In this report on 303 gliomas we show the highest frequency of TERT promoter mutations in gliobastomas (80%) followed by oligodendrogliomas (70%) and astrocytomas (39%). We observed positive association between TERT promoter and IDH mutations in oligodendroglial tumors (OR = 26.3; 95% CI 2.5–250.2) and inverse association in primary glioblastomas (OR = 0.13; 95% CI 0.03–0.58). Tumors with TERT promoter mutations compared to those without showed increased TERT transcription; we also showed difference in the transcription levels due to the two main mutations. Tumors with TERT promoter mutations had shorter telomeres than those without. The patients with only TERT promoter mutations showed worst survival (median survival 14.6 months) and patients with both IDH and TERT promoter mutations showed best survival (246.5 months). In patients with astrocytoma, the TERT promoter mutations only associated with poor survival (P < 0.0001); IDH mutations and 1p/19q deletions associated with increased survival (P = 0.0004). TERT promoter mutations in low grade gliomas associated with reduced progression free survival (HR 10.2; 95% CI 1.9 – 55.9). While our data affirm the role of TERT promoter mutations in glial tumors, effects on transcription and telomere length emphasise the importance of telomere biology in disease genesis and outcome.
Summary Purpose: Hippocampal mossy cells receive dense innervation from dentate granule cells and, in turn, mossy cells innervate both granule cells and interneurons. Mossy cell loss is thought to trigger granule cell mossy fiber sprouting, which may affect granule cell excitability. The aim of this study was to quantify mossy cell loss in two animal models of temporal lobe epilepsy, and determine whether there exists a relationship between mossy cell loss, mossy fiber sprouting, and granule cell dispersion. Methods: Representative hippocampal sections from p35 knockout mice and mice with unilateral intrahippocampal kainate injection were immunolabeled for GluR2/3, two subunits of the amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionate (AMPA) receptor and calretinin to identify mossy cells. Mossy fibers were immunostained against synaptoporin. Key Findings: p35 Knockout mice showed no hilar cell death, but moderate mossy fiber sprouting and granule cell dispersion. In the kainate‐injected hippocampus, there was an 80% and 85% reduction of GluR2/3‐ and GluR2/3/calretinin‐positive hilar neurons, respectively, and dense mossy fiber sprouting and significant granule cell dispersion. In the contralateral hippocampus there was a 52% loss of GluR2/3‐, but only a 20% loss of GluR2/3‐calretinin‐immunoreactive presumptive mossy cells, and granule cell dispersion; no mossy fiber sprouting was observed. Significance: These results indicate a probable lack of causality between mossy cell death and mossy fiber sprouting.
Purpose. To compare radiographic and clinical outcomes after anterior cervical discectomy in patients with cervical degenerative disc disease using PEEK cages or PMMA spacers with a minimum 1-year follow-up. Methods. Anterior cervical discectomy was performed in 107 patients in one or two levels using empty PEEK cages (51 levels), Sulcem PMMA spacers (49 levels) or Palacos PMMA spacers (41 levels) between January, 2005 and February, 2009. Bony fusion, subsidence, and sagittal alignment were retrospectively assessed in CT scans and radiographs at follow-up. Clinical outcome was measured using the VAS, NDI, and SF-36. Results. Bony fusion was assessed in 65% (PEEK cage), 57% (Sulcem), and 46% (Palacos) after a mean follow-up of 2.5 years. Mean subsidence was 2.3–2.6 mm without significant differences between the groups. The most pronounced loss of lordosis was found in PEEK cages (−4.1°). VAS was 3.1 (PEEK cage), 3.6 (Sulcem), and 2.7 (Palacos) without significant differences. Functional outcome in the PEEK cage and Palacos group was superior to the Sulcem group. Conclusions. The substitute groups showed differing fusion rates. Clinical outcome, however, appears to be generally not correlated with fusion status or subsidence. We could not specify a superior disc substitute for anterior cervical discectomy. This trial is registered with DRKS00003591.
Objective: To compare the radiation exposure with the scrub nurse, assistant surgeon, and anesthetist during minimally invasive transforaminal lumbar interbody fusion using conventional 2-dimensional (2D) fluoroscopy or 3D fluoroscopy-based navigation.Summary of Background Data: Minimally invasive spinal fusion techniques are related to higher radiation exposures compared with open techniques. Especially the routinely exposed surgical staff faces the risks of increased radiation exposure.Methods: In total, 41 patients with planned monosegmental minimally invasive transforaminal lumbar interbody fusion were randomized into the intraoperative imaging techniques 2D fluoroscopy or 3D navigation. Eye lens and film dosemeters were attached to defined locations of the scrub nurse, assistant surgeon, and anesthetist. Mann-Whitney U and Wilcoxon-matched pairs signed-rank test were used to compare dosemeter readings. This study was registered with the German Clinical Trials Register (DRKS00004514). Results:The radiation exposure per surgery was low for the scrub nurse, assistant surgeon, and anesthetist in both the 2D fluoroscopy and 3D navigation groups. The maximum average value of 0.057 ± 0.031 mSv was measured on the unprotected chest of the assistant surgeon and was thus slightly above the lower detection limit of the dosemeters (0.044 mSv). The annual occupational dose limit would be exceeded at the earliest after 571 operations for the unprotected eye lens of the assistant surgeon.Conclusions: Minimally invasive lumbar fusion surgery is possible with comparatively low radiation exposure to the assisting operating room personnel without exceeding the annual maximum occupational radiation exposure. However, there is no definite dose value below which ionizing radiation poses no risk. Consequently, radiation sparing work routines should be strictly followed.
BackgroundSome symptomatic degenerative conditions of the lumbar spine may be treated with spinal fusion if conservative treatment has failed. The minimally invasive technique of transforaminal lumbar interbody fusion (MIS TLIF) is increasingly used but has been found to generate increased radiation exposure to the patient and staff. Modern three-dimensional (3D) C-arm devices are capable of providing conventional two-dimensional fluoroscopic images (x-rays) as well as 3D image sets for intraoperative navigation. This study was designed to compare the radiation exposure between these two intraoperative imaging techniques in MIS TLIF procedures.MethodsThis study is a randomized controlled trial. Forty participants scheduled to undergo monosegmental MIS TLIF will be recruited and randomly allocated to one of two groups with respect to the applied intraoperative imaging technique: conventional fluoroscopy (FLUORO group) and 3D fluoroscopy-based navigation combined with conventional fluoroscopy (NAV group). Furthermore, patients scheduled to undergo bisegmental MIS TLIF during the recruitment period for monosegmental MIS TLIF will be assessed for eligibility and will be randomly assigned separately. The primary endpoint is the radiation exposure to the surgeon and is measured by dosimeter readings. Secondary endpoints are the radiation exposure to the assistant surgeon, scrub nurse, anesthetist, patient, and C-arm as well as radiation exposure in relation to the body mass index of the patient.DiscussionResults of this randomized study will help to compare the radiation exposure to the operating staff and patient during MIS TLIF procedures using conventional fluoroscopy versus 3D fluoroscopy-based navigation combined with conventional fluoroscopy. Furthermore, recommendations regarding the appropriate use of the investigated intraoperative imaging techniques will be made to improve radiation protection and to reduce radiation exposure.Trial registrationRegistration number of the German Clinical Trials Register: DRKS00004514. Registration date: 11 August 2012.
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