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Madhuri V.,Paediatric Orthopaedics Unit | Dutt V.,Paediatric Orthopaedics Unit | Gahukamble A.D.,Paediatric Orthopaedics Unit | Tharyan P.,Care Network
Evidence-Based Child Health | Year: 2014

Background: Fractures of the femoral shaft in children are relatively uncommon but serious injuries that disrupt the lives of children and their carers and can result in significant long-term disability. Treatment involves either surgical fixation, such as intramedullary nailing or external fixation, or conservative treatment involving prolonged immobilisation, often in hospital. Objectives: To assess the effects (benefits and harms) of interventions for treating femoral shaft fractures in children and adolescents. Search methods: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (accessed 16 August 2013), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2013 Issue 7), MEDLINE (1946 to August Week 1 2013), EMBASE (1980 to 2012 week 9), CINAHL (16 August 2013), clinical trials registries, conference proceedings and reference lists; and contacted trial authors and experts in the field. Selection criteria: Randomised and quasi-randomised controlled trials comparing conservative and surgical interventions for diaphyseal fractures of the femur in children under 18 years of age. Our primary outcomes were functional outcome measures, unacceptable malunion, and serious adverse events. Data collection and analysis: Two authors independently screened and selected trials, assessed risk of bias and extracted data. We assessed the overall quality of the evidence for each outcome for each comparison using the GRADE approach. We pooled data using a fixed-effect model. Main results: We included 10 trials (six randomised and four quasi-randomised) involving a total of 527 children (531 fractures). All trials were at some risk of bias, including performance bias as care provider blinding was not practical, but to a differing extent. Just one trial was at low risk of selection bias. Reflecting both the risk of bias and the imprecision of findings, we judged the quality of evidence to be 'low' for most outcomes, meaning that we are unsure about the estimates of effect. Most trials failed to report on self-assessed function or when children resumed their usual activities. The trials evaluated 10 different comparisons, belonging to three main categories. Surgical versus conservative treatment Four trials presenting data for 264 children aged 4 to 12 years made this comparison. Low quality evidence (one trial, 101 children) showed children had very similar function assessed using the RAND health status score at two years after surgery (external fixation) compared with conservative treatment (spica cast): mean 69 versus 68. The other three trials did not report on function. There was moderate quality evidence (four trials, 264 children, aged 4 to 12 years, followed up 3 to 24 months) that surgery reduced the risk of malunion (risk ratio (RR) 0.29, 95% confidence interval (CI) 0.15 to 0.59, 4 trials). Assuming an illustrative baseline risk of 115 malunions per 1000 in children treated conservatively, these data equate to 81 fewer (95% CI 47 to 97 fewer) malunions per 1000 in surgically-treated children. Conversely, low quality evidence indicated that there were more serious adverse events such as infections after surgery (RR 2.39, 95% CI 1.10 to 5.17, 4 trials). Assuming an illustrative baseline risk of 40 serious adverse events per 1000 for conservative treatment, these data equate to 56 more (95% CI 4 to 167 more) serious adverse events per 1000 children treated surgically. There was low quality evidence (one trial, 101 children) of similar satisfaction levels in children and parents with surgery involving external fixation and plaster cast only. However, there was low quality evidence (one trial, 46 children) that more parents were satisfied with intramedullary nailing than with traction followed by a cast, and that surgery reduced the time taken off from school. Comparisons of different methods of conservative treatment The three trials in this category made three different comparisons. We are very unsure if unacceptable malunion rates differ between immediate hip spica versus skeletal traction followed by spica in children aged 3 to 10 years followed up for six to eight weeks (RR 4.0, 95% CI 0.5 to 32.9; one trial, 42 children; very low quality evidence). Malunion rates at 5 to 10 years may not differ between traction followed by functional orthosis versus traction followed by spica cast in children aged 5 to 13 years (RR 0.98, 95% CI 0.46 to 2.12; one trial, 43 children; low quality evidence). We are very unsure (very low quality evidence) if either function or serious adverse events (zero events reported) differ between single-leg versus double-leg spica casts (one trial, 52 young children aged two to seven years). Low quality evidence on the same comparison indicates that single-leg casts are less awkward to manage by parents, more comfortable for the child and may require less time off work by the caregiver. Comparisons of different methods of surgical treatment The three trials in this category made three different comparisons. Very low quality evidence means that we are very unsure if the rates of malunion, serious adverse events, time to return to school or parental satisfaction actually differ in children whose fractures were fixed using elastic stable intramedullary nailing or external fixation (one trial, 19 children). The same applies to the rates of serious adverse events and time to resume full weight-bearing in children treated with dynamic versus static external fixation (one trial, 52 children). Very low quality evidence (one trial, 47 children) means that we do not know if malunion, serious adverse events and time to resume weight-bearing actually differ between intramedullary nailing versus submuscular plating. However, there could be more difficulties in plate removal subsequently. Authors' conclusions: There is insufficient evidence to determine if long-term function differs between surgical and conservative treatment. Surgery results in lower rates of malunion in children aged 4 to 12 years, but may increase the risk of serious adverse events. Elastic stable intramedullary nailing may reduce recovery time. There is insufficient evidence from comparisons of different methods of conservative treatment or of different methods of surgical treatment to draw conclusions on the relative effects of the treatments compared in the included trials. Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.


PubMed | Paediatric Orthopaedics Unit and Center for Stem Cell Research
Type: Journal Article | Journal: Annals of human genetics | Year: 2015

Fibrodysplasia Ossificans Progressiva (FOP) is a rare debilitating disorder characterized by congenital deformity of the great toes from infancy and postnatal heterotopic ossification. Activating mutations in the activin A receptor type 1 (ACVR1) gene are responsible for the disease. The most common allelic variant leading to FOP is c.617 G>A; p.R206H, however, other alleles have been reported with atypical phenotypes. We report 14 cases presenting to a referral institution in South India over a 3-year period. The patients were clinically diagnosed based on foot abnormality or abnormal ectopic ossification and were screened for ACVR1. The genetic analysis of ACVR1 identified the recurrent allelic variant in 12 of 14 patients. One of the remaining patients had a previously reported allele c.1067G>A; p.G356D in the 9th exon and the second allele c.983G>A; p.G328E in the 8th exon of ACVR1. The most common recurrent allele c.617 G>A; p.R206H is also the most common in Indian patients with FOP.


Ramesh S.,Paediatric Orthopaedics Unit | Rajagopal K.,Paediatric Orthopaedics Unit | Vaikkath D.,Sree Chitra Tirunal Institute for Medical Science and Technology | Nair P.D.,Sree Chitra Tirunal Institute for Medical Science and Technology | Madhuri V.,Paediatric Orthopaedics Unit
Biotechnology Letters | Year: 2014

Two encapsulation techniques for rabbit chondrocytes in chitosan/hyaluronic acid gel have been compared. The standard technique involves the cross-linking of chitosan and hyaluronic acid at 2:1 (w/w). In the modified technique, cells were initially added to 33 % of hyaluronic acid dialdehyde and the gelation process was completed with the remaining 67 %. This minimised the cell loss and improved the encapsulation of the cells. By the third week, the modified technique showed better seeding density, with matrix synthesis (per scaffold) of 11 μg as compared to 1.1 μg in the current technique. Relative expression of collagen II with the current technique and the modified technique were 6.4 % and ~1,600 % respectively. The modified technique was superior for matrix synthesis and maintenance of phenotype. © 2014 Springer Science+Business Media Dordrecht.


Arora S.,Paediatric Orthopaedics Unit | Dutt V.,Paediatric Orthopaedics Unit | Palocaren T.,Paediatric Orthopaedics Unit | Madhuri V.,Paediatric Orthopaedics Unit
Indian Journal of Orthopaedics | Year: 2013

Background: Slipped upper femoral epiphysis (SUFE) is the gradually acquired malalignment of the upper femoral epiphysis (capital) and the proximal femoral metaphysis. SUFE is uncommon in India, and there are no previous studies on outcome and clinical characteristics of patients with SUFE from India. This study evaluates the presentation, disease associations and outcome of SUFE from a tertiary care centre in India. Materials and Methods: Twenty six consecutive children with SUFE seen over a period of 4 years were reviewed. The clinical presentations, severity of the slip, surgical interventions (n=30) were assessed. Twenty one boys and five girls with a mean age 13.1 years (range 10-16 years) were included in the study. Four children had bilateral involvement. There were 4 rural and 22 urban children from the eastern and southern states of the country. The presentation was acute in 7, acute on chronic in 5, and chronic in 14, with a mean duration of symptoms of 51 days (range 3-120 days). Slips were stable in 16 and unstable in 10 children. Two children had adiposogenital syndrome. Body mass index was high in 12 out of 23 children. Vitamin D levels were low in 20 out of 21 children, with a mean vitamin D level of 12.61 ± 5 ng/ml. Eighteen children underwent in situ pinning. Eight children underwent capital realignment. Results: Clinical outcome as assessed by Merle d' Aubigne score was excellent in 6, good in 10, fair in 6 and poor in 1. Half of the in situ fixation patients underwent osteoplasty procedure for femoroacetabular impingement and 5 more were symptomatic. The head neck offset and angle after in situ pinning were -1.12 ± 3 mm and 66.05 ± 9.7°, respectively and this improved to 8.7 mm and 49°, respectively, after osteoplasty. One child in the pinning group had chondrolysis. Eight patients with severe slip underwent capital realignment. Mean followup was 20.15 months. The anterior head neck offset and angle were corrected to 6.8 ± 1.72 mm and 44.6 ± 7.0° mm, respectively. Two children with unstable slip in the capital realignment group had avascular necrosis which was diagnosed at presentation by bone scan. Conclusion: High BMI, vitamin D deficiency and endocrine disorders are associated with SUFE in India and should be evaluated as some of these are amenable to prevention and treatment. Most patients treated with in situ pinning developed femoroacetabular impingement. The early results after capital realignment procedure are encouraging and help to avoid a second procedure which is needed in a majority of patients who underwent in situ pinning.


Rajagopal K.,Paediatric Orthopaedics Unit | Chilbule S.K.,Paediatric Orthopaedics Unit | Madhuri V.,Paediatric Orthopaedics Unit
Cell and Tissue Banking | Year: 2014

Cryopreservation preserves cells at low temperature and creates a reserve for future use while executing the clinical translation. Unlike articular chondrocyte, cryopreservation protocol and its outcome are not described in iliac apophyseal chondrocytes, a potential source of chondrocytes in cartilage engineering. This study for the first time describes the cryopreservation of human iliac apophyseal chondrocytes. Four cartilage samples were procured from iliac crests of children undergoing hip surgery after consent. The total chondrocyte yield was divided into two groups. First group was grown as monolayer while second group was cryopreserved following the slow cooling method in the medium containing 10 % Dimethyl sulfoxide for 3 months. Group two cells were also grown as a monolayer following thawing. Viability, time to confluence, population doubling time and phenotype maintenance were compared for both the groups. Viability was 65.75 % after 3 months of cryopreservation at -196 C, as compared to 94.19 % for fresh chondrocytes (p = 0.001). Fresh and cryopreserved cells reached confluence on 10th and 15th day of culture respectively. Population doubling time was significantly more in fresh than cryopreserved chondrocytes on 10th (p = 0.0006) and 15th day (p = 0.0002) in culture. Both fresh and cryopreserved cells maintain their chondrocyte phenotype as assessed by immunocytochemistry. Relative gene expression by real time polymerase chain reaction showed similar upregulation of mRNA of Collagen 2, SOX 9, Aggrecan and Collagen 1 in cryopreserved chondrocyte as compared to fresh chondrocyte. Iliac apophyseal chondrocytes cryopreserved for 3 months maintained the phenotype successfully 2 weeks after thawing in culture. The viability and proliferation rates after thawing were adequate for a clinical translation of these cells. © 2013 Springer Science+Business Media Dordrecht.


Madhuri V.,Paediatric Orthopaedics Unit | Gahukamble A.,Paediatric Orthopaedics Unit
Evidence-Based Child Health | Year: 2014

Cochrane Review: Interventions for treating femoral shaft fractures in children and adolescents Madhuri V, Dutt V, Gahukamble AD, Tharyan P. Interventions for treating femoral shaft fractures in children and adolescents. Cochrane Database of Systematic Reviews 2014, Issue 7. Art. No.: CD009076. DOI: 10.1002/14651858.CD009076.pub2. This companion piece to the review, "Interventions for treating femoral shaft fractures in children and adolescents," contains the following pieces: The abstract of the review A commentary from one or more of the review authors, explaining why the review team felt the review was an important one to produce Some other recently published references on this topic Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.


Chilbule S.K.,Paediatric Orthopaedics Unit | Madhuri V.,Paediatric Orthopaedics Unit
Journal of Children's Orthopaedics | Year: 2012

Purpose: Pamidronate, used for the treatment of paediatric osteoporosis, reduces the fracture rate and improves ambulatory status. Intravenous pamidronate therapy has known complications which have not been stratified based on its dose and distribution. This study aims to assess the early minor and major medical and late surgical complications and the effect of the dose and regimen of infusion on these events in paediatric osteoporosis. Study design: Retrospective cohort. Materials and methods: Three regimens for pamidronate infusion were followed in sequential periods in 10 years. Regimen A delivered 1.5 mg/kg/day as a single dose once in 3 months. Regimen B delivered 2 mg/kg/day for 3 days twice a year, while regimen C delivered 1 mg/kg/day for 3 days every 3-4 months. Adverse events were classified as early (major and minor) or late (surgical). Results: Forty-eight children received 158 infusions using one of the three regimens. Twenty-nine complications occurred in 24 children. A significant difference in the complication rate was present among the three regimens (P = 0.005). Nineteen children had minor complications, mainly febrile reaction or asymptomatic hypocalcaemia. Four major complications consisting of one seizure, one respiratory distress and two hypocalcaemic tetany were encountered, all with regimen B. Intraoperative complication faced was loss of position due to splintering of the cortex while rush rodding. This was seen in 20% of the long bone segments operated in those who received pamidronate as compared to 4.4% of the segments which were operated prior to the initiation of pamidronate therapy; the odds of splintering were 5.4 times higher for those patients who were bone segment rodded after pamidronate therapy. Discussion: Intravenous pamidronate is associated with complications in 50% of children with paediatric osteoporosis, with a dose-dependent significant difference. Major complications are not uncommon with higher doses and can be avoided by increasing the number of doses per year and decreasing the dose per cycle. Surgical difficulty, when possible, can be avoided by correcting any major deformities at presentation prior to the induction of pamidronate therapy. © 2012 EPOS.


Madhuri V.,Paediatric Orthopaedics Unit | Dutt V.,Paediatric Orthopaedics Unit | Gahukamble A.D.,Paediatric Orthopaedics Unit | Tharyan P.,Paediatric Orthopaedics Unit
The Cochrane database of systematic reviews | Year: 2014

BACKGROUND: Fractures of the femoral shaft in children are relatively uncommon but serious injuries that disrupt the lives of children and their carers and can result in significant long-term disability. Treatment involves either surgical fixation, such as intramedullary nailing or external fixation, or conservative treatment involving prolonged immobilisation, often in hospital.OBJECTIVES: To assess the effects (benefits and harms) of interventions for treating femoral shaft fractures in children and adolescents.SEARCH METHODS: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (accessed 16 August 2013), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2013 Issue 7), MEDLINE (1946 to August Week 1 2013), EMBASE (1980 to 2012 week 9), CINAHL (16 August 2013), clinical trials registries, conference proceedings and reference lists; and contacted trial authors and experts in the field.SELECTION CRITERIA: Randomised and quasi-randomised controlled trials comparing conservative and surgical interventions for diaphyseal fractures of the femur in children under 18 years of age. Our primary outcomes were functional outcome measures, unacceptable malunion, and serious adverse events.DATA COLLECTION AND ANALYSIS: Two authors independently screened and selected trials, assessed risk of bias and extracted data. We assessed the overall quality of the evidence for each outcome for each comparison using the GRADE approach. We pooled data using a fixed-effect model.MAIN RESULTS: We included 10 trials (six randomised and four quasi-randomised) involving a total of 527 children (531 fractures). All trials were at some risk of bias, including performance bias as care provider blinding was not practical, but to a differing extent. Just one trial was at low risk of selection bias. Reflecting both the risk of bias and the imprecision of findings, we judged the quality of evidence to be 'low' for most outcomes, meaning that we are unsure about the estimates of effect. Most trials failed to report on self-assessed function or when children resumed their usual activities. The trials evaluated 10 different comparisons, belonging to three main categories. Surgical versus conservative treatment Four trials presenting data for 264 children aged 4 to 12 years made this comparison. Low quality evidence (one trial, 101 children) showed children had very similar function assessed using the RAND health status score at two years after surgery (external fixation) compared with conservative treatment (spica cast): mean 69 versus 68. The other three trials did not report on function. There was moderate quality evidence (four trials, 264 children, aged 4 to 12 years, followed up 3 to 24 months) that surgery reduced the risk of malunion (risk ratio (RR) 0.29, 95% confidence interval (CI) 0.15 to 0.59, 4 trials). Assuming an illustrative baseline risk of 115 malunions per 1000 in children treated conservatively, these data equate to 81 fewer (95% CI 47 to 97 fewer) malunions per 1000 in surgically-treated children. Conversely, low quality evidence indicated that there were more serious adverse events such as infections after surgery (RR 2.39, 95% CI 1.10 to 5.17, 4 trials). Assuming an illustrative baseline risk of 40 serious adverse events per 1000 for conservative treatment, these data equate to 56 more (95% CI 4 to 167 more) serious adverse events per 1000 children treated surgically. There was low quality evidence (one trial, 101 children) of similar satisfaction levels in children and parents with surgery involving external fixation and plaster cast only. However, there was low quality evidence (one trial, 46 children) that more parents were satisfied with intramedullary nailing than with traction followed by a cast, and that surgery reduced the time taken off from school. Comparisons of different methods of conservative treatmentThe three trials in this category made three different comparisons. We are very unsure if unacceptable malunion rates differ between immediate hip spica versus skeletal traction followed by spica in children aged 3 to 10 years followed up for six to eight weeks (RR 4.0, 95% CI 0.5 to 32.9; one trial, 42 children; very low quality evidence). Malunion rates at 5 to 10 years may not differ between traction followed by functional orthosis versus traction followed by spica cast in children aged 5 to 13 years (RR 0.98, 95% CI 0.46 to 2.12; one trial, 43 children; low quality evidence). We are very unsure (very low quality evidence) if either function or serious adverse events (zero events reported) differ between single-leg versus double-leg spica casts (one trial, 52 young children aged two to seven years). Low quality evidence on the same comparison indicates that single-leg casts are less awkward to manage by parents, more comfortable for the child and may require less time off work by the caregiver. Comparisons of different methods of surgical treatmentThe three trials in this category made three different comparisons. Very low quality evidence means that we are very unsure if the rates of malunion, serious adverse events, time to return to school or parental satisfaction actually differ in children whose fractures were fixed using elastic stable intramedullary nailing or external fixation (one trial, 19 children). The same applies to the rates of serious adverse events and time to resume full weight-bearing in children treated with dynamic versus static external fixation (one trial, 52 children). Very low quality evidence (one trial, 47 children) means that we do not know if malunion, serious adverse events and time to resume weight-bearing actually differ between intramedullary nailing versus submuscular plating. However, there could be more difficulties in plate removal subsequently.AUTHORS' CONCLUSIONS: There is insufficient evidence to determine if long-term function differs between surgical and conservative treatment. Surgery results in lower rates of malunion in children aged 4 to 12 years, but may increase the risk of serious adverse events. Elastic stable intramedullary nailing may reduce recovery time.There is insufficient evidence from comparisons of different methods of conservative treatment or of different methods of surgical treatment to draw conclusions on the relative effects of the treatments compared in the included trials.


PubMed | Paediatric Orthopaedics Unit
Type: Journal Article | Journal: Biotechnology letters | Year: 2014

Two encapsulation techniques for rabbit chondrocytes in chitosan/hyaluronic acid gel have been compared. The standard technique involves the cross-linking of chitosan and hyaluronic acid at 2:1 (w/w). In the modified technique, cells were initially added to 33% of hyaluronic acid dialdehyde and the gelation process was completed with the remaining 67%. This minimised the cell loss and improved the encapsulation of the cells. By the third week, the modified technique showed better seeding density, with matrix synthesis (per scaffold) of 11 g as compared to 1.1 g in the current technique. Relative expression of collagen II with the current technique and the modified technique were 6.4% and ~1,600% respectively. The modified technique was superior for matrix synthesis and maintenance of phenotype.


Gangadharan S.,Paediatric Orthopaedics Unit | Rathinam B.,Paediatric Orthopaedics Unit | Madhuri V.,Paediatric Orthopaedics Unit
Journal of Pediatric Orthopaedics Part B | Year: 2014

We encountered an iatrogenic radial nerve injury following Dorgan's lateral cross-pinning in a 5-year-old girl with a supracondylar fracture of the humerus. This prompted a cadaveric study to define a safe entry point for the proximal lateral Kirschner-wire. A child's cadaveric humerus was pinned laterally in three coronal planes, simulating the proximal entry pin. The radial nerve lay farthest from the wire in the posterolateral plane, 1 and 2 cm proximal to the lateral epicondyle. We report the first incidence of radial nerve injury with lateral cross-pinning and suggest that the wire should be placed posterolaterally within 2 cm from the lateral epicondyle. © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins.

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