scholarly journals Analysis of the common genetic component of large-vessel vasculitides through a meta-Immunochip strategy

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
F. David Carmona ◽  
◽  
Patrick Coit ◽  
Güher Saruhan-Direskeneli ◽  
José Hernández-Rodríguez ◽  
...  

Abstract Giant cell arteritis (GCA) and Takayasu’s arteritis (TAK) are major forms of large-vessel vasculitis (LVV) that share clinical features. To evaluate their genetic similarities, we analysed Immunochip genotyping data from 1,434 LVV patients and 3,814 unaffected controls. Genetic pleiotropy was also estimated. The HLA region harboured the main disease-specific associations. GCA was mostly associated with class II genes (HLA-DRB1/HLA-DQA1) whereas TAK was mostly associated with class I genes (HLA-B/MICA). Both the statistical significance and effect size of the HLA signals were considerably reduced in the cross-disease meta-analysis in comparison with the analysis of GCA and TAK separately. Consequently, no significant genetic correlation between these two diseases was observed when HLA variants were tested. Outside the HLA region, only one polymorphism located nearby the IL12B gene surpassed the study-wide significance threshold in the meta-analysis of the discovery datasets (rs755374, P = 7.54E-07; ORGCA = 1.19, ORTAK = 1.50). This marker was confirmed as novel GCA risk factor using four additional cohorts (PGCA = 5.52E-04, ORGCA = 1.16). Taken together, our results provide evidence of strong genetic differences between GCA and TAK in the HLA. Outside this region, common susceptibility factors were suggested, especially within the IL12B locus.

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
F. David Carmona ◽  
◽  
Patrick Coit ◽  
Güher Saruhan-Direskeneli ◽  
José Hernández-Rodríguez ◽  
...  

2021 ◽  
Vol 23 (2) ◽  
Author(s):  
Joanna Robson ◽  
Sarah Mackie ◽  
Catherine Hill

Abstract Purpose of Review The goal of this paper is to review current and future uses of patient-reported outcomes in large vessel vasculitis. The large vessel vasculitides comprise Giant Cell Arteritis and Takayasu arteritis; both are types of systemic vasculitis which affect the larger blood vessels. Patient-reported outcomes (PROs) capture the impact of these diseases on health-related quality of life. Recent Findings Generic PROs such as the SF-36 are currently used to compare HRQOL of people with GCA and TAK within clinical trials and observational studies and to make comparisons with the general population and HRQoL in other diseases. The development of a disease-specific PRO for GCA is currently underway. Beyond clinical trials, there is much interest in the use of PROs within routine clinical care, particularly E-PROs for remote use. Summary Further work will be needed to complete the development of disease-specific PROs for people with large vessel vasculitis and to establish feasibility, acceptability, and utility of E-PROs.


Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Jose Danilo Diestro ◽  
Adam Dmytriw ◽  
Gabriel Broocks ◽  
Andrew Kemmling ◽  
Karen Chen ◽  
...  

Background: Most trials for the endovascular thrombectomy (EVT) of large vessel ischemic stroke excluded patients with large core infarcts and low Alberta Stroke Program Early CT Score (ASPECTS). As a result, the current American Heart Association guidelines for acute ischemic stroke reserve Grade 1A recommendation for the use of EVT for patients with an ASPECTS of 6 or more. However recent data from the HERMES collaboration has shown that even stroke patients with large core infarcts may still benefit from EVT. Objectives: Through this systematic review, we aim to determine the safety and efficacy of EVT for large vessel ischemic stroke patients with low ASPECTS (5 or less). Methods: Medline, Cochrane Central Register of Systematic Reviews and ClinicalTrials.gov were searched for studies appraising the outcomes of EVT for low ASPECTS acute ischemic stroke patients. Patients with low ASPECTS who underwent EVT were compared to those who only received best medical therapy (BMT). A meta-analysis of proportions was done to compare the outcomes of the two groups in terms of symptomatic intracranial hemorrhage, mortality and good 3-month functional outcomes (modified Rankin Scale < 2). Results: Nine studies with a total of 1,196 acutes stroke patients with low ASPECTS (712 undergoing EVT and 484 with only BMT) were included in the study. There was a trend towards a higher rate of sICH in the EVT group (9.2%; 95% CI 6.1% to 13.6%; I 2 53.37%) compared to the BMT group (5.5%; 95% CI 3.7% to 8.1%; I 2 =0%) but this did not reach statistical significance (p=0.11). There was no difference (p=0.41) in the pooled 3-month mortality of EVT patients (30.7%; 95% CI 21.7 to 41.5%; I 2 84.23%) and BMT patients (36.6%; 95% CI 26.4% to 48.1%; I 2 76.2%). Patients who underwent EVT had significantly better (p=0.001) 3-month outcomes, with 27.7% (95% 21.8 to 34.5%; I 2 62.08%) of patients attaining an MRS 0-2 compared to only 3.7% (95% 2.3 to 5.9%; I 2 87.21%) of patients in the BMT. Conclusion: Our meta-analysis suggests that acute stroke patients with low ASPECTS score may still benefit from EVT. Larger registry based studies and randomized controlled trials are needed to further substantiate the findings of our review.


2017 ◽  
Vol 126 (2) ◽  
pp. 586-595 ◽  
Author(s):  
Christopher D. Wilson ◽  
Sam Safavi-Abbasi ◽  
Hai Sun ◽  
M. Yashar S. Kalani ◽  
Yan D. Zhao ◽  
...  

OBJECTIVE Aneurysmal subarachnoid hemorrhage (aSAH) may be complicated by hydrocephalus in 6.5%–67% of cases. Some patients with aSAH develop shunt dependency, which is often managed by ventriculoperitoneal shunt placement. The objectives of this study were to review published risk factors for shunt dependency in patients with aSAH, determine the level of evidence for each factor, and calculate the magnitude of each risk factor to better guide patient management. METHODS The authors searched PubMed and MEDLINE databases for Level A and Level B articles published through December 31, 2014, that describe factors affecting shunt dependency after aSAH and performed a systematic review and meta-analysis, stratifying the existing data according to level of evidence. RESULTS On the basis of the results of the meta-analysis, risk factors for shunt dependency included high Fisher grade (OR 7.74, 95% CI 4.47–13.41), acute hydrocephalus (OR 5.67, 95% CI 3.96–8.12), in-hospital complications (OR 4.91, 95% CI 2.79–8.64), presence of intraventricular blood (OR 3.93, 95% CI 2.80–5.52), high Hunt and Hess Scale score (OR 3.25, 95% CI 2.51–4.21), rehemorrhage (OR 2.21, 95% CI 1.24–3.95), posterior circulation location of the aneurysm (OR 1.85, 95% CI 1.35–2.53), and age ≥ 60 years (OR 1.81, 95% CI 1.50–2.19). The only risk factor included in the meta-analysis that did not reach statistical significance was female sex (OR 1.13, 95% CI 0.77–1.65). CONCLUSIONS The authors identified several risk factors for shunt dependency in aSAH patients that help predict which patients are likely to require a permanent shunt. Although some of these risk factors are not independent of each other, this information assists clinicians in identifying at-risk patients and managing their treatment.


Author(s):  
Haiying Guo ◽  
Shuli Chang ◽  
Xiaoqin Pi ◽  
Fang Hua ◽  
Han Jiang ◽  
...  

The association between periodontal disease and dementia/cognitive impairment continues to receive increasing attention. However, whether periodontal disease is a risk factor for dementia/cognitive impairment is still uncertain. This meta-analysis was conducted to comprehensively analyze the effect of periodontitis on dementia and cognitive impairment, and to assess the periodontal status of dementia patients at the same time. A literature search was undertaken on 19 October 2020 using PubMed, Web of Science, and Embase with different search terms. Two evaluators screened studies according to inclusion and exclusion criteria, and a third evaluator was involved if there were disagreements; this process was the same as that used for data extraction. Included studies were assessed with the Newcastle-Ottawa Scale (NOS), and results were analyzed using software Review Manager 5.2. Twenty observational studies were included. In the comparison between periodontitis and cognitive impairment, the odds ratio (OR) was 1.77 (95% confidence interval (CI), 1.31–2.38), which indicated that there was a strong relationship between periodontitis and cognitive impairment. There was no statistical significance in the effect of periodontitis on dementia (OR = 1.59; 95%CI, 0.92–2.76). The subgroup analysis revealed that moderate or severe periodontitis was significantly associated with dementia (OR = 2.13; 95%CI, 1.25–3.64). The mean difference (MD) of the community periodontal index (CPI) and clinical attachment level (CAL) was 0.25 (95%CI, 0.09–0.40) and 1.22 (95%CI, 0.61–1.83), respectively. In this meta-analysis, there was an association between periodontitis and cognitive impairment, and moderate or severe periodontitis was a risk factor for dementia. Additionally, the deterioration of periodontal status was observed among dementia patients.


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