scholarly journals Genetic Variants in PGE2 Receptors Modulate the Risk of Nephrosclerosis and Clinical Outcomes in These Patients

2021 ◽  
Vol 11 (8) ◽  
pp. 772
Author(s):  
Luz María González ◽  
Nicolás Roberto Robles ◽  
Sonia Mota-Zamorano ◽  
José Manuel Valdivielso ◽  
Juan López-Gómez ◽  
...  

Prostaglandin E2 (PGE2) is a major actor mediating renal injury. We aimed to determine genetic variability in the genes coding for its receptors (PTGER1-4) and study associations with nephrosclerosis risk and clinical outcomes. We identified 96 tag-SNPs capturing global variability in PTGER1-4 and screened 1209 nephrosclerosis patients and controls. The effect of these variants was evaluated by multivariate regression analyses. Two PTGER3 SNPs, rs11209730 and rs10399704, remained significant in a backward elimination regression model with other non-genetic variables (OR = 1.45 (1.07–1.95), p = 0.016 and OR = 0.71 (0.51–0.99), p = 0.041, respectively). In the nephrosclerosis patients, a proximal region of PTGER3 was tagged as relevant for eGFR (p values for identified SNPs ranged from 0.0003 to 0.038). Two consecutive PTGER3 SNPs, rs2284362 and rs2284363, significantly decreased systolic (p = 0.005 and p = 0.0005), diastolic (p = 0.039 and p = 0.005), and pulse pressure values (p = 0.038 and 0.014). Patients were followed for a median of 47 months (7–54) to evaluate cardiovascular (CV) risk. Cox regression analysis showed that carriers of the PTGER1rs2241360 T variant had better CV event-free survival than wild-type individuals (p = 0.029). In addition, PTGER3rs7533733 GG carriers had lower event-free survival than AA/AG patients (p = 0.011). Our results indicate that genetic variability in PGE2 receptors, particularly EP3, may be clinically relevant for nephrosclerosis and its associated CV risk.

2019 ◽  
Vol 44 (5) ◽  
pp. 1259-1270 ◽  
Author(s):  
Peter Yam-Kau Poon ◽  
Jack Kit-Chung Ng ◽  
Winston Wing-Shing Fung ◽  
Kai-Ming Chow ◽  
Bonnie Ching-Ha Kwan ◽  
...  

Background: Endocan is associated with endothelial dysfunction. In peritoneal dialysis (PD) patients, cardiovascular disease is a common cause of mortality. We examined the relationship between serum endocan level and clinical outcome of PD patients. Methods: We recruited 193 new PD patients (118 males, mean age 58.8 ± 11.6 years). Serum endocan levels were determined and stratified into tertile 1 (lowest) to 3 (highest). Nutritional status, arterial pulse wave velocity (PWV) and serum C-reactive protein (CRP) levels were measured. The patients were followed for at least 4 years for clinical outcomes. Results: For the whole cohort, patients with higher serum endocan levels had lower serum albumin and subjective global assessment score, higher carotid-femoral PWV, and higher serum CRP. For patients with suboptimal blood pressure (BP) control, cardiovascular event-free survival was 95.0, 95.5, and 78.5% for tertiles 1, 2, and 3 at 60 months respectively (p = 0.019). Multivariate Cox regression analysis showed that serum endocan level was an independent predictor of cardiovascular event-free survival. No association with cardiovascular event-free survival was found for patients with adequate BP control (95.0, 92.3, and 100% for tertile 1, 2, and 3 at 60 months, respectively, p = 0.6). Conclusions: Higher serum endocan level is associated with unfavourable nutritional, arterial and inflammatory conditions in PD patients. In patients with suboptimal BP control, higher serum endocan is also associated with worse cardiovascular outcome.


2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
Z Meiszterics ◽  
T Simor ◽  
R J Van Der Geest ◽  
N Farkas ◽  
B Gaszner

Abstract Introduction Increased aortic pulse wave velocity (PWV) as a strong predictor of major advanced cardiovascular events (MACE) has a prognostic relevance in patients after myocardial infarction (MI). Several non-invasive methods have been proposed for the assessment of arterial stiffness, but the PWV values show significant differences according to the applied techniques. Cardiac magnetic resonance imaging (CMR) provides an accurate method to measure PWV and infarct size in patients after MI. Purpose Calculated PWV values of CMR based phase-contrast (PC) and invasively validated oscillometric methods were compared in this prospective observational study. We aimed to evaluate the cut-off PWV values for each method, while MACE predicted and validated the prognostic value of high PWV in post-infarcted patients in a 6-year follow-up. Methods 3D aortic angiography and PC velocity imaging was performed using a Siemens Avanto 1,5 T CMR device. Oscillometric based Arteriograph (AG) was used to assess PWV using direct body surface distance measurements. The comparison between the two techniques was tested. Patients received follow-up for MACE comprising all-cause death, non-fatal MI, ischemic stroke, hospitalization for heart failure and coronary revascularization. Event-free survival was analysed using Kaplan-Meier plots and log-rank tests. Univariable and multivariable Cox regression analysis was performed to identify outcome predictors. Results 75 patients (56 male, 19 female, average age: 56±13 years) referred for CMR were investigated, of whom 50 had coronary artery disease (CAD) including 35 patients with previous MI developing ischaemic late gadolinium enhancement (LGE) pattern. AG and CMR derived PWV values were significantly correlated (rho: 0,343, p<0,05), however absolute PWV values were significantly higher for AG (median (IQR): 10,4 (9,2–11,9) vs. 6,44 (5,64–7,5); p<0,001). Bland Altman analysis showed an acceptable agreement with a mean difference of 3,7 m/s between the two measures. In patients with CAD significantly (p<0,01) higher PWV values were measured by AG and CMR, respectively. During the median follow-up of 6 years, totally 69 MACE events occurred. Optimized PWV cut-off values for MACE prediction were calculated (CMR: 6,47 m/s; AG: 9,625 m/s) by receiver operating characteristic analysis. Kaplan-Meier analysis in both methods showed a significantly lower event-free survival in case of high PWV (p<0,01, respectively). Cox regression analysis revealed PWV for both methods as a predictor of MACE (PWV CMR hazard ratio (HR): 2,6 (confidence interval (CI) 1,3–5,1), PWV AG HR: 3,1 (CI: 1,3–7,1), p<0,005, respectively). Conclusions Our study showed good agreement between the AG and CMR methods for PWV calculation. Both techniques are feasible for MACE prediction in postinfarcted patients. However, different AG and CMR PWV cut-off values were calculated to improve risk stratification. FUNDunding Acknowledgement Type of funding sources: None. Agreement between the two methods Kaplan-Meier event curves for MACE


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7581-7581
Author(s):  
R. Lai ◽  
E. D. Hsi ◽  
J. Mackey ◽  
S. Jung ◽  
J. L. Johnson ◽  
...  

7581 Background: CALGB 59804 was a phase I/II trial of gemcitabine, vinorelbine, and liposomal doxorubicin (GVD) for pts with relapsed Hodgkin lymphoma (HL). Overall response rate (RR) was 70% (manuscript in review). Plasma membrane nucleoside transporters such as hENT1 are important in transporting nucleoside analogs into cells to exert their pharmacologic effects. We hypothesized high hENT1 expression would predict better RR and outcome in pts treated with GVD. Methods: 58 of 91 pts enrolled in CALGB 59804 had sufficient tissue for study; 31 relapse biopsies and 27 initial diagnosis biopsies. Expression of hENT1 was evaluated by immunohistochemistry in formalin fixed tissue and scored independently by two hematopathologists (RL and EH) blinded to the clinical outcomes. Positivity for hENT1 was defined as >25% of Reed-Sternberg (RS) cells expressing hENT1. Expression was correlated with clinical factors, including IPS at relapse, as well as the overall (OS) and event-free survival (EFS). Results: Expression of hENT1 in RS cells was heterogeneous among cases. 28/58 cases (48%) were hENT1-positive. hENT1-expression was not associated with age, gender, stage, IPS (≤2 or >2), or maximum toxicity grade (≤2 or >2). Compared to hENT1-negative pts, hENT1-positive pts were less likely to have complete or partial response (19/30, 63% versus 22/28, 76%, P=0.20, chi square). hENT1 expression was not significantly associated with OS (P=0.18). Univariate log-rank analysis showed hENT1 positivity and IPS >2 correlated significantly with a lower EFS (P=0.05, and P=0.03, respectively). Multivariate Cox regression analysis confirmed that IPS >2 and hENT1 positivity were independent predictors of EFS (Hazard ratio 2.16, 95%CI 1.08–4.35, P=0.03; and Hazard ratio 2.10, 95% CI 1.06–4.19, P=0.03, respectively). P-values are two-sided. Conclusions: Contrary to our hypothesis, there is an inverse relationship between EFS and hENT1 expression in relapsed HL pts treated with GVD. High expression of hENT1 did not identify gemcitabine-sensitive disease, but may identify a biologically aggressive and/or treatment refractory subtype of HL. No significant financial relationships to disclose.


2006 ◽  
Vol 24 (15) ◽  
pp. 2332-2336 ◽  
Author(s):  
D. Maroeska W.M. te Loo ◽  
Willem A. Kamps ◽  
Anna van der Does-van den Berg ◽  
Elisabeth R. van Wering ◽  
Siebold S.N. de Graaf

Purpose To determine the significance of blasts in the CSF without pleiocytosis and a traumatic lumbar puncture in children with acute lymphoblastic leukemia (ALL). Patients and Methods We retrospectively studied a cohort of 526 patients treated in accordance with the virtually identical Dutch protocols ALL-7 and ALL-8. Patients were classified into five groups: CNS1, no blasts in the CSF cytospin; CNS2, blasts present in the cytospin, but leukocytes less than 5/μL; CNS3, blasts present and leukocytes more than 5/μL. Patients with a traumatic lumbar puncture (TLP; > 10 erythrocytes/mL) were classified as TLP+ (blasts present in the cytospin) or TLP− (no blasts). Results Median duration of follow-up was 13.2 years (range, 6.9 to 15.5 years). Event-free survival (EFS) was 72.6% (SE, 2.5%) for CNS1 patients (n = 304), 70.3% (SE, 4.7%) for CNS2 patients (n = 111), and 66.7% (SE, 19%) for CNS3 patients (n = 10; no significant difference in EFS between the groups). EFS was 58% (SE, 7.6%) for TLP+ patients (n = 62) and 82% (SE, 5.2%) for TLP− patients (n = 39; P < .01). Cox regression analysis identified TLP+ status as an independent prognostic factor (risk ratio, 3.5; 95% CI, 1.4 to 8.8; P = .007). Cumulative incidence of CNS relapses was 0.05 and 0.07 in CNS1 and CNS2 patients, respectively (not statistically significant). Conclusion In our experience, the presence of a low number of blasts in the CSF without pleiocytosis has no prognostic significance. In contrast, a traumatic lumbar puncture with blasts in the CSF specimen is associated with an inferior outcome.


2003 ◽  
Vol 21 (2) ◽  
pp. 184-188 ◽  
Author(s):  
Britta Bürger ◽  
Martin Zimmermann ◽  
Georg Mann ◽  
Joachim Kühl ◽  
Lutz Löning ◽  
...  

Purpose: To determine the significance of leukemic blasts or traumatic lumbar puncture (TLP) in diagnostic CSF of children enrolled in the Berlin-Frankfurt-Münster (BFM) Acute Lymphoblastic Leukemia–BFM-95 trial. Patients and Methods: A total of 2,021 patients were retrospectively evaluated according to initial central nervous system (CNS) status. Patients were classified as follows: CNS1 (CNS negative, n = 1,605), CNS2 (≤ 5 WBC/μL CSF with blasts, n = 103), CNS3 (CNS positive, n = 58), TLP+ (TLP with blasts, n = 135), or TLP− (TLP without blasts, n = 111). Patients with CNS2 and TLP+ status were eligible for two additional doses of intrathecal (IT) methotrexate (MTX). CNS3 patients received additional IT MTX and cranial irradiation (18 Gy). Results: CNS2, CNS3, and TLP+ groups contained a higher percentage of patients with unfavorable characteristics. Cox regression analysis identified TLP+ and CNS3 status as prognostically significant (CNS3): risk ratio (RR) = 2.3; 95% confidence interval [CI], 1.4 to 3.6; P = .0005; TLP+: RR = 1.5; 95% CI, 1.02 to 2.2; P = .04. Overall 5-year event-free survival (EFS) is 79%, for CNS1 it is 80%, and for TLP− it is 83%. CNS2 patients have an EFS of 80%, but the cumulative incidence of relapses with CNS involvement is higher compared with CNS1 patients (0.10 v 0.04). TLP+ patients have a significantly reduced EFS (73%, P = .003) because of an increased incidence of CNS relapses. CNS3 patients suffer from more systemic and CNS relapses (EFS 50%). Conclusion: CNS2 patients have the same prognosis as patients with CNS1 status, whereas the EFS of TLP+ patients is inferior to CNS1 but superior to CNS3 patients (P = .001). Both subgroups may have benefitted from additional IT MTX.


2021 ◽  
Vol 8 ◽  
Author(s):  
Ibrahim El-Battrawy ◽  
Assem Aweimer ◽  
Siegfried Lang ◽  
Uzair Ansari ◽  
Thorsten Gietzen ◽  
...  

Background: A considerable amount of evidence has shown that acute cardiovascular diseases exhibit specific temporal patterns in their onset.Aim: This study was performed to determine if takotsubo syndrome (TTS) shows chronobiological variations with short and long-term impacts on adverse events.Design: Our institutional database constituted a collective of 114 consecutive TTS patients between 2003 and 2015.Methods: Patients were divided into groups defined by the onset of TTS as per time of the day, day of the week, month and quarter of year.Results: TTS events were most common afternoon and least common in the night, indicating a wave-like pattern (p = 0.001) of manifestation. The occurrence of TTS events was similar among days of the week and weeks of the month. TTS patients diagnosed in the month of November and subsequently in the fourth quarter showed a significantly longer QTc interval. These patients also revealed a significantly lower event-free-survival over a 1-year follow-up. In a multivariate Cox regression analysis, TTS events occurring in the fourth quarter of year (HR 6.8, 95%CI: 1.3–35.9; p = 0.02) proved to be an independent predictor of lower event-free-survival.Conclusions: TTS seems to exhibit temporal preference in its onset, but nevertheless this possibly coincidental result needs to be analyzed in a large multicenter registry.


2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Cheng-Jui Lin ◽  
Chi-Feng Pan ◽  
Chih-Kuang Chuang ◽  
Fang-Ju Sun ◽  
Duen-Jen Wang ◽  
...  

Background/Aims. Previous studies have reported p-cresyl sulfate (PCS) was related to endothelial dysfunction and adverse clinical effect. We investigate the adverse effects of PCS on clinical outcomes in a chronic kidney disease (CKD) cohort study.Methods. 72 predialysis patients were enrolled from a single medical center. Serum biochemistry data and PCS were measured. The clinical outcomes including cardiovascular event, all-cause mortality, and dialysis event were recorded during a 3-year follow-up.Results. After adjusting other independent variables, multivariate Cox regression analysis showed age (HR: 1.12,P=0.01), cardiovascular disease history (HR: 6.28,P=0.02), and PCS (HR: 1.12,P=0.02) were independently associated with cardiovascular event; age (HR: 0.91,P<0.01), serum albumin (HR: 0.03,P<0.01), and PCS level (HR: 1.17,P<0.01) reached significant correlation with dialysis event. Kaplan-Meier analysis revealed that patients with higher serum p-cresyl sulfate (>6 mg/L) were significantly associated with cardiovascular and dialysis event (log rankP=0.03, log rankP<0.01, resp.).Conclusion. Our study shows serum PCS could be a valuable marker in predicting cardiovascular event and renal function progression in CKD patients without dialysis.


2021 ◽  
pp. 152660282199672
Author(s):  
Giovanni Tinelli ◽  
Marie Bonnet ◽  
Adrien Hertault ◽  
Simona Sica ◽  
Gian Luca Di Tanna ◽  
...  

Purpose: Evaluate the impact of hybrid operating room (HOR) guidance on the long-term clinical outcomes following fenestrated and branched endovascular repair (F-BEVAR) for complex aortic aneurysms. Materials and Methods: Prospectively collected registry data were retrospectively analyzed to compare the procedural, short- and long-term outcomes of consecutive F-BEVAR performed from January 2010 to December 2014 under standard mobile C-arm versus hybrid room guidance in a high-volume aortic center. Results: A total of 262 consecutive patients, including 133 patients treated with a mobile C-arm equipped operating room and 129 with a HOR guidance, were enrolled in this study. Patient radiation exposure and contrast media volume were significantly reduced in the HOR group. Short-term clinical outcomes were improved despite higher case complexity in the HOR group, with no statistical significance. At a median follow-up of 63.3 months (Q1 33.4, Q3 75.9) in the C-arm group, and 44.9 months (Q1 25.1, Q3 53.5, p=0.53) in the HOR group, there was no statistically significant difference in terms of target vessel occlusion and limb occlusion. When the endograft involved 3 or more fenestrations and/or branches (complex F-BEVAR), graft instability (36% vs 25%, p=0.035), reintervention on target vessels (20% vs 11%, p=0.019) and total reintervention rates (24% vs 15%, p=0.032) were significantly reduced in the HOR group. The multivariable Cox regression analysis did not show statistically significant differences for long-term death and aortic-related death between the 2 groups. Conclusion: Our study suggests that better long-term clinical outcomes could be observed when performing complex F-BEVAR in the latest generation HOR.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
K Matsushita ◽  
B Marchandot ◽  
M Kibler ◽  
C Sato ◽  
J Heger ◽  
...  

Abstract Introduction Paravalvular leakage (PVL) following transcatheter aortic valve replacement (TAVR) is associated with greater mortality. In clinical practice, determining PVL severity after TAVR remains challenging and often requires multiparametric assessment. Purpose This study sought to evaluate the respective value of various modalities of PVL assessments, including transthoracic echocardiography (TTE), cine-angiography, aortic regurgitation index (ARI), and closure time with adenosine diphosphate (CT-ADP), in the prediction of adverse clinical outcomes. Methods We included 1044 patients from our prospective TAVR registry between February 2010 and May 2019. Major adverse cardiac and cerebrovascular events (MACCE) was defined as a composite of all-cause death, myocardial infarction, stroke, and heart failure hospitalization within 1-year. Established cutoff values of ARI (&lt;25) and CT-ADP (&gt;180 sec) were used to assess the presence of PVL after TAVR. Results Moderate to severe PVL occurred in 14.2% and 5.2% of patients as measured by TTE and angiography. The rate of patients with ARI &lt;25 and CT-ADP &gt;180 sec were 36.5% and 24.9%, respectively. Among the four modalities, PVL evaluated by angiography predicted poorer clinical outcomes (Log rank test; p=0.001), whereas TTE, ARI &lt;25, and CT-ADP &gt;180 sec were not associated with 1-year MACCE. By multivariate Cox regression analysis, moderate to severe PVL by angiography was an independent predictor of 1-year MACCE (hazard ratio: 1.96; 95% confidence interval: 1.22–3.00; p=0.007). Conclusions Paravalvular leakage measured by angiography was evidenced as the most meaningful modality in the prediction of adverse clinical outcomes. Future multicenter studies are warranted to ensure these findings in the current TAVR era. Figure 1 Funding Acknowledgement Type of funding source: None


Neurosurgery ◽  
2021 ◽  
Author(s):  
Peng Wang ◽  
Chen Luo ◽  
Peng-jie Hong ◽  
Wen-ting Rui ◽  
Shuai Wu

Abstract BACKGROUND While maximizing extent of resection (EOR) is associated with longer survival in lower-grade glioma (LGG) patients, the number of cases remains insufficient in determining a EOR threshold to elucidate the clinical benefits, especially in IDH-wild-type LGG patients. OBJECTIVE To identify the effects of EOR on the survival outcomes of IDH-wild-type LGG patients. METHODS IDH-wild-type LGG patients were retrospectively reviewed. The effect of EOR and other predictor variables on overall survival (OS) and progression-free survival (PFS) was analyzed using Cox regression models and the Kaplan-Meier method. RESULTS A total of 94 patients (median OS: 48.9 mo; median follow-up: 30.6 mo) were included in this study. In the multivariable Cox regression analysis, postoperative residual volume was associated with prolonged OS (HR = 2.238; 95% confidence interval [CI], 1.130-4.435; P = .021) and PFS (HR = 2.075; 95% CI, 1.113-3.869; P = .022). Thresholds at a minimum EOR of 97.0% or a maximum residue of 3.0 cm3 were necessary to impact OS positively. For the telomerase reverse transcriptase (TERT)p-wild-type group, such an association was absent. Significant differences in survival existed between the TERTp-wild-type and mutant patients who underwent relatively incomplete resections (residual ≥2.0 cm3 + TERTp wild type: median OS of 62.6 mo [95% CI: 39.7-85.5 mo]; residual ≥2.0 cm3 + TERTp mutant: median OS of 20.0 mo [95% CI:14.6-25.4 mo]). CONCLUSION Our results support the core role of maximal safe resection in the treatment of IDH-wild-type LGGs, especially for IDH-wild-type + TERTp-mutant LGGs. Importantly, the survival benefits of surgery could only be elucidated at a high EOR cut-off point.


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