Bone In Children Research Articles

Identifying Key Differences Between Responders vs. Non-Responders to Immune Checkpoint Blockade for Metastatic Osteosarcoma (mOS)

Abstract Osteosarcoma is the most common childhood bone malignancy, with a sharp decline in survival rates upon metastasis. We have previously shown immune checkpoint blockade (ICB) of anti-CTLA-4/anti-PD-L1 for mice inoculated with a K7M2 metastatic osteosarcoma (mOS) cell line resulted in ~50% survival with complete tumor clearance, including recent analogous results upon replication of this treatment regimen. Differences in response rates to ICB are common among patients with the same malignancy across various cancers. Unlike inbred lab mice, human patients have diversity in genetic makeup and other factors, causing the discrepancy in ICB response to remain poorly understood. A culprit for these discrepancies is variance in circulating antibodies (Abs), which can indicate differences in disease presence, microbiome composition, or immune-modulating factors. Recent studies have characterized Ab patterns in sera by using microarrays with thousands of randomly sequenced peptides and incubating on them diluted sera. The Ab binding pattern on the microarray is termed an “immunosignature.” We have found that before inoculation with mOS or ICB, blood from mice displays distinct differences in immunosignatures between responders and non-responders, suggesting that the presence or absence of particular Abs may influence the outcome of ICB for mOS. Additionally, recent studies have discovered that ICB’s effectiveness can be associated with or even reliant on ICB recipients’ microbiome composition and that changes in microbiome composition can result in subsequent changes to circulating Abs. Here we analyze both differences in Ab composition and microbiome composition, highlighting their impact on ICB efficacy for mOS. Funding support for this work has been provided by a grant through the Sarcoma Foundation of America (SFA). Additional funding support for this work has been provided by a grant through the Graduate and Professional Student Association (GPSA) at Arizona State University.

A Case of Aplastic Anemia and Colon Cancer With Underlying Spliceosome Mutation: Is It an Incidental Finding or a Novel Association?

Alternative splicing is an epigenetic mechanism that plays a role in the development and function of antigen-specific lymphocytes. One such is the zinc-finger-RNA-binding-motif-and-serine/arginine-rich-2 (ZRSR2), which is clinically implicated in myelodysplastic syndrome and leukemia. Here, we present a case of a young male with myriad autoimmune conditions and adenocarcinoma of the colon in the setting of ZRSR2 mutation.A 28-year-old male with common variable immunodeficiency disease, atopic dermatitis, autoimmune gastroenteropathy, inflammatory polyarthropathy, primary bone marrow failure, colon cancer, and family history of Lynch syndrome was admitted to our hospital for an acute flare of autoimmune enteropathy secondary to subtherapeutic tacrolimus levels.He initially developed pancytopenia at the age of 26 years. Workup for HIV, hepatitis, cytomegalovirus, human-herpesvirus 6, parvovirus was negative. Partial thromboplastin time (PTT), international normalized ratio (INR), d-dimer, ferritin, iron profile, antinuclear antibodies (ANA) screen was unremarkable. Direct, indirect, and super-combs antibodies were undetectable. Chromosomal study for Fanconi-related chromosomal breakage and telomerase gene panel was negative. Flow cytometry did not reveal an abnormal clone. Bone marrow biopsy showed markedly hypocellular marrow with reduced trilineage hematopoiesis and 1% blasts with normal cytogenetics, immunohistochemistry, fluorescence in situ hybridization (FISH), and negative for myelodysplastic syndrome and paroxysmal nocturnal hemoglobinuria (PNH). Cincinnati inherited children’s bone marrow transplant (BMT) panel was negative. He was diagnosed with aplastic anemia and was treated with antithymocyte globulin, cyclosporine, prednisone, and currently tacrolimus. At the age of 26 years, he was diagnosed with colon cancer. Immunohistochemistry was positive for MLH1, but the confirmatory genetic testing for Lynch syndrome was negative. He underwent total proctocolectomy and ileostomy and is currently in remission. Next-generation sequencing of bone marrow revealed a germline homozygous ZRSR2 mutation. ZRSR2 spliceosome mutations are more common in males as it’s an X-linked gene. They are seen in myelodysplastic syndrome, leukemia, increased autoimmune phenomenon, and 35 cases of colon cancer associated with this mutation are reported. In the setting of aplastic anemia and lynch negative colon cancer, we suspect our patient could have aplastic anemia due to an autoimmune phenomenon, underlying common variable immunodeficiency disease (CVID), or the new ZRSR2 mutation could be playing a role. Further studies and research is warranted to determine its true association with the disease entities. The underlying contributing factor is ZRSR2 mutation.

Predictive Algorithms in the Diagnosis and Management of Pediatric Hip and Periarticular Infection.

➤ Although the criteria of Kocher et al. were an important advancement in our ability to diagnose septic arthritis of the hip early, the changing microbial landscape and availability of advanced imaging have rendered it insufficient for contemporary clinical use.➤ Routine use of magnetic resonance imaging and recognition of disseminated disease have prompted the development of algorithms to predict concurrent osteoarticular infection in cases of septic arthritis and osteomyelitis that were previously assumed to be "isolated."➤ Recent research has attempted to stratify childhood bone and joint infection (BJI) by severity to guide treatment planning. This is valuable, as patients with multifocal disease, more virulent pathogens, and immunocompromise can have longer hospital stays and require multiple surgeries.➤ The increasing prevalence of clinical prediction algorithms in childhood BJI is not completely matched by quality in methodology. Clinicians need to be wary of adopting predictive algorithms prior to robust external validation.

Subsequent Malignant Neoplasm of Bone in Children and Adolescent-Possibility of Multimodal Treatment.

Background: In recent years, modifications of treatment protocols introduced in pediatric oncology have resulted in a significant improvement in treatment outcomes. Unfortunately, the probability of subsequent malignant neoplasm (SMN) in this group of patients is 3 to 6 times higher than the general age-matched population. In this study, we sought to evaluate the treatment options for patients with secondary bone tumors after prior anti-cancer therapy. Materials and Methods: Twenty-four patients (median age 12.9 years) with subsequent malignant bone tumors were treated according to oncological guidelines for bone sarcoma during the period 1991–2020. All patients had a standard tumor imaging and laboratory evaluation. All toxicities were documented. Results: The median time from the first neoplasm to SMN was 7.6 years (range 2.4 to 16.3 years). All patients received chemotherapy and underwent surgery as a local control procedure. Two patients with Ewing sarcoma had additional radiation on the tumor bed. A complete response was achieved in 20 patients. With a median follow-up of 18.3 years (range 5.7 to 40.3 years), 18 patients (75%) are alive. The estimated 5-year post-subsequent bone malignant neoplasm survival was 74.5% (95% CI 55–95%). Fourteen patients required chemotherapy dose modification, and doxorubicin was discontinued in seven patients. One patient required a renal transplant two years after treatment. There were no other significant toxicities. Conclusions: The treatment of bone SMNs can be effective, although in many patients it is necessary to reduce the doses of drugs. Early detection and aggressive treatment can improve the outcome.

Global epidemiology of childhood bone and joint infection: a systematic review.

Childhood bone and joint infection (BJI) is a potentially severe disease that may have permanent sequelae, including growth impairment and limb deformity. It has been characterised in the literature with a focus on Western epidemiology; there are currently no reports detailing global epidemiology and bacteriology. This omits key data from determining temporal trends, appropriate antibiotic therapy, and resource allocation. This review aims to identify studies that characterise the incidence of childhood bone and joint infection or provide detailed bacteriology within their region. A systematic review of the literature was performed from 01/01/1980 to 31/12/2020. Data hasbeen analysed to give incidence of disease per 100,000 children, primary pathogen by country where available, and risk ratio (RR) for disease by ethnicity. This is applicable for areas that experience race-related inequitable burden of disease. Forty-four articles met the inclusion area; of these, seven were population-wide studies, primarily from Europe or the United States, and the remainder were cohort studies. Incidence could be derived from 26 studies compromising over 34, 000 children. Information on bacteriology was available from 39 publications (10, 957 cases). Methicillin-sensitive Staphylococcus aureus is the most common pathogen in the West. Recently, disease secondary to Kingella kingae and methicillin-resistant S. aureus has increased. Salmonella remains a dominant pathogen in African regions. Increased risk of disease is observed in Aboriginal, New Zealand Māori, Pacific, Indigenous Fijian, and Bedouin children. The current state of the literature detailing incidence of childhood BJI focuses on disease patterns from the West. There is a paucity of high-quality publications in the developing world. Despite these limitations, global trends in burden of disease show race-related inequitable risk of BJI. Temporal and regional variation in bacteriology can be demonstrated. III.

Histopathologic and Spectrometric Evaluation of Bony Components of Synostotic Suture and Parietal Bone in Children with Sagittal Synostosis.

Sagittal synostosis, the premature fusion of sagittal suture, is the most common form of craniosynostosis. The premature suture line closure restricts bone growth in the direction perpendicular to the suture line with frontal bossing, bitemporal narrowing, and often a characteristic palpable ridge along the fused sagittal suture. This study aimed to understand the characterization of the ossification process both in the synostotic suture and adjacent parietal bone. The surgical procedure for the 28 patients diagnosed with sagittal synostosis consisted of removing the synostotic bone as a whole, if possible, "Barrel-Stave" relaxation osteotomies, and strip osteotomies to the parietal and temporal bones perpendicular to the synostotic suture. The synostotic (group I) and parietal (group II) bone segments are obtained during osteotomies. Atomic absorption spectrometry was used to determine the amount of calcium in both groups, which is an indicator of ossification. Scanning electron microscopy and immunohistochemistry were employed to assess trabecular bone formation, osteoblastic density, and osteopontin, which is one of the in vivo indicators of new bone formation. Histopathologically, trabecular bone formation scores did not indicate any significant difference between the groups. However, the osteoblastic density and calcium accumulation in group I were higher than those in group II, and the difference was significant. Osteopontin staining scores in cells showing membranous and cytoplasmic staining with osteopontin antibodies significantly increased in group II. In this study, we found reduced differentiation of osteoblasts despite their increase in number. Moreover, the osteoblastic maturation rate was low in synostotic sutures, bone resorption becomes slower than new bone formation, and the remodeling rate is low in sagittal synostosis.

Morphological diagnosis of childhood bone marrow failure syndromes

In 2008, the World Health Organization proposed a provisional entity of childhood myelodysplastic syndrome (MDS) without a blasts increase, which was referred to as the refractory cytopenia of childhood (RCC). We performed a central review of bone marrow morphology in 252 children with acquired bone marrow failure syndromes to clarify the clinical relevance of the RCC. The RCC was divided two categories, namely, RCC without multilineage dysplasia (MLD) and RCC with MLD, which is similar to MDS with MLD in adult MDS. Furthermore, the clinical outcomes were investigated for cases diagnosed with aplastic anemia, RCC without MLD, and RCC with MLD. The response rates to immunosuppressive therapy and the incidence of the development of the new chromosomal aberration did not significantly differ among the three groups. The RCC with MLD can be adopted in childhood MDS since children with this condition exhibited a frequent chromosomal aberration at the time of diagnosis and a high frequency of secondary graft failure after a hematopoietic cell transplantation.

Associations of pregnancy phthalate concentrations and their mixture with early adolescent bone mineral content and density: The Health Outcomes and Measures of the Environment (HOME) study.

The developing fetus may be particularly susceptibility to environmental osteotoxicants, but studies of pregnancy phthalate exposures and childhood bone health are scarce. To examine relations of pregnancy phthalate exposure biomarkers with early adolescent bone mineral density (BMD) and bone mineral content (BMC) in a prospective birth cohort. We used data from 223 pregnant mothers and their children enrolled in a Cincinnati, OH area cohort from 2003 to 2006. We quantified monoethyl phthalate (MEP), monoisobutyl phthalate, monobutyl phthalate, monobenzyl phthalate, mono-(3-carboxypropyl) phthalate (MCPP), and four metabolites of di-2-ethylhexyl phthalate in maternal urine collected at 16 and 26weeks gestation, and calculated the average of creatinine-standardized concentrations. Using dual x-ray absorptiometry measures at age 12years, we calculated BMD and BMC Z-scores for six skeletal sites. In overall and sex-stratified models, we estimated covariate-adjusted associations per 2-fold increase in phthalate biomarker concentrations using linear regression, and estimated joint effects of the phthalate biomarkers mixture using Bayesian kernel machine regression (BKMR) and quantile g-computation. In single phthalate models, several biomarkers were positively associated with BMC and BMD. For example, each doubling of MEP and MCPP, 1/3rd distal radius BMD Z-score increased by 0.09 (95% CI: 0.01, 0.17) and 0.16 (95% CI: 0.01, 0.31), respectively. For phthalate mixtures, associations were generally U-shaped among males and positive-linear among females, using both statistical methods. Mixture associations were strongest with forearm sites: in BKMR models, increasing all biomarkers from the 50th to 90th percentile was associated with a 0.64 (95% CI: 0.01, 1.28) greater 1/3rd distal radius BMD Z-score in males, and a 0.49 (95% CI: -0.13, 1.10) greater ultradistal radius BMD Z-score in females. In this study, phthalate exposures during gestation were associated with increased BMD Z-scores in early adolescence, though further research is needed to determine implications for long-term skeletal health.

Pelatihan Pembuatan Keju untuk Memenuhi Kebutuhan Nutrisi Tulang dan Gigi Anak Masa Golden age

The Training of Making Cheese to Meet the Nutritional Needs of Children's Bones and Teeth during the Golden Age
 Golden age is a golden period of early childhood in conducting exploration activities in shaping children's character. In fulfilling the nutritional intake of children aged 3-5 years, there are 35% of children in Kukulu village who do not consume milk. This is due to the start of various activities of children in playing, so less consumption of milk. It causes the loss of appetite in consuming milk so that there are problems in the growth of children's bones and teeth. The purpose of program was to increase public knowledge in improving children's nutrition by processing milk into cheese so that the benefits and content of milk are maintained. The method of this community service was lecturing about the benefits of milk and the processing into cheese. Than, continued with training of cheese making in overcoming children who are less willing to consume milk. Evaluation data showe that about 80%-100% of the participants got the good and very good understanding about the material. And, about 80%-100% of them satisfied with satisfied with it.

High Prevalence of Gene Fusions and Copy Number Alterations in Pediatric Radiation Therapy-Induced Papillary and Follicular Thyroid Carcinomas.

Background: Childhood cancer survivors and bone marrow transplant recipients treated with radiation therapy (RT) are at increased risk for subsequent thyroid cancer. However, the genetic landscape of pediatric thyroid cancer, both primary and RT-induced, remains poorly defined, as pediatric papillary thyroid carcinoma (PTC) has been understudied compared with adults and data on pediatric follicular thyroid carcinoma (FTC) are virtually nonexistent. The objective of this study was to characterize and compare the molecular profiles of pediatric RT-induced PTC and FTC cases with primary pediatric thyroid cancers. Methods: A total of 41 differentiated thyroid carcinomas (11 RT cases and 30 primary cases) from 37 patients seen at Phoenix Children's Hospital between January 1, 2010 and December 31, 2019 were evaluated by targeted next-generation sequencing and/or BRAF immunohistochemistry. Results: Eighty-six percent (6/7) of RT-PTC harbored a gene fusion (GF) compared with 56% (14/25) of primary PTC; 14% (1/7) of RT-PTC had a single-nucleotide variant (SNV; specifically, a point mutation in the DICER1 gene) compared with 44% (11/25) of primary PTC (all of the latter had the BRAFV600E mutation). An exceedingly rare ROS1 fusion was identified in a child with RT-PTC. With respect to FTC, copy number alterations (CNAs) were seen in 75% (3/4) of RT cases compared with 40% (2/5) of primary cases. None of the RT-FTC had SNVs compared with 100% (5/5) of primary FTC. Conclusions: In children, the molecular profile of subsequent RT-induced thyroid cancers appears to differ from primary (sporadic and syndromic) cases, with a high prevalence of GFs in RT-PTC (similar to PTC occurring after the Chernobyl nuclear reactor accident) and CNAs in RT-FTC. A better understanding of the molecular mechanisms underlying these cancers may lead to more accurate diagnosis, prognosis, and treatment, as some of the genomic alterations are potentially targetable.

Effects of vitamin D and high dairy protein intake on bone mineralization and linear growth in 6- to 8-year-old children: the D-pro randomized trial

Vitamin D and dairy protein may stimulate bone mineralization and linear growth in children, but previous studies show inconsistent results and have not examined their combined effects. To investigate combined and separate effects of vitamin D supplementation and high-protein (HP) compared with normal-protein (NP) yogurt intake on children's bone mineralization and linear growth. In a 2×2-factorial trial, 200 healthy, 6- to 8-year-old, Danish, children with light skin (55°N) were randomized to 20µg/d vitamin D3 or placebo and to substitute 260g/d dairy with HP (10g protein/100g) or NP (3.5g protein/100g) yogurt for 24 weeks during an extended winter. Outcomes were total body less head (TBLH) and lumbar spine bone mineral density (BMD), bone mineral content (BMC), and bone area (BA) by dual-energy X-ray absorptiometry, height, and biomarkers of bone turnover and growth. The primary outcome was TBLH BMD. In total, 184 children (92%) completed the study. The baseline serum 25-hydroxyvitamin D was 80.8±17.2nmol/L, which increased by 7.2±14.1nmol/L and decreased by 32.3±17.5nmol/L with vitamin D and placebo, respectively. The baseline protein intake was 15.4±2.4 energy percentage (E%), which increased to 18.3±3.4 E% with HP. There were no vitamin D-yogurt interactions and no main effects of either intervention on TBLH BMD. However, vitamin D supplementation increased lumbar spine BMD and TBLH BMC compared to placebo, whereas HP groups showed lower increments in lumbar spine BMD, TBLH BMC and BA, and plasma osteocalcin compared to NP groups. Height, growth factors, and parathyroid hormone levels were unaffected. Although there were no effects on whole-body BMD, vitamin D increased bone mass and spinal BMD, whereas high compared with normal dairy protein intake had smaller incremental effects on these outcomes. This supports a recommended vitamin D intake of around 20µg/d during winter but not use of HP dairy products for improved bone mineralization among healthy, well-nourished children. This trial was registered at clinicaltrials.gov as NCT03956732.

O18 When joints vanish

O18 When joints vanish

Diagenesis of juvenile skeletal remains: A multimodal and multiscale approach to examine the post-mortem decay of children's bones

This study aimed to examine the degradation of juvenile skeletal remains with respect to adult counterparts from different burial settings in Milan, Italy. A multiscale and multimodal approach was applied to investigate bone diagenesis by combining chemical and mineralogical analyses with synchrotron radiation-based virtual histology. Certain differences could be observed between child and adult skeletal remains; juvenile bones exhibited (i) poorer histological conservation, with prominent general re-organisation of the observed three-dimensional original microstructure, resulting in denser structures with low porosity; (ii) bioapatites with low defective structures, with chemical compositions highly site-sensitive, exhibiting variation even within a single bone; (iii) organic matter highly variable in terms of quality, quantity, and arrangement, even within a single bone sample. Conversely, organic decay results in similar enrichment in calcium content both in juveniles and in adults. In conclusion, the present work points out high intra-individual skeletal preservation in archaeological juvenile bones with respect to adults, thus suggesting that immature and mature bone tissues deteriorate at different rates, foremost as a function of their intrinsic features (shape, porosity, histological structures, etc.), and secondarily under the influence of the burial environment.

Identifying periods of susceptibility to perfluoroalkyl substances and bone mineral density in early adolescence: the HOME Study

BACKGROUND AND AIM: Perfluoroalkyl substance (PFAS) exposures may affect childhood bone mineral density (BMD), but no studies have assessed periods of heightened susceptibility. We estimated associations of individual PFAS and their mixture during gestation and three times during childhood with BMD in early adolescence. METHODS: We examined 222 mother-child pairs enrolled in a prospective pregnancy and birth cohort in Cincinnati, OH from 2003-2006. We measured concentrations of perfluorooctanoic acid (PFOA), perfluorononanoic acid, perfluorohexanesulfonic acid, and perfluorooctanesulfonic acid in maternal serum collected at 16 weeks gestation and child serum collected at age 3, 8, and 12 years. At age 12 years, we measured areal BMD at six skeletal sites with dual x-ray absorptiometry and calculated height-, age-, sex-, and population ancestry-specific BMD Z-scores. Using linear regression, we estimated covariate-adjusted differences in BMD Z-scores per doubling of PFAS concentrations at each period. Using hierarchical Bayesian kernel machine regression (hBKMR), we estimated period-specific associations and posterior inclusion probabilities (PIPs) to determine periods of heightened susceptibility to PFAS mixtures. RESULTS:Associations were strongest for PFOA and forearm (1/3 distal radius) BMD, with differing periods of susceptibility for males and females. Among males, forearm BMD Z-score differences (95% confidence interval) per doubling of PFOA were -0.26 (-0.50, -0.02), -0.33 (-0.68, 0.02), -0.24 (-0.61, 0.13), and -0.00 (-0.30, 0.29) for gestation and ages 3, 8, and 12, respectively. Among females, the corresponding estimates were -0.12 (-0.38, 0.15), -0.07 (-0.44, 0.30), -0.30 (-0.76, 0.17), and -0.44 (-0.81, -0.07). Patterns were generally similar but weaker for other PFAS and skeletal sites. Period-specific PIPs from hBKMR models were highest for the PFAS mixture at age 8 for males (0.76) and age 12 for females (0.62). CONCLUSIONS:PFOA and PFAS mixtures were associated with lower BMD in early adolescence. Susceptibility to PFAS may occur earlier in life for males compared with females. KEYWORDS: Chemical exposures, Children's environmental health, Mixtures analysis, PFAS, Endocrine disrupting chemicals, Environmental epidemiology

First report of Kingella kingae diagnosed in pediatric bone and joint infections in Morocco

BackgroundThe progress of diagnostic strategies and molecular methods improved the detection of Kingella kingae in bone and joint infections, and now, Kingella kingae is being increasingly recognized as the most frequent cause of bone and joint infection BJI in early childhood. The main objective of this prospective study is to report the frequency of Kingella Kingae in negative culture bone and joint pediatric infections, and to describe the clinical and biologic features of these children.MethodsFrom December 2016 to June 2019, we selected all hospitalized patients with suspected BJI. When culture was negative on the fifth day, children under 10 years were subsequently included in the study, and PCR assay was performed systematically for researching K. kingae specific gene cpn60. Microbial culture and identification were made using standard bacteriological methods. The demographics, clinical, laboratory, radiographic and clinical features were reviewed from medical records.ResultsWe enrolled 65 children with culture negative BJI, 46 of them having under 10 years old have been screened for the cpn60 gene. Thus, the gene encoding Kingella kingae was positive for 27 BJI cases (58.7%). The mean age of children was 3.02 years, 55.6% were aged 6 months-4 years and 29.6% of them were aged 5–10 years. The male to female ratio was 1.7 and 16 cases (59.26%) occurred during the fall-winter period. The most frequent BJI type was septic arthritis (77.8%) and the most affected sites were knee (51.9%) and hip (37.0%). We recorded a mild clinical picture with normal to mildly raised inflammatory markers. All patients had good clinical and functional outcomes, with no serious orthopedic sequelae..ConclusionK kingae is an important pathogen of culture-negative BJI in Moroccan children. PCR testing should be performed in culture-negative cases of children not only in the typical age range of 6 months to 4 years. When implemented in the routine clinical microbiology laboratory, a specific K. kingae PCR assay can provide a better diagnostic performance of BJI.

Child-centered approach to prevent disability: An empirical study in the country area of Bangladesh

Malnutrition is a common problem where the prevalence of malnutrition and other vulnerabilities is very high in Bangladesh as well as other low and middle-income countries. Among the vulnerabilities, Rickets is a common bone disorder where bones soften and become prone to fractures and deformity. It is a childhood disorder and rare in industrialized nations but relatively common in some developing countries. Rickets is a significant public health problem in Bangladesh for the past two decades, with up to 8% of children clinically affected in some areas. Rickets was identified in 1991 by workers from Social Assistance and Rehabilitation of the Physically Vulnerable (SARPV) after a devastating cyclone. A survey was conducted in a village, and approximately 1% of children had rachitic deformities. A collaborative assessment revealed that Rickets was more common than suspected in Chakaria; it was not generally associated with vitamin D deficiency but was related to dietary calcium insufficiency. Insufficiency of dietary Calcium is the underlying cause, and treatment with Calcium (350–1,000 mg elemental calcium daily) is curative. Despite this simple treatment, very little is known about the proper management of affected children's bone deformities, and further studies are needed to determine the treatment and specific intervention. For this purpose, a subtle assessment of a child-centered approach to preventing disability is the foremost priority.

Pediatric skeletal diffusion-weighted magnetic resonance imaging: part 1 - technical considerations and optimization strategies.

Diffusion-weighted MRI, or DWI, is a fast, quantitative technique that is easily integrated into a morphological MR acquisition. The ability of DWI to aid in detecting multifocal skeletal pathology and in characterizing tissue cellularity to a level beyond that possible with other techniques makes it a niche component of multiparametric MR imaging of the skeleton. Besides its role in disease detection and establishing cellularity and character of osseous lesions, DWI continues to be examined as a surrogate biomarker for therapeutic response of several childhood bone tumors. There is increasing interest in harnessing DWI as a potential substitute to alternative modes of imaging evaluation that involve radiation or administration of intravenous contrast agent or radiopharmaceuticals, for example in early detection and diagnosis of capital femoral epiphyseal ischemia in cases of Legg-Calvé-Perthes disease, or diagnosis and staging of lymphoma. The expected evolution of skeletal diffusivity characteristics with maturation and the unique disease processes that affect the pediatric skeleton necessitate a pediatric-specific discussion. In this article, the author examines the developmentally appropriate normal appearances, technique, artifacts and pitfalls of pediatric skeletal DWI.

The use of the fibula flap in post oncologic reconstruction of long bone in pediatric patients: A retrospective cohort study

Pediatric sarcomas are the most common malignancies of bones in childhood. With advances in adjuvant treatment, limb salvage surgery has become common, increasing the demand of skeletal reconstruction. Traditional practice included bone grafting and transport. Recently, microsurgical tissue transfer in pediatric patients has become a well-accepted practice, with the fibula as an ideal biologic construct for long bone reconstruction. We aim to assess the success rate of this operation, including flap survival, bony union, weight-bearing ambulation, and complications. We identified 10 pediatric patients who underwent reconstruction of long bones (femur, humerus, or tibia) with a free fibula flap from January 2015 to January 2020. All patients received neoadjuvant chemotherapy 4 weeks prior to the surgical procedure followed by adjuvant chemotherapy. The average follow-up time was 15 months. We had no partial or total flap loss. Three of our patients passed away in the first post-operative year due to metastatic disease. In the remaining 7 patients, we had two long-term complications. The fibula of one patient did not exhibit hypertrophy, yet weight-bearing ambulation was achieved. The other patient had nonunion proximally that required bone grafting at 8 months post-operatively. After that, the same patient fractured her fibula and required surgical fixation. She was eventually able to achieve weight-bearing ambulation. The vascularized fibula flap is a reliable tool for reconstruction in children. Flap survival is similar to that of adults. Complication rate is low compared to that for other forms of reconstruction.

Modelling count data with an excess of zero values applied to childhood bone tumour incidence in Iraq.

Bone tumours are rarely found in children and adolescents (0- 19 years old), but there are reports from some provinces in Iraq indicating possible increases in the incidence of childhood bone cancer. Since counts are very low and often zero, or near zero, we fitted zero-inflated Poisson, zero-inflated negative binomial, Poisson hurdle, and negative binomial hurdle regression models to investigate these changes. We used data covering the 2000-2015 period taking age, gender and province into account with the aim of identifying potential health disparities. The results indicate that the zero-inflated Poisson is the most appropriate approach. We also found that, the incidence rate ratio of bone tumours for age groups of 5-9, 10-14 and 15-19 years were 134%, 490% and 723% higher, respectively, compared to the 0-4 year olds. The incidence rate was higher by 49% higher in males compared to females. Compared to 2000-2004, the rate was higher during 2005-2009 and 2010-2015 by 23% and 50%, respectively. In addition, the provinces Al-Muthana and Al-Diwaniyah in the South were found to have a higher incidence rate than other provinces. Join point analysis showed that the age-adjusted incidence rate had a significant, increasing trend, with an average percentage change of 3.1% during 2000-2015. The study suggests that further research into childhood tumours, bone tumours in particular, is needed. Reference to the effect of environmental factors in this group of medical disorders would be of special interest.

International Conference on Children's Bone Health Abstracts 2020

JBMR PlusVolume 5, Issue S3 e10458 AbstractsOpen Access Abstracts First published: 26 March 2021 https://doi.org/10.1002/jbm4.10458AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Volume5, IssueS3Supplement: Abstracts from the International Conference on Children's Bone Health Virtual Forum Meeting on Bone Fragility Disorders in Children, 18–20 November 2020March 2021e10458 This article also appears in:Abstracts from Select Conferences RelatedInformation