Cohort Study Examining the Association of Optimal Blood Pressure Control at Entry With Infrarenal Abdominal Aortic Aneurysm Growth

Background and Aim: The benefit of controlling cardiovascular risk factors in slowing the progression of small abdominal aortic aneurysm (AAA) is controversial. This study investigated the association of optimal blood pressure control at entry with the growth of small AAA. Methods and Results: A total of 1,293 patients with initial AAA diameter <50 mm were followed by a median 5 (inter-quartile range, IQR, 3–7) ultrasound scans for a median of 3.6 years (IQR 1.8, 5.3). Optimal blood pressure control was defined as blood pressure ≤140/90 mmHg at recruitment. The association of optimal blood pressure control at entry with AAA growth was assessed using linear mixed effects models adjusted for established risk factors of AAA growth and factors which were unequally distributed among the blood pressure groups. Optimal blood pressure control at entry was not significantly associated with AAA growth. In the risk factor adjusted model the mean difference in AAA growth between blood pressure groups was 0.04 mm/year (95% CI −0.20, 0.13; p = 0.65). The results were similar in sensitivity analyses excluding outliers or focused on systolic or diastolic blood pressure alone. Conclusions: This observational study suggests that optimal blood pressure control at entry is not associated with slower AAA growth

The efficacy of extraembryonic stem cells in improving blood flow within animal models of lower limb ischaemia

Background: Stem cell (SC) administration is a potential therapeutic strategy to improve blood supply in patients with peripheral artery disease (PAD). The aim of this systematic review and meta-analysis was to investigate the efficacy of extraembryonic tissue-derived SC (ETSC) in improving blood flow within animal models of hindlimb ischaemia (HLI).\ud \ud Methods: PubMed, ScienceDirect and Web of Science were searched to identify studies which investigated ETSCs within animal HLI models. A meta-analysis was performed focusing on the effect of ETSCs on limb blood flow assessed by laser Doppler imaging using a random effects model. Methodological quality was assessed using a newly devised quality assessment tool.\ud \ud Results: Five studies investigating umbilical cord-derived SCs (three studies), placental SCs (one study), amnion and chorionic SCs (one study) were included. A meta-analysis suggested that administration of ETSCs improved the restoration of blood flow within the HLI models used. The methodological quality of the included studies was assessed as poor. Problems identified included lack of randomised design and blinding of outcome assessors; that the animal models did not incorporate recognised risk factors for human PAD or atherosclerosis; the models used did not have established chronic ischaemia as is the cases in most patients presenting with PAD; and the studies lacked a clear rationale for the dosage and frequency of SCs administered.\ud \ud Conclusions: The identified studies suggest that ETSCs improve recovery of limb blood supply within current animal HLI models. Improved study quality is, however, needed to provide support for the likelihood of translating these findings to patients with PAD

Immune responses directed at egg proteins during experimental infection with the liver fluke Fasciola hepatica

Fasciola hepatica is responsible for human disease and economic livestock loss on a global scale. Unlike the well characterized schistosomes, only the adult and juvenile stages of F. hepatica are implicated in disease, whereas the freely voided egg is not thought to contribute to host–parasite interactions. We investigated specific immune responses to soluble F. hepatica egg proteins (SFHEP), during a 14-week experimental infection, demonstrating significant increases in anti-SFHEP IgG1 (P = 0·001), transforming growth factor beta-1 (P = 0·008) and IL-10 (P < 0·001) titres at the onset of egg production. Western blot analysis of soluble SFHEP demonstrates that protein bands migrating at 61·6, 54·8 and 44 kDa become sero-reactive before the appearance of eggs within host faeces. Therefore, expression of some egg-associated proteins indicates progression to chronic disease. Antigenic bands were investigated through mass spectrometry, identifying a protein disulphide isomerase (PDI) (61·6 kDa), an enolase and ferritin-related proteins (54·8 kDa), and a cocktail of dehydrogenases (44 kDa). Biochemical analysis of egg secretions reveals proteolytic activity, which increases over time, indicating that proteases may be continually secreted during the course of egg maturation. The implications of egg-specific immune responses and proteolytic secretions are further discussed

Effect of blood pressure lowering medications on leg ischemia in peripheral artery disease patients: A meta-analysis of randomised controlled trials

<div><p>Background</p><p>It has been suggested that anti-hypertensive medications may worsen leg ischemia in peripheral artery disease (PAD) patients. We undertook a meta-analysis to assess the effect of anti-hypertensive medications on measures of leg ischemia including maximum walking distance (MWD), pain free walking distance (PFWD) and ankle brachial pressure index (ABPI). A meta-regression was performed to evaluate whether the effect of the anti-hypertensive medications on mean arterial pressure (MAP) was associated with changes in ABPI, MWD or PFWD.</p><p>Method</p><p>A systematic literature search was performed to identify placebo controlled randomized control trials (RCT) testing anti-hypertensive medications, which reported baseline and follow-up measurements of: MAP and MWD, PFWD or ABPI in patients with intermittent claudication (IC) due to PAD.</p><p>Result</p><p>A meta-analysis was performed on 5 RCTs comprising a total of 180 and 127 patients receiving anti-hypertensive medications and placebo respectively. This analysis suggested that anti-hypertensive medication did not significantly affect MWD, PFWD or ABPI. In contrast, the meta-regression analysis showed that the reduction in MAP due to the anti-hypertensive drugs was positively correlated with increased MWD during follow-up (β = 8.371, p = 0.035). Heterogeneity across studies, as assessed by I², was high. The follow-up period within the included trials was generally short with 3 out of 5 studies having a follow-up period of ≤ 6 weeks.</p><p>Conclusion</p><p>This study suggests that anti-hypertensive treatment does not worsen but may improve leg ischemia in PAD patients. Larger multicenter trials with longer anti-hypertensive treatment periods are required to clarify the effect of anti-hypertensives on leg ischemia in PAD patients.</p></div

Forest plots illustrating the effect of anti-hypertensive medications on MWD.

<p>The x-axis is the effect size expressed as SMD (standardised mean difference). The forest plot also details the 95% confidence interval. The dotted line represents the overall effect calculated in this meta-analysis. The heterogeneity estimated as I² and Q associated with each analysis is also provided. (A) The effect of anti-hypertensive medications on MWD, (B) Subgroup analysis including trials with follow up period greater than and less than 1 month, (C) Subgroup analysis including trials which used ACE inhibitors. Abbreviations: ACE—angiotensin converting enzyme and MWD—maximum walking distance.</p

Results of the meta-regression analysis showing the association between reduction in blood pressure and improvement in MWD after being randomised to an anti-hypertensive drug.

<p>Fig 2 shows the association between reducing MAP and improving MWD in all the included trials. Abbreviations: β–regression coefficient, MAP—mean arterial pressure and MWD—maximum walking distance.</p

PRISMA flow chart outlining the literature search and the study selection process.

<p>PRISMA flow chart outlining the literature search and the study selection process.</p

Forest plot illustrating the effect of anti-hypertensive medications on ABPI.

<p>The x-axis is the effect size expressed as SMD (standardised mean difference). The forest plot also details the 95% confidence interval. The dotted line represents the overall effect calculated in this meta-analysis. The heterogeneity estimated as I² and Q is also provided. Abbreviation: ABPI—ankle brachial pressure index.</p

Forest plots illustrating the effect of anti-hypertensive medications on PFWD.

<p>The x-axis is the effect size expressed as SMD (standardised mean difference). The forest plot also details the 95% confidence interval. The dotted line represents the overall effect calculated in this meta-analysis. The heterogeneity estimated as I² and Q associated with each analysis is also provided. (A) The effect of anti-hypertensive medications on PFWD, (B) Subgroup analysis including trials which included ACE inhibitors. Abbreviations: ACE—angiotensin converting enzyme and PFWD—pain free walking distance.</p