
by YongJun Kim and Ji-Yeoun Lee
BioMedInformatics 2026, 6(4), 59; https://doi.org/10.3390/biomedinformatics6040059 - 13 Aug 2026
Viewed by 315
Abstract
Background: Deep learning models, particularly convolutional neural networks (CNNs), have shown promising performance for pneumonia detection using chest X-ray images. However, the impact of preprocessing, architecture selection, data augmentation, and ensemble strategies has not been systematically evaluated. This study investigated how these factors [...] Read more.
Background: Deep learning models, particularly convolutional neural networks (CNNs), have shown promising performance for pneumonia detection using chest X-ray images. However, the impact of preprocessing, architecture selection, data augmentation, and ensemble strategies has not been systematically evaluated. This study investigated how these factors affect model robustness and diagnostic performance. Methods: A public pediatric chest X-ray dataset was used to systematically evaluate pixel normalization methods, six CNN architectures, progressive data augmentation strategies for class imbalance, and both feature-level and decision-level ensemble approaches. Model performance was assessed by considering not only overall classification accuracy but also clinically relevant risk metrics, particularly false-negative rates. Results: Pixel normalization to the 0–1 range improved model convergence, while Xception and InceptionV3 achieved the best overall performance. Model-specific augmentation strategies were more effective than a fixed 1:1 class ratio for reducing false negatives. Feature-level ensembles tended to overfit, whereas decision-level ensembles provided more stable but only modest performance improvements. Conclusions: These findings demonstrate that reliable medical AI systems require systematic optimization of preprocessing techniques, model architecture, data augmentation strategies, and clinically meaningful evaluation metrics rather than maximizing a single performance indicator. The proposed framework provides practical guidelines for developing robust deep learning models for pneumonia diagnosis in clinical settings. Full article
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31 pages, 410 KB  
Review
Systemic Corticosteroids in Pediatric Community-Acquired Pneumonia: Evidence, Clinical Outcomes, and Phenotype-Based Therapeutic Considerations
by Marco Masetti, Giulia Zambelli, Sonia Rasmi, Elena Rossini, Salvatore Davide Tramonti, Mandy Ferrocino, Valentina Fainardi and Susanna Esposito
Pharmaceuticals 2026, 19(8), 1253; https://doi.org/10.3390/ph19081253 - 9 Aug 2026
Viewed by 432
Abstract
Background: Community-acquired pneumonia (CAP) remains a leading cause of pediatric morbidity and mortality worldwide, particularly in low-resource settings. Although antimicrobial therapy is the cornerstone of treatment, disease severity is often influenced not only by pathogen burden but also by dysregulated host inflammation. [...] Read more.
Background: Community-acquired pneumonia (CAP) remains a leading cause of pediatric morbidity and mortality worldwide, particularly in low-resource settings. Although antimicrobial therapy is the cornerstone of treatment, disease severity is often influenced not only by pathogen burden but also by dysregulated host inflammation. Systemic corticosteroids have therefore been investigated as adjunctive agents to reduce inflammation-mediated lung injury, but their role in children remains controversial. Methods: This narrative review summarizes current evidence on systemic corticosteroid use in pediatric pneumonia. The review focuses on biological mechanisms, clinical indications, patient selection, therapeutic regimens, timing and duration of therapy, clinical outcomes, and safety. Particular attention is given to severe CAP, Mycoplasma pneumoniae pneumonia, complicated pneumonia with parapneumonic effusion or empyema, viral pneumonia, wheezing-associated phenotypes, and immunocompromised children. Results: Available evidence suggests that corticosteroids may provide benefit in selected pediatric phenotypes characterized by severe inflammation, respiratory compromise, refractory disease, or airway hyperreactivity. Reported benefits include faster fever resolution, reduction in inflammatory markers, shorter hospital stay, more rapid clinical stabilization, and improved radiographic recovery, particularly in severe or refractory Mycoplasma pneumoniae pneumonia and selected complicated cases. However, findings are inconsistent, and treatment effects appear strongly dependent on etiology, disease severity, timing of administration, corticosteroid regimen, and patient phenotype. Routine use in uncomplicated CAP or unselected pediatric populations is not supported. Potential adverse effects include hyperglycemia, gastrointestinal and neurobehavioral symptoms, sleep disturbance, immunosuppression with an increased risk of secondary infection, delayed viral clearance in selected viral infections, and possible masking of inadequate anti-infective response or evolving complications. Conclusions: Current evidence supports a cautious, individualized, phenotype-driven approach to corticosteroid therapy in pediatric CAP. Well-designed pediatric randomized controlled trials are needed to define precise indications, optimal regimens, timing, and long-term safety. Full article
(This article belongs to the Special Issue Pediatric Drug Therapy: Safety, Efficacy, and Personalized Medicine)
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12 pages, 214 KB  
Article
Residual Disparities in US Children Hospitalized Due to All-Cause Pneumonia Following Implementation of Childhood PCV13 in National Immunization Program
by Mark H. Rozenbaum, Ahuva Averin, Derek Weycker, Rotem Lapidot, Amanda Miles, Maria J. Tort, Jeffrey Vietri, Alexander Lonshteyn and Stephen I. Pelton
Vaccines 2026, 14(8), 679; https://doi.org/10.3390/vaccines14080679 - 6 Aug 2026
Viewed by 365
Abstract
Background/Objectives: Pneumonia is a leading cause of hospitalization among children in the United States, with a disproportionate burden in certain racial, socioeconomic, and clinical subgroups. The 13-valent pneumococcal conjugate vaccine (PCV13), introduced in 2010, significantly reduced pneumococcal disease overall, but its effect [...] Read more.
Background/Objectives: Pneumonia is a leading cause of hospitalization among children in the United States, with a disproportionate burden in certain racial, socioeconomic, and clinical subgroups. The 13-valent pneumococcal conjugate vaccine (PCV13), introduced in 2010, significantly reduced pneumococcal disease overall, but its effect on disparities in all-cause hospitalized pneumonia (AC-hPNA) remains unclear. This study evaluated changes in AC-hPNA rates by age, race, comorbidity profile, and household income (HHI) before and after PCV13 implementation. Methods: A retrospective cohort study using Optum’s de-identified Clinformatics® DataMart (2007–2019) included children < 18 years. Rates (per 100,000 person-years) and incidence rate ratios were calculated for four periods: pre-PCV13 (2008–2009), peri-PCV13 (2010–2012), post-PCV13#1 (2013–2016), and post-PCV13#2 (2017–2019). Analyses were stratified by age group and, within each, by race, comorbidity profile (low, at-risk), and HHI. Results: Among 10.1 million children, AC-hPNA rates declined by 51–57% from pre-PCV13 to post-PCV13#2 across all age groups, with the largest reductions in children aged <2 years. Declines occurred across all race, comorbidity, and HHI subgroups; however, rates remained several-fold higher among at-risk children. Persistent disparities were observed among Black children < 2 years, children aged 2–5 years with HHI < $50,000, and children aged 6–17 years with HHI of $50,000–$99,999. Conclusions: Substantial reductions in rates of pediatric AC-hPNA were observed in the period subsequent to the introduction of routine PCV13, yet residual disparities persist among children with comorbidities and select racial and income groups. Targeted strategies are needed to address these gaps. Full article
(This article belongs to the Special Issue Pneumococcal Vaccine and Vaccination)
32 pages, 1311 KB  
Review
Intrapleural Fibrinolytic Therapy in the Management of Pediatric Pleural Empyema: A Narrative Review
by Susanna Esposito, Valentina Fainardi, Gaia Giorgia Arnesano and Nicola Principi
Pharmaceuticals 2026, 19(8), 1207; https://doi.org/10.3390/ph19081207 - 1 Aug 2026
Viewed by 507
Abstract
Background: Pediatric pleural empyema is a major complication of community-acquired pneumonia and remains associated with substantial morbidity despite advances in vaccination, antimicrobial therapy, and supportive care. Intrapleural fibrinolytic therapy has become an important minimally invasive treatment for complicated parapneumonic effusions and empyema, but [...] Read more.
Background: Pediatric pleural empyema is a major complication of community-acquired pneumonia and remains associated with substantial morbidity despite advances in vaccination, antimicrobial therapy, and supportive care. Intrapleural fibrinolytic therapy has become an important minimally invasive treatment for complicated parapneumonic effusions and empyema, but uncertainty persists regarding the optimal fibrinolytic agent, treatment protocols, patient selection, and indications for surgical intervention. Methods: A narrative review of the literature was conducted to summarize current evidence on the use of intrapleural fibrinolytic therapy in pediatric pleural empyema. Experimental studies, randomized controlled trials, observational studies, systematic reviews, meta-analyses, and international clinical practice guidelines were critically reviewed. Particular attention was paid to the biological rationale for fibrinolysis, pharmacological characteristics of available agents, comparative effectiveness with video-assisted thoracoscopic surgery (VATS), practical treatment protocols, safety, and future research priorities. Results: Intrapleural fibrinolysis effectively improves pleural drainage by lysing fibrin septations during the fibrinopurulent stage of empyema and is associated with shorter hospitalization compared with chest-tube drainage alone. Urokinase remains the fibrinolytic agent supported by the highest-quality pediatric randomized evidence, whereas alteplase has demonstrated favorable outcomes in observational studies and randomized comparisons with VATS. Current evidence indicates comparable clinical outcomes between fibrinolysis and primary VATS in appropriately selected children, although fibrinolysis is generally associated with lower treatment costs and avoidance of surgery in most patients. Conventional-dose fibrinolytic therapy has an acceptable safety profile, with clinically significant bleeding reported only rarely. Current pediatric evidence does not support the routine addition of DNase to tissue plasminogen activator. Conclusions: Intrapleural fibrinolytic therapy represents a safe, effective, and minimally invasive first-line treatment for most children with complicated parapneumonic effusions and pleural empyema requiring drainage. Management should be individualized within a multidisciplinary framework, integrating timely diagnosis, image-guided pleural drainage, appropriate antimicrobial therapy, and selective surgical intervention. Future multicenter studies are needed to optimize fibrinolytic protocols, validate predictive biomarkers, and further standardize clinical management. Full article
(This article belongs to the Special Issue Pediatric Drug Therapy: Safety, Efficacy, and Personalized Medicine)
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19 pages, 6171 KB  
Article
High-Dimensional Immune Profiling Reveals Innate-Adaptive Rebalancing and Subpopulation Trajectories in Pediatric Severe Mycoplasma pneumoniae Pneumonia
by Chen Shen, Deze Li, Xiaotong Wang, Yang Sun, Huiwen Zheng, Hao Chen, Xin Ni and Shunying Zhao
Diagnostics 2026, 16(15), 2429; https://doi.org/10.3390/diagnostics16152429 - 31 Jul 2026
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Abstract
Background: Severe Mycoplasma pneumoniae pneumonia (SMPP) presents with heterogeneous clinical complications and imaging manifestations, including pleural effusion (PE), bronchiolitis obliterans (BO), and distinct imaging/bronchoscopic phenotypes. The precise systemic immune subpopulation dynamics underlying these distinct phenotypes remain poorly defined. Methods: We conducted [...] Read more.
Background: Severe Mycoplasma pneumoniae pneumonia (SMPP) presents with heterogeneous clinical complications and imaging manifestations, including pleural effusion (PE), bronchiolitis obliterans (BO), and distinct imaging/bronchoscopic phenotypes. The precise systemic immune subpopulation dynamics underlying these distinct phenotypes remain poorly defined. Methods: We conducted flow cytometric profiling of peripheral blood mononuclear cells (PBMCs) from pediatric patients to compare mild MPP (MMPP-N) and severe MPP subtypes. SMPP patients were stratified into subgroups including those with BO (SMPP&BO, n = 3), PE (SMPP&PE), and three imaging/bronchoscopic phenotypes: Group A (SMPP-GA, mucous plugs), Group B (SMPP-GB, mucosal necrosis), and Group C (SMPP-GC, diffuse bronchiolitis). Composite immune indices and multi-marker discriminant analysis were constructed for secondary analysis. Results: Comprehensive high-dimensional profiling suggested that a fundamental innate-adaptive immune rebalancing may represent a key pathophysiological axis in severe disease. Patients with PE exhibited massive CD16 monocyte expansion (Delta = 40.0%) coupled with CD8+ Teff collapse (Delta = −9.2%). Preliminary data also suggest BO may be marked by CD56CD11C+ monocyte depletion (Delta = −23.1%, n = 3), warranting further validation. Imaging subgroup profiling revealed that SMPP-GC featured major B-cell maturation alterations (HLADR+CD45RAhigh expansion and CD38+CD25low depletion). Composite indices including the Adaptive Exhaustion Score suggested discriminatory power (AUC = 0.90 for PE vs. uncomplicated SMPP). The Innate-Adaptive Ratio increased progressively with severity (Spearman rho = +0.40, p = 0.0002). Conclusions: SMPP is not immunologically uniform. Innate-adaptive rebalancing underlies complication-specific phenotypes: inflammatory monocyte mobilization with adaptive exhaustion is strongly associated with PE, whereas B-cell maturation alterations characterize diffuse bronchiolitis. These findings identify potential biomarker candidates for patient stratification, though small-cohort observations require extensive validation in larger prospective studies. Full article
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23 pages, 4133 KB  
Article
Integrating Local and Global Representation Learning for Pediatric Pneumonia Detection: A Hybrid CNN–Transformer Ensemble Framework
by Ece Meltem Yalçın, Hayriye Tanyıldız, Serpil Aslan, Mustafa Yıldız, Damla Ağaçkıran and Gül Fidan
Diagnostics 2026, 16(15), 2399; https://doi.org/10.3390/diagnostics16152399 - 30 Jul 2026
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Abstract
Background/Objectives: Pneumonia remains a leading cause of childhood morbidity and mortality worldwide. Accurate interpretation of pediatric chest radiographs is challenging because of anatomical variability, subtle radiographic findings, and inter-observer variability. This study evaluates different CNN–Transformer ensemble strategies for pediatric pneumonia detection by [...] Read more.
Background/Objectives: Pneumonia remains a leading cause of childhood morbidity and mortality worldwide. Accurate interpretation of pediatric chest radiographs is challenging because of anatomical variability, subtle radiographic findings, and inter-observer variability. This study evaluates different CNN–Transformer ensemble strategies for pediatric pneumonia detection by combining complementary local and global image representations. Methods: Experiments were conducted on the publicly available Pediatric Pneumonia Chest X-ray dataset containing 5856 radiographs. EfficientNetV2-S was used to extract local features, whereas Swin Transformer-T modeled global anatomical relationships. Soft voting, weighted voting, and stacking were evaluated under a unified training protocol. Image preprocessing, data augmentation, and Weighted Random Sampling were applied to improve robustness and address class imbalance. Performance was assessed using an independent hold-out test set and five-fold cross-validation. Grad-CAM was used to interpret model predictions. Results: Ensemble learning improved classification performance compared with individual models while revealing different trade-offs among fusion strategies. The Soft Ensemble achieved the highest hold-out accuracy (96.96%) and F1-score (97.59%). The Hybrid CNN–Transformer Stacking model achieved the highest sensitivity (99.49%) and produced the fewest false-negative predictions (n = 2), while demonstrating the most consistent performance across five-fold cross-validation. Grad-CAM visualizations indicated that the CNN and Transformer models captured complementary radiographic information. Conclusions: The proposed framework demonstrates that different ensemble strategies offer distinct advantages. Soft voting provided the best overall hold-out performance, whereas stacking minimized false-negative predictions and achieved the highest sensitivity, indicating its potential for AI-assisted pediatric pneumonia screening. Full article
(This article belongs to the Special Issue Artificial Intelligence for Health and Medicine—2nd Edition)
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12 pages, 935 KB  
Article
Analysis of Clinical Indicators in Pediatric Patients with Acinetobacter baumannii and Klebsiella pneumoniae Infections
by Yiyao Bao, Lingling Dai, Mingming Zhou and Chao Tang
J. Clin. Med. 2026, 15(15), 5914; https://doi.org/10.3390/jcm15155914 - 29 Jul 2026
Viewed by 282
Abstract
Background: Acinetobacter baumannii and Klebsiella pneumoniae are important causes of hospital-acquired infections in pediatric patients, but comparative data on their clinical manifestations and inflammatory biomarkers remain limited. Methods: We retrospectively analyzed 55 children with single-positive blood cultures for A. baumannii (n [...] Read more.
Background: Acinetobacter baumannii and Klebsiella pneumoniae are important causes of hospital-acquired infections in pediatric patients, but comparative data on their clinical manifestations and inflammatory biomarkers remain limited. Methods: We retrospectively analyzed 55 children with single-positive blood cultures for A. baumannii (n = 20) or K. pneumoniae (n = 35), together with 30 healthy controls. Results: CRP, IL-6, and IL-10 were higher in infected children than in healthy controls. Logistic regression identified CRP and the IL-6/IL-10 ratio as exploratory correlates of infection. In ROC analyses distinguishing infected children from healthy controls, IL-6 showed the highest AUC, followed by IL-10 and CRP. In pathogen-level analyses, the IL-6/IL-10 ratio and lipase showed exploratory discriminatory signals. Conclusions: In this small retrospective case–control cohort, CRP, IL-6, and IL-10 were associated with microbiologically confirmed infection. Lipase may represent a potential biomarker for differentiating A. baumannii from K. pneumoniae infection, but its clinical utility requires prospective validation in larger multicenter cohorts using clinically relevant inpatient control groups. Full article
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