Clinical Characteristics and Whole Exome Sequencing Analysis in Serbian Cases of Clubfoot Deformity-Single Center Study.

BACKGROUND: Recognized as one of the most serious musculoskeletal deformities, occurring in 1-2 per 1000 newborns, 80% of clubfeet are idiopathic while 20% present with associated malformations. The etiopathogenesis of clubfoot is described as multifactorial, including both genetic and environmental risk factors. The aim of this study was to analyze possible genetic causes of isolated and syndromic clubfoot in Serbian children, as well as to correlate clinical and genetic characteristics that would provide insight into clubfoot etiopathogenesis and possibly contribute to global knowledge about clinical features of different genetically defined disorders. METHODS: We evaluated 50 randomly selected, eligible children with clubfoot aged 3 to 16 years that were initially hospitalized and treated at University Children's Hospital between November 2006 and November 2022. The tested parameters were gender, age, dominant foot, affected foot, degree of deformity, treatment, neuromuscular disorders, positive family history, and maternal smoking. According to the presence of defined genetic mutation/s by whole exome sequencing (WES), patients were separated into two groups: positive (with genetic mutation/s) and negative (without genetic mutation/s). RESULTS: Seven patients were found to be positive, i.e., with genetic mutation/s. A statistically significant difference between categorical variables was found for families with a history of clubfoot, where more than half (57.14%) of patients with confirmed genetic mutation/s also had a family history of genetic mutation/s (p = 0.023). CONCLUSIONS: The results from this study further expand the genetic epidemiology of clubfoot. This study contributes to the establishment of genetic diagnostic strategies in pediatric patients with this condition, which can lead to more efficient genetic diagnosis.

Fractals in the Neurosciences: A Translational Geographical Approach.

The chapter presents three new fractal indices (fractal fragmentation index, fractal tentacularity index, and fractal anisotropy index) and normalized Kolmogorov complexity with proven applicability in geographic research, developed by the authors, and the possibility of their future use in neuroscience. The research demonstrates the relevance of fractal analysis in different fields and the basic concepts and principles of fractal geometry being sufficient for the development of models relevant to the studied reality. Also, the research highlighted the need to continue interdisciplinary research based on known fractal indicators, as well as the development of new analysis methods with the translational potential between fields.

Recognizing the Frequency of Exposure to Cyberbullying in Children: The Results of the National HBSC Study in Serbia.

Nowadays, children are able to enrich their reality via the Internet. Unfortunately, this may increase their risk of becoming victims of cyberbullying. We analyzed the health characteristics and risk behavior of two cohorts of children in Serbia; those who reported being exposed to cyberbullying and those who did not. The statistical differences and logistic regression models were applied to the data on 3267 students collected from 64 schools participating in the 2017 Serbian Study on health behavior in school-age children (HBSC). Children exposed to cyberbullying reported having the following health problems on a daily basis: headache (18.5%), back pain (19.5%), depression (21.6%), irritability or bad mood (17.7%), nervousness (16.0%), sleep problems (16.1%), and dizziness (21.2%). As for the different types of risk behavior, cigarette smoking ranging from six to nine days ever was the most prevalent (26.9%). It was followed closely by getting drunk more than 10 times ever (24.1%). Compared to non-victims, victims were found to be at a higher risk of perceived back pain (OR = 2.27), depression (OR = 1.43), irritability or bad mood (OR = 2.07), nervousness (OR = 2.23), and dizziness (OR = 2.43) as well as being injured once or twice (OR = 1.98) or three or more times (OR = 4.09). Victims were associated with further risk factors: having smoked more than five cigarettes ever in life (OR = 1.73) and having gotten drunk two to three times (OR = 1.71) or four or more times (OR = 1.65). As the number of school-age children using social media continues to rise, we must prioritize educating them about self-help and community resources for addressing related health issues with greater speed and intensity. The findings from Serbia suggest that while children may be aware of their health issues, they may be unaware of their link to cyberbullying, which could hinder their ability to address these issues promptly. The respondents' attention to the health implications of cyberbullying could be increased by reformulating the survey questions used in the HBSC study.

Higher rate of progesterone receptor positivity in skeletal metastases of breast cancer with a pathological fracture vs those without fracture.

Identifying risk factors for fracture occurrence in breast cancer (BC) skeletal metastases (SM) may guide the management of such bone deposits. There is sparse evidence regarding receptor status in SM and their relationship to fracture occurrence. Our study aimed to determine the relationship between estrogen (ER), progesterone (PR) and HER2 receptor status and Ki-67 index and fracture occurrence in SM of BC. Exactly 152 samples of SM of BC obtained from individual patients were evaluated. The status of the aforementioned receptors and Ki67 index were determined in SMs samples. Their expression was compared between SM that did and did not develop a fracture. Ninety-one cases sustained a pathological fracture at the SM site, and 61 did not. Patients who sustained a pathological fracture had a higher rate of PR positivity at their SMs as compared to those with no fracture. There was no significant difference between the two groups concerning ER, HER2+ or Ki67 status. SMs secondary to BC with a fracture are more likely to be PR positive than those with no fracture. Determining the receptor status in SMs may identify high-risk groups for fracture occurrence, and determining the PR status may also guide surgical and hormonal therapy.

The Role of MRI in the Diagnosis of Solid Pseudopapillary Neoplasm of the Pancreas and Its Mimickers: A Case-Based Review with Emphasis on Differential Diagnosis.

Solid pseudopapillary neoplasm (SPN) is rare pancreatic tumor occurring most commonly in young females. The typical imaging appearance of SPN is of well-defined, encapsulated, and large heterogeneous tumors, consisting of solid and cystic components due to various degrees of intralesional hemorrhage and necrosis. However, atypical imaging presentation in the form of small solid tumors or uniformly cystic lesions might also be seen, which can be explained by specific pathological characteristics. Other imaging features such as a round shape, the absence of main pancreatic duct dilatation, and slow growth, in combination with vague symptoms, favor the diagnosis of SPNs. Nevertheless, the radiological findings of SPN might overlap with other solid and cystic pancreatic neoplasms, such as neuroendocrine tumors, serous and mucinous neoplasms, and even small pancreatic adenocarcinomas. In addition, a few benign non-tumorous conditions including walled-of-necrosis, and intrapancreatic accessory spleen may also pose diagnostic dilemmas simulating SPNs on imaging studies. The aim of this manuscript is to provide a comprehensive overview of the typical and atypical imaging features of SPNs and to describe useful tips for differential diagnosis with its potential mimickers.

Morphometric Parameters and MRI Morphological Changes of the Knee and Patella in Physically Active Adolescents.

Background and Objectives: The immature skeleton in a pediatric population exposed to frequent physical activity might be extremely prone to injuries, with possible consequences later in adulthood. The main aim of this study is to present specific morphometric parameters and magnetic resonance imaging (MRI) morphological changes of the knee and patella in a physically active pediatric population. Additionally, we wanted to investigate the morphological risk factors for patellar instability. Materials and Methods: The study included the MRI findings of 193 physically active pediatric patients with knee pain. The participants underwent sports activities for 5 to 8 h per week. Two divisions were performed: by age and by patellar type. We evaluated three age groups: group 1 (age 11-14), group 2 (age 15-17), and group 3 (age 18-21 years). In addition, participants were divided by the patellar type (according to Wiberg) into three groups. The following morphometric parameters were calculated: lateral trochlear inclination (LTI), the tibial tubercle-trochlear groove distance (TT-TG), trochlear facet asymmetry (TFA), Insall-Salvati index, modified Insall-Salvati index, Caton-Deschamps index, articular overlap, morphology ratio and contact surface ratio. Results: We found a statistically significant association between patellar type groups in LTI (p < 0.001), TFA (p < 0.001), Insal-Salvati (p = 0.001) index, and Caton-Deschamps index (p = 0.018). According to age groups, we found statistical significance in the Caton-Deschamps index (p = 0.039). The most frequent knee injury parameter, according to Wiberg, in physically active pediatric patients was patella type 2 in boys and type 3 in girls. Conclusions: The MRI morphometric parameters observed in our study might be factors of prediction of knee injury in physically active children. In addition, it might be very useful in sports programs to improve the biomechanics of the knee in order to reduce the injury rate in sports-active children.

Directionally Sensitive Fractal Radiomics Compatible With Irregularly Shaped Magnetic Resonance Tumor Regions of Interest: Association With Osteosarcoma Chemoresistance.

BACKGROUND: Computational analysis of routinely acquired MRI has potential to improve the tumor chemoresistance prediction and to provide decision support in precision medicine, which may extend patient survival. Most radiomic analytical methods are compatible only with rectangular regions of interest (ROIs) and irregular tumor shape is therefore an important limitation. Furthermore, the currently used analytical methods are not directionally sensitive. PURPOSE: To implement a tumor analysis that is directionally sensitive and compatible with irregularly shaped ROIs. STUDY TYPE: Retrospective. SUBJECTS: A total of 54 patients with histopathologic diagnosis of primary osteosarcoma on tubular long bones and with prechemotherapy MRI. FIELD STRENGTH/SEQUENCE: A 1.5 T, T2-weighted-short-tau-inversion-recovery-fast-spin-echo. ASSESSMENT: A model to explore associations with osteosarcoma chemo-responsiveness included MRI data obtained before OsteoSa MAP neoadjuvant cytotoxic chemotherapy. Osteosarcoma morphology was analyzed in the MRI data by calculation of the nondirectional two-dimensional (2D) and directional and nondirectional one-dimensional (1D) Higuchi dimensions (Dh). MAP chemotherapy response was assessed by histopathological necrosis. STATISTICAL TESTS: The area under the receiver operating characteristic (ROC) curve (AUC) evaluated the association of the calculated features with the actual chemoresponsiveness, using tumor histopathological necrosis (95%) as the endpoint. Least absolute shrinkage and selection operator (LASSO) machine learning and multivariable regression were used for feature selection. Significance was set at <0.05. RESULTS: The nondirectional 1D Dh reached an AUC of 0.88 in association with the 95% tumor necrosis, while the directional 1D analysis along 180 radial lines significantly improved this association according to the Hanley/McNeil test, reaching an AUC of 0.95. The model defined by variable selection using LASSO reached an AUC of 0.98. The directional analysis showed an optimal predictive range between 90° and 97° and revealed structural osteosarcoma anisotropy manifested by its directionally dependent textural properties. DATA CONCLUSION: Directionally sensitive radiomics had superior predictive performance in comparison to the standard nondirectional image analysis algorithms with AUCs reaching 0.95 and full compatibility with irregularly shaped ROIs. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 1.

The Magnetic Resonance Imaging Pattern of the Lesions Caused by Knee Overuse in the Pediatric Population.

Background and Objectives: Excessive use of the knee in patients with immature locomotor systems leads to a whole spectrum of morphological changes with possible consequences in adulthood. This study aimed to examine the morphological pattern in magnetic resonance imaging (MRI) that is associated with recurrent pain due to increased physical activity in children. Materials and Methods: This was a retrospective study conducted among pediatric patients treated at the University Children's Hospital in Belgrade in 2018 and 2019. MRI findings of patients who reported recurrent pain in the knee joint during physical activity and who were without any pathological findings on both clinical examination and knee radiographs were included in the study. Results: MRI findings of 168 patients (73 boys and 95 girls, mean age 14.07 ± 3.34 years) were assessed. Meniscus and cartilage lesions were the most commonly detected morphological findings: meniscus lesions in 49.4%, cartilage ruptures in 44.6%, and cartilage edema in 26.2% of patients. The medial meniscus was more often injured in girls (p = 0.030), while boys were more prone to other joint injuries (p = 0.016), re-injury of the same joint (p = 0.036), bone bruises (p < 0.001), and ligament injuries (p = 0.001). In children older than 15 years, tibial plateau cartilage edema (p = 0.016), chondromalacia patellae (p = 0.005), and retropatellar effusion (p = 0.011) were detected more frequently compared to younger children. Conclusions: Children reporting recurrent knee pain due to increased physical activity, without any detected pathological findings on clinical examination and knee radiography, may have morphological changes that can be detected on MRI. Timely diagnosis of joint lesions should play a significant role in preventing permanent joint dysfunction in the pediatric population as well as in preventing the development of musculoskeletal diseases in adulthood.

Vitamin D and Forearm Fractures in Children Preliminary Findings: Risk Factors and Correlation between Low-Energy and High-Energy Fractures.

Background: The forearm is the most common fracture site in childhood, accounting for every fourth pediatric fracture. It is well described that vitamin D is involved in the regulation of bone mineralization and skeletal homeostasis by the regulation of calcium absorption. The aim of our study was to determine the influence of 25-hydroxyvitamin D levels on forearm fracture falls in a pediatric population, depending on level of energy impact. Additionally, we also aimed to evaluate the correlation between 25-hydroxyvitamin D levels and other tested risk factors for pediatric fractures. Methods: We evaluated 50 eligible children aged 3 to 12 years with a forearm fracture. According to energy impact, patients were grouped into low-energy fractures (LEF) and high-energy fractures (HEF) groups. The general characteristics of the patients included age, gender, sport participation, and fractured bone and its localization. We analyzed 25-hydroxyvitamin D, parathyroid hormone (PTH), calcium, magnesium, phosphate, C-reactive protein (CRP) levels, and body mass index (BMI). Results: There is a significant difference in the 25-hydroxyvitamin D levels distribution between LEF and HEF (p < 0.001) and PTH levels (p = 0.002). For magnesium levels, calcium levels, phosphate levels, and CRP levels, there were no significant differences in their frequency distribution. For the group of patients with LEF, there is a significantly positive correlation between 25-hydroxyvitamin D and calcium levels (p = 0.019) and a borderline significantly positive correlation between 25-hydroxyvitamin D and magnesium levels (p = 0.050). For the group of patients with HEF, there was only a significantly positive correlation between 25-hydroxyvitamin D and PTH levels (p < 0.001). Conclusions: Children with LEF were more frequently insufficient in 25-hydroxyvitamin D levels but had normal calcium levels, compared to the ones with HEF. These findings suggest that LEF and HEF in children might to a certain degree have different pathophysiological mechanisms.

Computational analysis of MRIs predicts osteosarcoma chemoresponsiveness.

Aim: This study aimed to improve osteosarcoma chemoresponsiveness prediction by optimization of computational analysis of MRIs. Patients & methods: Our retrospective predictive model involved osteosarcoma patients with MRI scans performed before OsteoSa MAP neoadjuvant cytotoxic chemotherapy. Results: We found that several monofractal and multifractal algorithms were able to classify tumors according to their chemoresponsiveness. The predictive clues were defined as morphological complexity, homogeneity and fractality. The monofractal feature CV for Λ'(G) provided the best predictive association (area under the ROC curve = 0.88; p <0.001), followed by   Y-axis intersection of the regression line  for â€Šbox fractal dimension, r²â€Š for  FDM and tumor circularity. Conclusion: This is the first full-scale study to indicate that computational analysis of pretreatment MRIs could provide imaging biomarkers for the classification of osteosarcoma according to their chemoresponsiveness.

Glucose and lipid metabolism disorders in children and adolescents with spinal muscular atrophy types 2 and 3.

We aimed to estimate the prevalence of glucose and lipid metabolism disorders in children and adolescents with spinal muscular atrophy (SMA) types 2 and 3. A cross-sectional study was conducted. Medical history, anthropometric measurements, pubertal status, blood chemistry (glucose and insulin levels, lipid profile, aminotransferases, and hemoglobin A1c [HbA1c]), and liver ultrasound were obtained in all patients. Oral glucose tolerance test was performed in those with body mass index (BMI) >25th percentile or glucose or HbA1c levels in the prediabetic range. A total of 37 patients with SMA (22 type 2, 15 type 3) with a median age of 8.5 years (range 2-18.9 years) were included. Eleven patients (29.7%) met the criteria for prediabetes, but none had overt type 2 diabetes. Dyslipidemia was detected in 11 patients (29.7%), and 4 (10.8%) had hepatic steatosis on ultrasound. Sixteen patients (43.2%) had at least one abnormal finding (prediabetes, dyslipidemia, or hepatic steatosis); all but one were non-ambulatory and 12 (75%) had BMI ≥85th percentile. One young child developed fasting hypoglycemia. Our results suggest that non-ambulatory overweight/obese SMA patients are particularly prone to abnormalities in glucose and lipid metabolism. Young underweight patients might develop fasting hypoglycemia.

Atypical localization of intraosseous angioleiomyoma in the rib of a pediatric patient: a case report.

BACKGROUND: This is the first reported case of a primary intraosseous angioleiomyoma and the second case of a primary leiomyoma of the rib, irrespective of age. Angioleiomyomas mostly occur in patients of advanced age, in any part of the body, particularly the lower extremities and present as painful, slow-growing nodules in the dermis, subcutaneous fat or deep fascia. Other localizations, especially bone, are considered extremely rare, as well as their occurrence in paediatric patients. CASE PRESENTATION: A 10-year-old girl was admitted to the orthopaedic surgery department for further assessment of a pain localized in the posterior part of the right hemithorax. After magnetic resonance imaging (MRI) and surgical biopsy, intraosseus angioleiomyoma of the fourth rib was diagnosed by histopathology examination. Atypical costal localization of this type of a benign tumour presents diagnostic difficulty, especially in children. The differential diagnoses included cartilaginous tumours, Ewing sarcoma, fibrous dysplasia, Langerhans cell histiocytosis, intraosseous haemangioma and metastatic tumours. We report a detailed diagnostic procedure including MRI, selective angiography and histopathologic examination. CONCLUSION: Diagnosis of intraosseous angioleiomyoma is difficult due to the extreme rarity of this tumour and absence of pathognomonic radiological signs. Although very rarely identified in bones and young age group, radiographers and reporting doctors should be aware of this possible angioleiomyoma presentation and supported by the provided detailed diagnostic information.

A posttraumatic pseudoaneurysm of the left radial artery as a result of a stab wound in an 8-year-old girl.

Pseudoaneurysms arise from a disruption of arterial wall continuity and are most commonly related to a penetrating trauma, an arterial wall inflammation or iatrogenic causes. They differ from real aneurysms due to a lack of one or more layers of the arterial wall. The frequency of peripheral artery pseudoaneurysms in the upper extremities is less than in the lower extremities and its most common cause is a gunshot or a stab wound. The risk of a rupture is higher than in true aneurysms due to a lack of wall layers, therefore requiring surgical treatment in most cases. Here we describe an unusual case of an 8-year-old girl who presented to the emergency department complaining of swelling and pain in her left distal forearm. One month before admission she experienced a penetrating trauma in the same area due to a self inflicted stab wound. After clinical and duplex ultrasonography evaluation the tumefaction proved to be a posttraumatic pseudoaneurysm of the left radial artery.

Fractal and Gray Level Cooccurrence Matrix Computational Analysis of Primary Osteosarcoma Magnetic Resonance Images Predicts the Chemotherapy Response.

The prediction of induction chemotherapy response at the time of diagnosis may improve outcomes in osteosarcoma by allowing for personalized tailoring of therapy. The aim of this study was thus to investigate the predictive potential of the so far unexploited computational analysis of osteosarcoma magnetic resonance (MR) images. Fractal and gray level cooccurrence matrix (GLCM) algorithms were employed in retrospective analysis of MR images of primary osteosarcoma localized in distal femur prior to the OsteoSa induction chemotherapy. The predicted and actual chemotherapy response outcomes were then compared by means of receiver operating characteristic (ROC) analysis and accuracy calculation. Dbin, Λ, and SCN were the standard fractal and GLCM features which significantly associated with the chemotherapy outcome, but only in one of the analyzed planes. Our newly developed normalized fractal dimension, called the space-filling ratio (SFR) exerted an independent and much better predictive value with the prediction significance accomplished in two of the three imaging planes, with accuracy of 82% and area under the ROC curve of 0.20 (95% confidence interval 0-0.41). In conclusion, SFR as the newly designed fractal coefficient provided superior predictive performance in comparison to standard image analysis features, presumably by compensating for the tumor size variation in MR images.

Case report of acute vitamin D intoxication in an infant.

INTRODUCTION: Vitamin D intoxication represents a rare and potentially serious pathological condition caused by the excess of calcium and phosphorus. We are presenting an infant with vitamin D intoxication due to excessive daily administration, as well as therapeutic procedures that prevented its adverse effects. CASE OUTLINE: A 1.5-month-old female infant, born at term, exclusively breastfed and without any complaints and abnormalities of physical findings, was observed due to the data that during the preceding month, by her mother's mistake, she had received about 200,000 IU of vitamin D3. Laboratory analyses showed a high serum level of 25(OH)D (>400 nmol/L) and calcium (2.72 mmol/L), lowered PTH (6.6 pg/ml) and high urinary calcium/creatinine ratio (1.6), while other findings, including urotract ultrasonography image, were within normal limits. Treatment based on the discontinuation of vitamin D administration, infant's forced water intake, as well as the application of 2-month prednisolone and 4-month phenobarbitone and furosemide, resulted in complete normalization of the laboratory indicators of vitamin D overdose, as well as the prevention of its adverse effects. CONCLUSION: By timely recognition and adequate treatment, including triple therapy with prednisolone, phenobarbitone and furosemide, adverse effects of acute vitamin D intoxication can be prevented.

Acute patellar dislocation in adolescents: operative versus nonoperative treatment.

PURPOSE: The purpose of this prospective non-randomised study was to compare the efficacy of two opposed methods, operative and conservative. Our hypothesis was that if the method was selected correctly, on an individual basis, the results should be approximately equal. METHODS: The study included 37 adolescents aged between 12 and 16 years, with a mean follow up of 6.1 years. The presence of a significant loose body, confirmed by precise imaging, was the key for selecting operative or arthroscopic treatment. In both groups of patients, we evaluated functional knee scores and the incidence of residual patellofemoral disorders. RESULTS: We confirmed our hypothesis using the t-test to compare functional results and a test for comparison of proportions for incidence of residual disorders. There was no statistically significant difference (p=0.091) between operatively and conservatively treated groups with regard to functional results. The same statistical outcome emerged when comparing incidences of re-dislocation (p=0.854), or other major patellar instabilities (p=0.856), between the groups. CONCLUSIONS: The results obtained should not promote a non-operative method on the basis of lower risk, but do support an individual approach based on precise diagnosis and defined criteria.