scholarly journals Increased Expression of PAD4 in Neutrophils of MPO-ANCA Associated Vasculitis and its Correlation with the Vasculitis Activity

Author(s):  
Menglu Pan ◽  
Sen Wang ◽  
Meijuan Zheng ◽  
Weici Zhang ◽  
Zongwen Shuai

Myeloperoxidase (MPO)-specific anti-neutrophil cytoplasmic autoantibody (ANCA) associated vasculitis (MPO-AAV) is the most common ANCA associated vasculitis (AAV) in china and other East Asian countries. Its pathogenesis remained elusive. We evaluated the expression of peptidylarginine deiminase (PAD4) in neutrophils from MPO-AAV and explored the relationship between the expression and the vasculitis activity, and also investigated the pathogenic mechanism. 40 patients initially diagnosed with MPO-AAV in the active state and 40 comparable healthy controls (HC) were enrolled in this study. The patient disease activity were evaluated with Birmingham Vasculitis Activity Index version 3 (BVAS-V3). The expression of PAD4 in their neutrophils, which was described as percentage of PAD4+ neutrophils in all neutrophils and mean fluorescence intensity (MFI) of PAD4+ neutrophils, was measured by flow cytometry (FCM). Their serum level of NETs, C5a and MPO-ANCA were detected using enzyme linked immunosorbent assay (ELISA). The percentage of PAD4+ neutrophils, MFI of PAD4+ neutrophils, the levels of serum NETs and C5a were markedly higher in patient group than that in HC group. Meanwhile, in patient group, the percentage of PAD4+ neutrophils, MFI of PAD4+ neutrophils and MPO-ANCA presented significantly correlation with NETs. Although univariable analysis showed the percentage of PAD4+ neutrophils, MFI of PAD4+ neutrophils, NETs, C5a and MPO-ANCA had respective correlation with BVAS, multivariable analysis indicated that only the percentage of PAD4+ neutrophils as well as the level of serious MPO-ANCA owned independent correlations with BVAS.PAD4 might be a new potential target for MPO-AAV treatment in the future.

2021 ◽  
pp. 135245852110100
Author(s):  
Manuel Comabella ◽  
Margareta A Clarke ◽  
Sabine Schaedelin ◽  
Mar Tintoré ◽  
Deborah Pareto ◽  
...  

Background: Chronic active lesions with iron rims have prognostic implications in patients with multiple sclerosis. Objective: To assess the relationship between iron rims and levels of chitinase 3-like 1 (CHI3L1), neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) in patients with a first demyelinating event. Methods: Iron rims were identified using 3T susceptibility-weighted imaging. Serum NfL and GFAP levels were measured by single-molecule array assays. CSF (cerebrospinal fluid) CHI3L1 levels were measured by enzyme-linked immunosorbent assay (ELISA). Results: Sixty-one patients were included in the study. The presence of iron rims was associated with higher T2 lesion volume and higher number of gadolinium-enhancing lesions. In univariable analysis, having ⩾2 iron rims (vs 0) was associated with increased CSF CHI3L1 levels (β = 1.41; 95% confidence interval (CI) = 1.10–1.79; p < 0.01) and serum NfL levels (β = 2.30; 95% CI = 1.47–3.60; p < 0.01). In multivariable analysis, however, only CSF CHI3L1 levels remained significantly associated with the presence of iron rim lesions (β = 1.45; 95% CI = 1.11–1.90; p < 0.01). The presence of ⩾2 iron rims was not associated with increased serum GFAP levels in univariable or multivariable analyses. Conclusion: These findings support an important contribution of activated microglia/macrophages to the pathophysiology of chronic active lesions with iron rims in patients with a first demyelinating event.


BMC Surgery ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Simonette R. Mallard ◽  
◽  
Kari A. Clifford ◽  
R. Park ◽  
Kim Cousins ◽  
...  

Abstract Background To identify whether compliance with Enhanced Recovery After Surgery (ERAS) Society recommendations is associated with length of stay (LOS) in a New Zealand hospital for patients undergoing segmental colectomy in mixed acute and elective general surgery wards. Methods Consecutive elective colorectal surgeries (n = 770) between October 2012 and February 2019 were audited. Patients with non-segmental colectomies, multi-organ surgeries, LOS > 14 days, and those who died were excluded. Logistic regression was used to determine the relationship between patient demographics, compliance with ERAS guidelines, and suboptimal LOS (> 4 days). Results Analysis included 376 patients. Age, surgery prior to 2014, surgical approach, non-colorectal surgical team, operation type, and complications were significantly associated with suboptimal LOS. Non-compliance with ERAS recommendations for laparoscopy [OR 8.9, 95% CI (4.52, 19.67)], removal of indwelling catheters (IDC) [OR 3.14, 95% CI (1.85, 5.51)], use of abdominal drains [OR 4.27, 95% CI (0.99, 18.35)], and removal of PCA [OR 8.71, 95% CI (1.78, 157.27)], were associated with suboptimal LOS (univariable analysis). Multivariable analysis showed that age, surgical team, late removal of IDC, and open approach were independent predictors of suboptimal LOS. Conclusions Non-compliance with ERAS guidelines for laparoscopic approach and early removal of IDC was higher among procedures performed by non-colorectal surgery teams, and was also associated with adverse postoperative events and suboptimal LOS. This study demonstrates the importance of the surgical team’s expertise in affecting surgical outcomes, and did not find significant independent associations between most individual ERAS guidelines and suboptimal LOS once adjusting for other factors.


2021 ◽  
Vol 8 ◽  
Author(s):  
Zhong Zhong ◽  
Dan Luo ◽  
Ning Luo ◽  
Bin Li ◽  
Dongying Fu ◽  
...  

Background: Increased serum hepcidin-25 level is associated with excess mortality in hemodialysis patients. However, there is a dearth of published information about its predictive effect for survival in patients on peritoneal dialysis (PD). The purpose of this study is to evaluate the association of serum hepcidin-25 with the risk of mortality in PD patients.Methods: Serum hepcidin-25 level was measured using an enzyme-linked immunosorbent assay in a prospective cohort study of PD patients with stored serum samples at baseline. Multivariate linear regression model was used to determine clinical characteristics associated with serum hepcidin-25 concentration. We evaluated the relationship between serum hepcidin-25 and all-cause mortality using a Cox proportional hazards model and the relationship between hepcidin-25 and cardiovascular (CV) and infection-related deaths using competing-risks regression models.Results: In total, 513 PD patients were included in this study. The median serum hepcidin-25 level was 40.9 (17.9–85.9) ng/mL. Body mass index and serum ferritin were positively correlated with serum hepcidin-25 levels. During a median follow-up period of 64.1 months, 122 (24%) patients died, including 61 (50%) CV deaths and 32 (26%) infection-related deaths. In multivariable analysis, patients with the highest tertile of serum hepcidin-25 had a greater risk of all-cause [adjusted hazard ratio (aHR) 1.85, 95% confidence interval (95%CI), 1.14 to 3.00, P = 0.013] and infection-related mortality (adjusted subdistribution hazard ratio [aSHR], 2.61; 95%CI, 1.01 to 6.76, P = 0.049) when compared with those in the second tertile. However, no significant relationship was observed between serum hepcidin-25 and CV mortality.Conclusions: Higher baseline serum hepcidin-25 level was associated with increased risk for all-cause and infection-related mortality in PD patients.


2019 ◽  
Vol 16 (4) ◽  
pp. 365-372 ◽  
Author(s):  
Qishuai Liu ◽  
Li Wang ◽  
Guizhen Yan ◽  
Weifa Zhang ◽  
Zhigang Huan ◽  
...  

Background: MicroRNAs (miRNA) are known to play a key role in the etiology and treatment of epilepsy through controlling the expression of gene. However, miR-125a-5p in the epilepsy is little known. Epilepsy in rat models was induced by Pentylenetetrazol (PTZ) and miR- 125a-5p profiles in the hippocampus were investigated in our experiment. Also, the relationship between miR-125a-5p and calmodulin-dependent protein kinase IV (CAMK4) was identified and the related mechanism was also illustrated. Methods: The miR-125a-5p mRNA expression levels were evaluated by quantitative real time polymerase chain reaction (qRT-PCR). Western Blot (WB) was used to analyze the CAMK4 protein expression levels. Seizure score, latency and duration were determined based on a Racine scale. The enzyme-linked immunosorbent assay (ELISA) was used to analyze the inflammatory factor expression. The relationship between miR-125a-5p and CAMK4 was detected through dual luciferase assay. Results: Downregulation of miR-125a-5p was observed in the hippocampus of PTZ-induced epilepsy rats. The overexpression of miR-125a-5p attenuated seizure and decreased inflammatory factor level in the hippocampus of PTZ-induced rats. The miR-125a-5p alleviated epileptic seizure and inflammation in PTZ-induced rats by suppressing its target gene, CAMK4. Conclusion: miR-125a-5p may represent a novel therapeutic treatment for PTZ-induced epilepsy by preventing the activation of CAMK4.


Lupus ◽  
2020 ◽  
Vol 29 (2) ◽  
pp. 182-190
Author(s):  
W Batista Cicarini ◽  
R C Figueiredo Duarte ◽  
K Silvestre Ferreira ◽  
C de Mello Gomes Loures ◽  
R Vargas Consoli ◽  
...  

We have explored the relationship between possible hemostatic changes and clinical manifestation of the systemic lupus erythematosus (SLE) as a function of greater or lesser disease activity according to Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) criteria. Endothelial injury and hypercoagulability were investigated in patients with SLE by measuring thrombomodulin (TM), D-dimer (DDi) and thrombin generation (TG) potential. A total of 90 participants were distributed into three groups: 1) women with SLE presenting with low disease activity (laSLE) (SLEDAI-2K ≤ 4), 2) women with SLE presenting with moderate to high disease activity (mhaSLE) (SLEDAI-2K > 4), and 3) a control group comprising healthy women. Levels of TM and DDi were higher both in the laSLE and mhaSLE groups compared to controls and in mhaSLE compared to the laSLE group. With respect to TG assay, lagtime and endogen thrombin potential, low concentrations of tissue factor provided the best results for discrimination among groups. Analysis of these data allow us to conclude that TM, DDi and TG are potentially useful markers for discriminating patients with very active from those with lower active disease. Higher SLE activity may cause endothelial injury, resulting in higher TG and consequently a hypercoagulability state underlying the picture of thrombosis common in this inflammatory disease.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 524.1-524
Author(s):  
R. Dos-Santos ◽  
F. Otero ◽  
E. Perez-Pampín ◽  
A. Mera Varela

Background:Periodontal disease (PD) has been widely studied in the pathogenesis of rheumatoid arthritis (RA). As well, its relationship with severity and disease activity, has also been investigated with ambiguous results. It has been suggested that the improvement of oral health could enhance disease activity scores.1 PD prevalence worldwide stands around 60% in older adults (>65 years) and its frequency increases with aging.2Objectives:To asses oral health in RA patients and to identify predictors of PD in this population.Methods:Patients diagnosed of RA at treatment with biological, classical or targeted synthetic disease modifying anti-rheumatic drugs (b/cs/tsDMARDs) in the aforementioned hospital during 2020 performed a dental review with a specialized periodontal odontologist. Oral health patterns were given for all patients, following criteria of American Academy of Periodontology, and reevaluation of disease activity was made 2 months later.Clinical, demographic and treatment data were collected from participants.Univariable logistic regression was performed to identify predictors of PD. Variables with p<0.20 were selected for multivariable analysis.Stata 15.1 was used to perform statistical analysis.Results:81 patients were recruited. 82.72% were female. Mean age was 56.17 years (SD 14.15) and mean time since diagnosis was 15.58 years (SD 8.17). 25% were current or past smokers. 21 patients had comorbidities (arterial hypertension the most frequent). 66.67% were rheumatoid factor (RF) positive and 72.73% anti-citrullinated peptide autoantibody (ACPA) positive. Median erythrocyte sedimentation rate (ESR) was 12 mm (IQR 6;23) and mean C-reactive protein (CRP) was 0.48 mg/dl (SD 1.18). Mean disease activity score (DAS28-VSG) at the testing time was 2.62 (SD 1.21) and after 2 months was 2.39 (SD 0.97). 96.30% of patients were at treatment with csDMARDs, 64.20% with glucocorticoids, 96.30% with bDMARDs and 6 patients with tsDMARDs.Univariable analysis identified higher age, at least one autoantibody positive and ESR/CRP as potential predictors of medium/severe PD (p<0.20). Multivariable testing including these variables pointed out higher age, lower ESR and at least one autoantibody positive (OR 1.09 [CI95% 1.04-1.14] p=0.001, OR 0.18 [CI95% 0.04-0.95] p=0.044 and OR 0.94 [CI95% 0.88-1.00] p=0.042, respectively) as predictors of medium or severe PD (≥3 mm interdental clinical attachment loss).Univariable analysis identified higher age, the presence of any comorbidity and anti tumour-necrosis factor alpha treatment (anti-TNF) as potential predictors of severe PD (p<0.20). Multivariable testing including these variables pointed out higher age (OR 1.15 [CI95%1.02-1.30] p=0.026) as predictor of severe PD (≥5 mm interdental clinical attachment loss).Conclusion:Periodontal disease is still an extended health problem among the entire population. Its prevalence in RA is increased, therefore higher age and RF or ACPA positive are risk factors for developing severe PD. This analysis might suggest that an aggressive management of PD could implement better responses in DAS28. Also anti-TNF treatment could delimit a “penumbra” group of patients at risk of developing severe PD, where intensive manage could modify the final outcome.References:[1]C O Bingham, M Moni. Periodontal disease and rheumatoid arthritis: the evidence accumulates for complex pathobiologic interactions. Curr Opin Rheumatol. 2013;25(3):345-353.[2]P Carvajal. Periodontal disease as a public health problem: the challenge for primary health care. Rev Clin Periodoncia inplantol. 2016;9(2):177-183.Disclosure of Interests:None declared


Energies ◽  
2021 ◽  
Vol 14 (12) ◽  
pp. 3470
Author(s):  
Xueqing Kang ◽  
Farman Ullah Khan ◽  
Raza Ullah ◽  
Muhammad Arif ◽  
Shams Ur Rehman ◽  
...  

In selected South Asian countries, the study intends to investigate the relationship between urban population (UP), carbon dioxide (CO2), trade openness (TO), gross domestic product (GDP), foreign direct investment (FDI), and renewable energy (RE). Fully modified ordinary least square (FMOLS) and dynamic ordinary least square (DOLS) models for estimation were used in the study, which covered yearly data from 1990 to 2019. We used Levin–Lin–Chu, Im–Pesaran–Shin, and Fisher PP tests for the stationarity of the variables. The outcomes of the panel cointegration approach looked at whether there was a long-run equilibrium nexus between selected variables in Pakistan, Bangladesh, India, and Sri Lanka. The FMOLS approach was also used to assess the relationship, and the results suggest that there is a significant and negative nexus between FDI and renewable energy in south Asian nations. The study’s findings reveal a strong and favorable relationship between GDP and renewable energy use. In South Asian nations (Sri Lanka, Pakistan, India, and Bangladesh), the FMOLS and DOLS findings are nearly identical, but the authors used the DOLS model for robustification. According to the findings, policymakers in South Asian economies (Sri Lanka, Pakistan, India, and Bangladesh) should view GDP and FDI as fundamental policy instruments for environmental sustainability. To reduce reliance on hazardous energy sources, the government should also reassure financial sectors to participate in renewable energy.


2021 ◽  
Vol 10 (13) ◽  
pp. 2927
Author(s):  
Amaar Obaid Hassan ◽  
Gregory Y. H. Lip ◽  
Arnaud Bisson ◽  
Julien Herbert ◽  
Alexandre Bodin ◽  
...  

There are limited data on the relationship of acute dental infections with hospitalisation and new-onset atrial fibrillation (AF). This study aimed to assess the relationship between acute periapical abscess and incident AF. This was a retrospective cohort study from a French national database of patients hospitalized in 2013 (3.4 million patients) with at least five years of follow up. In total, 3,056,291 adults (55.1% female) required hospital admission in French hospitals in 2013 while not having a history of AF. Of 4693 patients classified as having dental periapical abscess, 435 (9.27%) developed AF, compared to 326,241 (10.69%) without dental periapical abscess that developed AF over a mean follow-up of 4.8 ± 1.7 years. Multivariable analysis indicated that dental periapical abscess acted as an independent predictor for new onset AF (p < 0.01). The CHA2DS2VASc score in patients with acute dental periapical abscess had moderate predictive value for development of AF, with Area Under the Curve (AUC) 0.73 (95% CI, 0.71–0.76). An increased risk of new onset AF was identified for individuals hospitalized with dental periapical abscess. Careful follow up of patients with severe, acute dental periapical infections is needed for incident AF, as well as investigations of possible mechanisms linking these conditions.


2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Benson J. Ouma ◽  
Paul Bangirana ◽  
John M. Ssenkusu ◽  
Dibyadyuti Datta ◽  
Robert O. Opoka ◽  
...  

Abstract Background Elevated angiopoietin-2 (Angpt-2) concentrations are associated with worse overall neurocognitive function in severe malaria survivors, but the specific domains affected have not been elucidated. Methods Ugandan children with severe malaria underwent neurocognitive evaluation a week after hospital discharge and at 6, 12 and 24 months follow-up. The relationship between Angpt-2 concentrations and age-adjusted, cognitive sub-scale z-scores over time were evaluated using linear mixed effects models, adjusting for disease severity (coma, acute kidney injury, number of seizures in hospital) and sociodemographic factors (age, gender, height-for-age z-score, socio-economic status, enrichment in the home environment, parental education, and any preschool education of the child). The Mullen Scales of Early Learning was used in children < 5 years and the Kaufman Assessment Battery for Children 2nd edition was used in children ≥ 5 years of age. Angpt-2 levels were measured on admission plasma samples by enzyme-linked immunosorbent assay. Adjustment for multiple comparisons was conducted using the Benjamini–Hochberg Procedure of False Discovery Rate. Results Increased admission Angpt-2 concentration was associated with worse outcomes in all domains (fine and gross motor, visual reception, receptive and expressive language) in children < 5 years of age at the time of severe malaria episode, and worse simultaneous processing and learning in children < 5 years of age at the time of severe malaria who were tested when ≥ 5 years of age. No association was seen between Angpt-2 levels and cognitive outcomes in children ≥ 5 years at the time of severe malaria episode, but numbers of children and testing time points were lower for children ≥ 5 years at the time of severe malaria episode. Conclusion Elevated Angpt-2 concentration in children with severe malaria is associated with worse outcomes in multiple neurocognitive domains. The relationship between Angpt-2 and worse cognition is evident in children < 5 years of age at the time of severe malaria presentation and in selected domains in older years.


2021 ◽  
pp. 1-8
Author(s):  
Ki-Woong Nam ◽  
Chi Kyung Kim ◽  
Sungwook Yu ◽  
Jong-Won Chung ◽  
Oh Young Bang ◽  
...  

<b><i>Background:</i></b> Stroke risk scores (CHADS<sub>2</sub> and CHA<sub>2</sub>DS<sub>2</sub>-VASc) not only predict the risk of stroke in atrial fibrillation (AF) patients, but have also been associated with prognosis after stroke. <b><i>Objective:</i></b> The aim of this study was to evaluate the relationship between stroke risk scores and early neurological deterioration (END) in ischemic stroke patients with AF. <b><i>Methods:</i></b> We included consecutive ischemic stroke patients with AF admitted between January 2013 and December 2015. CHADS<sub>2</sub> and CHA<sub>2</sub>DS<sub>2</sub>-VASc scores were calculated using the established scoring system. END was defined as an increase ≥2 on the total National Institutes of Health Stroke Scale (NIHSS) score or ≥1 on the motor NIHSS score within the first 72 h of admission. <b><i>Results:</i></b> A total of 2,099 ischemic stroke patients with AF were included. In multivariable analysis, CHA<sub>2</sub>DS<sub>2</sub>-VASc score (adjusted odds ratio [aOR] = 1.17, 95% confidence interval [CI] = 1.04–1.31) was significantly associated with END after adjusting for confounders. Initial NIHSS score, use of anticoagulants, and intracranial atherosclerosis (ICAS) were also found to be closely associated with END, independent of the CHA<sub>2</sub>DS<sub>2</sub>-VASc score. Multivariable analysis stratified by the presence of ICAS demonstrated that both CHA<sub>2</sub>DS<sub>2</sub>-VASc (aOR = 1.20, 95% CI = 1.04–1.38) and CHADS<sub>2</sub> scores (aOR = 1.24, 95% CI = 1.01–1.52) were closely related to END in only patients with ICAS. In patients without ICAS, neither of the risk scores were associated with END. <b><i>Conclusions:</i></b> High CHA<sub>2</sub>DS<sub>2</sub>-VASc score was associated with END in ischemic stroke patients with AF. This close relationship is more pronounced in patients with ICAS.


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