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Acute infections of bone and joints are medical emergencies. Early diagnosis and treatment are essential for limb salvage and prevention of deformities. Data from developing countries are essential to develop region-specific treatment guidelines including choice of empiric antibiotics. We reviewed electronic medical records of children (≤ 12 years old) admitted to the pediatrics or orthopedics department of a tertiary care hospital in South India from 2013 to 2017 with a diagnosis of septic arthritis and/or osteomyelitis. Clinical, microbiological, and follow-up data were collected and analyzed. The median (interquartile range, IQR) age of the children (N = 207) was 48 (7.5–105) months. Acute infections were more common in infants, whereas chronic cases were common in children > 5 years of age. Staphylococcus aureus (71%) was the most common organism identified. Gram-negative organisms were more frequently isolated in infants compared with older children. Blood and/or wound culture positivity was 78% (N = 161) overall and 78% (N = 31) in chronic cases. The median (IQR) duration of antibiotics was 7 (5–8) weeks. Sequelae and readmissions occurred in 47% (N = 81) of the 172 patients followed for a year. Culture positivity rates especially of wound were high even after receiving antibiotics.

Fibrodysplasia ossificans progressiva (FOP) is a rare and devastating genetic disease, in which soft connective tissue is converted into heterotopic bone through an endochondral ossification process. Patients succumb early as they gradually become trapped in a second skeleton of heterotopic bone. Although the underlying genetic defect is long known, the inherent complexity of the disease has hindered the discovery of effective preventions and treatments. New developments in the gene therapy field have motivated its consideration as an attractive therapeutic option for FOP. However, the immune system's role in FOP activation and the as-yet unknown primary causative cell, are crucial issues which must be taken into account in the therapy design. While gene therapy offers a potential therapeutic solution, more knowledge about FOP is needed to enable its optimal and safe application.

Elastic stable intramedullary nailing (ESIN) is the current preferred method for treating diaphyseal femur fractures in children. Introduction of the submuscular locked plate (SMP) fixation construct has opened the debate on treatment options for pediatric diaphyseal femur fractures in the older children and adolescents. A randomized controlled trial (RCT) protocol was designed to compare ESIN and SMP for diaphyseal femur fractures in children. An open-labelled RCT comparing SMP with ESIN was conducted from January 2013 to June 2016, for children aged 6-15 years with closed, acute femoral diaphyseal fractures. Randomization was done through computer-generated randomization sequence and opaque-sealed envelopes. Rate of adverse surgical events including unplanned re-operations was assessed as the primary outcome and secondary analysis was done for time to union, degree of malunion, limb length discrepancy, functional outcome at 2 years, surgical duration and blood loss, radiation exposure, hospital stay, cost incurred and secondary implant removal procedure. Forty children were randomized with allocation concealment. There were three adverse events in the SMP arm and five in the ESIN arm. Fifteen children with SMP underwent routine implant removal compared to only three children with ESIN (P0.001). Both ESIN and SMP are equally safe, viable and effective options for treating pediatric diaphyseal femoral fractures. However, the additional cost of secondary surgery for implant removal in the SMP group proved to be a deterrent factor, which led to ESIN being the preferred option in our resource-limited setting.

Objective Hypertrophic cartilage formation is a major setback in mesenchymal stem cells (MSCs)–mediated cartilage repair, and overcoming it requires optimization of differentiation. Here, we tested the miR-140 activated collagen hydrogel for the chondrogenic differentiation of MSCs and to produce hyaline cartilage. Methods Bone marrow MSCs isolated from 3 patients were pretreated with miR-140 and then chondrogenic differentiated. The 3-dimensional (3D) transfection potential of 5 different transfection reagents (Polyethylenimine, Lipofectamine, TransIT-X2, Amide:Cholesterol-based liposomes [AmC] and AmC pegylated with Tocofersolan [AmCTOC]) was compared and the reagent that showed higher green fluorescent protein (GFP) expression was selected. Finally, the collagen hydrogel was activated using miR-140-transfection complex and sustained delivered to MSCs during chondrogenic differentiation. After differentiation, the outcome was assessed by reverse transcription–polymerase chain reaction (RT-PCR), histology, immunohistochemistry, and compared with scrambled miRNA treated control. Results Pretreatment of MSCs with miR-140 significantly increased the expression of cartilage-specific genes ( COL2A1, SOX9, and ACAN) with reduced hypertrophic chondrocyte ( COL10A1) marker expression and better safranin-O staining than the control. The AmCTOC liposome showed a significant increase in 3D transfection of GFP expressing plasmid than the others. Furthermore, the knockdown of GAPDH using siRNA in HEK cells and expression of GFP mRNA in human bone marrow MSCs confirmed the 3D-transfection efficiency of AmCTOC. The sustained delivery of miR-140 using activated matrix formed a hyaline cartilage-like tissue with minimal COL10A1 expression in RT-PCR and immunohistochemistry. Conclusion Our results demonstrated the therapeutic potential of miR-140-activated hydrogel for MSCs-based cartilage tissue engineering, which could also be used for endogenous stem cells–mediated cartilage repair.

OBJECTIVE: This study tested the long-term efficacy of two synthetic scaffolds for osteochondral defects and compare the outcomes with that of an established technique that uses monolayer cultured chondrocytes in a rabbit model. METHODS: Articular cartilage defect was created in both knees of 18 rabbits and divided into three groups of six in each. The defects in first group receiving cells loaded on Scaffold A (polyvinyl alcohol–polycaprolactone semi-interpenetrating polymer network (Monophasic, PVA–PCL semi-IPN), the second on Scaffold B (biphasic, PVA–PCL incorporated with bioglass as the lower layer), and the third group received chondrocytes alone. One animal from each group was sacrificed at 2 months and the rest at 1 year. O’Driscoll’s score measured the quality of cartilage repair. RESULTS: The histological outcome had good scores (22, 20, and 19) for all three groups at 2 months. At 1-year follow-up, the chondrocyte alone group had the best scores (mean 20.0 ± 1.4), while the group treated by PVA–PCL semi-IPN scaffolds fared better (mean 15 ± 4.2) than the group that received biphasic scaffolds (mean 11.8 ± 5.9). In all three groups, defects treated without cells scored less than the transplant. CONCLUSION: These results indicate that while these scaffolds with chondrocytes perform well initially, their late outcome is disappointing. We propose that for all scaffold-based tissue repairs, a long-term evaluation should be mandatory. The slow degrading scaffolds need further modifications to improve the milieu for long-term growth of chondrocytes and their hyaline phenotype for the better incorporation of tissue-engineered constructs.

Rabbit model is commonly used to demonstrate the proof of concept in cartilage tissue engineering. However, limited studies have attempted to find an ideal source of rabbit mesenchymal stem cells (MSCs) for cartilage repair. This study aimed to compare the in vitro chondrogenic potential of rabbit MSCs isolated from three sources namely infrapatellar fat pad (IFP), periosteum (P) and bone marrow (BM).Rabbit MSCs from three sources were isolated and characterized using flow cytometry and multi-lineage differentiation assay. Cell proliferation was assessed using trypan blue dye exclusion test; in vitro chondrogenic potential was evaluated by histology and gene expression and the outcomes were compared amongst the three MSC sources.MSCs from three sources shared similar morphology and expressed99 per cent positive for CD44 and CD81 and3 per cent positive for negative markers CD34, CD90 and human leukocyte antigen - DR isotype (HLA-DR). The BM-MSCs and IFP-MSCs showed significantly higher cell proliferation (P0.001) than the P-MSCs from passage 4. Histologically, BM-MSCs formed a thicker cartilage pellet (P0.01) with abundant matrix deposition than IFP and P-MSCs during chondrogenic differentiation. The collagen type 2 staining was significantly (P0.05) higher in BM-MSCs than the other two sources. These outcomes were further confirmed by gene expression, where the BM-MSCs demonstrated significantly higher expression (P0.01) of cartilage-specific markers (COL2A1, SOX9 and ACAN) with less hypertrophy.This study demonstrated that BM-MSCs had superior chondrogenic potential and generated better cartilage than IFP and P-MSCs in rabbits. Thus, BM-MSCs remain a promising candidate for rabbit articular cartilage regeneration.

Modified Woodward's procedure improves shoulder movement and cosmesis. There is a paucity of literature reporting objective assessment of functional outcomes. We report cosmetic and functional outcomes in Sprengel's deformity treated with modified Woodward's procedure. Children aged 12 years and under, who underwent Modified Woodward's procedure from January 2006 to December 2014 were included in the prospective study. Improvement in Cavendish grade, Rigault scale, and shoulder movements was noted. Pediatric outcomes data collection instrument (PODCI) and simple shoulder test (SST) scores were assigned at the final follow-up. Statistical analysis was conducted with paired T-test and Wilcoxon signed-rank tests. Fourteen patients (one bilateral) with a mean follow-up of 4.5 years (1-8 years) were analyzed. The mean age at surgery was 5.7 years (3-12 years). Ten (71%) patients had omovertebral bars. Six patients had Klippel-Feil syndrome including one with cervical hemivertebrae with anterior chest wall deficiency. Cavendish grade and Rigault scale improved significantly (P < 0.05). Mean shoulder abduction and forward flexion improved by 37.3° (P < 0.001) and 38.7° (P < 0.001), respectively. The mean normative PODCI score was 24.07 (reported normative score ranges from -146 to 53) and the SST score was 9.64 (reported score ranges from 0 to 12). SST scores demonstrated a moderate correlation with shoulder function. Patients without associated anomalies had better cosmetic (P = 0.057) and functional (P = 0.029) improvement. Modified Woodward's procedure improved cosmesis and provided near-normal functional outcomes in children irrespective of age and sex. Better improvement was noted in children without anomalies.

Objective Chondrogenic differentiation of mesenchymal stem cells (MSCs) into hyaline cartilage is complicated by terminal hypertrophic differentiation. In growth plate, parathyroid hormone–related peptide (1-34) (PTHrP) plays a crucial role in maintaining chondrocytes in their proliferation state by counteracting the hypertrophic differentiation. This study aims to test the effect of PTHrP supplementation at different time points on chondrogenic differentiation of MSCs and assess the final quality of differentiated chondrocytes. Methods Human periosteum and bone marrow MSCs isolated from 3 patient samples (donor unmatched) were characterized by flow cytometry and multilineage differentiation. The cells were differentiated into chondrocytes in the presence of transforming growth factor-β (TGF-β) and the PTHrP (1-34) was added from 4th or 14th day of culture. The outcome was analyzed by histology, immunohistochemistry, and gene expression. Results Flow cytometry and multilineage differentiation confirmed that the cells isolated from periosteum and bone marrow exhibited the phenotype of MSCs. During chondrogenic differentiation, pellets that received PTHrP from the 4th day of culture showed a significant reduction in hypertrophic markers (COL10A1 and RUNX) than the addition of PTHrP from the 14th day and TGF-β alone treated samples. Furthermore, 4th day supplementation of PTHrP significantly improved the expression of cartilage-specific markers (COL2A1, SOX9, ACAN) in both periosteum and bone marrow-derived MSCs. Histology and immunostaining with collagen type X data corroborated the gene expression outcomes. Conclusion The outcome showed that supplementing PTHrP from the 4th day of chondrogenic differentiation produced better chondrocytes with less hypertrophic markers in both bone marrow and periosteal-derived MSCs.

IntroductionChildhood cancer is a leading cause of death. It is unclear whether the COVID-19 pandemic has impacted childhood cancer mortality. In this study, we aimed to establish all-cause mortality rates for childhood cancers during the COVID-19 pandemic and determine the factors associated with mortality.MethodsProspective cohort study in 109 institutions in 41 countries. Inclusion criteria: children ResultsAll-cause mortality was 3.4% (n=71/2084) at 30-day follow-up, 5.7% (n=113/1969) at 90-day follow-up and 13.0% (n=206/1581) at 12-month follow-up. The median time from diagnosis to multidisciplinary team (MDT) plan was longest in low-income countries (7 days, IQR 3–11). Multivariable analysis revealed several factors associated with 12-month mortality, including low-income (OR 6.99 (95% CI 2.49 to 19.68); pConclusionsChildren with cancer are more likely to die within 30 days if infected with SARS-CoV-2. However, timely treatment reduced odds of death. This report provides crucial information to balance the benefits of providing anticancer therapy against the risks of SARS-CoV-2 infection in children with cancer.

BACKGROUND Substantial evidence exists to show the positive effects of radialextracorporeal shock wave therapy (ESWT) on bone formation. However, it is unknown whether rESWT can act locally at the growth plate level to stimulate linear bone growth. One way to achieve this is to stimulate chondrogenesis in the growth plate without depending on circulating systemic growth factors. We wished to see whether rESWT would stimulate metatarsal rat growth plates in the absence of vascularity and associated systemic growth factors. QUESTIONS/PURPOSES To study the direct effects of rESWT on growth plate chondrogenesis, we asked: (1) Does rESWT stimulate longitudinal bone growth of ex vivo cultured bones? (2) Does rESWT cause any morphological changes in the growth plate? (3) Does rESWT locally activate proteins specific to growth plate chondrogenesis? METHODS Metatarsal bones from rat fetuses were untreated (controls: n = 15) or exposed to a single application of rESWT at a low dose (500 impulses, 5 Hz, 90 mJ; n = 15), mid-dose (500 impulses, 5 Hz, 120 mJ; n = 14) or high dose (500 impulses, 10 Hz, 180 mJ; n = 34) and cultured for 14 days. Bone lengths were measured on Days 0, 4, 7, and 14. After 14 days of culturing, growth plate morphology was assessed with a histomorphometric analysis in which hypertrophic cell size (> 7 µm) and hypertrophic zone height were measured (n = 6 bones each). Immunostaining for specific regulatory proteins involved in chondrogenesis and corresponding staining were quantitated digitally by a single observer using the automated threshold method in ImageJ software (n = 6 bones per group). A p value < 0.05 indicated a significant difference. RESULTS The bone length in the high-dose rESWT group was increased compared with that in untreated controls (4.46 mm ± 0.75 mm; 95% confidence interval, 3.28-3.71 and control: 3.50 mm ± 0.38 mm; 95% CI, 4.19-4.72; p = 0.01). Mechanistic studies of the growth plate's cartilage revealed that high-dose rESWT increased the number of proliferative chondrocytes compared with untreated control bones (1363 ± 393 immunopositive cells per bone and 500 ± 413 immunopositive cells per bone, respectively; p = 0.04) and increased the diameter of hypertrophic chondrocytes (18 ± 3 µm and 13 ± 3 µm, respectively; p < 0.001). This was accompanied by activation of insulin-like growth factor-1 (1015 ± 322 immunopositive cells per bone and 270 ± 121 immunopositive cells per bone, respectively; p = 0.043) and nuclear factor-kappa beta signaling (1029 ± 262 immunopositive cells per bone and 350 ± 60 immunopositive cells per bone, respectively; p = 0.01) and increased levels of the anti-apoptotic proteins B-cell lymphoma 2 (718 ± 86 immunopositive cells per bone and 35 ± 11 immunopositive cells per bone, respectively; p < 0.001) and B-cell lymphoma-extra-large (107 ± 7 immunopositive cells per bone and 34 ± 6 immunopositive cells per bone, respectively; p < 0.001). CONCLUSION In a model of cultured fetal rat metatarsals, rESWT increased longitudinal bone growth by locally inducing chondrogenesis. To verify whether rESWT can also stimulate bone growth in the presence of systemic circulatory factors, further studies are needed. CLINICAL RELEVANCE This preclinical proof-of-concept study shows that high-dose rESWT can stimulate longitudinal bone growth and growth plate chondrogenesis in cultured fetal rat metatarsal bones. A confirmatory in vivo study in skeletally immature animals must be performed before any clinical studies.

We describe a technique for optimal use of fibula in reconstruction of type II tibial hemimelia. Six affected children with mean age of 1.4 years and treated over a 5-year period were reviewed. All underwent staged reconstruction by lowering the fibula to below knee level using Ilizarov soft tissue distraction, transfer of distal fibula under proximal tibia, and foot centralization. Mean follow-up period was 3.6 years (range: 1.6-6.05 years). Mean age at follow-up was 4.4 years, and increase in length was 4.08 cm. Tibiofibular union and foot centralization were universally achieved. Mild residual equinovarus deformity was present in three children and braced. Our technique allowed significant length gain and foot centralization in toddlers without distraction osteogenesis.

Background: The aim of this study was to assess the applicability and performance of the Shriners Hospital Upper Extremity Evaluation (SHUEE) and to determine its usefulness in clinical decision-making and as an outcome measure with reference to Indian children suffering from cerebral palsy. Materials and Methods: The SHUEE videos of 40 children with cerebral palsy with spastic hemiplegia or asymmetrical diplegia were analyzed and scored. Seven children had undergone upper extremity surgery based on a preoperative evaluation. All seven had a postoperative evaluation. Pre- and postoperative scores were compared. Intra- and interobserver reliability was assessed. The level of familiarity and comfort of the children with the assigned tasks was gauged. Results: Analysis of the scores revealed that patients could be categorized into three discrete groups based on the modified House scores and Spontaneous Functional Analysis (SFA) scores, which helps in identifying the patients who would benefit from surgical intervention. In the seven children who were operated, there was a mean increase in the postoperative SFA (2.97, P = 0.259), Dynamic Positional Analysis (3.15, P = 0.229) and Grasp/Release Analysis (4.96, P = 0.334) scores, though the differences were not statistically significant. There was excellent intraobserver (r - 0.98) and interobserver reliability (r - 0.97, 0.96) based on the intraclass correlation coefficient. The children were familiar with the assigned tasks and were not duly uncomfortable while attempting to perform them. Conclusions: SHUEE is a useful modality to assess upper limb function in Indian children with cerebral palsy, and can be used as a decision-making tool and mode of documentation.

On 6 and 7 of February 2019, Center for Stem cell Research (CSCR) and Pediatric orthopedic Unit at Christian Medical College (CMC), Vellore, conducted a meet on Translational Research in Osteogenesis Imperfecta and Cell Therapy. Osteogenesis Imperfecta (OI) is a disease in which the individual has weak brittle bones which fracture easily, resulting in multiple fractures throughout their childhood. Children become deformed and often do not walk or grow normally. The meeting was conducted to highlight the newer advances and therapies for osteogenesis imperfecta and bring regulatory processes and challenges that need to be addressed.

Objective The process of longitudinal bone growth occurs at the growth plate where the chondrocytes undergo apparent structural and molecular changes to promote growth. Recent reports suggest that radial shockwave treatment (rSWT) stimulates bone length in cultured fetal rat metatarsals. Therefore, we investigated if rSWT has similar growth promoting effects on cultured human growth plate fragments and addressed the same in a preclinical in vivo rabbit model by subjecting their growth plates to rSWT. Methods Short-term effects of high-energy rSWT were evaluated in a unique model of cultured human growth plate cartilage (n = 5) wherein samples exposed to rSWT were assessed for chondrogenic markers at 24 h in comparison to unexposed samples obtained from the same limb. Local in vivo effects were studied in six-week-old rabbits who had their distal femurs exposed to four weekly sessions of rSWT at low- and high-energy levels (n = 4 each). At sacrifice, histomorphometric and immunohistochemistry analyses were performed. For effect on longitudinal growth, proximal tibiae of 22-week-old rabbits (n = 12) were asymmetrically exposed to rSWT; the contralateral side served as untreated controls. At sacrifice, the final bone length was measured. Results In the ex vivo model of cultured human growth plate cartilage, rSWT exposure upregulated SOX9 and COL2A1 compared to control. In the immature rabbit model, an increased number of proliferative chondrocytes and column density was seen for both the energy levels. In the adolescent rabbits, an increase in tibial length was observed after the fourth session of high-energy rSWT and until six-weeks after rSWT compared to the untreated limb. Conclusions Our preliminary experimental results suggest that rSWT may serve as a non-invasive treatment and possibly a safe strategy to stimulate longitudinal bone growth. However, further studies are needed to assess the in vivo effects of rSWT in models of disturbed bone growth.

Purpose We aimed to understand the challenges facing children’s surgical care providers globally and realistic interventions to mitigate the catastrophic impact of COVID-19 on children’s surgery. Methods Two online Action Planning Forums (APFs) were organized by the Global Initiative for Children’s Surgery (GICS) with a geographically diverse panel representing four children’s surgical, anesthesia, and nursing subspecialties. Qualitative analysis was performed to identify codes, themes, and subthemes. Results The most frequently reported challenges were delayed access to care for children; fear among the public and patients; unavailability of appropriate personal protective equipment (PPE); diversion of resources toward COVID-19 care; and interruption in student and trainee hands-on education. To address these challenges, panelists recommended human resource and funding support to minimize backlog; setting up international, multi-center studies for systematic data collection specifically for children; providing online educational opportunities for trainees and students in the form of large and small group discussions; developing best practice guidelines; and, most importantly, adapting solutions to local needs. Conclusion Identification of key challenges and interventions to mitigate the impact of the COVID-19 pandemic on global children’s surgery via an objective, targeted needs assessment serves as an essential first step. Key interventions in these areas are underway.

INTRODUCTION: The superficial zone of articular cartilage (AC) is vital for its function and biomechanics. The damaged AC gets vascularized and undergoes hypertrophy and ossification. Studies have highlighted these two as the major causative factors in osteoarthritis (OA). We aimed at preventing the OA progression in a rat knee instability model by inhibiting the vascular ingrowth and ossification using VEGF and BMP antagonist. A WNT agonist was also used to promote AC regeneration because of its protective effect on the superficial layer. METHODS: Rat knee OA was created by surgical excision of the medial meniscus and medial collateral ligament. Forty rats were divided into two groups of twenty each for surgical control and tests (surgery + intra-articular injection of drugs every two weeks). Ten animals from each group were sacrificed at four and eight weeks. Histology was mainly used to evaluate the outcome. RESULTS: A surgical OA model was successfully created with higher histological scores for operated knees, both in short- (P = 0.0001) and long-term (P = 0.001). Modified Mankin score was lesser in the test animals as compared to control (P = 0.17) in the short-term, but the trend was reversed in the long-term (P = 0.13). Subgroup analysis revealed that repeated injections in the anterolateral compartment contributed to higher scores in the lateral (P = 0.03) and anterior (P = 0.03) compartment of the knee in the long-term. CONCLUSION: The combinatorial approach was effective in controlling the OA in short-term. Further studies are needed to test the sustained drug delivery system to improve the outcome.

Background Osteogenesis imperfecta (OI) is a rare genetic disease characterized by bone fragility, with a wide range in the severity of clinical manifestations. The majority of cases are due to mutations in the COL1A1 or COL1A2 genes, which encode type I collagen. Mesenchymal stem cells (MSCs), as the progenitors of the osteoblasts, the main type I collagen secreting cell type in the bone, have been proposed and tested as an innovative therapy for OI with promising but transient outcomes. Methods To overcome the short‐term effect of MSCs therapy, we performed a phase I clinical trial based on reiterative infusions of histocompatible MSCs, administered in a 2.5‐year period, in two pediatric patients affected by severe and moderate OI. The aim of this study was to assess the safety and effectiveness of this cell therapy in nonimmunosuppressed OI patients. The host response to MSCs was studied by analyzing the sera from OI patients, collected before, during, and after the cell therapy. Results We first demonstrated that the sequential administration of MSCs was safe and improved the bone parameters and quality of life of OI patients along the cell treatment plus 2‐year follow‐up period. Moreover, the study of the mechanism of action indicated that MSCs therapy elicited a pro‐osteogenic paracrine response in patients, especially noticeable in the patient affected by severe OI. Conclusions Our results demonstrate the feasibility and potential of reiterative MSCs infusion for two pediatric OI and highlight the paracrine response shown by patients as a consequence of MSCs treatment., TERCELOI clinical trial addresses fundamental issues concerning the feasibility, security and potential of 5 MSCs infusions in two non immunosuppressed Osteogenesis Imperfecta pediatric patients. This trial allowed us to elucidate the mechanism of action of MSCs therapy, characterized by a pro‐osteogenic paracrine response. For that, we studied the protein and miRNA levels in sera from patients (collected before, along and after the cell treatment) besides unraveling the transcriptomic alterations due to those sera presence, and demonstrating their functional capabilities.

In childhood medulloblastoma patients, the hedgehog antagonist vismodegib is an effective anti-cancer treatment but unfortunately induces irreversible growth arrests and growth impairment limiting its use in skeletally immature patients. We hypothesized that radial shock wave treatment (rSWT) may protect drug-induced growth impairment owing to its osteogenic effects. Fetal rat metatarsal bones were exposed to vismodegib (day 0–5; 100 nM) and/or rSWT (single session); other bones from day 1 were continuously exposed to a Gli1 antagonist (GANT61; 10 µM) and/or rSWT (single session). Control bones were untreated. The bone length was measured at intervals; histomorphometric analysis and immunostaining for PCNA, Gli1, and Ihh were performed on the sectioned bones. Bones treated with vismodegib showed impaired bone growth, reduced height of the resting-proliferative zone and reduced hypertrophic cell size compared to control. In vismodegib treated bones, a single session of rSWT partially rescued bone growth, increased the growth velocity, hypertrophic cell size, and restored growth plate morphology. Bones exposed to GANT61 showed impaired bone growth and disorganized growth plate while when combined with rSWT these effects were partially prevented. Locally applied rSWT had a chondroprotective effect in rat metatarsal bones and suggest a novel strategy to prevent growth impairment caused by vismodegib.

Osteogenesis imperfecta (OI) is a group of inherited disorders with increased bone fragility and wide genetic heterogeneity. We report the outcome of clinical exome sequencing validated by Sanger sequencing in clinically diagnosed 54 OI patients in Indian population. In 52 patients, we report 20 new variants involving both dominant and recessive OI-specific genes and correlate these with phenotypes. COL1A1 and COL1A2 gene variants were identified in 44.23%, of which 28.84% were glycine substitution abnormalities. Two novel compound heterozygous variants in the FKBP10 gene were seen in two unrelated probands. A novel heterogeneous duplication of chromosomal region chr17: 48268168-48278884 from exons 1-33 of the COL1A1 gene was found in one proband. In five probands, there were additional variants in association with OI. These were ANO5 in association with CRTAP in two probands of the same family causing gnathodiaphyseal dysplasia, COL5A2 with LEPRE1 causing Ehlers Danlos syndrome, COL11A1 in addition to COL1A1 causing Stickler syndrome, and a previously unreported combination of SLC34A1 gene variant with FKBP10 leading to Fanconi renal tubular syndrome type II. Our findings demonstrate the efficacy of clinical exome sequencing in screening OI patients, classifying its subtypes, and identifying associated disorders in consanguineous populations.

Case An 11-year-old child who presented with a postseptic gap nonunion of 4 cm in the proximal humerus was treated with a customized hydroxyapatite-tricalcium phosphate-tricalcium silicate composite (HASi) scaffold loaded with culture-expanded autologous bone marrow-derived mesenchymal stem cells (MSCs) primed into osteogenic lineage. Union occurred at 3 months, and at 3 years, the child had improved joint mobility, with radiographic and computed tomographic imaging evidence of incorporation of the graft. Conclusions This case demonstrated the feasibility of MSC directed into osteogenic lineage on HASi to repair a long bone defect owing to postseptic osteomyelitis, a condition notorious for a high failure rate.

Supplemental material, Table_S1 for Early Addition of Parathyroid Hormone–Related Peptide Regulates the Hypertrophic Differentiation of Mesenchymal Stem Cells by Karthikeyan Rajagopal, Sowmya Ramesh and Vrisha Madhuri in CARTILAGE

Case A severe acquired constriction band in the proximal calf in an infant treated with a below-knee cast, which was protected with a waterproof sheet secured with a rubber band, is described. The radiological and computed tomography features of an elastic band causing the acquired constriction are presented for their novelty and uniqueness in the complication of cast treatment. Conclusions The waterproof covering of plaster casts in children secured with a rubber band to prevent soiling can cause an acquired constriction band, which mimics osteomyelitis. The imaging modalities showed the elastic band shadow cutting through the bone and soft tissues as demonstrated in this case. We recommend that the complication can be prevented by avoiding the use of elastic bands to hold the waterproofing covers for the cast.

We evaluated the novel application of supracutaneous locked plates in pediatric open tibia fractures. Pediatric open tibia fractures stabilized with a locked supracutaneous plate from January 2011 to December 2014 were reviewed. Twenty-eight children, mean age 8.9 years, with 29 open tibia fractures were included. Nine of these children who had metaphyseal or metadiaphyseal fractures did not require joint spanning. The mean follow-up duration was 13.5 months. The mean time to uneventful union was 11.46 weeks, with no unacceptable malunion. Supracutaneous locked plates showed early union and no refractures. They could favorably replace tubular external fixators in stabilizing pediatric open tibia fractures.

Context: Percutaneous radiofrequency ablation (RFA) of osteoid osteoma has a high technical and clinical success rate. However, there is limited data on its use in the pediatric population, especially in technically challenging locations. Objective: The objective of this study was to assess the safety and efficacy of CT-guided percutaneous RFA of osteoid osteoma in pediatric population. Subjects and Methods: From June 2009 to May 2014, thirty patients with osteoid osteoma were treated with CT-guided RFA in common (25 cases) and technically challenging (five cases: four near articular surface and one in sacrum) locations. Therapy was performed under general anesthesia with a three-array expandable RF probe for 6 min at 90°C and power of 60–100 W. The patients were discharged next day under instruction. The treatment success was evaluated in terms of pain relief before and after (1 day, 1 month, and 6 months) treatment. Results: Technical success was achieved in all patients (100%). Primary clinical success was 96.66% (29 of total 30 patients) despite the pediatric population and atypical location. One patient had persistent pain after 1 month duration and were treated successfully with a second procedure (secondary success rate was 100%). One patient had immediate complication of weakness of right hand and fingers extension. No delayed complications were observed. Conclusions: CT-guided RFA is relatively safe and highly effective for treatment of osteoid osteoma in pediatric population, even in technically difficult locations. Advance in Knowledge: Our study showed that if technical success is 100% and if strict desired temperature (90°C) can be maintained for desired time (6 min) using controlled power (wattage) delivery (60–100 W), then high clinical success can be achieved even in pediatric population similar to adult population.

Idiopathic chondrolysis of the hip is a rare condition without known antecedent cause, in which there is rapid destruction of articular cartilage, followed by varying degrees of regeneration or remodeling. In the early stage, the differential diagnosis includes especially tuberculous arthritis and seronegative spondylo-arthropathy. Our MRI-based classification with clinical correlations is presented, as are our surgical rationale, protocol and post-operative care regime.