Development of a score for assessment of radiologic damage in large-vessel vasculitis (Combined Arteritis Damage Score, CARDS)

OBJECTIVES: Outcome assessment in large-vessel vasculitis (LVV) remains challenging and this impairs patient management and the conduct of clinical studies. Previous proposals for outcome tools have not included imaging. This study aimed to develop an imaging score to quantify damage in LVV and to assess the difference between Takayasu (TAK) and giant cell arteritis (GCA). METHODS: Ninety-six patients (41 TAK, 55 GCA) were identified from local registries at two University Hospitals in the UK. Radiologic lesions including stenosis, occlusion and aneurysm were evaluated in 25 arterial regions by enhanced computed tomography or magnetic resonance angiography. Lesion correlation with combined damage assessment scores was employed in a multiple regression analysis to define the weight of individual lesions and develop a damage index. RESULTS: A numerical damage index was developed: the “Combined Arteritis Damage Score (CARDS)”. The index was derived from a formula: number of regions with mild stenosis × 0.6 + number of regions with moderate to severe stenosis × 1.2 + number with occlusions × 1.6 + number with aneurysms × 0.8 in 25 arterial regions. The median CARDS was higher in TAK than GCA (4.1 and 0.6, interquartile range 1.3-5.7 and 0-3, p<0.001). CONCLUSIONS: We have developed a damage assessment tool, CARDS, based on imaging in LVV of potential value to clinical studies and patient management. TAK and GCA differ in the radiologic severity of disease.Dr. Daiki Nakagomi is supported by the Japan College of Rheumatology and Shimoshizu Hospital, National Hospital Organization. This project was supported by the Cambridge Biomedical Research Centre

Novel ultrasonographic Halo Score for giant cell arteritis:assessment of diagnostic accuracy and association with ocular ischaemia

OBJECTIVES: Ultrasound of temporal and axillary arteries may reveal vessel wall inflammation in patients with giant cell arteritis (GCA). We developed a ultrasound scoring system to quantify the extent of vascular inflammation and investigated its diagnostic accuracy and association with clinical factors in GCA. METHODS: This is a prospective study including 89 patients suspected of having GCA, of whom 58 had a confirmed clinical diagnosis of GCA after 6 months follow-up. All patients underwent bilateral ultrasound examination of the three temporal artery (TA) segments and axillary arteries, prior to TA biopsy. The extent of vascular inflammation was quantified by (1) counting the number of TA segments and axillary arteries with a halo and (2) calculating a composite Halo Score that also incorporated the thickness of each halo. RESULTS: Halo counts and Halo Scores showed moderate diagnostic accuracy for a clinical diagnosis of GCA. They correlated positively with systemic inflammation. When compared with the halo count, the Halo Score correlated better with C-reactive protein (CRP) levels and allowed to firmly establish the diagnosis of GCA in more patients. Higher halo counts and Halo Scores were associated with a higher risk of ocular ischaemia. They allowed to identify subgroups of patients with low risk (≤5%) and high risk of ocular ischaemia (>30%). CONCLUSIONS: Ultrasound halo scoring allows to quantify the extent of vascular inflammation in GCA. Extensive vascular inflammation on ultrasound may provide strong diagnostic confirmation and associates with ocular ischaemia in GCA

Ultrasonographic Halo Score in giant cell arteritis:association with intimal hyperplasia and ischaemic sight loss

OBJECTIVES: We investigated the relationship between the ultrasonographic Halo Score and temporal artery biopsy (TAB) findings in GCA. METHODS: This is a prospective study including 90 patients suspected of having GCA. Ultrasonography of temporal/axillary arteries and a TAB were obtained in all patients at baseline. An experienced pathologist evaluated whether TAB findings were consistent with GCA, and whether transmural inflammation, giant cells and intimal hyperplasia were present. Ultrasonographic Halo Scores were determined. Receiver operating characteristic analysis was performed. RESULTS: Twenty-seven patients had a positive TAB, while 32 patients with a negative TAB received a clinical diagnosis of GCA after 6 months of follow-up. Patients with a positive TAB showed higher Halo Scores than patients with a negative TAB. The presence of intimal hyperplasia in the biopsy, rather than the presence of transmural inflammation or giant cells, was associated with elevated Halo Scores in patients with GCA. The Halo Score discriminated well between TAB-positive patients with and without intimal hyperplasia, as indicated by an area under the curve of 0.82 in the receiver operating characteristic analysis. Patients with a positive TAB and intimal hyperplasia more frequently presented with ocular ischaemia (40%) than the other patients with GCA (13–14%). CONCLUSION: The ultrasonographic Halo Score may help to identify a subset of GCA patients with intimal hyperplasia, a TAB feature associated with ischaemic sight loss

Presence of exon 5-deleted oestrogen receptor in human breast cancer: functional analysis and clinical significance.

A variant form of the human oestrogen receptor (ER) mRNA lacking sequences encoded within exon 5 has been described (Fuqua SAW, Fitzgerald SD, Chamness GC, Tandon AK, McDonnell DP, Nawaz Z, O'Malloy BW, McGuire WL 1991, Cancer Res 51: 105-109). We have examined the expression of the exon 5-deleted ER (HE delta5) mRNA variant in breast biopsies using reverse transcriptase polymerase chain reaction (RT - PCR). HE delta5 mRNA was present in only 13% of non-malignant breast tissues compared with 32% of carcinomas (95% CI, P=0.05). Presence of the HE delta5 mRNA was associated with the presence of immunohistochemically detected ER (P=0.015) and progesterone receptor (PR) (P=0.02). There was a positive correlation between the presence of HE delta5 and disease-free survival (P=0.05), suggesting that the presence of HE delta5 may be an indicator of better prognosis. We have raised a monoclonal antibody specific to the C-terminal amino acids of HE delta5. This antibody recognized the variant but not the wild-type ER protein. We show that HE delta5 protein is present in breast cancer using immunohistochemical techniques. We also analysed trans-activation by HE delta5 in mammalian cells and showed that, in MCF-7 cells, HE delta5 competes with wild-type ER to inhibit ERE-dependent trans-activation. Our results indicate that this variant is unlikely to be responsible for endocrine resistance of breast cancer, but its presence at both the mRNA and protein level suggest that it may, nevertheless, be involved in regulating the expression of oestrogen-responsive genes in breast cancer

CO2 absorption into aqueous ammonia using membrane contactors: Role of solvent chemistry and pore size on solids formation for low energy solvent regeneration

Solids formation can substanitally reduce the energy penalty for ammonia solvent regeneration in carbon capture and storage (CCS), but has been demonstrated in the literature to be difficult to control. This study examines the use of hollow fibre membrane contactors, as this indirect contact mediated between liquid and gas phases in this geometry could improve the regulation of solids formation. Under conditions comparable to existing literature, NH4HCO3 was evidenced to primarily crystallise in the gas-phase (lumen-side of the membrane) due to the high vapour pressure of ammonia, which promotes gaseous transmission from the solvent. Investigation of solvent reactivity demonstrated how equilibria dependent reactions controlled the onset of NH4HCO3 nucleation in the solvent, and limited ‘slip’ through transfomation of ammonia into its protonated form which occurs prior to the phase change. Crystallisation in the solvent was also dependent upon ammonia concentration, where sufficient supersaturation must develop to overcome the activation energy for nucleation. However, this has to be complemented with a reduction in solvent temperature to offset vapour pressure and limit the risk of gas-phase crystallisation. While changes to the solvent chemistry were sufficient to shift from gas-phase to liquid phase crystallisation, wetting was observed immediately after nucleation in the solvent. This was explained by a local region of supersaturation within the coarse membrane pores that promoted a high nucleation rate, altering the material contact angle of the membrane sufficient for solvent to breakthrough into the gas phase. Adoption of a narrower pore size membrane was shown to dissipate wetting after crystallisation in the solvent, illustrating membrane contactors as a stable platform for the sustained separation of CO2 coupled with its simultaneous transformation into a solid. Through resolving previous challenges experienced with solids formation in multiple reactor configurations, the cost benefit of using ammonia as a solvent can be realised, which is critical to enabling economically viable CCS for the transition to net zero, and can be exploited within hollow fibre membrane contactors, eliciting considerable process intensification over existing reactor designs for CCS