ABSTRACT
PURPOSE: Navigation is emerging as a useful adjunct in percutaneous, minimally invasive spinal surgery (MIS). The aim of this study was to compare C-Arm navigated, O-Arm navigated and conventional 2D-fluoroscopy assisted MIS thoracic and lumbosacral spine fixation techniques in terms of operating time, radiation exposure and accuracy of pedicle screw (PS) placement. METHODS: Retrospective observational study of 152 consecutive adults who underwent MIS fixations for spinal instability: 96 2D-fluoroscopy assisted, 39 3D-C-Arm navigated and 27 using O-Arm navigated. RESULTS: O-Arm navigation significantly reduced PS misplacement (1.23%, p) compared to 3D-C-Arm navigation (7.29%, p = 0.0082) and 2D-fluoro guided placement (5.16%, p = 0379). 3D-C-Arm navigation was associated with lower procedural radiation exposure of the patient (0.4 mSv) than O-Arm navigation (3.24 mSv) or 2D-fluoro guidance (1.5 mSv). Operative time was comparable between three modalities. CONCLUSIONS: O-Arm navigation provides greater accuracy of percutaneous instrumentation placement with an acceptable procedural radiation dose delivered to the patients and comparable operative times. These slides can be retrieved under Electronic Supplementary material.
Subject(s)
Fluoroscopy/methods , Fracture Fixation, Internal/methods , Minimally Invasive Surgical Procedures/methods , Spinal Diseases/surgery , Surgery, Computer-Assisted/methods , Adolescent , Adult , Aged , Aged, 80 and over , Female , Fluoroscopy/adverse effects , Fracture Fixation, Internal/adverse effects , Humans , Imaging, Three-Dimensional/methods , Male , Middle Aged , Minimally Invasive Surgical Procedures/adverse effects , Operative Time , Pedicle Screws/statistics & numerical data , Radiation Exposure/statistics & numerical data , Retrospective Studies , Surgery, Computer-Assisted/adverse effects , Young AdultABSTRACT
Prelamin A accumulation and persistent DNA damage response (DDR) are hallmarks of vascular smooth muscle cell (VSMC) ageing and dysfunction. Although prelamin A is proposed to interfere with DNA repair, our understanding of the crosstalk between prelamin A and the repair process remains limited. The extracellular signal-regulated kinases 1 and 2 (ERK1/2) have emerged as key players in the DDR and are known to enhance ataxia telangiectasia-mutated protein (ATM) activity at DNA lesions, and in this study, we identified a novel relationship between prelamin A accumulation and ERK1/2 nuclear compartmentalisation during VSMC ageing. We show both prelamin A accumulation and increased DNA damage occur concomitantly, before VSMC replicative senescence, and induce the localisation of ERK1/2 to promyelocytic leukaemia protein nuclear bodies (PML NBs) at the sites of DNA damage via nesprin-2 and lamin A interactions. Importantly, VSMCs treated with DNA damaging agents also displayed prelamin A accumulation and ERK compartmentalisation at PML NBs, suggesting that prelamin A and nesprin-2 are novel components of the DDR. In support of this, disruption of ERK compartmentalisation at PML NBs, by either depletion of nesprin-2 or lamins A/C, resulted in the loss of ATM from DNA lesions. However, ATM signalling and DNA repair remained intact after lamins A/C depletion, whereas nesprin-2 disruption ablated downstream Chk2 activation and induced genomic instability. We conclude that lamins A/C and PML act as scaffolds to organise DNA-repair foci and compartmentalise nesprin-2/ERK signalling. However, nesprin-2/ERK signalling fidelity, but not their compartmentalisation at PML NBs, is essential for efficient DDR in VSMCs.
Subject(s)
DNA Damage , Microfilament Proteins/metabolism , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 3/metabolism , Muscle, Smooth, Vascular/cytology , Muscle, Smooth, Vascular/metabolism , Nerve Tissue Proteins/metabolism , Nuclear Proteins/metabolism , Adult , Cell Cycle/physiology , Cellular Senescence/physiology , DNA Repair , Female , Humans , Intranuclear Inclusion Bodies/genetics , Intranuclear Inclusion Bodies/metabolism , Lamin Type A/metabolism , Male , Microfilament Proteins/genetics , Middle Aged , Mitogen-Activated Protein Kinase 1/genetics , Mitogen-Activated Protein Kinase 3/genetics , Muscle, Smooth, Vascular/enzymology , Nerve Tissue Proteins/genetics , Nuclear Proteins/genetics , Transfection , Young AdultABSTRACT
Pulmonary hypertension is an orphan disease that until recently has received limited attention within the wider medical community. This has changed distinctly in the last 10 years with the advent of new classes of therapy and a renewed interest in mechanisms of pathogenesis. This review utilized information gathered from recent conferences, and a review of the literature was conducted using MedLine and Pubmed. Accepted mechanisms of pathogenesis and currently available treatments are presented. We will discuss interesting new concepts in pathogenesis, including the importance of genetic forms of the disease and in particular the transforming growth factor receptor superfamily and the evolving evidence of the contribution of dysregulated immunity. Areas of research may yield therapeutic benefits in the not-too-distant future, including anti-proliferative therapies and stem cell therapy.
