The development of paranasal sinuses in patients with cystic fibrosis: sinuses volume analysis.

BACKGROUND: Cystic fibrosis (CF) is a severe systemic disease that affects many aspects of patients' lives. It is known that the progression of the disease adversely affects lower and upper airways including the paranasal sinuses. However, its impact on sinus development in the pediatric population is not fully examined. The purpose of this study was to evaluate the development of the paranasal sinuses in a pediatric population with CF and compare it to a control group consisting of healthy children. METHODS: The results of computed tomography (CT) scans of children with the disease and the control group were evaluated. The study included 114 CT images of children in the study group and 126 images of healthy children aged 0-18 years. The volumes of maxillary, frontal, and sphenoid sinuses were analyzed. The obtained results were compared with those of the control group and analyzed statistically. RESULTS: The volume and the development of the paranasal sinuses in both groups increased with age, but statistically significant differences were found between the study and the control group. CONCLUSIONS: The obtained results provide valuable knowledge regarding the impact of the CF on sinuses development. Also, they may be important in understanding the progression of the disease and its influence on the quality and length of life of patients. The results may contribute to enhanced diagnostics and have implications for improving therapy for patients with chronic sinusitis associated with CF.

Double Heterozygous Pathogenic Variants in the LOX and PKD1 Genes in a 5-Year-Old Patient with Thoracic Aortic Aneurysm and Polycystic Kidney Disease.

Familial thoracic aortic aneurysms and dissections may occur as an isolated hereditary trait or as part of connective tissue disorders with Mendelian inheritance, but severe cardiovascular disease in pediatric patients is extremely rare. There is growing knowledge on pathogenic variants causing the disease; however, much of the phenotypic variability and gene-gene interactions remain to be discovered. We present a case report of a 5.5-year-old girl with an aortic aneurysm and concomitant polycystic kidney disease. Whole exome sequencing was performed, followed by family screening by amplicon deep sequencing and diagnostic imaging studies. In the proband, two pathogenic variants were identified: p.Tyr257Ter in the LOX gene inherited from her mother, and p.Thr2977Ile in the PKD1 gene inherited from her father. All adult carriers of either of these variants showed symptoms of aortic disease. We conclude that the coexistence of two independent genetic variants in the proband may be the reason for an early onset of disease.

Central Diabetes Insipidus in Children as a Diagnostic Challenge.

Central diabetes insipidus (CDI) is a disorder in the pediatric population resulting from antidiuretic hormone deficiency. The excessive production of dilute urine characterizes it and manifests with polyuria, nocturia, and polydipsia. The diagnostics of CDI is often challenging, especially concerning the underlying condition of the disease. This article highlights the diverse clinical presentation of children with CDI and diagnostic difficulties among patients with polyuria and polydipsia. The article also reviews the etiology, symptoms, diagnostic workup, and management of CDI. We present 4 pediatric patients (aged 3-13.5 years) diagnosed with CDI of different etiology: 1 due to septo-optic dysplasia/optic nerve hypoplasia and 3 due to acquired processes such as Langerhans cell histiocytosis and germ cell tumor in 2 patients. Central diabetes insipidus was the first manifestation of a tumor or granuloma in all presented patients with acquired pathology. The patients sometimes need long-term follow-up to establish the proper final diagnosis.

The Effect of Conjugated Linoleic Acid Supplementation on Densitometric Parameters in Overweight and Obese Women-A Randomised Controlled Trial.

Background and Objectives: Conjugated linoleic acid (CLA) can improve bone health in animals, yet the effects on humans have not been consistent. Therefore, this parallel randomised controlled trial aimed to assess the effect of CLA supplementation on bone mineral density (BMD) and content (BMC) in overweight or obese women. Materials and Methods: The study population included 74 women who were divided into the CLA (n = 37) and control (n = 37) groups. The CLA group received six capsules per day containing approximately 3 g of cis-9, trans-11 and trans-10, cis-12 CLA isomers in a 50:50 ratio. The control group received the same number of placebo capsules that contained sunflower oil. BMC and BMD at total body, lumbar spine (L1-L4), and femoral neck were measured before and after a three-month intervention. Results: The comparison of BMC and BMD for the total body, lumbar spine (L1-L4), and femoral neck before and after the intervention showed no differences between the groups. However, a within-group analysis demonstrated a significant increase in BMC (p = 0.0100) and BMD (p = 0.0397) at lumbar spine (L1-L4) in the CLA group. Nevertheless, there were no significant differences between the CLA and placebo groups in changes in all analysed densitometric parameters. Conclusions: Altogether, three-month CLA supplementation in overweight and obese women did not improve bone health, although the short intervention period could have limited our findings, long-term intervention studies are needed. The study protocol was registered in the German Clinical Trials Register database (ID: DRKS00010462, date of registration: 4 May 2016).

From KIT-mutated into wild-type: dedifferentiation of gastrointestinal stromal tumor in adolescent patient-a case report.

Background: Gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm of the gastrointestinal tract, usually found in elderly adults. It is infrequent among pediatric patients and usually differs from adult-type disease in terms of histopathology and molecular features. Case Description: We describe the management of the disease in a 10-year-old female patient diagnosed with a GIST of the stomach. In total, she has undergone successively total tumor resection, unsuccessful imatinib treatment and subtotal gastric resection at relapse. The first genetic test from primary tumor confirmed KIT mutations in exons 13 and 17, while the repeated genetic screening using tumor sample from subtotal gastric resection revealed no KIT or platelet-derived growth factor receptor α (PDGFRA) genes mutations. Such dedifferentiation from adult type (thus KIT-mutated) into wild-type (without KIT or PDGFRA mutation) has not been reported so far to the best of our knowledge. Currently, the patient is observed, and no further pharmacological nor surgical treatment has been administered. Conclusions: The case underlines the importance of genetic profiling combined with non-standard diagnostics (both histopathological and radiological) due to the treatment efficacy prediction. We moreover emphasize the necessity to create worldwide standards on the diagnostics and treatment of GIST in pediatric patients that would include options of targeted therapies.

Children with back pain - a radiologist's approach.

Purpose: The aim of the study was to analyse magnetic resonance imaging (MRI) of paediatric patients referred because of back pain. Material and methods: The retrospective analysis included the medical records of 328 patients referred in 2020-2022 to the Department of Paediatric Radiology for spine examination. The criterion for inclusion in the analysed group was back pain as the dominant symptom. This symptom occurred in 20% (68 patients) of referrals for MRI examinations. The examination was performed with the 3T Magnetom Spectra. Results: In 68 patients aged 2 to 17 years, with back pain as the first diagnosis, 53% (36 patients - 16 girls and 20 boys) showed abnormalities. The rest of the tests were assessed as normal. Among the patients with an abnormal MR image, the largest group were children with degenerative changes diagnosed: 10 children (28%) aged 13-17 years. In 9 patients (25%) aged 2-16 years the final diagnosis qualified the patients to the group of oncological diagnoses. Another group of 7 (19%) patients, aged 6-14 years, comprised children diagnosed with inflammation. The group of 5 patients, aged 3-17 years, presented symptoms most likely related to the trauma. One 7-year-old boy was diagnosed with large calcifications within the intervertebral disc. Conclusions: Back pain, with accompanying neurological symptoms, should not be underestimated. Although in most clinical situations the MR image is normal, in the case of persistent symptoms and neurological abnormalities confirmed by the clinician, extending the diagnostics with MR imaging should be considered. This imaging can accelerate the correct diagnostic path or make a very precise diagnosis.

MRI and Pulmonary Function Tests' Results as Ventilation Inhomogeneity Markers in Children and Adolescents with Cystic Fibrosis.

Magnetic resonance imaging (MRI) of the chest is becoming more available in the detection and monitoring of early changes in lung function and structure in patients with cystic fibrosis (CF). The aim of this study was to assess the relationship between pulmonary function tests (PFT) and perfusion deficits in CF children measured by MRI. We performed a retrospective analysis of the perfusion lung MRI scans and the results of spirometry, oscillometry, body plethysmography, single-breath carbon monoxide uptake, and multiple-breath washout technique (MBW). There were statistically significant correlations between the MRI perfusion scores and MBW parameters (2.5% LCI, M1/M0, M2/M0), spirometry parameters (FEV1, FVC, FEF25/75), reactance indices in impulse oscillometry (X5Hz, X10Hz), total lung capacity (TLC) measured in single breath carbon monoxide uptake, markers of air-trapping in body plethysmography (RV, RV/TLC), and the diffusing capacity of the lungs for carbon monoxide. We also observed significant differences in the aforementioned PFT variables between the patient groups divided based on perfusion scores. We noted a correlation between markers of functional lung deficits measured by the MRI and PFTs in CF children. MRI perfusion abnormalities were reflected sooner in the course of the disease than PFT abnormalities.

Deep Learning-Based Segmentation and Volume Calculation of Pediatric Lymphoma on Contrast-Enhanced Computed Tomographies.

Lymphomas are the ninth most common malignant neoplasms as of 2020 and the most common blood malignancies in the developed world. There are multiple approaches to lymphoma staging and monitoring, but all of the currently available ones, generally based either on 2-dimensional measurements performed on CT scans or metabolic assessment on FDG PET/CT, have some disadvantages, including high inter- and intraobserver variability and lack of clear cut-off points. The aim of this paper was to present a novel approach to fully automated segmentation of thoracic lymphoma in pediatric patients. Manual segmentations of 30 CT scans from 30 different were prepared by the authors. nnU-Net, an open-source deep learning-based segmentation method, was used for the automatic segmentation. The highest Dice score achieved by the model was 0.81 (SD = 0.17) on the test set, which proves the potential feasibility of the method, albeit it must be underlined that studies on larger datasets and featuring external validation are required. The trained model, along with training and test data, is shared publicly to facilitate further research on the topic.

Successful Treatment of Large B-Cell Lymphoma in a Child with Compound Heterozygous Mutation in the ATM Gene.

Ataxia-telangiectasia (AT) is a multisystemic neurodegenerative inborn error of immunity (IEI) characterized by DNA repair defect, chromosomal instability, and hypersensitivity to ionizing radiation. Impaired DNA double-strand break repair determines a high risk of developing hematological malignancies, especially lymphoproliferative diseases. Poor response to treatment, excessive chemotherapy toxicities, and the need for avoiding exposure to ionizing radiation make the successful clinical management of patients with AT challenging for oncologists. We describe the favorable outcome of the LBCL with IRF4 rearrangement at stage III in a 7-year-old female patient diagnosed with AT. The patient was treated according to the B-HR arm of the INTER-B-NHL-COP 2010 protocol, including the administration of rituximab, cyclophosphamide, methotrexate, prednisone, etc. She presented excessive treatment toxicities despite individually reduced doses of methotrexate and cyclophosphamide. However, in the MRI there was no significant reduction in pathologic lymph nodes after three immunochemotherapy courses. Therefore, a lymph node biopsy was taken. Its subsequent histopathological examination revealed tuberculosis-like changes, though tuberculosis suspicion was excluded. After two following immunochemotherapy courses, PET-CT confirmed complete remission. From March 2022 onwards, the patient has remained in remission under the care of the outpatient children's oncology clinic.

Extracellular vesicles-derived miRNAs as mediators of pulmonary exacerbation in pediatric cystic fibrosis.

Children with cystic fibrosis (CF) suffer from chronic inflammation and recurrent pulmonary exacerbations (PEs). We aimed to test whether a specific miRNA could be associated with the occurrence of PE. We sequenced extracellular vesicle (EV)-derived miRNA in sputum (n= 20), exhaled breath condensate (EBC) (n= 11), and serum (n= 8) samples from pediatric patients during PE and the stable stage of CF. Four miRNAs: let-7c, miR-16, miR-25-3p and miR-146a, have been selected for validation in a larger group with reverse transcription quantitative real-time PCR (RT-qPCR) in sputum and serum, or droplet digital PCR (ddPCR) in EBC. Next-generation sequencing (NGS) differential expression analysis was done in Base Space, and the correlation between miRNAs expression and clinical data was calculated with Statistica. Functional annotation of selected miRNAs and their potential target genes was performed with miRDip and DAVID software. There were no differences in miRNA expression between stable and exacerbation in sputum and in serum. Validation of four selected miRNAs showed significant downregulation of miR-146a in serum. A panel of all four miRNAs (peripherally) was the best predictive model of exacerbation (p< 0.001, AUC = 0.96). Expression of airway miR-25-3p improved the diagnostic value of FEV1% pred and FVC% pred, while peripheral miR-146a improved the predictive model of C-reactive protein and neutrophilia.In silicoanalysis revealed a potential role for selected miRNAs in regulating processes associated with inflammation and tissue remodeling. We demonstrated that EVs contained in peripheral blood as well as local biomaterials can act as carriers for miRNAs with the diagnostic potential of predicting exacerbation in pediatric CF.

Imaging in children with ataxia-telangiectasia-The radiologist's approach.

Ataxia-telangiectasia (A-T) is a syndromic inborn error of immunity (IEI) characterized by genomic instability, defective reparation of the DNA double-strand breaks, and hypersensitivity to ionizing radiation disturbing cellular homeostasis. The role of imaging diagnostics and the conscious choice of safe and advantageous imaging technique, as well as its correct interpretation, are crucial in the diagnostic process and monitoring of children with A-T. This study aimed at defining the role of a radiologist in the early diagnosis of A-T, as well as in detecting and tracking disease complications associated with infections, inflammation, lymphoproliferation, organ-specific immunopathology, and malignancy. Based on our single-center experience, retrospective analysis of investigations using ionizing radiation-free techniques, ultrasound (US), and Magnetic Resonance Imaging (MRI), was performed on regularly followed-up 11 pediatric A-T patients, 6 girls and 5 boys, aged from 2 to 18 years, with the longest period of observation coming to over 13 years. Our attention was especially drawn to the abnormalities that were observed in the US and MRI examinations of the lungs, abdominal cavity, and lymph nodes. The abdominal US showed no abnormalities in organ dimensions or echostructure in 4 out of 11 children studied, yet in the other 7, during follow-up examinations, hepato- and/or splenomegaly, mesenteric, visceral, and paraaortic lymphadenopathy were observable. In 2 patients, focal changes in the liver and spleen were shown, and in one patient progressive abdominal lymphadenopathy corresponded with the diagnosis of non-Hodgkin lymphoma (NHL). The lung US revealed multiple subpleural consolidations and B line artifacts related to the interstitial-alveolar syndrome in 5 patients, accompanied by pleural effusion in one of them. The MRI investigation of the lung enabled the detection of lymphatic nodal masses in the mediastinum, with concomitant airway lesions characteristic of bronchiectasis and focal parenchymal consolidations in one A-T patient with chronic respiratory failure. This patient also manifested organomegaly and granulomatous liver disease in abdominal MRI examination. Our study shows that the use of modern US capabilities and MRI is safe and efficient, thereby serving as a recommended advantageous imaging diagnostic tool in monitoring children with IEI and DNA instability syndromes.

SARS-CoV-2 attacks the weakest point - COVID-19 course in a pediatric patient with Friedreich's ataxia.

COVID-19 pandemic is the biggest epidemiologic problem of the 21st century. A severe course of SARS-CoV-2 infection in children is rare. Sometimes, especially in patients with chronic disease, COVID-19 may be insidious and life-threatening. This article presents the course of COVID-19 in a 17-year-old boy with Friedreich's ataxia-induced hypertrophic cardiomyopathy. Although, the main symptoms of COVID-19 (i.e., fever, cough) were moderate at the beginning of the illness, the patient's condition deteriorated rapidly due to cardiac problems, atrial fibrillation, and heart failure. The patient required antiarrhythmic treatment and pharmacological and electrical cardioversion. Moreover, because of pneumonia requiring supplemental oxygen, remdesivir and convalescent plasma therapy was given to the patient., The administration of the antiviral treatment was crucial to the patient's recovery.

Clinical Picture and Risk Factors of Severe Respiratory Symptoms in COVID-19 in Children.

Children with COVID-19 develop moderate symptoms in most cases. Thus, a proportion of children requires hospital admission. The study aimed to assess the history, clinical and laboratory parameters in children with COVID-19 concerning the severity of respiratory symptoms. The study included 332 children (median age 57 months) with COVID-19. History data, clinical findings, laboratory parameters, treatment, and outcome, were evaluated. Children were compared in the groups that varied in the severity of symptoms of respiratory tract involvement. Children who required oxygen therapy represented 8.73%, and intensive care 1.5% of the whole cohort. Comorbidities were present in 126 patients (37.95%). Factors increasing the risk of oxygen therapy included comorbidities (odds ratio (OR) = 92.39; 95% confidence interval (95% CI) = (4.19; 2036.90); p < 0.00001), dyspnea (OR = 45.81; 95% CI (4.05; 518.21); p < 0.00001), auscultation abnormalities (OR = 34.33; 95% CI (2.59; 454.64); p < 0.00001). Lactate dehydrogenase (LDH) > 280 IU/L and creatinine kinase > 192 IU/L were parameters with a good area under the curve (0.804-LDH) and a positive predictive value (42.9%-CK). The clinical course of COVID-19 was mild to moderate in most patients. Children with comorbidities, dyspnea, or abnormalities on auscultation are at risk of oxygen therapy. Laboratory parameters potentially useful in patients evaluated for the severe course are LDH > 200 IU/L and CK > 192 IU/L.

Semi-Automatic Volumetric and Standard Three-Dimensional Measurements for Primary Tumor Evaluation and Response to Treatment Assessment in Pediatric Rhabdomyosarcoma.

Current prognostic classification of rhabdomyosarcoma in children requires precise measurements of the tumor. The purpose of the study was to compare the standard three-dimensional (3D) measurements with semi-automatic tumor volume measurement method concerning assessment of the primary tumor size and the degree of response to treatment for rhabdomyosarcoma in children. Magnetic Resonance Imaging data on 31 children with treated rhabdomyosarcoma based on the Cooperative Weichteilsarkom Studiengruppe (CWS) guidance was evaluated. Tumor sizes were measured by two methods: 3D standard measurements and semi-automatic tumor volume measurement (VOI) at diagnosis, and after 9 and 17/18 weeks of the induction chemotherapy. Response to treatment and prediction values were assessed. The tumor volume medians calculated using VOI were significantly higher in comparison with those calculated using the 3D method both during the diagnosis as well as after 9 weeks of the chemotherapy and during the 17-18th week of the treatment. The volume measurements based on the generalized estimating equations on the VOI method were significantly better than the 3D method (p = 0.037). The volumetric measurements alone can hardly be considered an unequivocal marker used to make decisions on modification of the therapy in patients with rhabdomyosarcoma.

Invitation to participate in a multi-center study for validation of cerebral computed tomography angiography and computed tomography perfusion in the determination of cerebral circulatory arrest during brain death/death by neurological criteria diagnosis procedure in paediatric population below 12 years of age.

We would like to invite paediatric intensive care units (PICU) to join our multi-center trial concerning patient population < 12 y/o and aiming at: • validation of computed tomography angiography (CTA)/computed tomography perfusion (CTP) tests for brain death/death by neurological criteria (BD/DNC) diagnosis procedures, • validation of duplex Doppler insonation of extracranial segments of the internal cerebral arteries and the vertebral arteries for choosing an optimal time for CTA/CTP testing.

Granulomatous Lymphocytic Interstitial Lung Disease in a Spectrum of Pediatric Primary Immunodeficiencies.

BACKGROUND: Granulomatous lymphocytic interstitial lung disease (GLILD) has been increasingly recognized in children affected with primary immunodeficiencies (PIDs). In this study, we aimed to better characterize the spectrum of pediatric PIDs coexisting with GLILD including clinical and immunological predictors, thoracic imaging findings, and histopathologic features. METHODS: We respectively reviewed records of six representative cases of children, three of them affected with common variable immunodeficiency (CVID) and three with syndromic immunodeficiencies, in whom a diagnosis of GLILD was established based on clinical, radiological, and histopathologic findings. Clinical and immunological predictors for GLILD were also analyzed in the patients studied. RESULTS: All the children with GLILD had a history of autoimmune phenomena, organ-specific immunopathology, and immune dysregulation. Defective B-cell maturation and deficiency of memory B cells were found in all the children with GLILD. The radiological and histopathological features consistent with the diagnosis of GLILD, granulomatous disease, and lymphoid hyperplasia, were accompanied by chronic airway disease with bronchiectasis in children with CVID and syndromic PIDs. CONCLUSIONS: Our study shows that both CVID and syndromic PIDs may be complicated with GLILD. Further studies are required to understand the predictive value of coexisting autoimmunity and immune dysregulation in the recognition of GLILD in children with PIDs.

The Important Role of the Radiologist in Determining the Indications for the Surgical Treatment of Neuroblastoma with Vascular Image-Defined Risk Factors: A Case Report.

The International Neuroblastoma Risk Group Staging System (INRGSS) is based on the age of patients and preoperative imaging, with attention paid to whether the primary tumor is affected by one or more of specific image-defined risk factors (IDRFs). This publication presents a 2.5-year-old boy with neuroblastoma who had an accidental ligation of the celiac trunk during tumor resection. The consequences of this complication were pancreatic and spleen ischemia and necrosis, ischemia, and perforation of the common bile duct, gallbladder, stomach, and duodenum. The aim of this publication was to highlight the great role of the radiologist in determining the indications for neuroblastoma tumor removal, especially with current vascular IDRFs, and to show how the radiologist's insightful approach can save the patient from irreversible complications.

Simultaneous Occurrence of Choriocarcinoma in an Infant and Mother.

Infantile choriocarcinoma is an extremely rare disease. We present a case study of a 1-month-old male with choriocarcinoma diagnosed simultaneously with his mother. On admission to hospital, the disease was very advanced and massive progression and multi-organ failure caused the death of the patient despite the implemented treatment. It was too late to save the child's life, but early enough to save his mother. The authors believe that the serum levels of hCG should be determined in every newborn with anemia and liver tumor, especially when the mother has a positive history of miscarriage.

Wide spectrum of clinical picture of COVID-19 in children - From mild to severe disease.

INTRODUCTION: Children account for a relatively small proportion of laboratory-confirmed SARS-CoV-2 infections. In children, COVID-19 usually has a relatively mild course. However, in rare cases, severe disorders can be observed, and clinical manifestations may differ from adults. PURPOSE: The aim of this study is to analyse the frequency, clinical picture and outcome of COVID-19 in children based on the experience from the tertiary care centre and regional sanitary-epidemiological office. METHODS: We report a study regarding 106 cases of confirmed SARS-CoV-2 infection cases in PCR from a nasopharyngeal swab (age range 1-month - 17-years). In all cases, history was taken. In children who required hospital admission, physical examination and laboratory test were performed according to clinical indications. RESULTS: Twelve of the patients required admission to the hospital. The most common symptoms were anosmia and dysgeusia (75%) and headaches (49%) in outpatients and fever in hospitalised children (75%). Three children from the hospitalised group developed a severe course with increased inflammatory indexes. The clinical picture was more severe in younger children from the hospitalised group. Treatment options were regarded individually in all cases. CONCLUSION: Our study is the first tour knowledge regarding the clinical course of COVID-19 in Polish children. In general, the clinical course of COVID-19 was mild with anosmia and dysgeusia as the most common symptoms. However, in hospitalised children, a severe progression of the disease and less typical signs as aplastic anaemia may be developed.