Volumetric versus single slice measurements of core abdominal muscle for Sarcopenia

Objectives: We investigated whether total psoas muscle area (TPMA) was representative of the total psoas muscle volume (TPMV). Secondly, we assessed whether there was a relationship between the two commonly used single slice measurements of sarcopenia, TPMA and total abdominal muscle area (TAMA). Methods: Pre-operative CT imaging of 110 patients undergoing elective endovascular aneurysm repair were analysed by two trained independent observers. TPMA was measured at individual vertebral levels between the second lumbar vertebrae and sacrum. TPMV was also estimated between the second lumbar vertebrae and sacrum. TAMA was measured at the third lumbar vertebrae (L3). Observer differences were assessed using Bland-Altman plots. Associations between the different measures were assessed using linear regression and Pearson's correlation. Results: We found single slice measurements of the TPMA to be representative of the TPMV at individual levels between L2 to the sacrum. The strongest association was seen at L3 (adjusted regression coefficient 16.7, 95% CI 12.1 to 21.4, p < 0.001). There was no association between TPMA and TAMA (adjusted regression coefficient - 0.7, 95% CI - 4.1 to 2.8, p = 0.710). Conclusions: We demonstrate that measurements of the TPMA between L2 to the sacrum are representative of the TPMV, with the greatest association at the third lumbar vertebrae. There was no association between the TPMA and TAMA. Advances in Knowledge: We demonstrate that a single slice measurement of TPMA at L3 is representative of the muscle volume, contrary to previous criticism. Future sarcopenia studies can continue to measure TPMA which is representative of the TPMV

Validation of two-dimensional vertebral body parameters in estimating patient height in elderly patients

Objectives: Standardised comparison of abdominal muscle and adipose tissue is often utilised in morphometric clinical research. Whilst measurements are traditionally standardised against the patient’s height, this may not be always practically feasible. The aim of this study was to investigate the relationship between measurements of the vertebral body and patient height. Methods: We analysed cross-sectional CT scans. Measurements of the vertebral body area (VBA), anteroposterior vertebral body diameter (APVBD) and lateral vertebral body diameter (LVBD) were made by two independent investigators by manual tracing. Patients were randomly divided into two groups: Group 1 standardisation and Group 2 validation. We compared height and vertebral body parameters from patients in Group 1 and mathematically modelled this relationship. We then utilised the model to predict the height of patients in Group 2 and compared this with their actual height. Observer variability was assessed using Bland–Altman plots and t-tests of differences. Results: CT scans from 382 patients were analysed. No significant intraobserver or interobserver differences were apparent when measuring vertebral body parameters. We describe models which enable the prediction of the patients’ height using the measured VBA, APVBD and LVBD. No significant differences were observed between the patients predicted and actual heights in the validation group. Conclusions: We demonstrate an important relationship between measurements of the patient’s height and the vertebral body. This can be utilised in future research when the patient’s height has not been measured. Advances in knowledge: In the absence of the patient’s height, we demonstrate that two-dimensional vertebral body parameters may be reliably used to standardise morphometric measurements

Vascular Smooth Muscle Cell PIEZO-1 in Abdominal Aortic Aneurysm Formation

Background An Abdominal Aortic Aneurysm (AAA) is a potentially life-threatening condition with no current disease-specific pharmacological therapies targeting aneurysm growth. Aortic vascular smooth muscle cells (VSMCs) maintain aortic vascular tone, due to their mature contractile differentiated phenotype. However, they can phenotypically switch to a de-differentiated cells which has shown to play a role in the aneurysmal disease process. PIEZO-1 is a calcium-permeable shear stress sensor previously shown to contribute to hypertension-induced wall remodelling and has recently AAA disease. Despite this, evidence potentially linking PIEZO-1 to AAA pathophysiological processes remains limited. Methods The hypothesis that activation of the PIEZO-1 mechanosensor in aortic VSMCs by stressors drives vascular remodelling (i.e. cell proliferation and stiffness) was assessed using in-vitro and in-vivo models. Non-diseased aortic VSMCs were exposed to constant oscillatory shear force, uni-axial stretch and high and low matrix stiffnesses. Additionally, cells were physiologically stressed by undergoing multiple cell passages, treated with the PIEZO-1 agonist Yoda-1 and cultured in serum-deprived media. Calcium imaging, using Yoda-1 to quantify PIEZO-1-dependent intracellular calcium entry, was performed. Cell behaviour was characterised using proliferation and migration assays. C57BL6/J [wild-type] and PIEZO-1 smMHCCre-ER(T2) [transgenic] male mice underwent aneurysm induction surgery to assess for changes in PIEZO expression. Serial ultrasound imaging was performed to quantify the anatomical changes. Quantitatively PCR was used to assess the expression of PIEZO mechanosensors, krüppel-like transcription factor 2 (KLF-2), krüppel-like transcription factor 4 (KLF-4) and transglutaminase 2 (TG2). Results PIEZO-1 was expressed in both non-diseased VSMCs as well as VSMCs obtained from aneurysmal tissue. PIEZO-1 mRNA was shown to be elevated in aortic VSMCs following treatment with the PIEZO-1 agonist Yoda-1, the application of constant oscillatory shear stress, and cell culture with serum-deprived media. Proliferation was significantly slower following prolonged stimulation with PIEZO-1. Although there was no physiological evidence linking vessel distensibility or matrix stiffness to PIEZO-1, there is a suggestion that PIEZO-1 influences the mRNA expression of TG2. Functional knockdown of PIEZO-1 in VASCs could not be reliably achieved. Furthermore, the knockdown of VSMC PIEZO-1 in transgenic was inconclusive. Never the less the was a significant increase in both PIEZO mechanosensors at day 7 following surgery in C57BL6/J mice, however only PIEZO-2 remained significantly elevated at day 14. Conclusions In this thesis, VSMC PIEZO mechanosensors were shown to be able to detect and adapt to common mechanical stimuli and stressors likely to be experienced in the AAA microenvironment. The role of PIEZO-1 in aneurysmal disease may be one that is transient and potentially of limited clinical significance. However, further investigation is required to confirm the findings of this thesis and interrogate the role of PIEZO-2

Endovascular aneurysm repair:Is imaging surveillance robust, and does it influence long-term mortality?

Purpose: Endovascular aneurysm repair (EVAR) is the dominant treatment strategy for abdominal aortic aneurysms. However, as a result of uncertainty regarding long-term durability, an ongoing imaging surveillance program is required. The aim of the study was to assess EVAR surveillance in Scotland and its effect on all-cause and aneurysm-related mortality.&lt;p&gt;&lt;/p&gt; Methods: A retrospective analysis of all EVAR procedures carried out in the four main Scottish vascular units. The primary outcome measure was the implementation of post-EVAR imaging surveillance across Scotland. Patients were identified locally and then categorized as having complete, incomplete, or no surveillance. Secondary outcome measures were all-cause mortality and aneurysm-related mortality. Cause of death was obtained from death certificates.&lt;p&gt;&lt;/p&gt; Results: Data were available for 569 patients from the years 2001 to 2012. All centers had data for a minimum of 5 contiguous years. Surveillance ranged from 1.66 to 4.55 years (median 3.03 years). Overall, 53 % had complete imaging surveillance, 43 % incomplete, and 4 % none. For the whole cohort, all-cause 5-year mortality was 33.5 % (95 % confidence interval 28.0–38.6) and aneurysm-related mortality was 4.5 % (.8–7.3). All-cause mortality in patients with complete, incomplete, and no imaging was 49.9 % (39.2–58.6), 19.1 % (12.6–25.2), and 47.2 % (17.7–66.2), respectively. Aneurysm-related mortality was 3.7 % (1.8–7.4), 4.4 % (2.2–8.9), and 9.5 % (2.5–33.0), respectively. All-cause mortality was significantly higher in patients with complete compared to incomplete imaging surveillance (p &#60; 0.001). No significant differences were observed in aneurysm-related mortality (p = 0.2).&lt;p&gt;&lt;/p&gt; Conclusion: Only half of EVAR patients underwent complete long-term imaging surveillance. However, incomplete imaging could not be linked to any increase in mortality. Further work is required to establish the role and deliverability of EVAR imaging surveillance