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16 pages, 1758 KiB  
Case Report
3D Printing Today, AI Tomorrow: Rethinking Apert Syndrome Surgery in Low-Resource Settings
by Maria Bajwa, Mustafa Pasha and Zafar Bajwa
Healthcare 2025, 13(15), 1844; https://doi.org/10.3390/healthcare13151844 - 29 Jul 2025
Viewed by 230
Abstract
Background/Objectives: This case study presents the first documented use of a low-cost, simulated, patient-specific three-dimensional (3D) printed model to support presurgical planning for an infant with Apert syndrome in a resource-limited setting. The primary objectives are to (1) demonstrate the value of 3D [...] Read more.
Background/Objectives: This case study presents the first documented use of a low-cost, simulated, patient-specific three-dimensional (3D) printed model to support presurgical planning for an infant with Apert syndrome in a resource-limited setting. The primary objectives are to (1) demonstrate the value of 3D printing as a simulation tool for preoperative planning in low-resource environments and (2) identify opportunities for future AI-enhanced simulation models in craniofacial surgical planning. Methods: High-resolution CT data were segmented using InVesalius 3, with mesh refinement performed in ANSYS SpaceClaim (version 2021). The cranial model was fabricated using fused deposition modeling (FDM) on a Creality Ender-3 printer with Acrylonitrile Butadiene Styrene (ABS) filament. Results: The resulting 3D-printed simulated model enabled the surgical team to assess cranial anatomy, simulate incision placement, and rehearse osteotomies. These steps contributed to a reduction in operative time and fewer complications during surgery. Conclusions: This case demonstrates the value of accessible 3D printing as a simulation tool in surgical planning within low-resource settings. Building on this success, the study highlights potential points for AI integration, such as automated image segmentation and model reconstruction, to increase efficiency and scalability in future 3D-printed simulation models. Full article
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15 pages, 9369 KiB  
Review
Pediatric Congenital Lung Malformation: Advanced Imaging Techniques in Pre- and Neonatal Evaluation
by Gabriele Masselli, Chiara Di Bella, George Hadjidekov, Carlos Carnelli, Francesco Morini, Silvia Ceccanti, Fabio Midulla and Denis A. Cozzi
Diagnostics 2025, 15(9), 1112; https://doi.org/10.3390/diagnostics15091112 - 27 Apr 2025
Viewed by 512
Abstract
Pediatric congenital lung malformations (CLMs) comprise a spectrum of developmental anomalies of lung parenchyma, airways, and vasculature. CLMs are increasingly diagnosed prenatally but remain best characterized by postnatal cross-sectional imaging. During pregnancy, ultrasound (US) and fetal magnetic resonance imaging (MRI) are commonly used [...] Read more.
Pediatric congenital lung malformations (CLMs) comprise a spectrum of developmental anomalies of lung parenchyma, airways, and vasculature. CLMs are increasingly diagnosed prenatally but remain best characterized by postnatal cross-sectional imaging. During pregnancy, ultrasound (US) and fetal magnetic resonance imaging (MRI) are commonly used to monitor lung lesions. Management of CLMs, including imaging, in infants and young children depends on associated symptoms and institutional standards. Chest CT angiography (CTA) is usually the most appropriate initial postnatal imaging modality for assessing prenatally diagnosed or clinically suspected CLMs in asymptomatic infants and children. Magnetic resonance (MR) imaging/magnetic resonance angiography (MRA) may be considered as a complementary, problem-solving, imaging modality for evaluation of CLMs during fetal and neonatal periods. This article presents contemporary perspectives on the imaging approach to pediatric patients with suspected CLMs and reviews up-to-date radiologic findings and clinical characteristics of CLMs. Full article
(This article belongs to the Special Issue Advances in Gynecological and Pediatric Imaging)
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13 pages, 578 KiB  
Article
From Warm to Cold: Feeding Cold Milk to Preterm Infants with Uncoordinated Oral Feeding Patterns
by Louisa Ferrara-Gonzalez, Ranjith Kamity, Zeyar Htun, Vikramaditya Dumpa, Shahidul Islam and Nazeeh Hanna
Nutrients 2025, 17(9), 1457; https://doi.org/10.3390/nu17091457 - 26 Apr 2025
Cited by 1 | Viewed by 856
Abstract
Background/Objectives: Premature infants frequently experience feeding difficulties due to the disrupted coordination of sucking, swallowing, and breathing, increasing the risk of airway compromise. In adults with dysphagia, cold liquids can enhance swallowing by stimulating sensory receptors in the pharyngeal mucosa. We previously [...] Read more.
Background/Objectives: Premature infants frequently experience feeding difficulties due to the disrupted coordination of sucking, swallowing, and breathing, increasing the risk of airway compromise. In adults with dysphagia, cold liquids can enhance swallowing by stimulating sensory receptors in the pharyngeal mucosa. We previously demonstrated that short-duration feeding with cold liquid significantly reduces dysphagia in preterm infants; however, the impact of an entire feeding with cold milk remains unexplored. This study aimed to evaluate the safety of cold milk feedings in preterm infants with uncoordinated feeding patterns and their impact on their feeding performance. Methods: Preterm infants with uncoordinated feeding patterns (n = 26) were randomized to be fed milk at either room temperature (RT) or cold temperature (CT) using an experimental, randomized crossover design. We monitored axillary and gastric content temperatures, mesenteric blood flow, and feeding performance. Results: There were no significant differences in mesenteric blood flow Doppler measurements or axillary body temperatures between the CT and RT feeding conditions. However, a reduction in gastric content temperatures of 3.6 °F and 2.7 °F was observed at one and thirty minutes following CT feeding, respectively. No evidence of cold stress, increased episodes of apnea or bradycardia, gastric residuals, or emesis was noted in infants during or after the CT feeding condition. Feeding performance outcomes did not differ significantly regarding milk transfer rate (p = 0.781) or proficiency (p = 0.425). However, the quality score on the Infant-Driven Feeding Scale (IDFS) showed a significant improvement following CT feeding (p = 0.001). Conclusions: Cold milk feeding can be a safe therapeutic option for preterm infants. This underscores the potential for further comprehensive investigations to evaluate cold milk feeding as an effective therapeutic strategy for managing feeding and swallowing difficulties in preterm infants. The study was registered at clinicaltrials.org under #NCT04421482. Full article
15 pages, 429 KiB  
Article
Computed Tomography Findings of Children Under 3 Years of Age with Mild Traumatic Brain Injury (TBI) and No Neurological Focal Signs
by Ksenija Markovic, Goran Djuricic, Djordje Milojkovic, Dusan Banovac, Kristina Davidovic, Dragan Vasin, Jelena Sisevic, Slavisa Zagorac, Boris Gluscevic, Dejan Bokonjic, Vuk Djulejic and Natasa Milic
J. Clin. Med. 2025, 14(8), 2728; https://doi.org/10.3390/jcm14082728 - 16 Apr 2025
Viewed by 730
Abstract
Background/Objectives: Mild traumatic brain injury (mTBI) is a leading cause of pediatric emergency department visits, particularly among children under three years old. Although computed tomography (CT) is the gold standard for diagnosing intracranial injuries, its use in young children poses radiation risks. [...] Read more.
Background/Objectives: Mild traumatic brain injury (mTBI) is a leading cause of pediatric emergency department visits, particularly among children under three years old. Although computed tomography (CT) is the gold standard for diagnosing intracranial injuries, its use in young children poses radiation risks. Identifying reliable clinical indicators that justify CT imaging is essential for optimizing both patient safety and resource utilization. Objective: This study aimed to evaluate CT findings in children under three years of age with mTBI and no focal neurological deficits, as well as to identify clinical predictors associated with skull fractures and intracranial injuries. Methods: A retrospective analysis was conducted on 224 children under 36 months who presented with mTBI to a tertiary pediatric hospital from July 2019 to July 2024. Demographic data, injury mechanisms, clinical presentation and CT findings were evaluated. Univariate and multivariate regression analyses were performed to identify risk factors associated with skull fractures and intracranial injuries. Results: Falls accounted for 96.4% of injuries, with the majority occurring from heights of 0.5–1 m. The parietal region was the most frequently affected site (38%). Skull fractures were present in 46% of cases and were primarily linear (92.8%). Intracranial hematomas were identified in 13.8% of cases, while brain edema was observed in 7.6%. Significant predictors of skull fractures included age under 12 months (p < 0.001), falls from 0.5–1 m (p = 0.005), somnolence (p = 0.030), scalp swelling (p = 0.001) and indentation of the scalp (p = 0.016). Parietal bone involvement was the strongest predictor of both skull fractures (OR = 7.116, p < 0.001) and intracranial hematomas (OR = 4.993, p < 0.001). Conversely, frontal bone involvement was associated with a lower likelihood of fractures and hematomas. Conclusions: The findings highlight key clinical indicators that can guide decision-making for CT imaging in children with mTBI. Infants under 12 months, falls from moderate heights and parietal bone involvement significantly increase the risk of fractures and intracranial injuries. A more refined diagnostic approach could help reduce unnecessary CT scans while ensuring the timely identification of clinically significant injuries. Full article
(This article belongs to the Section Brain Injury)
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23 pages, 3275 KiB  
Review
The Evaluation, Diagnosis, and Management of Ovarian Cysts, Masses, and Their Complications in Fetuses, Infants, Children, and Adolescents
by Marko Bašković, Dubravko Habek, Luca Zaninović, Ivan Milas and Zenon Pogorelić
Healthcare 2025, 13(7), 775; https://doi.org/10.3390/healthcare13070775 - 31 Mar 2025
Cited by 1 | Viewed by 3624
Abstract
The majority of abdominal masses in female children derive from the ovaries. Ovarian masses in pediatric populations can vary from simple functional cysts to malignant neoplasms. Their incidence, clinical presentation, and histological distribution vary across age groups. In the assessment of ovarian masses [...] Read more.
The majority of abdominal masses in female children derive from the ovaries. Ovarian masses in pediatric populations can vary from simple functional cysts to malignant neoplasms. Their incidence, clinical presentation, and histological distribution vary across age groups. In the assessment of ovarian masses in children, the primary aim is to determine the probability of malignancy, as the treatment approaches for benign and malignant lesions are significantly distinct. The primary imaging tool for evaluating ovarian cysts and masses is ultrasound, which can assess the size, location, and characteristics of masses. Magnetic resonance imaging (MRI) or computed tomography (CT) may be used for further evaluation if ultrasound findings are inconclusive or if malignancy is suspected, especially in older adolescents. Serum markers may be considered in older adolescents to help assess the risk of malignancy, though it is less useful in younger populations due to normal developmental variations. Many functional ovarian cysts, especially those detected in fetuses or infants, often resolve spontaneously without intervention. Surgical intervention is indicated in cases of large cysts that cause symptoms, or if there are concerns for malignancy. Common procedures include primarily ovarian sparing laparoscopy or laparotomy. Complications like torsion, rupture, or hemorrhage may require urgent surgical intervention. Treatment should be performed in specialized centers to avoid unnecessary oophorectomies and ensure the best possible outcome for the patient. This comprehensive review aims to provide an overview of the evaluation, diagnosis, and treatment of ovarian masses in the pediatric population. Emphasis is placed on the particularities of the lesions and their management in relation to age subgroups. Full article
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13 pages, 2232 KiB  
Article
The Orthopedic Strategy for Patients with Larsen Syndrome
by Ali Al Kaissi, Alexander Gubin, Sergey Ryabykh, Vasileios Dougales, Hamza Al Kaissi, Susanne Gerit Kircher and Franz Grill
Surg. Tech. Dev. 2025, 14(2), 10; https://doi.org/10.3390/std14020010 - 25 Mar 2025
Viewed by 565
Abstract
Background: Facial features are the first basic sign of medical knowledge of children and adults with congenital malformations. Children born with multiple contractures almost always receive the misdiagnosis of arthrogryposis multiplex. Larsen syndrome can easily be diagnosed at birth via the proper interpretations [...] Read more.
Background: Facial features are the first basic sign of medical knowledge of children and adults with congenital malformations. Children born with multiple contractures almost always receive the misdiagnosis of arthrogryposis multiplex. Larsen syndrome can easily be diagnosed at birth via the proper interpretations of its characteristic facial features and multiple dislocations. Comprehensive clinical diagnosis can facilitate an orthopedic strategy for early treatment and can enhance the recognition of unreported craniocervical malformation complexes. Material and Methods: Six children (four boys and two girls, with ages ranging from a few months to 7 years old) were referred to our department for diagnosis and treatment. All children received their first misdiagnosis by the pediatricians as manifesting arthrogryposis multiplex congenita. The clinical phenotype was our first decisive tool for diagnosis. All children exhibited the classical phenotype of dish-like facies associated with multiple joint dislocations. Radiological phenotypic characteristics confirmed our clinical diagnosis of Larsen syndrome. Three children out of six showed unpleasant cervical spine deformities. The first child, a 2-year-old, became tetraplegic after minor trauma. One child presented with progressive rigid cervical kyphosis. The third child was a product of a first-relative marriage and was born with congenital tetraplegia. A genotype was carried out for confirmation. Results: Three children underwent open reduction for congenital hip and knee dislocations. One child underwent spinal fusion CO-C7 because of tetraplegia. A 3D-reformatted and reconstruction CT scan of the craniocervical junction showed two forms of unusual dys-segmentation, firstly along C2-3 effectively causing the development of acute-angle cervical kyphosis. Secondly, an infant with congenital tetraplegia showed a serious previously undescribed atlanto–axial malformation complex. Namely, atlanto–axial maldevelopment (dys-segmentation) of (C1/C2) was associated with hypoplasia of the anterior and the posterior rings of the atlas. Genetic tests of these children were compatible with the autosomal dominant type of Larsen syndrome and manifested a heterozygous mutation in FLNB mapped 3p14.3, encoding an actin-binding protein, filamin B. The child with congenital tetraplegia showed no mutations in FLNB, though his clinical and radiological phenotype and his family history of first-relative marriage were totally compatible with the diagnosis of the autosomal recessive type of Larsen syndrome. Conclusions: Our strategy was and still is based on a coherent clinical and radiological diagnosis, which is based on comprehensive clinical and radiological phenotypic characterizations. We implemented a 3D-reformatted CT scan to further understand the craniocervical junction pathology in three children. Strikingly, prenatal onset of lethal maldevelopment (dys-segmentation) of the atlanto–axial spine segments has been diagnosed in an infant with congenital tetraplagia. A less serious cervical spine malformation was detected in two children who presented with progressive acute-angle cervico and cervico-thoracic kyphosis. Our clinical strategy can form the basis for a thorough clinical assessment for infants and children born with multiple malformation complexes and can lead to recognition of novel understandings. Full article
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18 pages, 3085 KiB  
Article
Whole-Exome Sequencing Identifies Novel GATA5/6 Variants in Right-Sided Congenital Heart Defects
by Gloria K. E. Zodanu, John H. Hwang, Jordan Mudery, Carlos Sisniega, Xuedong Kang, Lee-Kai Wang, Alexander Barsegian, Reshma M. Biniwale, Ming-Sing Si, Nancy J. Halnon, UCLA Congenital Heart Defects-BioCore Faculty, Wayne W. Grody, Gary M. Satou, Glen S. Van Arsdell, Stanly F. Nelson and Marlin Touma
Int. J. Mol. Sci. 2025, 26(5), 2115; https://doi.org/10.3390/ijms26052115 - 27 Feb 2025
Viewed by 1194
Abstract
One out of every hundred live births present with congenital heart abnormalities caused by the aberrant development of the embryonic cardiovascular system. The conserved zinc finger transcription factor proteins, which include GATA binding protein 5 (GATA5) and GATA binding protein (GATA6) play important [...] Read more.
One out of every hundred live births present with congenital heart abnormalities caused by the aberrant development of the embryonic cardiovascular system. The conserved zinc finger transcription factor proteins, which include GATA binding protein 5 (GATA5) and GATA binding protein (GATA6) play important roles in embryonic development and their inactivation may result in congenital heart defects (CHDs). In this study, we performed genotypic–phenotypic analyses in two families affected by right-sided CHD diagnosed by echocardiography imaging. Proband A presented with pulmonary valve stenosis, and proband B presented with complex CHD involving the right heart structures. For variant detection, we employed whole-genome single-nucleotide polymorphism (SNP) microarray and family-based whole-exome sequencing (WES) studies. Proband A is a full-term infant who was admitted to the neonatal intensive care unit (NICU) at five days of life for pulmonary valve stenosis (PVS). Genomic studies revealed a normal SNP microarray; however, quad WES analysis identified a novel heterozygous [Chr20:g.61041597C>G (p.Arg237Pro)] variant in the GATA5 gene. Further analysis confirmed that the novel variant was inherited from the mother but was absent in the father and the maternal uncle with a history of heart murmur. Proband B was born prematurely at 35 weeks gestation with a prenatally diagnosed complex CHD. A postnatal evaluation revealed right-sided heart defects including pulmonary atresia with intact ventricular septum (PA/IVS), right ventricular hypoplasia, tricuspid valve hypoplasia, hypoplastic main and bilateral branch pulmonary arteries, and possible coronary sinusoids. Cardiac catheterization yielded anatomy and hemodynamics unfavorable to repair. Hence, heart transplantation was indicated. Upon genomic testing, a normal SNP microarray was observed, while trio WES analysis identified a novel heterozygous [Chr18:c.1757C>T (p.Pro586Leu)] variant in the GATA6 gene. This variant was inherited from the father, who carries a clinical diagnosis of tetralogy of Fallot. These findings provide new insights into novel GATA5/6 variants, elaborate on the genotypic and phenotypic association, and highlight the critical role of GATA5 and GATA6 transcription factors in a wide spectrum of right-sided CHDs. Full article
(This article belongs to the Special Issue Genetic Variations in Human Diseases: 2nd Edition)
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13 pages, 655 KiB  
Article
Pharmacokinetic Analysis of an Isoniazid Suspension Among Spanish Children Under 6 Years of Age
by Antoni Noguera-Julian, Emma Wilhelmi, Maria Cussó, Rob Aarnoutse, Angela Colbers, Loreto Martorell, Maria Goretti López-Ramos, Joan Vinent, Rosa Farré, Dolors Soy, Sílvia Simó-Nebot and Clàudia Fortuny
Antibiotics 2025, 14(1), 74; https://doi.org/10.3390/antibiotics14010074 - 12 Jan 2025
Viewed by 929
Abstract
Background: Isoniazid (INH) remains a first-line drug for the treatment of tuberculosis (TB) in young children. In 2010, the WHO recommended an increase in the daily dose of INH up to 10 (7–15) mg/kg. Currently, there are no INH suspensions available in [...] Read more.
Background: Isoniazid (INH) remains a first-line drug for the treatment of tuberculosis (TB) in young children. In 2010, the WHO recommended an increase in the daily dose of INH up to 10 (7–15) mg/kg. Currently, there are no INH suspensions available in Europe. Methods: We aimed to characterize the pharmacokinetics of a licensed INH suspension (10 mg/mL, Pharmascience Inc., Montreal, QC, Canada) in children receiving INH daily at 10 mg/kg in a single-center, open-label, non-randomized, phase IIa clinical trial (EudraCT Number: 2016-002000-31) in Barcelona (Spain). Samples were analyzed using a validated UPLC-UV assay. The N-acetyltransferase 2 gene was examined to determine the acetylation status. A non-compartmental pharmacokinetic analysis was conducted. Results: Twenty-four patients (12 females) were included (primary chemoprophylaxis, n = 12; TB treatment, n = 9; and TB infection preventive treatment, n = 3). The acetylator statuses were homozygous fast (n = 3), heterozygous intermediate (n = 18), and homozygous slow (n = 2; unavailable in one patient). The INH median (IQR) Cmax and AUC0–24h values were 6.1 (4.5–8.2) mg/L and 23.0 (11.2–35.4) h∙mg/L; adult targets (>3 mg/L and 11.6–26.3 h∙mg/L) were not achieved in three and six cases, respectively. Gender, age at assessment (<2 or >2 years), and INH monotherapy (vs. combined TB treatment) had no impact on pharmacokinetic parameters. Significant differences in Cmax (p = 0.030) and AUC0–24h (p = 0.011) values were observed based on acetylator status. Treatment was well tolerated, and no severe adverse events were observed; three patients developed asymptomatic mildly elevated alanine aminotransferase levels. Conclusions: In infants and children receiving a daily INH suspension at 10 mg/kg, no safety concerns were raised, and the target adult levels were reached in the majority of patients. Full article
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9 pages, 969 KiB  
Case Report
Successful Pregnancy Outcome in a Patient Treated with Pembrolizumab and Exposed to Fluoro-Deoxyglucose (18F-FDG) PET/CT: Case Report and Review of Literature
by Anna Lucia Mastricci, Felice Sorrentino, Elisa Giansiracusa, Erika Zanzarelli, Graziana Silvana De Lucia, Vincenza Fernanda Fesce, Luigi Nappi and Lorenzo Vasciaveo
Biomedicines 2025, 13(1), 140; https://doi.org/10.3390/biomedicines13010140 - 9 Jan 2025
Viewed by 1070
Abstract
Background: Hodgkin lymphoma (HL) is a common malignancy among women of reproductive age. Some pregnancies occur during oncological treatments or diagnostic follow-ups, often involving contraindicated procedures. HL is fluorodeoxyglucose-avid; therefore, its staging is generally performed with 18F-FDG PET/CT, a diagnostic method contraindicated [...] Read more.
Background: Hodgkin lymphoma (HL) is a common malignancy among women of reproductive age. Some pregnancies occur during oncological treatments or diagnostic follow-ups, often involving contraindicated procedures. HL is fluorodeoxyglucose-avid; therefore, its staging is generally performed with 18F-FDG PET/CT, a diagnostic method contraindicated during pregnancy. Immune checkpoint inhibitors (ICIs), such as pembrolizumab, are innovative therapies for relapsed HL (rHL) with significant efficacy. However, ICIs can impair immune tolerance, potentially increasing immune-related adverse events. The PD-1/PD-L1 pathway, targeted by pembrolizumab, plays a critical role in maternal–fetal immune adaptation, raising concerns about its safety during pregnancy. Case Report: We report the case of a 36-year-old woman diagnosed with rHL who unknowingly became pregnant during treatment with pembrolizumab and 18F-FDG PET/CT scans. The pregnancy was diagnosed at 24 weeks, after five cycles of pembrolizumab during the first two trimesters and an 18F-FDG PET/CT scan in the first trimester. Following multidisciplinary counseling, the pregnancy was closely monitored, culminating in the delivery of a healthy male infant at 37.5 weeks. Conclusions: This case highlights a favorable maternal–fetal outcome despite exposure to pembrolizumab and 18F-FDG PET/CT during pregnancy. Given the limited data on such exposures, case reports like this are essential for improving counseling and management strategies. Further research and registries are crucial to provide robust evidence for clinical decision-making in these complex scenarios. Full article
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12 pages, 517 KiB  
Study Protocol
Safety, Tolerability, and Immunogenicity of the InvaplexAR-Detox Shigella Vaccine Co-Administered with the dmLT Adjuvant in Dutch and Zambian Adults: Study Protocol for a Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Phase Ia/b Clinical Trial
by Geert V. T. Roozen, Nsofwa Sukwa, Masuzyo Chirwa, Jessica A. White, Marcus Estrada, Nicole Maier, Kevin R. Turbyfill, Renee M. Laird, Akamol E. Suvarnapunya, Aicha Sayeh, Flavia D’Alessio, Candice Marion, Laura Pattacini, Marie-Astrid Hoogerwerf, Rajagopal Murugan, Manuela Terrinoni, Jan R. Holmgren, Sodiomon B. Sirima, Sophie Houard, Michelo Simuyandi and Meta Roestenbergadd Show full author list remove Hide full author list
Vaccines 2025, 13(1), 48; https://doi.org/10.3390/vaccines13010048 - 8 Jan 2025
Cited by 2 | Viewed by 1423
Abstract
Background: Shigella infections remain endemic in places with poor sanitation and are a leading cause of diarrheal mortality globally, as well as a major contributor to gut enteropathy and stunting. There are currently no licensed vaccines for shigellosis but it has been estimated [...] Read more.
Background: Shigella infections remain endemic in places with poor sanitation and are a leading cause of diarrheal mortality globally, as well as a major contributor to gut enteropathy and stunting. There are currently no licensed vaccines for shigellosis but it has been estimated that an effective vaccine could avert 590,000 deaths over a 20-year period. A challenge to effective Shigella vaccine development has been the low immunogenicity and protective efficacy of candidate Shigella vaccines in infants and young children. Additionally, a new vaccine might be less immunogenic in a highly endemic setting compared to a low endemic setting (“vaccine hyporesponsiveness”). The use of a potent adjuvant enhancing both mucosal and systemic immunity might overcome these problems. InvaplexAR-Detox is an injectable Shigella vaccine that uses a novel combination of conserved invasion plasmid antigen proteins and a serotype-specific bacterial lipopolysaccharide attenuated for safe intramuscular administration. The adjuvant dmLT has been shown to enhance Shigella immune responses in mice, has safely been administered intramuscularly, and was shown to enhance immune responses in healthy volunteers when given in combination with other antigens in phase I trials. This article describes the protocol of a study that will be the first to assess the safety, tolerability, and immunogenicity of InvaplexAR-Detox co-administered with dmLT in healthy adults in low-endemic and high-endemic settings. Methods: In a multi-center, randomized, double-blind, and placebo-controlled dose-escalation phase Ia/b trial, the safety, tolerability, and immunogenicity of three intramuscular vaccinations administered 4 weeks apart with 2.5 µg or 10 µg of InvaplexAR-Detox vaccine, alone or in combination with 0.1 µg of the dmLT adjuvant, will first be assessed in a total of 50 healthy Dutch adults (phase Ia) and subsequently in 35 healthy Zambian adults (phase Ib) aged 18–50 years. The primary outcome is safety, and secondary outcomes are humoral and cellular immune responses to the adjuvanted or non-adjuvanted vaccine. Discussion: This trial is part of the ShigaPlexIM project that aims to advance the early clinical development of an injectable Shigella vaccine and to make the vaccine available for late-stage clinical development. This trial addresses the issue of hyporesponsiveness in an early stage of clinical development by testing the vaccine and adjuvant in an endemic setting (Zambia) after the first-in-human administration and the dose-escalation has proven safe and tolerable in a low-endemic setting (Netherlands). Besides strengthening the vaccine pipeline against a major diarrheal disease, another goal of the ShigaPlexIM project is to stimulate capacity building and strengthen global North-South relations in clinical research. Trial registration: EU CT number: 2023-506394-35-02, ClinicalTrials.gov identifier: NCT05961059. Full article
(This article belongs to the Special Issue Recent Scientific Advances in Vaccines for Shigella)
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12 pages, 730 KiB  
Article
Macronutrient Intake and Food Categories’ Contribution to Daily Energy Intake According to BMI in Primary School Children in Croatia
by Lidija Šoher, Daniela Čačić Kenjerić, Martina Pavlić, Ivana Rumbak, Nataša Šarlija, Ana Ilić and Darja Sokolić
Nutrients 2024, 16(24), 4400; https://doi.org/10.3390/nu16244400 - 21 Dec 2024
Cited by 1 | Viewed by 1476
Abstract
Background: Nutritional status in childhood is associated with a number of short- and long-term health effects. The rising prevalence of childhood obesity highlights the necessity of understanding dietary patterns in children. The study provides an assessment of energy and macronutrient intake and food [...] Read more.
Background: Nutritional status in childhood is associated with a number of short- and long-term health effects. The rising prevalence of childhood obesity highlights the necessity of understanding dietary patterns in children. The study provides an assessment of energy and macronutrient intake and food categories’ contribution to energy intake in Croatian primary school children, according to BMI status. Methods: To assess dietary habits, results of the National Food Consumption Survey on Infants and Children based on EU Menu methodology (OC/EFSA/DATA/2016/02 CT3) were used. The sample included 476 children, aged 6 to under 10 years. Results: Results indicated that one in four children was overweight or obese (27.7%). In total, the mean energy intake was 1598.4 ± 380.3 kcal/day, with 30.7% of the children above the recommended energy intake. Cereals, cereal products, and potato food category were the primary sources of energy, which is in line with the recommendations, with protein and fat intakes exceeding recommended levels. Substantial contribution of sweets and low contribution of fruits and vegetables were observed across all BMI categories, with the difference in energy contribution of fruits (p = 0.041) and vegetables (p = 0.033). The meat, poultry, fish, and eggs category were the contributors to energy intake from protein and fat, in the majority of BMI groups. Conclusions: In the obese group, higher energy intake from certain food subgroups was recorded, stressing the need for a more detailed dietary assessment. The study’s cross-sectional design limits causal inferences, indicating a need for future longitudinal research to better understand the dynamics of dietary patterns and BMI status in primary school children. Full article
(This article belongs to the Section Pediatric Nutrition)
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13 pages, 266 KiB  
Review
Lung Ultrasound in Neonatal Respiratory Distress Syndrome: A Narrative Review of the Last 10 Years
by Federico Costa, Annachiara Titolo, Mandy Ferrocino, Eleonora Biagi, Valentina Dell’Orto, Serafina Perrone and Susanna Esposito
Diagnostics 2024, 14(24), 2793; https://doi.org/10.3390/diagnostics14242793 (registering DOI) - 12 Dec 2024
Cited by 3 | Viewed by 2256
Abstract
Neonatal respiratory distress syndrome (RDS) is a common and potentially life-threatening condition in preterm infants, primarily due to surfactant deficiency. Early and accurate diagnosis is critical to guide timely interventions such as surfactant administration and respiratory support. Traditionally, chest X-rays have been used [...] Read more.
Neonatal respiratory distress syndrome (RDS) is a common and potentially life-threatening condition in preterm infants, primarily due to surfactant deficiency. Early and accurate diagnosis is critical to guide timely interventions such as surfactant administration and respiratory support. Traditionally, chest X-rays have been used for diagnosis, but lung ultrasound (LUS) has gained prominence due to its non-invasive, radiation-free, and bedside applicability. Compared to chest X-rays and CT scans, LUS demonstrates superior sensitivity and specificity in diagnosing RDS, particularly in identifying surfactant need and predicting CPAP failure. Additionally, LUS offers real-time imaging without radiation exposure, an advantage over other modalities. However, its broader adoption is limited by challenges in standardizing training, ensuring diagnostic reproducibility, and validating scoring systems, especially in resource-limited settings. This narrative review aims to evaluate the role of LUS in the diagnosis and management of neonatal RDS over the past decade, focusing on its clinical utility, scoring systems, and emerging applications. We reviewed the literature from 2013 to 2023, focusing on studies evaluating LUS’ diagnostic accuracy, scoring systems, and its potential role in guiding surfactant therapy and predicting CPAP failure. Despite its benefits, addressing the variability in operator expertise and integrating artificial intelligence to enhance usability are crucial for ensuring LUS’ efficacy across diverse clinical environments. Future research should prioritize standardizing training and scoring protocols to facilitate wider implementation and optimize neonatal respiratory care outcomes. Full article
(This article belongs to the Special Issue Maternal–Fetal and Neonatal Diagnostics)
23 pages, 3021 KiB  
Article
Increased Levels of hsa-miR-199a-3p and hsa-miR-382-5p in Maternal and Neonatal Blood Plasma in the Case of Placenta Accreta Spectrum
by Angelika V. Timofeeva, Ivan S. Fedorov, Anastasia D. Nikonets, Alla M. Tarasova, Ekaterina N. Balashova, Dmitry N. Degtyarev and Gennady T. Sukhikh
Int. J. Mol. Sci. 2024, 25(24), 13309; https://doi.org/10.3390/ijms252413309 - 11 Dec 2024
Cited by 1 | Viewed by 1223
Abstract
Despite the increasing number of placenta accreta spectrum (PAS) cases in recent years, its impact on neonatal outcomes and respiratory morbidity, as well as the underlying pathogenetic mechanism, has not yet been extensively studied. Moreover, no study has yet demonstrated the effectiveness of [...] Read more.
Despite the increasing number of placenta accreta spectrum (PAS) cases in recent years, its impact on neonatal outcomes and respiratory morbidity, as well as the underlying pathogenetic mechanism, has not yet been extensively studied. Moreover, no study has yet demonstrated the effectiveness of antenatal corticosteroid therapy (CT) for the prevention of respiratory distress syndrome (RDS) in newborns of mothers with PAS at the molecular level. In this regard, microRNA (miRNA) profiling by small RNA deep sequencing and quantitative real-time PCR was performed on 160 blood plasma samples from preterm infants (gestational age: 33–36 weeks) and their mothers who had been diagnosed with or without PAS depending on the timing of the antenatal RDS prophylaxis. A significant increase in hsa-miR-199a-3p and hsa-miR-382-5p levels was observed in the blood plasma of the newborns from mothers with PAS compared to the control group. A clear trend toward the normalization of hsa-miR-199a-3p and hsa-miR-382-5p levels in the neonatal blood plasma of the PAS groups was observed when CT was administered within 14 days before delivery, but not beyond 14 days. Direct correlations were found among the hsa-miR-382-5p level in neonatal blood plasma and the hsa-miR-199a-3p level in the same sample (r = 0.49; p < 0.001), the oxygen requirements in the NICU (r = 0.41; p = 0.001), the duration of the NICU stay (r = 0.31; p = 0.019), and the severity of the newborn’s condition based on the NEOMOD scale (r = 0.36; p = 0.005). Logistic regression models based on the maternal plasma levels of hsa-miR-199a-3p and hsa-miR-382-5p predicted the need for cardiotonic therapy, invasive mechanical ventilation, or high-frequency oscillatory ventilation in newborns during the early neonatal period, with a sensitivity of 95–100%. According to the literary data, these miRNAs regulate fetal organogenesis via IGF-1, the formation of proper lung tissue architecture, surfactant synthesis in alveolar cells, and vascular tone. Full article
(This article belongs to the Special Issue The Role of miRNA in Human Diseases)
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15 pages, 2643 KiB  
Article
Patient-Specific Circulating Tumor DNA for Monitoring Response to Menin Inhibitor Treatment in Preclinical Models of Infant Leukemia
by Louise Doculara, Kathryn Evans, J. Justin Gooding, Narges Bayat and Richard B. Lock
Cancers 2024, 16(23), 3990; https://doi.org/10.3390/cancers16233990 - 28 Nov 2024
Viewed by 1090
Abstract
Background: In infant KMT2A (MLL1)-rearranged (MLL-r) acute lymphoblastic leukemia (ALL), early relapse and treatment response are currently monitored through invasive repeated bone marrow (BM) biopsies. Circulating tumor DNA (ctDNA) in peripheral blood (PB) provides a minimally invasive alternative, allowing for more [...] Read more.
Background: In infant KMT2A (MLL1)-rearranged (MLL-r) acute lymphoblastic leukemia (ALL), early relapse and treatment response are currently monitored through invasive repeated bone marrow (BM) biopsies. Circulating tumor DNA (ctDNA) in peripheral blood (PB) provides a minimally invasive alternative, allowing for more frequent disease monitoring. However, a poor understanding of ctDNA dynamics has hampered its clinical translation. We explored the predictive value of ctDNA for detecting minimal/measurable residual disease (MRD) and drug response in a patient-derived xenograft (PDX) model of infant MLL-r ALL. Methods: Immune-deficient mice engrafted with three MLL-r ALL PDXs were monitored for ctDNA levels before and after treatment with the menin inhibitor SNDX-50469. Results: The amount of ctDNA detected strongly correlated with leukemia burden during initial engraftment prior to drug treatment. However, following SNDX-50469 treatment, the leukemic burden assessed by either PB leukemia cells through flow cytometry or ctDNA levels through droplet digital polymerase chain reaction (ddPCR) was discrepant. This divergence could be attributed to the persistence of leukemia cells in the spleen and BM, highlighting the ability of ctDNA to reflect disease dynamics in key leukemia infiltration sites. Conclusions: Notably, ctDNA analysis proved to be a superior predictor of MRD compared to PB assessment alone, especially in instances of low disease burden. These findings highlight the potential of ctDNA as a sensitive biomarker for monitoring treatment response and detecting MRD in infant MLL-r ALL. Full article
(This article belongs to the Section Pediatric Oncology)
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14 pages, 2430 KiB  
Article
Preliminary Study on Type I Interferon as a Mucosal Adjuvant for Human Respiratory Syncytial Virus F Protein
by Hongqiao Hu, Li Zhang, Lei Cao, Jie Jiang, Yuqing Shi, Hong Guo, Yang Wang, Hai Li and Yan Zhang
Vaccines 2024, 12(11), 1297; https://doi.org/10.3390/vaccines12111297 - 20 Nov 2024
Viewed by 1295
Abstract
Background: Human respiratory syncytial virus (HRSV) imposes a significant disease burden on infants and the elderly. Intranasal immunization using attenuated live vaccines and certain vector vaccines against HRSV has completed phase II clinical trials with good safety and efficacy.Recombinant protein vaccines for mucosal [...] Read more.
Background: Human respiratory syncytial virus (HRSV) imposes a significant disease burden on infants and the elderly. Intranasal immunization using attenuated live vaccines and certain vector vaccines against HRSV has completed phase II clinical trials with good safety and efficacy.Recombinant protein vaccines for mucosal immunization require potent mucosal adjuvants. Type I interferon (IFN), as a natural mucosal adjuvant, significantly enhances antigen-presenting cell processing and antigen presentation, promoting the production of T and B cells. Methods: This study utilized human α2b interferon (IFN-human) and mouse α2 interferon (IFN-mouse) as nasal mucosal adjuvants in combination with fusion protein (F). Intranasal immunization was performed on BALB/c mice to evaluate the immunogenicity of the formulation in vivo. Results: Compared to the F protein immunization group, mice in the F + IFN-Human and F + IFN-Mouse experimental groups exhibited significantly increased neutralizing antibody titers and augmented secretion of IFN-γ and IL-4 by lymphocytes,  and both of them could induce the production of high-titer specific IgA antibodies in mice (p < 0.001).The F + IFN-Human immunization induced the highest IgG and IgG1 antibody titers in mice; however, the F + IFN-Mouse immunization group elicited the highest neutralizing antibody titers (598), lowest viral loads in the lungs (Ct value of 31), and fastest weight recovery in mice. Moreover, mice in the F + IFN-Mouse immunization group displayed the mildest lung pathological damage (Total score of pathological injury was 2). Conclusions: In conclusion, IFN-Mouse, as a mucosal adjuvant for HRSV recombinant protein vaccines, demonstrated superior protective effects in mice compared to IFN-Human adjuvants. Full article
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