Safety of Pedicle Screws in Adolescent Idiopathic Scoliosis Surgery

To review existing publications on the safety of pedicle screw insertions in adolescent idiopathic scoliosis (AIS). Despite having increased risk for neurological and visceral injuries, the use of pedicle screws have led to increased correction rates in scoliosis surgery. A review was performed on topics pertinent to pedicle screw insertion in AIS, which included pedicle morphometry in AIS, structures at risk during pedicle screw insertion, and accuracy and safety of various pedicle screw insertion techniques. The importance of computer navigation and future research regarding pedicle screw placement in AIS were also briefly reviewed. Many authors have reported abnormal pedicle anatomy in AIS. Injury to the neural structures was highest over the apical region, whereas aortic injury was the highest at T5 and T10. In the proximal thoracic spine, the esophagus could be injured even with screws as short as 25 mm. Overall pedicle perforation rates for perforations >0 and >2 mm (assessed by computed tomography) ranged from 6.4% to 65.0% and 3.7% to 29.9%, respectively. The critical pedicle perforation (>2 mm excluding lateral thoracic) and anterior perforation (>0 mm) rates was reported to range from 1.5% to 14.5% and 0.0% to 16.1%, respectively. Pedicle perforation rates were lower with the use of computer navigation. The incidence of neurological adverse events after scoliosis surgery was 0.06%–1.9%. Aortic injury has only been observed in case reports. According to the available literature, pedicle screw insertion in AIS is considered safe with low rates of clinical adverse events. Moreover, the use of navigation technology has been shown to reduce pedicle perforation rates

Minimally Invasive Spinal Stabilization Using Fluoroscopic-Guided Percutaneous Screws as a Form of Palliative Surgery in Patients with Spinal Metastasis

Study DesignProspective cohort study.PurposeTo report the outcome of 50 patients with spinal metastases treated with minimally invasive stabilization (MISt) using fluoroscopic guided percutaneous pedicle screws with/without minimally invasive decompression.Overview of LiteratureThe advent of minimally invasive percutaneous pedicle screw stabilization system has revolutionized the treatment of spinal metastasis.MethodsBetween 2008 and 2013, 50 cases of spinal metastasis with pathological fracture(s) with/without neurology deficit were treated by MISt at our institution. The patients were assessed by Tomita score, pain score, operation time, blood loss, neurological recovery, time to ambulation and survival.ResultsThe mean Tomita score was 6.3±2.4. Thirty seven patients (74.0%) required minimally invasive decompression in addition to MISt. The mean operating time was 2.3±0.5 hours for MISt alone and 3.4±1.2 hours for MISt with decompression. Mean blood loss for MISt alone and MISt with decompression was 0.4±0.2 L and 1.7±0.9 L, respectively. MISt provided a statistically significant reduction in visual analog scale pain score with mean preoperative score of 7.9±1.4 that was significantly decreased to 2.5±1.2 postoperatively (p=0.000). For patients with neurological deficit, 70% displayed improvement of one Frankel grade and 5% had an improvement of 2 Frankel grades. No patient was bed-ridden postoperatively, with the average time to ambulation of 3.4±1.8 days. The mean overall survival time was 11.3 months (range, 2–51 months). Those with a Tomita score <8 survived significantly longer than those a Tomita score ≥8 with a mean survival of 14.1±12.5 months and 6.8±4.9 months, respectively (p=0.019). There were no surgical complications, except one case of implant failure.ConclusionsMISt is an acceptable treatment option for spinal metastatic patients, providing good relief of instability back pain with no major complications

Cervical Supine Side-Bending versus Cervical Supine Traction Radiographs: Which Is Better in Predicting Proximal Thoracic Flexibility for Lenke 1 and 2 Adolescent Idiopathic Scoliosis?

Study Design Prospective cohort study. Purpose This study compared cervical supine side-bending (CSSB) and cervical supine traction (CST) radiographs to assess the flexibility and predict the correctability of the proximal thoracic (PT) curve for patients with adolescent idiopathic scoliosis (AIS) classified as Lenke 1 and 2. Overview of Literature Knowledge of the flexibility of the PT curve is crucial in the management of patients with AIS. There are no reports comparing CSSB and CST radiographs to assess this parameter. Methods Thirty patients with Lenke 1 and 2 AIS scheduled for posterior spinal fusion surgery were recruited. A standing whole spine radiography and physician-supervised CSSB and CST radiographies were performed. Patient demographic and radiological parameters were recorded, including age, gender, weight, height, body mass index, PT angle, main thoracic angle, CSSB PT angle, CST PT angle, and postoperative PT angle. From the data collected, the curve flexibility and curve correction index were calculated and compared. Results CSSB had a significantly (p <0.05) smaller PT angle (16.6°±10.4°) in comparison to CST (23.7°±10.7°). CSSB had significantly (p <0.05) greater flexibility (44.2%±19.7%) in comparison to CST (19.5%±18.1%). The CSSB correction index (1.2±0.9) was significantly closer to 1 in comparison to the CST correction index (4.4±5.3). There was no difference (p =0.72) between the CSSB PT angle (16.6°±10.4°) and the postoperative PT angle (16.1°±7.5°). However, the CST PT angle (23.7°±10.7°) was significantly (p <0.05) larger than the postoperative PT angle (16.1°±7.5°). Conclusions CSSB radiographs were better for demonstrating PT flexibility and more accurately predicted correctability in comparison to the CST radiographs

Surgical Morphometry of C1 and C2 Vertebrae: A Three-Dimensional Computed Tomography Analysis of 180 Chinese, Indian, and Malay Patients

Study DesignClinical imaging study.PurposeTo study the surgical morphometry of C1 and C2 vertebrae in Chinese, Indian, and Malay patients.Overview of LiteratureC1 lateral mass and C2 pedicle screw fixation is gaining popularity. However, there is a lack of C1–C2 morphometric data for the Asian population.MethodsComputed tomography analysis of 180 subjects (60 subjects each belonging to Chinese, Indian, and Malay populations) using simulation software was performed. Length and angulations of C1 lateral mass (C1LM) and C2 pedicle (C2P) screws were assessed.ResultsThe predicted C1LM screw length was between 23.2 and 30.2 mm. The safe zone of trajectories was within 11.0°±7.7° laterally to 29.1°±6.2° medially in the axial plane and 37.0°±10.2° caudally to 20.9°±7.8° cephalically in the sagittal plane. The shortest and longest predicted C2P screw lengths were 22.1±2.8 mm and 28.5±3.2 mm, respectively. The safe trajectories were from 25.1° to 39.3° medially in the axial plane and 32.3° to 45.9° cephalically in the sagittal plane.ConclusionsC1LM screw length was 23–30 mm with the axial safe zone from 11° laterally to 29° medially and sagittal safe zone at 21° cephalically. C2P screw length was 22–28 mm with axial safe zone from 26° to 40° medially and sagittal safe zone from 32° to 46° cephalically. These data serve as an important reference for Chinese, Indian, and Malay populations during C1–C2 instrumentation

Surgical Correction in Patients with Lumbar Degenerative Kyphosis Who Had Low Bone Mineral Density: An Analysis of 40 Patients with a Minimum Follow-Up of Two Years

Study DesignRetrospective study.PurposeTo investigate influence of bone mineral density (BMD) on the surgical correction of lumbar degenerative kyphosis (LDK).Overview of LiteratureNo studies so far have reported the influence of BMD on the surgical correction of LDK.MethodsForty LDK patients with more than 2 years follow-up were studied. Pelvic incidence (PI), pelvic tilt, sacral slope, sagittal vertical axis (SVA), lumbar lordosis (LL), and thoracic kyphosis were measured preoperatively, immediate postoperatively and at final follow-up. Adverse outcomes: proximal adjacent fractures, sagittal decompensation, pseudoarthrosis, and cage subsidence were documented.ResultsThere were 37 females and 3 males. Average age was 65.1±4.5 years and mean follow-up was 34.2±16.7 months. 42.5% were Takemitsu type 3 curves, 27.5% type 2, 20.0% type 4 and 10.0% type 1. 37.5% had osteopenia, 40.0% osteoporosis and 22.5% had severe osteoporosis. SVA improved from 237.0±96.7 mm preoperatively to 45.3±41.8 mm postoperatively (p=0.000). LL improved from 10.5°±14.7° to -40.6°±10.9° postoperatively (p=0.000). At final follow-up SVA deteriorated to 89.8±72.2 mm and LL to 34.7°±15.8° (p=0.000). The association between late sagittal decompensation, pseudoarthrosis, or proximal adjacent fractures and osteoporosis was insignificant. The difference between immediate postoperative LL and PI (PIDiff) had a significant association with sagittal decompensation and pseudoarthrosis.ConclusionsOsteoporosis did not influence the degree of correction, late sagittal decompensation, proximal adjacent fractures, and pseudoarthrosis in LDK. PIDiff had a significant association with sagittal decompensation and pseudoarthrosis

Neurological Recovery in Two Patients with Cauda Equina Syndrome Secondary to L5 Lumbar Spine Giant Cell Tumour after Treatment with Denosumab without Surgery

We report two patients with cauda equina syndrome (CES) secondary to L5 giant cell tumour (GCT) who achieved good neurological recovery after treatment with denosumab without surgery. The first patient was a 26-year-old man with L5 GCT causing CES who regained bowel and urinary control, muscle power improvement from grade 2 to grade 4 and Oswestry disability index (ODI) improvement from 48 to 23 after denosumab treatment. The second patient was a 25-year-old woman with L5 GCT causing CES who regained bowel and urinary control, muscle power improvement from grade 0 to grade 4 and ODI improvement from 42 to 20 after denosumab treatment. The usage of denosumab in the treatment of patients with CES due to GCT allows potential neurological recovery without any surgical intervention. If surgery is not contraindicated, more time is obtained to prepare the patient preoperatively to attain safer surgery and to achieve complete tumour clearance

Molecular landscape of IDH-mutant primary astrocytoma Grade IV/glioblastomas

WHO 2016 classified glioblastomas into IDH-mutant and IDH-wildtype with the former having a better prognosis but there was no study on IDH-mutant primary glioblastomas only, as previous series included secondary glioblastomas. We recruited a series of 67 IDH-mutant primary glioblastomas/astrocytoma IV without a prior low-grade astrocytoma and examined them using DNA-methylation profiling, targeted sequencing, RNA sequencing and TERT promoter sequencing, and correlated the molecular findings with clinical parameters. The median OS of 39.4 months of 64 cases and PFS of 25.9 months of 57 cases were better than the survival data of IDH-wildtype glioblastomas and IDH-mutant secondary glioblastomas retrieved from datasets. The molecular features often seen in glioblastomas, such as EGFR amplification, combined +7/-10, and TERT promoter mutations were only observed in 6/53 (11.3%), 4/53 (7.5%), and 2/67 (3.0%) cases, respectively, and gene fusions were found only in two cases. The main mechanism for telomere maintenance appeared to be alternative lengthening of telomeres as ATRX mutation was found in 34/53 (64.2%) cases. In t-SNE analyses of DNA-methylation profiles, with an exceptional of one case, a majority of our cases clustered to IDH-mutant high-grade astrocytoma subclass (40/53; 75.5%) and the rest to IDH-mutant astrocytoma subclass (12/53; 22.6%). The latter was also enriched with G-CIMP high cases (12/12; 100%). G-CIMP-high status and MGMT promoter methylation were independent good prognosticators for OS (p = 0.022 and p = 0.002, respectively) and TP53 mutation was an independent poor prognosticator (p = 0.013) when correlated with other clinical parameters. Homozygous deletion of CDKN2A/B was not correlated with OS (p = 0.197) and PFS (p = 0.278). PDGFRA amplification or mutation was found in 16/59 (27.1%) of cases and was correlated with G-CIMP-low status (p = 0.010). Aside from the three well-known pathways of pathogenesis in glioblastomas, chromatin modifying and mismatch repair pathways were common aberrations (88.7% and 20.8%, respectively), the former due to high frequency of ATRX involvement. We conclude that IDH-mutant primary glioblastomas have better prognosis than secondary glioblastomas and have major molecular differences from other commoner glioblastomas. G-CIMP subgroups, MGMT promoter methylation, and TP53 mutation are useful prognostic adjuncts

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead