Fetal Scoliosis: Natural History and Outcomes.

Introduction: Scoliosis can be detected on prenatal ultrasonography and may be associated with structural and syndromic abnormalities. Associations and pregnancy outcomes related to the prenatal diagnosis of scoliosis are poorly understood.

Methods: A retrospective cohort study was undertaken at a tertiary referral center in London.

Large symptomatic sacral Tarlov cyst in a paediatric patient: case report and technical note on a new variation of surgical technique to overcome one-way check-valve mechanism.

Purpose: Symptomatic Tarlov cysts in children with a possible underlying one-way check-valve mechanism are very rare. We aim to introduce a new variation of the surgical technique to overcome a check-valve mechanism.

Methods: A 15-years-old girl presented with double incontinence and anogenital numbness due to a large sacral Tarlov-cyst with possibly underlying one-way check valve mechanisms as suggested by preoperative computed tomography myelography.

Chemotherapy May Obviate Prophylactic Femoral Nail Surgery for Multiple Myeloma Patients With High Mirels' Score Lesions and Impending Pathological Hip Fracture.

Bone involvement presents in >80% of patients with multiple myeloma. This causes lytic lesions for which prophylactic surgery is indicated to prevent pathological fractures if the lesion is graded ≥9/12 on Mirels' score. Although successful, these surgeries have risks and extended recovery periods.

PTPN11 Mosaicism Causes a Spectrum of Pigmentary and Vascular Neurocutaneous Disorders and Predisposes to Melanoma.

Phakomatosis pigmentovascularis is a diagnosis that denotes the coexistence of pigmentary and vascular birthmarks of specific types, accompanied by variable multisystem involvement, including CNS disease, asymmetrical growth, and a predisposition to malignancy. Using a tight phenotypic group and high-depth next-generation sequencing of affected tissues, we discover here clonal mosaic variants in gene PTPN11 encoding SHP2 phosphatase as a cause of phakomatosis pigmentovascularis type III or spilorosea. Within an individual, the same variant is found in distinct pigmentary and vascular birthmarks and is undetectable in blood.

Surgeon-Directed Neuromonitoring in Adolescent Spinal Deformity Surgery Safely Assesses Neurological Function.

Background Spinal deformity correction is associated with the risk of intra-operative neurological injury. Surgeon-directed monitoring (SDM) of transcranial motor-evoked potentials (TcMEP) is an option to monitor intra-operative spinal cord function. We report a retrospective analysis of a prospective database to assess the safety of this technique in spinal deformity correction in adolescent patients.

Is the AO spine thoracolumbar injury classification system reliable and practical? a systematic review.

Controversy surrounding the classification of thoracolumbar injuries has given rise to various classification systems over the years, including the most recent AOSpine Thoracolumbar Injury Classification System (ATLICS). This systematic review aims to provide an up-to-date evaluation of the literature, including assessment of a further three studies not analysed in previous reviews. In doing so, this is the first systematic review to include the reliability among non-spine subspecialty professionals and to document the wide variety between reliability across studies, particularly with regard to sub-type classification.

Tranexamic acid use in a patient with sickle cell disease undergoing posterior scoliosis correction surgery: safely mitigating bleeding and vaso-occlusive crises.

A 15-year-old female with 2-year post-menarchal adolescent idiopathic scoliosis and sickle cell disease (SCD) underwent posterior scoliosis correction surgery. SCD is associated with higher rates of surgical complications, and these patients require careful management to prevent vaso-occlusive sickle cell crises (VOSCC); scoliosis correction surgery can be associated with high morbidity and mortality, including significant blood loss. Multiple techniques were employed to successfully prevent VOSCC in this patient including a preoperative transfusion, meticulous haemostasis at osteotomy sites, not performing a costoplasty despite presence of a rib hump, maintenance of intraoperative mean arterial pressure below 70 mmHg, aggressive postoperative hydration and the use of intraoperative tranexamic acid (TXA).

An assessment of the distance between the phrenic nerve and major intrathoracic structures.

Background: There is a lack of consensus in the literature regarding phrenic nerve proximity to thoracic structures at the level of the diaphragm. This study was undertaken to provide thoracic surgeons data on phrenic nerve location in order to reduce iatrogenic injury during invasive surgery.

Methods: Bilateral thoracic dissection was performed on 43 embalmed human cadavers (25 males; 18 females) and data was obtained from 33 left and 40 right phrenic nerves.

Pedicle distraction increases intervertebral and spinal canal area in a cadaver and bone model.

Introduction: Lumbar spinal stenosis is degenerative narrowing of the spinal canal and/or intervertebral foramen causing compression of the spinal cord and nerve roots. Traditional decompression techniques can often cause significant trauma and vertebral instability. This paper evaluates a method of increasing pedicle length to decompress the spinal and intervertebral foramen, which could be done minimally invasive.

Large-scale Sequencing of Testicular Germ Cell Tumour (TGCT) Cases Excludes Major TGCT Predisposition Gene.

Unlabelled: Testicular germ cell tumour (TGCT), the most common cancer in young men, has a significant heritable basis that has long raised questions as to the existence of underlying major high-penetrance susceptibility gene(s). To determine the contribution of rare gene mutations to the inherited risk of TGCT, we analysed germline whole-exome data for 919 TGCT cases and 1609 cancer-free controls. We compared frequencies between TGCT cases and controls of rare (<1%) and low-frequency (1-5%) coding variants (1) individually and (2) collapsed at the gene level via burden testing (T1, disruptive; T2, all deleterious; and T3, all nonsynonymous) using Fisher's exact test with Bonferroni correction of significance thresholds.

The clinicopathological and gene expression patterns associated with ulceration of primary melanoma.

Ulceration of primary melanomas is associated with poor prognosis yet is reported to predict benefit from adjuvant interferon. To better understand the biological processes involved, clinicopathological factors associated with ulceration were determined in 1804 patients. From this cohort, 348 primary tumor blocks were sampled to generate gene expression data using a 502-gene cancer panel and 195 blocks were used for immunohistochemistry to detect macrophage infiltration and vessel density.

Vitamin D and melanoma.

Recreational sun exposure and sunburn are causal for melanoma but the risk is strongly genetically determined. Health promotion advice about sun protection should be aimed at susceptible individuals (pale skin, freckles, large numbers of melanocytic nevi and a family history). We discuss here the evidence that sun-sensitive people have lower vitamin D levels and that, in practice, it is very difficult for such individuals to achieve sufficient levels without supplementation in the UK at least.

Chemoprevention in Lynch syndrome.

CAPP1 tested aspirin 600 mg/day and/or resistant starch 30 g/day in 200 adolescent FAP carriers. Aspirin treatment resulted in a non-significant reduction in polyp number and a significant reduction in polyp size among patients treated with aspirin for more than 1 year. CAPP2 RCT used the same interventions in 937 Lynch syndrome patients, the first RCT to have cancer prevention as the primary endpoint.

Evaluation of PAX3 genetic variants and nevus number.

The presence of a high nevus number is the strongest phenotypic predictor of melanoma risk. Here, we describe the results of a three-stage study directed at identifying risk variants for the high nevus phenotype. At the first stage, 263 melanoma cases from Barcelona were genotyped for 223 single-nucleotide polymorphisms (SNPs) in 39 candidate genes.

Lynch syndrome: history, causes, diagnosis, treatment and prevention (CAPP2 trial).

Hereditary cancer due to pathological mutations in the mismatch repair gene family is now known as Lynch syndrome and affects at least 1 in 1,000 people, resulting in a 30-50% cancer risk most often involving the colorectum and endometrium. Annual or biennial colonoscopy reduces cancer deaths and many offer gynaecological surveillance, but most other associated cancers are not amenable to early detection. As microsatellite instability testing and tumour immunohistochemistry become routine, case finding will improve.

Genetics, inheritance and strategies for prevention in populations at high risk of colorectal cancer (CRC).

Hereditary forms of colorectal cancer account for less than 5 % of colorectal cancer but attract disproportionate attention because they offer an opportunity for effective surgical prophylaxis, influence the health of the wider family and give insight into the critical pathways of carcinogenesis. Familial Adenomatous Polyposis (FAP) due to loss of the APC gene and Lynch syndrome or Hereditary Non-Polyposis Colon Cancer (HNPCC) due to breakdown in MisMatch Repair are the principal syndromes of broader interest and both have been the subject of chemoprevention trials. There has been a longstanding interest in non-steroidal anti inflammatories in FAP where trials have shown regression of polyps with the "pro drug"sulindac and the selective COX2 inhibitors though impact on long-term cancer risk is not confirmed.

Genome-wide association study identifies novel loci predisposing to cutaneous melanoma.

We performed a multistage genome-wide association study of melanoma. In a discovery cohort of 1804 melanoma cases and 1026 controls, we identified loci at chromosomes 15q13.1 (HERC2/OCA2 region) and 16q24.

People of the British Isles: preliminary analysis of genotypes and surnames in a UK-control population.

There is a great deal of interest in a fine-scale population structure in the UK, both as a signature of historical immigration events and because of the effect population structure may have on disease association studies. Although population structure appears to have a minor impact on the current generation of genome-wide association studies, it is likely to have a significant part in the next generation of studies designed to search for rare variants. A powerful way of detecting such structure is to control and document carefully the provenance of the samples involved.

Replication of the recessive STBMS1 locus but with dominant inheritance.

Purpose: Strabismus is a common eye disorder with a prevalence of 1% to 4%. Comitant strabismus accounts for approximately 75% of all strabismus, yet more is known about the less common incomitant disorders. Comitant strabismus is at least partly inherited, but only one recessive genetic susceptibility locus, on chromosome 7p, has been identified in one family.

The genetics of melanoma.

Melanoma is an increasingly common cancer and in order to direct preventative advice at those at risk, an understanding of susceptibility is crucial. This review summarizes what is known about common low-risk genes (such as those controlling red hair) and rare high-risk genes.

Diet and genetic factors associated with iron status in middle-aged women.

Background: Gene mutations associated with iron overload have been identified. How food and nutrient intakes affect iron status in persons who may be at risk of iron overload because their genetic status is unknown.

Objective: The objective was to determine the relation between food and nutrient intakes, HFE genotype, and iron status.

A combined genomewide linkage scan of 1,233 families for prostate cancer-susceptibility genes conducted by the international consortium for prostate cancer genetics.

Evidence of the existence of major prostate cancer (PC)-susceptibility genes has been provided by multiple segregation analyses. Although genomewide screens have been performed in over a dozen independent studies, few chromosomal regions have been consistently identified as regions of interest. One of the major difficulties is genetic heterogeneity, possibly due to multiple, incompletely penetrant PC-susceptibility genes.

Premature coronary artery disease shows no evidence of linkage to loci encoding for tissue inhibitors of matrix metalloproteinases.

Tissue inhibitors of metalloproteinases (TIMP1, TIMP2, TIMP3) are naturally occurring inhibitors of matrix metalloproteinases (MMPs). It has been proposed that MMPs have a role in weakening the fibrous cap and subsequent plaque rupture. We hypothesized that TIMP polymorphisms could predispose to premature coronary artery disease.

Can resistant starch and/or aspirin prevent the development of colonic neoplasia? The Concerted Action Polyp Prevention (CAPP) 1 Study.

Loss of function of the adenomatous polyposis coli (APC) tumour suppressor gene through truncating mutations or other means is an early event in most colo-rectal cancer (CRC). The APC gene encodes a large multifunctional protein that plays key roles in several cellular processes, including the wnt signalling pathway where an intact APC protein is essential for down regulation of beta-catenin. The APC protein also plays a role in regulation of cell proliferation, differentiation, apoptosis, cell-cell adhesion, cell migration and chromosomal stability during mitosis.