Outcomes and complications following flexible intramedullary nailing for the treatment of tibial fractures in children: a meta-analysis.

INTRODUCTION: Tibial shaft fractures are common occurrence in children and surgical treatment is sometimes required, particularly in unstable or open fractures, and in polytrauma. The aim of this study was to investigate the available evidence on the efficacy and safety of flexible intramedullary nailing (FIN) for both open and closed tibia fractures in children, exploring the main surgical outcomes and rate of complications. MATERIALS AND METHODS: Pubmed/Medline, Scopus and Cochrane Central databases were searched following the PRISMA guideline. Studies reporting on the outcomes of FIN for paediatric tibia shaft fractures were included. Weighted means were evaluated for surgical outcomes. Meta-analysis of proportion and odd ratios were used to analyse total complication rates and differences between open and closed fractures. RESULTS: Twenty-eight studies (835 patients) were included; the mean age was 11.0 ± 3.0 years. The mean follow-up was 22.5 ± 13.5 months; the mean time to full weight-bearing was 7.5 ± 3.7 weeks. The total complication rate was 28.1% (minor = 20.7%, major = 6.3%); this was greater in open fractures (13.6% vs 5.1%, p = 0.007). The rate of union was 97.5%, with a mean time to union of 11.9 ± 7.2 weeks. Malunion was found in 8.5% cases, delayed union in 3.8%, non-union in 1.4%, symptomatic hardware in 5.1%, leg-length discrepancy in 5.0%, superficial infections in 2.3%, deep infections in 1.0%, compartment syndromes in 1.4%, and refracture in 0.2%. Almost all patients returned to unrestricted physical activity. CONCLUSIONS: FIN offers excellent outcomes for the treatment of paediatric tibia shaft fractures. Patients presenting with an open fracture have a higher but acceptable complication rate. Comparative studies are needed to clarify if other treatments have superior outcomes.

The developmental and genetic basis of 'clubfoot' in the peroneal muscular atrophy mutant mouse.

Genetic factors underlying the human limb abnormality congenital talipes equinovarus ('clubfoot') remain incompletely understood. The spontaneous autosomal recessive mouse 'peroneal muscular atrophy' mutant (PMA) is a faithful morphological model of human clubfoot. In PMA mice, the dorsal (peroneal) branches of the sciatic nerves are absent. In this study, the primary developmental defect was identified as a reduced growth of sciatic nerve lateral motor column (LMC) neurons leading to failure to project to dorsal (peroneal) lower limb muscle blocks. The pma mutation was mapped and a candidate gene encoding LIM-domain kinase 1 (Limk1) identified, which is upregulated in mutant lateral LMC motor neurons. Genetic and molecular analyses showed that the mutation acts in the EphA4-Limk1-Cfl1/cofilin-actin pathway to modulate growth cone extension/collapse. In the chicken, both experimental upregulation of Limk1 by electroporation and pharmacological inhibition of actin turnover led to defects in hindlimb spinal motor neuron growth and pathfinding, and mimicked the clubfoot phenotype. The data support a neuromuscular aetiology for clubfoot and provide a mechanistic framework to understand clubfoot in humans.

Transcranial Doppler and Magnetic Resonance in Tanzanian Children With Sickle Cell Disease.

Background and Purpose- We determined prevalences of neurological complications, vascular abnormality, and infarction in Tanzanian children with sickle cell disease. Methods- Children with sickle cell disease were consecutively enrolled for transcranial Doppler; those with slightly elevated (>150 cm/s), low (<50 cm/s) or absent cerebral blood flow velocity (CBFv) were invited for brain magnetic resonance imaging and magnetic resonance angiography. Results- Of 200 children (median age 9; range 6-13 years; 105 [2.5%] boys), 21 (11%) and 15 (8%) had previous seizures and unilateral weakness, respectively. Twenty-eight (14%) had elevated and 39 (20%) had low/absent CBFv, all associated with lower hemoglobin level, but not higher indirect bilirubin level. On multivariable analysis, CBFv>150 cm/s was associated with frequent painful crises and low hemoglobin level. Absent/low CBFv was associated with low hemoglobin level and history of unilateral weakness. In 49 out of 67 children with low/absent/elevated transcranial Doppler undergoing magnetic resonance imaging, 43% had infarction, whereas 24 out of 48 (50%) magnetic resonance angiographies were abnormal. One had hemorrhagic infarction; none had microbleeds. Posterior circulation infarcts occurred in 14%. Of 11 children with previous seizure undergoing magnetic resonance imaging, 10 (91%) had infarction (5 silent) compared with 11 out of 38 (29%) of the remainder ( P=0.003). Of 7 children with clinical stroke, 2 had recurrent stroke and 3 died; 4 out of 5 had absent CBFv. Of 193 without stroke, 1 died and 1 had a stroke; both had absent CBFv. Conclusions- In one-third of Tanzanian children with sickle cell disease, CBFv is outside the normal range, associated with frequent painful crises and low hemoglobin level, but not hemolysis. Half have abnormal magnetic resonance angiography. African children with sickle cell disease should be evaluated with transcranial Doppler; those with low/absent/elevated CBFv should undergo magnetic resonance imaging/magnetic resonance angiography.

Cerebral perfusion characteristics show differences in younger versus older children with sickle cell anaemia: Results from a multiple-inflow-time arterial spin labelling study.

Sickle cell anaemia (SCA) is associated with chronic anaemia and oxygen desaturation, which elevate cerebral blood flow (CBF) and increase the risk of neurocognitive complications. Arterial spin labelling (ASL) provides a methodology for measuring CBF non-invasively; however, ASL techniques using only a single inflow time are not sufficient to fully characterize abnormal haemodynamic behaviour in SCA. This study investigated haemodynamic parameters from a multi-inflow-time ASL acquisition in younger (8-12 years) and older (13-18 years) children with SCA with and without silent cerebral infarction (SCI+/-) (n = 20 and 19 respectively, 6 and 4 SCI+ respectively) and healthy controls (n = 9 and 7 respectively). Compared with controls, CBF was elevated globally in both groups of patients. In the younger SCA patients, blood oxygen content was negatively correlated with CBF in the middle and posterior cerebral artery territories and significantly positively correlated with bolus arrival time (BAT) in the anterior and middle cerebral artery territories. In older children, SCA patients had significantly shorter BAT than healthy controls and there was a significant negative correlation between CBF and oxygen content only in the territory of the posterior cerebral artery, with a trend for a correlation in the anterior cerebral artery but no relationship for the middle cerebral artery territory. In the younger group, SCI+ patients had significantly higher CBF in the posterior cerebral artery territory (SCI+ mean = 92.78 ml/100 g/min; SCI- mean = 72.71 ml/100 g/min; F = 4.28, p = 0.04), but this no longer reached significance when two children with abnormal transcranial Doppler and one with haemoglobin SC disease were excluded, and there were no significant differences between patients with and without SCI in the older children. With age, there appears to be increasing disparity between patients and controls in terms of the relationship between CBF and oxygen content in the anterior circulation, potentially predicting the risk of acute and chronic compromise of brain tissue.

Interventions for treating ankle fractures in children.

BACKGROUND: Ankle fractures, which usually occur after a twisting incident, are a diverse collection of injuries with different levels of complexity and severity. They have an incidence of 1 in 1000 a year in children. Treatment generally involves splints and casts for minor fractures and surgical fixation with screws, plates and pins followed by immobilisation for more serious fractures. OBJECTIVES: To assess the effects (benefits and harms) of different interventions for treating ankle fractures in children. SEARCH METHODS: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (22 September 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (2015, Issue 8), MEDLINE (1946 to September Week 2 2015), MEDLINE In-Process & Other Non-Indexed Citations (21 September 2015), EMBASE (1980 to 2015 Week 38), CINAHL (1937 to 22 September 2015), trial registers (17 February 2015), conference proceedings and reference lists of articles. SELECTION CRITERIA: We included randomised and quasi-randomised controlled trials evaluating interventions for treating ankle fractures in children. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles, abstracts and full articles for inclusion, assessed risk of bias and collected data. We undertook no meta-analysis. MAIN RESULTS: We included three randomised controlled trials reporting results for 189 children, all of whom had a clinical diagnosis of a "low risk" ankle fracture. These were predominantly classified as undisplaced Salter-Harris type I fractures of the distal fibula. All three trials compared non-surgical management options. The three trials were at high risk of bias, primarily relating to the impracticality of blinding participants and treating clinicians to the allocated interventions.Two trials compared the Aircast Air-Stirrup ankle brace versus a rigid cast, which was a removable fibreglass posterior splint in one trial (trial A) and a below-knee fibreglass walking cast in the other trial (trial B). In trial A, both devices were removed at around two weeks. In trial B, removal of the brace was optional after five days, while the walking cast was removed after three weeks. There was low-quality evidence of clinically important differences in function scores at four weeks in favour of the brace groups of both trials. Function was measured using the Activities Scale for Kids-performance (ASKp; score range 0 to 100, higher scores mean better function) in trial A and using a modified version of the ASKp score (range 0 to 100%, higher percentages mean better function) in trial B. The results for trial A (40 participants) were median 91.9 in the brace group versus 84.2 in the splint group. The results for trial B (104 participants) were 91.3% versus 85.3%; mean difference (MD) 6.00% favouring brace (95% confidence interval (CI) 1.38% to 10.62%). Trial B indicated that 5% amounted to a clinically relevant difference in the modified ASKp score. Neither trial reported on unacceptable anatomy or related outcomes or long-term follow-up. There was very low-quality evidence relating to adverse events, none of which were serious. Trial A found twice as many children with pressure-related complications in the brace group (10 of 20 versus 5 of 20). In contrast, trial B found four times as many children in the cast group had adverse outcomes assessed in terms of an unscheduled visit to a healthcare provider (4 of 54 versus 16 of 50). Both trials linked some of the adverse events in the brace group with the failure to wear a protective sock. There was very low-quality evidence indicating an earlier return to pre-injury activity in the brace groups in both trials. Trial B provided low-quality evidence that children much prefer five days or more wearing an ankle brace than three weeks immobilised in a walking ankle cast. There was moderate-quality evidence of a lack of difference between the two groups in pain at four weeks.The third trial compared the Tubigrip bandage plus crutches and advice versus a plaster of Paris walking cast for two weeks and reported results at four weeks' follow-up for 45 children with an inversion injury of the ankle. The trial found very low-quality evidence of little difference in pain and function between the two groups, measured using a non-validated pain and function score at four weeks. The trial did not report on adverse effects. There was very low-quality evidence of an earlier return to normal activities, averaging six days, in children treated with Tubigrip (mean 14.17 days for Tubigrip versus 20.19 days for cast; MD -6.02 days, 95% CI -8.92 to -3.12 days).Recent evidence from magnetic resonance imaging studies of the main category of injury evaluated in these three trials suggests that most of the injuries in these trials were sprains or bone bruises rather than fractures of the distal fibular growth plate. AUTHORS' CONCLUSIONS: There is low-quality evidence of a quicker recovery of self reported function at four weeks in children with clinically diagnosed low-risk ankle fractures who are treated with an ankle brace compared with those treated with a rigid cast, especially a non-removable walking cast. There is otherwise a lack of evidence from randomised controlled trials to inform clinical practice for children with ankle fractures. Research to identify and address priority questions on the treatment of these common fractures is needed.

White Matter Damage Relates to Oxygen Saturation in Children With Sickle Cell Anemia Without Silent Cerebral Infarcts.

BACKGROUND AND PURPOSE: Sickle cell anemia is associated with compromised oxygen-carrying capability of hemoglobin and a high incidence of overt and silent stroke. However, in children with no evidence of cerebral infarction, there are changes in brain morphometry relative to healthy controls, which may be related to chronic anemia and oxygen desaturation. METHODS: A whole-brain tract-based spatial statistics analysis was carried out in 25 children with sickle cell anemia with no evidence of abnormality on T2-weighted magnetic resonance imaging (13 male, age range: 8-18 years) and 14 age- and race-matched controls (7 male, age range: 10-19 years) to determine the extent of white matter injury. The hypotheses that white matter damage is related to daytime peripheral oxygen saturation and steady-state hemoglobin were tested. RESULTS: Fractional anisotropy was found to be significantly lower in patients in the subcortical white matter (corticospinal tract and cerebellum), whereas mean diffusivity and radial diffusivity were higher in patients in widespread areas. There was a significant negative relationship between radial diffusivity and oxygen saturation (P<0.05) in the anterior corpus callosum and a trend-level negative relationship between radial diffusivity and hemoglobin (P<0.1) in the midbody of the corpus callosum. CONCLUSIONS: These data show widespread white matter abnormalities in a sample of asymptomatic children with sickle cell anemia, and provides for the first time direct evidence of a relationship between brain microstructure and markers of disease severity (eg, peripheral oxygen saturation and steady-state hemoglobin). This study suggests that diffusion tensor imaging metrics may serve as a biomarker for future trials of reducing hypoxic exposure.

How Critical is Patient Positioning in Radiographic Assessment of the Hip in Cerebral Palsy When Measuring Migration Percentage?

BACKGROUND: Migration percentage (MP) is an accepted method of assessing lateral displacement of the femoral head in children with cerebral palsy (CP). Difficulty in positioning of patients for pelvic radiography remains a concern for the reliability of the MP. METHODS: This 2-part quantitative study examined 100 anteroposterior pelvic radiographs for children with CP. Fifty were from a region that had a positioning protocol for hip surveillance of children with CP and 50 images were from a region without. Images were assessed for acceptability of position in relation to hip abduction/adduction and/or pelvic rotation.Ten images deemed Acceptable or Borderline from the region with no protocol were then randomly selected. MP was measured on 2 separate occasions by 5 children's orthopaedic surgeons and statistically analyzed for intrarater and interrater reliability. RESULTS: There was no statistically significant difference in the acceptability of images between the 2 regions with 60% to 66% of the images meeting the criteria outright. When allowances were made for slight variation of abduction/adduction within 5 degrees, 74% to 80% of the images were acceptable.Reliability was variable with limits of agreement between 4.96% and 15.15%. Observers more familiar with the software measuring package had higher reliability within and between occasions. Variability within and between observers decreased as MP increased. CONCLUSIONS: Poor positioning did not appear to be the main reason for the variation in reliability of MP. Repeat measurements were reliable although standardized technique, training, and familiarity with software measuring programmes did influence outcomes.

The Bangladesh clubfoot project: audit of 2-year outcomes of Ponseti treatment in 400 children.

BACKGROUND: Congenital clubfoot deformity can cause significant disability, and if left untreated, may further impoverish those in developing countries, like Bangladesh. The Ponseti method has been strategically introduced in Bangladesh by a nongovernment organization, Walk For Life (WFL). WFL has provided free treatment for over 8000 Bangladeshi children with clubfeet, sustained by local ownership, and international support. This audit assesses the 2-year results in children for whom treatment began before the age of 3 years. METHODS: The 10 largest WFL clinics, of the 24 across Bangladesh, were pragmatically accessed in this audit availing 1442 subjects meeting the study criteria, from which 400 children were randomly selected and examined. A specific assessment tool was developed and validated. RESULTS: Results for 400 cases were returned: 269 males, 131 females. Typical clubfeet comprised 79% of cases, and 55% were bilateral. A tenotomy rate of 79%, and brace use after 2 years of 85%, were notable findings. Functionally, most children could walk independently (99.0%), run (95.5%), squat (93.3%), and manage steps unassisted (93.0%). The ability to squat was the most indicative outcome measure, correlating with: less corrective casts, good and continued brace use, nonvarus heel position, good ankle range of motion, good Bangla clubfoot scores, and the ability to walk. Relapsing deformity was suspected with heel varus (18.0% left; 21.5% right). Parental satisfaction was very high, but cost of 3000 Taka ($US 38.48) was deemed unaffordable by 59%. CONCLUSIONS: The outcomes in young children after 2 years of Ponseti treatment for clubfoot deformity showed that 99% were able to walk independently. The assessment tool developed for this study avails ongoing monitoring. Without the patronage of WFL, most of these children would not have had access to treatment, and be unable to walk. LEVEL OF EVIDENCE: Level II-lesser-quality prospective study.

Bilateral Anterior Cruciate Ligament Reconstruction with All-Inside Technique for Adolescent: A Review of the Literature and Case Report.

Introduction: Simultaneous bilateral anterior cruciate ligament (ACL) ruptures are rare, especially in the pediatric population, with very limited evidence. We aimed to review the current literature and present a case study of an adolescent patient who underwent bilateral reconstruction with hamstrings autograft in a single-stage with a partial transphyseal "all-inside" technique. Literature Review: The limited evidence reports that the incidence of growth disturbance following ACL reconstruction in the skeletally immature is 2.6% with no significant difference between a partial transphyseal and an all-epiphyseal technique. Regarding graft choice in the skeletally immature, no significant difference has been found in function using hamstrings versus bone-to-bone patella autograft. The all-inside technique has shown good outcomes in the skeletally immature with no cases of growth disturbance observed in the literature reviewed. Patients spend less days in hospital and return to sport sooner following simultaneous reconstruction versus staged. Case Report: A 15-year-old male footballer underwent simultaneous reconstruction of bilateral ACL ruptures through a partial transphyseal "all-inside" technique with hamstrings autografts. He began physiotherapy according to local protocol and was discharged from hospital on Day 4 post-operative. He returned to competitive sports 11 months postoperatively with no intraoperative or post-operative complications. Conclusion: This case suggests that bilateral simultaneous ACL reconstruction is a safe management strategy in the rare case of bilateral ruptures in the skeletally immature, which adds to the evidence base. The number of required hospital stays was reduced and there was return to sport in a comparative time frame to unilateral ACL reconstruction rehabilitation.

The Bangladesh clubfoot project: the first 5000 feet.

BACKGROUND: Bangladesh is one of the most populous countries in the world at 160 million with 1/3 existing below the poverty line. With an annual birth rate of approximately 3.2 million, an estimated incidence of 1:900 live births, the country has approximately 5000 new cases of idiopathic congenital talipes equinovarus per annum. The Bangladesh sustainable clubfoot program, Walk for Life (WFL), was conceived to respond to this unmet need. METHODS: WFL started in 2009 and has rapidly grown to 35 clinics. Overseas experts initially increased local capacity by training a team of national paramedical staff. Government support enabled integration with the public hospital system and enhanced sustainability. WFL has supplied materials, educational, administrative, and clinical support throughout. All recruited cases underwent Ponseti casting. Demographic, Pirani scores, cast, tenotomy, and bracing data have been prospectively collected from all patients. Detailed review has been undertaken for 1040 patients after 12 months of treatment in 3 divisions of Bangladesh. RESULTS: Between 2009 and 2011, 6069 feet (3922 patients) were recruited to the project. Of these 1643 feet (1040 patients) have completed a minimum of 1-year follow-up. The male:female ratio was 2.7:1 with a mean age of 22 months at presentation (range, 0 to 36). Typical idiopathic congenital talipes equinovarus responded in a median of 5 casts (range, 1 to 25) with 76% undergoing tenotomy. Thirteen percent were atypical feet requiring a median of 5 casts. The percentage of patients missing at the 12-month point was 12%. Two percent of patients experienced complications. CONCLUSIONS: The Bangladesh clubfoot program demonstrates that rapid case ascertainment is possible in a developing world setting with appropriate logistical support. The use of local physiotherapists and paramedics yielded good clinical outcomes in an environment with full access to clinical review and ongoing training. A higher than expected number of atypical cases have been noted, requiring modified Ponseti treatment. Complications have been few at this early stage. LEVEL OF EVIDENCE: Level 2-therapeutic study.

Volcanic glass from the 1.8 ka Taupo eruption (New Zealand) detected in Antarctic ice at ~ 230 CE.

Chemical anomalies in polar ice core records are frequently linked to volcanism; however, without the presence of (crypto)tephra particles, links to specific eruptions remain speculative. Correlating tephras yields estimates of eruption timing and potential source volcano, offers refinement of ice core chronologies, and provides insights into volcanic impacts. Here, we report on sparse rhyolitic glass shards detected in the Roosevelt Island Climate Evolution (RICE) ice core (West Antarctica), attributed to the 1.8 ka Taupo eruption (New Zealand)-one of the largest and most energetic Holocene eruptions globally. Six shards of a distinctive geochemical composition, identical within analytical uncertainties to proximal Taupo glass, are accompanied by a single shard indistinguishable from glass of the ~25.5 ka Oruanui supereruption, also from Taupo volcano. This double fingerprint uniquely identifies the source volcano and helps link the shards to the climactic phase of the Taupo eruption. The englacial Taupo-derived glass shards coincide with a particle spike and conductivity anomaly at 278.84 m core depth, along with trachytic glass from a local Antarctic eruption of Mt. Melbourne. The assessed age of the sampled ice is 230 ± 19 CE (95% confidence), confirming that the published radiocarbon wiggle-match date of 232 ± 10 CE (2 SD) for the Taupo eruption is robust.

Assessment of calf volume in Congenital Talipes Equinovarus by computer analysed digital photography.

The development of evidence-based approaches to the Congenital Talipes Equinovarus (CTEV) is impaired by the diversity of assessment techniques available, many of which have not been validated. Highly objective evaluation techniques that reflect the deformity and permit comparison between studies may lack the necessary link to functional features that are paramount to the patient, namely pain and mobility. Calf wasting is an acknowledged but little investigated component of the pathology. The rapid evolution of digital photography and computerised analytical techniques has yielded an opportunity to explore their role in the assessment of this common paediatric Orthopaedic pathology. This study presents the use of a cost-effective digital photographic assessment technique of maximal calf circumference and calf volume. These indices reflect the muscular development in the calf and therefore have significance in the functional assessment of CTEV and may represent an index of severity. Subjectivity has been limited by computerisation of the analysis process. The technique could easily be adapted to other volumetric analyses.

Seizure-induced miosis.

Ictal autonomic pupillary dilation is common; however, miosis is rare. We describe a case of focal seizures secondary to cortical dysplasia presenting with bilateral pupillary miosis, rendered seizure free by resective surgery. The seizure-onset zone was localized within the left middle parietal gyrus by intracranial electrographic recording. Seizure onset was coincident with focal left centroparietal fast spike activity on electroencephalography (EEG). A large region of the left frontocentral cortical dysplasia was demonstrated on magnetic resonance imaging (MRI). Complete resection of the area of cortical dysplasia and additional cortical regions of ictal activity, identified using intracranial EEG, rendered the patient seizure free.

Eligibility for dapagliflozin in unselected patients hospitalised with decompensated heart failure.

Patients with heart failure with reduced ejection fraction (HFrEF) who received the sodium-glucose co-transport 2 inhibitor, dapagliflozin, in the DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) study have a significant reduction in worsening heart failure (HF) and cardiovascular death. It is uncertain what proportion of patients admitted to a large regional cardiac centre with decompensated heart failure would be eligible for dapagliflozin post-discharge based on their characteristics at discharge. The DAPA-HF study criteria were retrospectively applied to a cohort of 521 consecutive patients referred to the inpatient HF service in a tertiary cardiac centre in South West Wales between April 2017 and April 2018. Inclusion criteria: left ventricular ejection fraction (LVEF) < 40%, New York Heart Association (NYHA) class II-IV symptoms and an elevated N-terminal pro-B-type naturietic peptide (NT-proBNP). Exclusion criteria: systolic blood pressure (SBP) < 95 mmHg, estimated glomerular filtration rate (eGFR) < 30 ml/min/1.73 m2 or type 1 diabetes mellitus. We did not have complete NTproBNP data for the cohort, as it was not routinely measured at the time in our institute. There were 478 patients, mean age 78 ± 13 years, 57% male and 91% NYHA class II-IV symptoms, were included in the analysis. Of these, 247 patients had HFrEF, 219 (46%) patients met the inclusion criteria, 231 (48%) were excluded as LVEF was > 40%, and 48 (10%) were excluded with NYHA class I symptoms. Of the 219 patients who met the inclusion criteria, 13 (5.9%) had a SBP < 95 mmHg, 48 (22%) had eGFR < 30 ml/min/1.73 m2, leaving 136 (28.5% of total and 55% of those with HFrEF) who met DAPA-HF study criteria. In our study, 28.5% of all heart failure admissions and 55% of patients with HFrEF would be eligible for dapagliflozin post-discharge according to the DAPA-HF study entry criteria.

Micro-magnetic resonance imaging and embryological analysis of wild-type and pma mutant mice with clubfoot.

Gross similarities between the external appearance of the hind limbs of the peroneal muscle atrophy (pma) mouse mutant and congenital talipes equinovarus (CTEV), a human disorder historically referred to as 'clubfoot', suggested that this mutant could be a useful model. We used micro-magnetic resonance imaging to visualize the detailed anatomy of the hind limb defect in mutant pma mice and performed 3D comparisons between mutant and wild-type hind limbs. We found that the pma foot demonstrates supination (i.e. adduction and inversion of the mid foot and fore foot together with plantar flexion of the ankle and toes) and that the tibiale and distal tarsals display 3D abnormalities in positioning. The size and shape of the tibia, fibula, tarsal and metatarsal bones are similar to the wild-type. Hypoplasia of the muscles in the antero-lateral (peroneal) compartment was also demonstrated. The resemblance of these features to those seen in CTEV suggests that the pma mouse is a possibly useful model for the human condition. To understand how the observed deformities in the pma mouse hind foot arise during embryonic development, we followed the process of foot rotation in both wild-type and pma mutant mice. Rotation of the hind foot in mouse embryos of wild-type strains (CD-1 and C57/Black) occurs from embryonic day 14.5 onwards with rotation in C57/Black taking longer. In embryos from both strains, rotation of the right hind foot more commonly precedes rotation of the left. In pma mutants, the initiation of rotation is often delayed and rotation is slower and does not reach completion. If the usefulness of the pma mutant as a model is confirmed, then these findings on pma mouse embryos, when extrapolated to humans, would support a long-standing hypothesis that CTEV is due to the failure of completion of the normal process of rotation and angulation, historically known as the 'arrested development hypothesis'.

Adult peroxisomal acyl-coenzyme A oxidase deficiency with cerebellar and brainstem atrophy.

Peroxisomal acyl-coenzyme A oxidase deficiency (formerly also called pseudoneonatal adrenoleucodystrophy) is a disorder of peroxisomal fatty acid oxidation with a severe presentation. Most patients present at birth or in early infancy, and the mean age of death was 5 years in a recently published cohort of 22 patients. Brain imaging shows a progressive leucodystrophy. The authors report here the first adult patients (two siblings, 52 and 55 years old) with peroxisomal acyl-coenzyme A oxidase deficiency with a remarkably mild clinical presentation. Magnetic resonance brain imaging revealed profound atrophy of the brainstem and cerebellum.

Facial features in children with idiopathic congenital talipes equinovarus.

We assessed whether there is a recognisable pattern of facial morphology in photographs of a series of 62 children with idiopathic congenital talipes equinovarus (CTEV). Photographs were scored for a number of facial characteristics by a research team comprising orthopaedic surgeons and clinical geneticists, to identify a subgroup of children with idiopathic CTEV, who shared characteristic facial features. Seven children were identified as having a "CTEV face". There was good correlation between the "CTEV face" and the individual facial features. Repeatability of the assessment was good, and there was good correlation between the geneticists and the orthopaedic surgeons, suggesting that no special training in dysmorphology is required to identify the "CT EV face". There is a subgroup of children with idiopathic CTEV who can be reliably identified by their facial characteristics. The significance of this finding is unclear but it may be of use in clinical genetic studies, and studies of the aetiology of CTEV.

Subjective and objective outcome in congenital clubfoot; a comparative study of 204 children.

BACKGROUND: Outcome following management of congenital talipes equinovarus (clubfoot) can be assessed in a number of ways. Bjonness stated simply that "the patient is the final judge of whether he has a good foot"; a purely subjective assessment. Others have employed objective measures. Combining subjective evaluation with a more objective assessment of movement and position of the foot, is likely to give a more comprehensive picture of the final result of clubfoot. The purpose of this study was to compare subjective and objective outcome following management of clubfoot, and evaluate sex differences in outcome. METHODS: We used a patient-administered subjective assessment of outcome following treatment of clubfoot and compared it with objective anthropometry and range of movement of the ankle to assess and compare subjective and objective outcome in clubfoot. Statistical analysis was performed using Pearson correlation coefficients. Significance was tested using Student's t-test test. RESULTS: Objective outcome can be assessed using length of the foot, calf circumference and range of movement at the ankle. These are easy to measure, reproducible, and correlate well with subjective outcome. Objective outcome is comparable for boys and girls. However, subjectively, female patients and their parents are less happy with the results of management of clubfoot. CONCLUSION: There is a correlation between the anthropometric measures and the subjective outcome and an objective grading can be designed using foot length, calf muscle bulk and range of movement at the ankle.

Comment on "Rapid cooling and cold storage in a silicic magma reservoir recorded in individual crystals".

Rubin et al (Reports, 16 June 2017, p. 1154) proposed that gradients in lithium abundance in zircons from a rhyolitic eruption in New Zealand reflected short-lived residence at magmatic temperatures interleaved with long-term "cold" (<650°C) storage. Important issues arise with the interpretation of these lithium gradients and consequent crystal thermal histories that raise concerns about the validity of this conclusion.

Lack of seasonal variation in idiopathic talipes equinovarus.

BACKGROUND: One proposed etiology of idiopathic talipes equinovarus is an in utero enterovirus infection. Enterovirus infections demonstrate seasonal variation in temperate climates. METHODS: We collected data on 1202 children with idiopathic talipes equinovarus born in the Northeastern United States, Midwestern United States, and the United Kingdom to investigate a seasonal variation in this congenital deformity. Birth date, gestational age at the time of delivery, gender, race, and laterality were tabulated and subjected to univariate and bivariate analyses. RESULTS: There were 774 boys and 428 girls with idiopathic talipes equinovarus. The birth location was the United Kingdom (458 children), the Midwestern United States (426 children), and the Northeastern United States (318 children). No significant differences were detected among the geographic groups with respect to gender, race, or laterality, and no variation in month of birth or month of conception was noted. CONCLUSIONS: This study does not support an in utero enterovirus infection as an etiology of idiopathic talipes equinovarus in industrialized populations.