Validation of a fornix depth measurer: a putative tool for the assessment of progressive cicatrising conjunctivitis

Background/aims Documentation of conjunctival forniceal foreshortening in cases of progressive cicatrising conjunctivitis (PCC) is important in ascertaining disease stage and progression. Lower fornix shortening is often documented subjectively or semi-objectively, whereas upper forniceal obliteration is seldom quantified. Although tools such as fornix depth measurers (FDMs) have been described, their designs limit upper fornix measurement. The purpose of this study was to custom-design a FDM to evaluate the upper fornix and to assess variability in gauging fornix depth. \ud \ud Methods A polymethylmethacrylate FDM was constructed using industry-standard jewellery computer software and machinery. Two observers undertook a prospective independent evaluation of central lower fornix depth in a heterogeneous cohort of patients with clinically normal and abnormal conjunctival fornices both subjectively and by using the FDM (in mm). Upper central fornix depth was also measured. Agreement was assessed using Bland–Altman plots. \ud \ud Results Fifty-one eyes were evaluated. There was 100% intraobserver agreement to within 1 mm for each observer for lower fornix measurement. The mean difference in fornix depth loss using the FDM between observer 1 and 2 was 1.19%, with 95% confidence of agreement (±2SD) of −15% to +20%. In total, 86% (44/51) of measurements taken by the two observers agreed to within 10% of total lower fornix depth (ie, ±1 mm) versus only 63% (32/51) of the subjective measurements. Mean upper fornix difference was 0.57 mm, with 95% confidence of agreement of between −2 and + 3 mm. \ud \ud Conclusions This custom-designed FDM is well tolerated by patients and shows low intraobserver and interobserver variability. This enables repeatable and reproducible measurement of upper and lower fornix depths, facilitating improved rates of detection and better monitoring of progression of conjunctival scarring

The applicability of commonly used predictive scoring systems in Indigenous Australians with sepsis: An observational study

Background Indigenous Australians suffer a disproportionate burden of sepsis, however, the performance of scoring systems that predict mortality in Indigenous patients with critical illness is incompletely defined. Materials and methods The study was performed at an Australian tertiary-referral hospital between January 2014 and June 2017, and enrolled consecutive Indigenous and non-Indigenous adults admitted to ICU with sepsis. The ability of the ANZROD, APACHE-II, APACHE-III, SAPS-II, SOFA and qSOFA scores to predict death before ICU discharge in the two populations was compared. Results There were 442 individuals enrolled in the study, 145 (33%) identified as Indigenous. Indigenous patients were younger than non-Indigenous patients (median (interquartile range (IQR) 53 (43-60) versus 65 (52-73) years, p = 0.0001) and comorbidity was more common (118/145 (81%) versus 204/297 (69%), p = 0.005). Comorbidities that were more common in the Indigenous patients included diabetes mellitus (84/145 (58%) versus 67/297 (23%), p<0.0001), renal disease (56/145 (39%) versus 29/297 (10%), p<0.0001) and cardiovascular disease (58/145 (40%) versus 83/297 (28%), p = 0.01). The use of supportive care (including vasopressors, mechanical ventilation and renal replacement therapy) was similar in Indigenous and non-Indigenous patients, and the two populations had an overall case-fatality rate that was comparable (17/145 (12%) and 38/297 (13%) (p = 0.75)), although Indigenous patients died at a younger age (median (IQR): 54 (50-60) versus 70 (61-76) years, p = 0.0001). There was no significant difference in the ability of any the scores to predict mortality in the two populations. Conclusions Although the crude case-fatality rates of Indigenous and non-Indigenous Australians admitted to ICU with sepsis is comparable, Indigenous patients die at a much younger age. Despite this, the ability of commonly used scoring systems to predict outcome in Indigenous Australians is similar to that of non-Indigenous Australians, supporting their use in ICUs with a significant Indigenous patient population and in clinical trials that enrol Indigenous Australians

Elevation of conjunctival epithelial CD45INTCD11b⁺CD16⁺CD14⁻ neutrophils in ocular Stevens-Johnson syndrome and toxic epidermal necrolysis

PURPOSE. Ocular complications related to Stevens-Johnson Syndrome (SJS)–Toxic Epidermal Necrolysis (TEN) may persist and progress after resolution of systemic disease. This is thought to be related in part to persistent ocular innate-immune signaling. In this study, our aim was to characterize infiltrative conjunctival cellular profiles during acute (<12 months) and chronic (>12 months) disease. METHODS. Consecutive patients presenting with SJS-TEN over a 12-month period were followed for 1 year. Detailed clinical examination and conjunctival impression cell recovery was analyzed by flow cytometry for the presence of intraepithelial leukocytes and compared with healthy controls (n = 21). RESULTS. Ten patients were recruited of whom six had acute disease and five were classified as TEN (SCORTEN = 1, n = 4). Conjunctival inflammation was graded as absent/mild in a total of nine patients; but despite this, evidence of fornix shrinkage was observed in nine subjects. This inversely correlated with disease duration (P < 0.05). A reduction in percentage of CD8αβ(+) T cells compared with controls (80% vs. 57%; P < 0.01) was associated with a corresponding increase in the number/percentage of CD45(INT)CD11b(+)CD16(+)CD14(−) neutrophils (186 vs. 3.4, P < 0.01, 31% vs. 0.8%, P < 0.001). Neutrophils inversely correlated with disease duration (r = −0.71, P = 0.03), yet there was no absolute change in the CD8αβ(+) or neutrophil populations during the study period (P = 1.0). CONCLUSIONS. These data highlight that a neutrophilic infiltrate is present in mildly inflamed or clinically quiescent conjunctival mucosa in patients with ocular SJS-TEN, where neutrophil numbers inversely correlate with disease duration. Neutrophil persistence endorses the hypothesis of an unresolved innate-inflammatory process that might account for disease progression

The role of reperfusion injury in photodynamic therapy with 5-aminolaevulinic acid – a study on normal rat colon

Reperfusion injury can occur when blood flow is restored after a transient period of ischaemia. The resulting cascade of reactive oxygen species damages tissue. This mechanism may contribute to the tissue damage produced by 5-aminolaevulinic acid-induced photodynamic therapy, if this treatment temporarily depletes oxygen in an area that is subsequently reoxygenated. This was investigated in the normal colon of female Wistar rats. All animals received 200 mg kg−1 5-aminolaevulinic acid intravenously 2 h prior to 25 J (100 mW) of 628 nm light, which was delivered continuously or fractionated (5 J/150 second dark interval/20 J). Animals were recovered following surgery, killed 3 days later and the photodynamic therapy lesion measured macroscopically. The effects of reperfusion injury were removed from the experiments either through the administration of free radical scavengers (superoxide dismutase (10 mg kg−1) and catalase (7.5 mg kg−1) in combination) or allopurinol (an inhibitor of xanthine oxidase (50 mg kg−1)). Prior administration of the free radical scavengers and allopurinol abolished the macroscopic damage produced by 5-aminolaevulinic acid photodynamic therapy in this model, regardless of the light regime employed. As the specific inhibitor of xanthine oxidase (allopurinol) protected against photodynamic therapy damage, it is concluded that reperfusion injury is involved in the mechanism of photodynamic therapy in the rat colon

Cytokine production and antigen recognition by human mucosal homing conjunctival effector memory CD8+ T cells

PURPOSE. Conjunctival epithelial T cells are dominated by CD3(+)CD56-TCRαβ(+)CD8αβ(+) lymphocytes. In this study we explored the antigen experience status, mucosal homing phenotype, cytokine expression, and viral antigen recognition of conjunctival epithelial CD8(+) T cells from healthy individuals. METHODS. Following ocular surface impression cytology, conjunctival cells were recovered by gentle agitation and analyzed by flow cytometry for cell surface markers, cytokine production (stimulated by phorbol 12-myristate 13-acetate [PMA]/ionomycin), and Epstein-Barr virus (EBV)/cytomegalovirus (CMV) immunodominant epitope recognition using major histocompatibility complex (MHC) class I peptide tetramers. RESULTS. In contrast to peripheral blood, conjunctival epithelial CD8(+) T cells were dominantly CD45RA(−)CCR7(−) effector memory cells, and the vast majority expressed the mucosal homing integrin αEβ7. Conjunctival memory CD8(+) T cells maintained effector functions with the ability to secrete IFN-γ and expression of Granzyme B, although they expressed significantly reduced amounts per cell compared to peripheral blood T cells. Interestingly, herpetic virus-specific CD8(+) T cells recognizing epitopes derived from EBV and CMV could be detected in the conjunctival cells of healthy virus carriers, although they were generally at lower frequencies than in the peripheral blood of the same donor. Virus-specific conjunctival CD8(+) T cells were dominated by CD45RA(−)CCR7(−) effector memory cells that expressed αEβ7. CONCLUSIONS. These data demonstrate that the majority of conjunctival epithelial CD8(+) T cells are mucosal homing αEβ7(+) effector memory T cells, which can recognize viral epitopes and are capable of secreting Granzyme B and IFN-γ

Results from the project ‘Acceptance of CO2 capture and storage: economics, policy and technology (ACCSEPT)’

AbstractACCSEPT was a two-year research project (2005–2007) funded under the 6th research framework programme of the European Commission. The project leader was Det Norske Veritas (DNV), and the partners were Baker and McKenzie, the Energy Research Centre of the Netherlands (ECN), the Institute for European Environmental Policy (IEEP), Tyndall Centre for Climate Change Research, and Judge Business School of the University of Cambridge.There were three main focuses of the project: a Europe-wide survey of stakeholders and their opinions on CCS; stakeholder consultation through two workshops; and research into the economics, regulation, legal and social aspects of CCS. The project website is www.accsept.org, where all the outputs and related material can be found.This paper summarizes the conclusions of the work

Sensitivity of a national coronial database for monitoring unnatural deaths among ex-prisoners in Australia

<p>Abstract</p> <p>Background</p> <p>The period immediately after release from custody is a time of marked vulnerability and increased risk of death for ex-prisoners. Despite this, there is currently no routine, national system for monitoring ex-prisoner mortality in Australia. This study subsequently aimed to evaluate the sensitivity of Australia's National Coroners Information System (NCIS) for identifying reportable deaths among prisoners and ex-prisoners.</p> <p>Findings</p> <p>Prisoner and ex-prisoner deaths identified through an independent search of the NCIS were compared with 'gold standard' records of prisoner and ex-prisoner deaths, generated from a national monitoring system and a state-based record linkage study, respectively. Of 294 known deaths in custody from 2001-2007, an independent search of the NCIS identified 229, giving a sensitivity of 77.9% (72.8%-82.3%). Of 677 known deaths among ex-prisoners from 2001-2007, an independent search of the NCIS identified 37, giving a sensitivity of 5.5% (4.0-7.4%). Ex-prisoner deaths that were detected were disproportionately drug-related, occurring within the first four weeks post-release, among younger prisoners and among those with more than two prior prison admissions.</p> <p>Conclusions</p> <p>Although a search of the NCIS detected the majority of reportable deaths among prisoners, it was only able to detect a small minority of reportable deaths among ex-prisoners. This suggests that the NCIS is not effective for monitoring mortality among ex-prisoners in Australia. Given the elevated rates of mortality among ex-prisoners in Australia and elsewhere, there remains an urgent need to establish a process for routine monitoring of ex-prisoner mortality, preferably through record linkage.</p

Interaction between integrin α9β1 and vascular cell adhesion molecule-1 (VCAM-1) inhibits neutrophil apoptosis

According to the prevailing paradigm, neutrophils are short-lived cells that undergo spontaneous apoptosis within 24 hours of their release from the bone marrow. However, neutrophil survival can be significantly prolonged within inflamed tissue by cytokines, inflammatory mediators, and hypoxia. During screening experiments aimed at identifying the effect of the adhesive microenvironment on neutrophil survival, we found that VCAM-1 (CD106) was able to delay both spontaneous and Fas-induced apoptosis. VCAM-1-mediated survival was as efficient as that induced by the cytokine IFN-β and provided an additive, increased delay in apoptosis when given in combination with IFN-β. VCAM-1 delivered its antiapoptotic effect through binding the integrin α9β1. The α9β 1 signaling pathway shares significant features with the IFN-β survival signaling pathway, requiring PI3 kinase, NF-κB activation, as well as de novo protein synthesis, but the kinetics of NF-κB activation by VCAM-1 were slower and more sustained compared with IFN-β. This study demonstrates a novel functional role for α9β1 in neutrophil biology and suggests that adhesive signaling pathways provide an important extrinsic checkpoint for the resolution of inflammatory responses in tissues