Orthopaedic management of Hurler’s disease after hematopoietic stem cell transplantation: a systematic review

The introduction of hematopoietic stem cell transplantation (HSCT) has significantly improved the life-span of Hurler patients (mucopolysaccharidosis type I-H, MPS I-H). Yet, the musculoskeletal manifestations seem largely unresponsive to HSCT. In order to facilitate evidence based management, the aim of the current study was to give a systematic overview of the orthopaedic complications and motor functioning of Hurler's patients after HSCT. A systematic review was conducted of the medical literature published from January 1981 to June 2010. Two reviewers independently assessed all eligible citations, as identified from the Pubmed and Embase databases. A pre-developed data extraction form was used to systematically collect information on the prevalence of radiological and clinical signs, and on the orthopaedic treatments and outcomes. A total of 32 studies, including 399 patient reports were identified. The most frequent musculoskeletal abnormalities were odontoid hypoplasia (72%), thoracolumbar kyphosis (81%), genu valgum (70%), hip dysplasia (90%) and carpal tunnel syndrome (63%), which were often treated surgically during the first decade of life. The overall complication rate of surgical interventions was 13.5%. Motor functioning was further hampered due to reduced joint mobility, hand dexterity, motor development and longitudinal growth. Stem cell transplantation does not halt the progression of a large range of disabling musculoskeletal abnormalities in Hurler's disease. Although prospective data on the quantification, progression and treatment of these deformities were very limited, early surgical intervention is often advocated. Prospective data collection will be mandatory to achieve better evidence on the effect of treatment strategies

Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns

Epigenetic processes, including DNA methylation (DNAm), are among the mechanisms allowing integration of genetic and environmental factors to shape cellular function. While many studies have investigated either environmental or genetic contributions to DNAm, few have assessed their integrated effects. Here we examine the relative contributions of prenatal environmental factors and genotype on DNA methylation in neonatal blood at variably methylated regions (VMRs) in 4 independent cohorts (overall n = 2365). We use Akaike’s information criterion to test which factors best explain variability of methylation in the cohort-specific VMRs: several prenatal environmental factors (E), genotypes in cis (G), or their additive (G + E) or interaction (GxE) effects. Genetic and environmental factors in combination best explain DNAm at the majority of VMRs. The CpGs best explained by either G, G + E or GxE are functionally distinct. The enrichment of genetic variants from GxE models in GWAS for complex disorders supports their importance for disease ris

Single-stage closing–opening wedge osteotomy of spine to correct severe post-tubercular kyphotic deformities of the spine: a 3-year follow-up of 17 patients

The correction of severe post-tubercular kyphosis (PTK) is complex and has the disadvantage of being multiple staged with a high morbidity. Here, we describe the procedure and results of closing–opening osteotomy for correction of PTK which shortens the posterior column and opens the anterior column appropriately to correct the deformity without altering the length of the spinal cord. Seventeen patients with PTK (10 males; 7 females) with an average age of 18.3 ± 10.6 years (range 4–40 years) formed the study group. There were ten thoracolumbar, one lumbar and six thoracic deformities. The number of vertebrae involved ranged from 2 to 5 (average 2.8). Preoperative kyphosis averaged 69.2° ± 25.1° (range 42°–104°) which included ten patients with deformity greater than 60°. The average vertebral body loss was 2.01 ± 0.79 (range 1.1–4.1). The neurological status was normal in 13 patients, Frankel’s grade D in three patients and grade C in one. Posterior stabilization with pedicle screw instrumentation was followed by a preoperatively calculated wedge resection. Anterior column reconstruction was performed using rib grafts in four, tricortical iliac bone graft in five, cages in six, and bone chips alone and fibular graft in one patient each. Average operating time was 280 min (200–340 min) with an average blood loss of 820 ml (range 500–1,600 ml). The postoperative kyphosis averaged 32.4° ± 19.5° (range 8°–62°). The percentage correction of kyphosis achieved was 56.8 ± 14.6% (range 32–83%). No patient with normal preoperative neurological status showed deterioration in neurology after surgery. The last follow-up was at an average of 43 ± 4 months (range 32–64 months). The average loss of correction at the last follow-up was 5.4° (range 3°–9°). At the last follow-up, the mean preoperative pain visual analogue scale score decreased significantly from 9.2 (range 8–10 points) to 1.5 (range 1–2 points). There was also a significant decrease in mean preoperative Oswestry’s Disability Index from 56.4 (range 46–68) to 10.6 (range 6–15). Complications were superficial wound infections in two, neurological deterioration in one, temporary jaundice in one and implant failure requiring revision in one. Single-stage closing–opening wedge osteotomy is an effective method to correct severe PTK. The procedure has the advantage of being a posterior only, single-stage correction, which allows for significant correction with minimal complications