Tracing 2D Growth of Pancreatic Tumoroids Using the Combination of Image Processing Techniques and Mini-Opto Tomography Imaging System.

Objectives: In this study, we aimed to trace the 2D growth development of tumoroids produced with MIA PaCa-2 pancreatic cancer cells at different time points. Methods We cultured 3 different tumoroids with 0.5%, 0.8%, and 1.5% agarose concentrations and calculated the growth rate of the tumoroids with their images acquired at 9 imaging time points by mini-Opto tomography imaging system applying image processing techniques. We used the metrics contrast-to-noise ratio (CNR), peak signal-to-noise ratio (PSNR), and mean squared error (MSE) to analyze the distinguishability of the tumoroid structure from its surroundings, quantitatively. Additionally, we calculated the increase of the radius, the perimeter, and the area of 3 tumoroids over a time period. Results In the quantitative assessment, the bilateral and Gaussian filters gave the highest CNR values (ie, Gaussian filter: at each of 9 imaging time points in range of 1.715 to 15.142 for image set-1). The median filter gave the highest values in PSNR in the range of 43.108 to 47.904 for image set-2 and gave the lowest values in MSE in the range of 0.604 to 2.599 for image set-3. The areas of tumoroids with 0.5%, 0.8%, and 1.5% agarose concentrations were 1.014 mm2, 1.047 mm2, and 0.530 mm2 in the imaging time point-1 and 33.535 mm2, 4.538 mm2, and 2.017 mm2 in the imaging time point-9. The tumoroids with 0.5%, 0.8%, and 1.5% agarose concentrations grew up to times of 33.07, 4.33, and 3.80 in area size over this period, respectively. Conclusions The growth rate and the widest borders of the different tumoroids in a time interval could be detected automatically and successfully. This study that combines the image processing techniques with mini-Opto tomography imaging system ensured significant results in observing the tumoroid's growth rate and enlarging border over time, which is very critical to provide an emerging methodology in vitro cancer studies.

A Realistic Breast Phantom Proposal for 3D Image Reconstruction in Digital Breast Tomosynthesis.

Objectives: Iterative (eg, simultaneous algebraic reconstruction technique [SART]) and analytical (eg, filtered back projection [FBP]) image reconstruction techniques have been suggested to provide adequate three-dimensional (3D) images of the breast for capturing microcalcifications in digital breast tomosynthesis (DBT). To decide on the reconstruction method in clinical DBT, it must first be tested in a simulation resembling the real clinical environment. The purpose of this study is to introduce a 3D realistic breast phantom for determining the reconstruction method in clinical applications. Methods: We designed a 3D realistic breast phantom with varying dimensions (643-5123) mimicking some structures of a real breast such as milk ducts, lobules, and ribs using TomoPhantom software. We generated microcalcifications, which mimic cancerous cells, with a separate MATLAB code and embedded them into the phantom for testing and benchmark studies in DBT. To validate the characterization of the phantom, we tested the distinguishability of microcalcifications by performing 3D image reconstruction methods (SART and FBP) using Laboratory of Computer Vision (LAVI) open-source reconstruction toolbox. Results: The creation times of the proposed realistic breast phantom were seconds of 2.5916, 8.4626, 57.6858, and 472.1734 for 643, 1283, 2563, and 5123, respectively. We presented reconstructed images and quantitative results of the phantom for SART (1-2-4-8 iterations) and FBP, with 11 to 23 projections. We determined qualitatively and quantitatively that SART (2-4 iter.) yields better results than FBP. For example, for 23 projections, the contrast-to-noise ratio (CNR) values of SART (2 iter.) and FBP were 2.871 and 0.497, respectively. Conclusions: We created a computationally efficient realistic breast phantom that is eligible for reconstruction and includes anatomical structures and microcalcifications, successfully. By proposing this breast phantom, we provided the opportunity to test which reconstruction methods can be used in clinical applications vary according to various parameters such as the No. of iterations and projections in DBT.

An alternative approach to tracing the volumic proliferation development of an entire tumor spheroid in 3D through a mini-Opto tomography platform.

Microscopy, which is listed among the major in-situ imaging applications, allows to derive information from a biological sample on the existing architectural structures of cells and tissues and their changes over time. Large biological samples such as tumor spheroids cannot be imaged within one field of view, regional imaging in different areas and subsequent stitching are required to attain the full picture. Microscopy is not typically used to produce full-size visualization of tumor spheroids measuring a few millimeters in size. In this study, we propose a 3D volume imaging technique for tracing the growth of an entire tumor spheroid measuring up to 10 mm using a miniaturized optical (mini-Opto) tomography platform. We performed a primary analysis of the 3D imaging for the MIA PaCa-2 pancreatic tumoroid employing its 2D images produced with the mini-Opto tomography from different angles ranging from -25 ° to +25 ° at six different three-day-apart time points of consecutive image acquisition. These 2D images were reconstructed by using a 3D image reconstruction algorithm that we developed based on the algebraic reconstruction technique (ART). We were able to reconstruct the 3D images of the tumoroid to achieve 800 × 800-pixel 50-layer images at resolutions of 5-25 µm. We also created its 3D visuals to understand more clearly how its volume changed and how it looked over weeks. The volume of the tumor was calculated to be 6.761 mm3 at the first imaging time point and 46.899 mm3 15 days after the first (at the sixth time point), which is 6.94 times larger in volume. The mini-Opto tomography can be considered more advantageous than commercial microscopy because it is portable, more cost-effective, and easier to use, and enables full-size visualization of biological samples measuring a few millimeters in size.

Linear and non-linear dynamics of the epidemics: System identification based parametric prediction models for the pandemic outbreaks.

Coronavirus disease 2019 (COVID-19) has endured constituting formidable economic, social, educational, and phycological challenges for the societies. Moreover, during pandemic outbreaks, the hospitals are overwhelmed with patients requiring more intensive care units and intubation equipment. Therein, to cope with these urgent healthcare demands, the state authorities seek ways to develop policies based on the estimated future casualties. These policies are mainly non-pharmacological policies including the restrictions, curfews, closures, and lockdowns. In this paper, we construct three model structures of the SpInItIbD-N (suspicious Sp, infected In, intensive care It, intubated Ib, and dead D together with the non-pharmacological policies N) holding two key targets. The first one is to predict the future COVID-19 casualties including the intensive care and intubated ones, which directly determine the need for urgent healthcare facilities, and the second one is to analyse the linear and non-linear dynamics of the COVID-19 pandemic under the non-pharmacological policies. In this respect, we have modified the non-pharmacological policies and incorporated them within the models whose parameters are learned from the available data. The trained models with the data released by the Turkish Health Ministry confirmed that the linear SpInItIbD-N model yields more accurate results under the imposed non-pharmacological policies. It is important to note that the non-pharmacological policies have a damping effect on the pandemic casualties and this can dominate the non-linear dynamics. Herein, a model without pharmacological or non-pharmacological policies might have more dominant non-linear dynamics. In addition, the paper considers two machine learning approaches to optimize the unknown parameters of the constructed models. The results show that the recursive neural network has superior performance for learning nonlinear dynamics. However, the batch least squares outperforms in the presence of linear dynamics and stochastic data. The estimated future pandemic casualties with the linear SpInItIbD-N model confirm that the suspicious, infected, and dead casualties converge to zero from 200000, 1400, 200 casualties, respectively. The convergences occur in 120 days under the current conditions.

Development of a Multi-Dimensional Parametric Model With Non-Pharmacological Policies for Predicting the COVID-19 Pandemic Casualties.

Coronavirus Disease 2019 (COVID-19) has spread the world resulting in detrimental effects on human health, lives, societies, and economies. The state authorities mostly take non-pharmacological actions against the outbreak since there are no confirmed vaccines or treatments yet. In this paper, we developed Suspicious-Infected-Death with Non-Pharmacological policies (SpID-N) model to analyze the properties of the COVID-19 casualties and also estimate the future behavior of the outbreak. We can state the key contributions of the paper with three folds. Firstly, we propose the SpID-N model covering the higher-order internal dynamics which cause the peaks in the casualties. Secondly, we parametrize the non-pharmacological policies such as the curfews on people with chronic disease, people age over 65, people age under 20, restrictions on the weekends and holidays, and closure of the schools and universities. Thirdly, we explicitly incorporate the internal and coupled dynamics of the model with these multi-dimensional non-pharmacological policies. The corresponding higher-order and strongly coupled model has utterly unknown parameters and we construct a batch type Least Square (LS) based optimization algorithm to learn these unknown parameters from the available data. The parametric model and the predicted future casualties are analyzed extensively.

A Novel Parametric Model for the Prediction and Analysis of the COVID-19 Casualties.

Coronavirus disease (COVID-19) outbreak has affected billions of people, where millions of them have been infected and thousands of them have lost their lives. In addition, to constraint the spread of the virus, economies have been shut down, curfews and restrictions have interrupted the social lives. Currently, the key question in minds is the future impacts of the virus on the people. It is a fact that the parametric modelling and analyses of the pandemic viruses are able to provide crucial information about the character and also future behaviour of the viruses. This paper initially reviews and analyses the Susceptible-Infected-Recovered (SIR) model, which is extensively considered for the estimation of the COVID-19 casualties. Then, this paper introduces a novel comprehensive higher-order, multi-dimensional, strongly coupled, and parametric Suspicious-Infected-Death (SpID) model. The mathematical analysis results performed by using the casualties in Turkey show that the COVID-19 dynamics are inside the slightly oscillatory, stable (bounded) region, although some of the dynamics are close to the instability region (unbounded). However, analysis with the data just after lifting the restrictions reveals that the dynamics of the COVID-19 are moderately unstable, which would blow up if no actions are taken. The developed model estimates that the number of the infected and death individuals will converge zero around 300 days whereas the number of the suspicious individuals will require about a thousand days to be minimized under the current conditions. Even though the developed model is used to estimate the casualties in Turkey, it can be easily trained with the data from the other countries and used for the estimation of the corresponding COVID-19 casualties.

A miniaturized optical tomography platform for volumetric imaging of engineered living systems.

Volumetric optical microscopy approaches that enable acquisition of three-dimensional (3D) information from a biological sample are attractive for numerous non-invasive imaging applications. The unprecedented structural details that these techniques provide have helped in our understanding of different aspects of architecture of cells, tissues, and organ systems as they occur in their natural states. Nonetheless, the instrumentation for most of these techniques is sophisticated, bulky, and costly, and is less affordable to most laboratory settings. Several miniature imagers based on webcams or low-cost sensors featuring easy assembly have been reported, for in situ imaging of biological structures at low costs. However, they have not been able to achieve the ability of 3D imaging throughout the entire volumes for spatiotemporal analyses of the structural changes in these specimens. Here we present a miniaturized optical tomography (mini-Opto) platform for low-cost, volumetric characterization of engineered living systems through hardware optimizations as well as applications of an optimized algebraic algorithm for image reconstruction.

An iterative reconstruction algorithm for digital breast tomosynthesis imaging using real data at three radiation doses.

BACKGROUND: Iterative image reconstruction in Digital Breast Tomosynthesis (DBT) is a developing modality that produces three-dimensional (3D) reconstructed images of a breast to detect suspicious lesions. Algebraic reconstruction technique (ART), one of the iterative image reconstruction methods, was applied to reconstruct 3D data of breast and is becoming as one alternative method for the conventional image reconstruction techniques such as filtered back projection (FBP) in DBT imaging. OBJECTIVE: A new majorization-minimization (MM) algorithm was presented for TV denoising of signals. In the field of DBT, however, the algorithm has not yet been applied. In this study, we proposed a new method of "ART+TV3D+MM," which applies (MM) algorithm to the images reconstructed by ART+TV3D for different imaging dose levels to investigate a possible reduction of radiation dose. METHODS: Projections of a real breast phantom (CD Pasmam 1054) were acquired with a Siemens MAMMOMAT DBT system. The proposed new method was repeated and tested with 3 different radiation dose levels. The quality of the images reconstructed using the proposed new method were compared with those generated by the commonly used FBP method using both qualitative and quantitative assessments. RESULTS: The new method showed superior results in terms of visual assessment, contrast to noise ratios (CNR), full width at half maximum (FWHM) values and 1D profiles compared with FBP of the Siemens MAMMOMAT. CNR values were evaluated for two different region of interests (ROIs). For instance, CNR values of ROI-2 of FBP and of new method were 1.670 and 1.978 at 100 mAs, respectively. Moreover, while CNR value of ROI-1 of FBP at 100 mAs was 0.955, CNR value of ROI-1 of using new method at 100 mAs was 48.163. FWHM values for FBP and the new method were 2.328 and 1.765 at 56 mAs, 2.032 and 1.661 at 100 mAs, and 2.111 and 1.736 at 199 mAs, respectively. CONCLUSIONS: The results support that using the new method of "ART+TV3D+MM" could help decrease the radiation dose level, which is one of the most critical limitations of DBT imaging.

Oculoauriculofrontonasal Dysplasia Syndrome With Additional Clinical Features.

Oculo-auriculo-vertebral spectrum and frontonasal dysplasia are two well-known examples of dysmorphology syndromes. Oculoauriculofrontonasal syndrome (OAFNS) is a clinical entity involving the characteristics of both OAVS and FND and is thought to be a result of the abnormal development of structures in the first and the second branchial arches, including the abnormal morphogenesis of maxillary processes. Herein we report a case of OAFNS with cliteral hypertrophy, premaxillary teeth, and inguinal hernia, features not previously reported in the literature.

Evaluation of Etanercept Treatment in Newborn Rat Model with Hyperoxic Lung Injury.

BACKGROUND: Many factors contribute to the development of BPD basically by increasing inflammation in preterm lungs. However, premature neonates have insufficient anti-inflammatory capacity. We aimed to evaluate the effect of etanercept, an anti-TNF agent, on BPD development in newborn rat model with hyperoxia-induced lung injury. METHODS: Thirty-two newborn rats were divided into 3 groups as control group (Group 1, n = 11), hyperoxia + placebo group (Group 2, n = 10), and hyperoxia + etanercept group (Group 3, n = 11). Histopathological and biochemical analysis were performed in order to assess inflammation and oxidative stress. Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activities, and malondialdehyde (MDA) levels were studied, histopathological scoring and radial alveolar count were applied in lung tissue. Lamellar body membrane protein, vascular endothelial growth factor (VEGF), nuclear factor-kappaB (NF-κB) gene expressions were studied in immunohistochemical evaluation of tissue samples. All three groups were compared with each other in terms of all parameters. RESULTS: SOD and GSH-Px activities were significantly higher, whereas MDA levels were lower in group 3, compared to group 2 (p < 0.001). Histopathological scores were lower, lamellar body membrane protein expression and radial alveolar count were higher in group 3 (p < 0.05). NF-κB expression was higher in group 2, but lower in group 3 in comparison with group 1. Expression of VEGF was decreased in group 2 but came close to group 1 with etanercept treatment in group 3. CONCLUSIONS: We found etanercept treatment to be protective in newborn rats with hyperoxia-induced lung damage.

Comparison of the efficacy of once- and twice-daily colchicine dosage in pediatric patients with familial Mediterranean fever--a randomized controlled noninferiority trial.

BACKGROUND: In this study, we examined the efficacy and safety of a once-daily dosage schema of colchicine compared with a twice-daily dosage schema in pediatric patients with familial Mediterranean fever (FMF). METHODS: In this 24-week, multicenter, randomized controlled noninferiority trial, pediatric patients newly diagnosed with FMF carrying a homozygous or compound heterozygous mutation and not receiving any treatment were included. Patients were randomly assigned using a block randomization method to receive treatment with a once- or twice-daily dosage. Clinical and laboratory characteristics and medication side effects were recorded and compared between groups. The study was carried out in compliance with Good Clinical Practice and the Consolidated Standards for Reporting of Trials (CONSORT) statement. RESULTS: A total of 92 patients were selected, and 79 patients completed the study. There were 42 patients in the once-daily dosage group and 37 in the twice-daily dosage group. The results indicated that the once-daily dosage was not inferior to the twice-daily dosage regarding decrease in attack frequency and duration as well as improvement in clinical findings and Mor severity scores. Alterations in laboratory findings indicating inflammation, such as erythrocyte sedimentation rate, C-reactive protein, and serum amyloid A, were similar in both groups. The rates of drug side effects were similar between the once- and twice-daily dosage groups, implying comparable safety of colchicine, with the exception of diarrhea, which was slightly higher in the once-daily dosage group. CONCLUSIONS: Using colchicine with either a once- or twice-daily dosage provides similar clinical and laboratory improvements. Considering both efficacy and safety, colchicine can be prescribed with a once-daily dosage. TRIAL REGISTRATION ID: ClinicalTrials.gov identifier NCT02602028 . Registered 5 November 2015.

Interleukin-8 and Its Receptors in Human Milk from Mothers of Full-Term and Premature Infants.

In addition to its nutritional benefits, human milk also has bioactive elements. Limited immunological functions of newborns are supported and altered by the immunological elements of mother milk. Chemokines are of importance among these immune factors. Interleukin-8 (IL-8) has been demonstrated in mother's milk, and its receptors, CXC chemokine receptors (CXCR)-1 and CXCR-2, were detected on cells, responsible for immunological reactions and mammary glandular cells. The soluble forms of these receptors are yet to be described in human milk. In this study, it was aimed to assess the IL-8 levels and the concentrations of its receptors in colostrum and mature mother's milk in regard to preterm and term delivery. The results of this study indicated a decline in IL-8 levels with the lactation stage, but no difference was observed between term and preterm mother's milk. Regarding the CXCR-1 and CXCR-2, the concentrations of these receptors were similar in both colostrum and mature milk. Furthermore, there was not any significant difference between term and preterm mother's milk. In conclusion, this is the first study to investigate the concentrations of CXCR-1 and CXCR-2 with the levels of IL-8 in colostrum and mature human milk of term and preterm newborns. The alterations in IL-8 levels were similar in some of the studies reported. CXCR-1 and CXCR-2 levels did not demonstrate any significant difference. Further studies are required to investigate the soluble forms of these receptors and their relation to IL-8 with larger cohort.

Development of a medication adherence scale for familial Mediterranean fever (MASIF) in a cohort of Turkish children.

OBJECTIVES: To develop and assess the validity and reliability of an adherence scale concerning medical treatment in paediatric FMF patients. METHODS: The Medication Adherence Scale in FMF Patients (MASIF) is a 18-item questionnaire that evaluates adherence to medication in four domains. Validation of the instrument was accomplished in paediatric FMF patients (aged 2-18 years) under medication at least for 6 months. The first step was to build up the scale through qualitative approach (with interviews using semi-structured questions). Validation analyses included assessment of feasibility, face and content validity; construct validity, internal consistency and test-retest reliability. RESULTS: One hundred and fifty patients with FMF were enrolled in the study. The mean age of the patients was 11.11±4.02 years and 48.7% of them were male. The MASIF was found to be feasible and valid for both face and content. It correlated with the Morisky Medication Adherence Scale as a gold standard thereby demonstrating good construct validity (r=0.515, p<0.001). Assessment of content validity identified four subscales. The internal consistency, Cronbach's alpha was 0.728. There was a positive and significant correlation between test and retest scores (r=0.843; p<0.001). Also, a significant correlation between parents' and children's reports (r=0.781, p<0.001). CONCLUSIONS: Based on these results, the use of this scale to assess and follow up the adherence to treatment in paediatric FMF patients under medical treatment is recommended.

Endothelial function in patients with familial Mediterranean fever-related amyloidosis and association with cardiovascular events.

OBJECTIVES: Secondary amyloidosis is the most important complication of FMF and endothelial function is more severely impaired. Elevated asymmetric dimethyl arginine (ADMA) may mediate the excess cardiovascular disease (CVD) risk of this group. We aimed to compare endothelial function characteristics, including ADMA, in patients with FMF-related amyloidosis and primary glomerulopathies and to define risk factors for a CVD event. METHODS: We undertook a cross-sectional study with prospective follow-up including consecutive patients with FMF-related amyloidosis (n = 98) or other non-diabetic glomerulopathies (n = 102). All patients had nephrotic-range proteinuria and normal glomerular filtration rate. Flow-mediated dilatation (FMD) was assessed and ADMA levels, CRP and pentraxin 3 (PTX3) were determined. Patients were followed for cardiovascular events. RESULTS: Amyloidosis patients secondary to FMF showed higher levels of ADMA, CRP and PTX3 and lower FMD as compared with patients with other glomerulopathies. Cardiovascular events (n = 54) were registered during 3 years of follow-up. Increased ADMA levels and lower FMD were observed in patients with cardiovascular risk in both groups, but especially in individuals with amyloidosis. CONCLUSION: Patients with FMF-related amyloidosis have increased CVD event risk, probably related to the high ADMA levels, elevated inflammatory markers and decreased FMD measures observed in these patients.

Results from a multicentre international registry of familial Mediterranean fever: impact of environment on the expression of a monogenic disease in children.

BACKGROUND AND AIM: Familial Mediterranean fever (FMF) is an autoinflammatory disease caused by mutations of the MEFV gene. We analyse the impact of ethnic, environmental and genetic factors on the severity of disease presentation in a large international registry. METHODS: Demographic, genetic and clinical data from validated paediatric FMF patients enrolled in the Eurofever registry were analysed. Three subgroups were considered: (i) patients living in the eastern Mediterranean countries; (ii) patients with an eastern Mediterranean ancestry living in western Europe; (iii) Caucasian patients living in western European countries. A score for disease severity at presentation was elaborated. RESULTS: Since November 2009, 346 FMF paediatric patients were enrolled in the Eurofever registry. The genetic and demographic features (ethnicity, age of onset, age at diagnosis) were similar among eastern Mediterranean patients whether they lived in their countries or western European countries. European patients had a lower frequency of the high penetrance M694V mutation and a significant delay of diagnosis (p<0.002). Patients living in eastern Mediterranean countries had a higher frequency of fever episodes/year and more frequent arthritis, pericarditis, chest pain, abdominal pain and vomiting compared to the other two groups. Multivariate analysis showed that the variables independently associated with severity of disease presentation were country of residence, presence of M694V mutation and positive family history. CONCLUSIONS: Eastern Mediterranean FMF patients have a milder disease phenotype once they migrate to Europe, reflecting the effect of environment on the expression of a monogenic disease.

The invisible part of the iceberg: qualitative aspects of childhood vasculitis.

OBJECTIVES: The aim of this study was to develop a multidimensional assessment instrument named 'Juvenile Vasculitis Multidimensional Assessment Report' (J-VAMAR) to measure all the domains of the vasculitis. In this qualitative study, it is primarily aimed to enrich the item generation for the J-VAMAR. METHODS: Twelve children with vasculitis and their mothers (n=12) were enrolled in this study. The data were collected using both a demographic data form and a semi-structured interview form. The study was performed on individual patient face-to face interview. Data were analysed by grounded theory and the N Vivo 9 software program. RESULTS: Four categories were obtained. These categories were (i) physical effects of the illness, (ii) emotional effects of the illness, (iii) social effects of the illness and (iv) experienced challenges related to treatment process. In the physical effect category severe pain, physical limitations, weakness and fatigue; in emotional effect category thought of death, hopelessness and dissatisfaction about body image; in the social effects category decrease in academic performance, absenteeism to school and concealing the sickness from friends were the most common features. In the fourth category, subjects complained of lifelong drug use and frequency of daily drug consumptions. CONCLUSIONS: These results provide evidence-based data for the assessment of children with vasculitis by several domains including physical, emotional and social aspects as well as treatment protocols. The study provides the basis and/or justification for selecting the domains that the developing multidimensional instrument should include.

Evaluation of the current disease severity scores in paediatric FMF: is it necessary to develop a new one?

OBJECTIVES: Modified adult disease severity scoring systems are being used for childhood FMF. We aim to test the clinical consistency of two common severity scoring systems and to evaluate the correlation of scores with the type of FMF mutations in paediatric FMF patients since certain mutations are prone to severe disease. METHODS: Two hundred and fifty-eight children with FMF were cross-sectionally studied. Assessment of the disease severity was performed by using the modified scoring systems of Mor et al. and Pras et al. Genetic analysis was performed using PCR and restriction endonuclease digestion methods for the presence of 15 FMF gene mutations. FMF mutations were grouped into three based on well-known genotypic-phenotypic associations. Correlation between the mutation groups and the severity scoring systems was assessed. The consistency of the severity scoring systems was evaluated. RESULTS: The results of two scoring systems were not statistically consistent with each other (κ = 0.171). This inconsistency persisted even in a more homogeneous subgroup of patients with only homozygote mutations of M694V, M680I and M694I (κ = 0.125). There was no correlation between the mutation groups and either of the scoring systems (P = 0.002, r = 0,196 for scoring systems of Mor et al.; P = 0.009, r = 0.162 for Pras et al.). CONCLUSIONS: The inconsistency of the two scoring systems and lack of correlation between the scoring systems and mutation groups raises concerns about the reliability of these scoring systems in children. There is a need to develop a scoring system in children based on a prospective registry.