Association of the CC genotype of the regulatory BCL2 promoter polymorphism (−938C>A) with better 2-year survival in patients with glioblastoma multiforme

2011 ◽  
Vol 114 (6) ◽  
pp. 1631-1639 ◽  
Author(s):  
Nicolai El Hindy ◽  
Hagen S. Bachmann ◽  
Nicole Lambertz ◽  
Michael Adamzik ◽  
Holger Nückel ◽  
...  

Object Bcl-2 plays a key role in the downregulation of apoptosis and proliferation and leads to increased chemoresistance in glioblastoma multiforme (GBM). The authors investigated the role of a common regulatory single-nucleotide polymorphism (−938C>A), which is located in the inhibitory P2 promoter of BCL2. Methods Data from 160 patients suffering from GBM were retrospectively evaluated. Study inclusion criteria consisted of available DNA and, in patients still alive, a follow-up of at least 24 months. Results were analyzed with respect to the basic clinical data, type of surgical intervention (gross-total resection [GTR] versus stereotactic biopsy [SB]), adjuvant therapy, MGMT promoter methylation, and survival at the 2-year follow-up. Results At the 2-year follow-up, 127 (79.4%) of the 160 patients had died. Kaplan-Meier curves revealed a significantly higher rate of survival for homo- and heterozygous C-allele carriers (p = 0.031). In the GTR group, the survival rate was 47.1% for homozygous C-allele carriers, 32.0% for heterozygous C-allele carriers, and only 21.4% for homozygous A-allele carriers (p = 0.024). The SB group showed no genotype-dependent differences. Multivariable Cox regression revealed that the BCL2 (−938AA) genotype was an independent negative prognostic factor for 2-year survival in the GTR group according to the BCL2 (−938CC) genotype reference group (hazard ratio 2.50, 95% CI 1.14–5.48, p = 0.022). Conclusions These results suggested that the (−938C>A) polymorphism is a survival prognosticator as well as a marker for a high-risk group among patients with GBM who underwent GTR.

2020 ◽  
Vol 26 ◽  
pp. 107602962094858
Author(s):  
Yan Bai ◽  
Ying-Ying Zheng ◽  
Jun-Nan Tang ◽  
Xu-Ming Yang ◽  
Qian-Qian Guo ◽  
...  

The role of activation of the coagulation and fibrinolysis system in the pathogenesis and prognosis of cardiovascular diseases (CVDs) has drawn wide attention. Recently, the D-dimer to fibrinogen ratio (DFR) is considered as a useful biomarker for the diagnosis and prognosis of ischemic stroke and pulmonary embolism. However, few studies have explored the relationship between DFR and cardiovascular disease. In our study, patients were divided into 2 groups according to DFR value: the lower group (DFR < 0.52, n = 2123) and the higher group (DFR ≥ 0.52, n = 1073). The primary outcome was all-cause mortality (ACM) and cardiac mortality (CM). The average follow-up time was 37.59 ± 22.24 months. We found that there were significant differences between the 2 groups in term of ACM (2.4% vs 6.6%, P < 0.001) and CM (1.5% vs 4.0%, P < 0.001). Kaplan–Meier analyses showed that elevated DFR had higher incidences of ACM (log rank P < 0.001) and CM (log rank P < 0.001). Multivariate Cox regression analyses showed that DFR was an independent predictor of ACM (HR = 1.743, 95%CI: 1.187-2.559 P = 0.005) and CM (HR = 1.695, 95%CI: 1.033-2.781 P = 0.037). This study indicates that DFR is an independent and novel predictor of long-term ACM and CM in post-PCI patients with CAD.


2020 ◽  
Vol 14 ◽  
pp. 117955492093660
Author(s):  
Rossana Berardi ◽  
Silvia Rinaldi ◽  
Giulio Belfiori ◽  
Stefano Partelli ◽  
Stefano Crippa ◽  
...  

Objectives: Hyponatraemia represents a negative prognostic factor in patients with cancer. The aim of this study was to assess, for the first time, the role of hyponatraemia in patients undergoing radical surgery for pancreatic ductal adenocarcinoma. Methods: A total of 89 patients with stage I-III pancreatic ductal adenocarcinoma underwent radical surgery between November 2012 and October 2014. Relapse-free survival (RFS) and disease-specific survival (DSS) were estimated using Kaplan-Meier method. A Cox regression model was carried out for univariate and multivariate analyses. Fisher exact test was used to estimate correlation between variables. Results: In total, 12 patients (14%) presented with hyponatraemia at diagnosis. The median DSS was 20 months in patients with hyponatraemia and not reached in patients with eunatraemia ( P < .1073), while a statistical significant difference was observed in terms of median RFS (10 months vs 17 months, respectively; P = .0233). Considering clinical features (hyponatraemia, smoke and alcoholic habit, diabetes, pain, and jaundice), patients with 4 or more of these factors had a worse prognosis (mDSS: 30 months vs not reached; hazard ratio [HR]: 0.40, 95% confidence interval [CI] = 0.16-0.80; P = .0120). Conclusions: The presence of hyponatraemia and its prompt correction at the diagnosis time should be considered for the correct management of patients with pancreatic carcinoma.


2020 ◽  
Vol 14 (12) ◽  
pp. 1127-1137
Author(s):  
Tong-Tong Zhang ◽  
Yi-Qing Zhu ◽  
Hong-Qing Cai ◽  
Jun-Wen Zheng ◽  
Jia-Jie Hao ◽  
...  

Aim: This study aimed to develop an effective risk predictor for patients with stage II and III colorectal cancer (CRC). Materials & methods: The prognostic value of p-mTOR (Ser2448) levels was analyzed using Kaplan–Meier survival analysis and Cox regression analysis. Results: The levels of p-mTOR were increased in CRC specimens and significantly correlated with poor prognosis in patients with stage II and III CRC. Notably, the p-mTOR level was an independent poor prognostic factor for disease-free survival and overall survival in stage II CRC. Conclusion: Aberrant mTOR activation was significantly associated with the risk of recurrence or death in patients with stage II and III CRC, thus this activated proteins that may serve as a potential biomarker for high-risk CRC.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A Bielecka-Dabrowa ◽  
P Gasiorek ◽  
A Sakowicz ◽  
M Banach

Abstract Purpose The study aimed to identify echocardiographic, hemodynamic and biochemical predictors of unfavourable prognosis after ischemic strokes of undetermined etiology (ESUS) in patients (pts) at age <65. Methods Out of 520 ischemic stroke pts we selected 64 pts diagnosed with ESUS [mean age 54 (SD: 47–58) years, 42% males] and additional 36 without stroke but with similar risk profile, which were treated as a reference group [age 53 (SD: 47–58) years, 61% males]. All pts underwent echocardiography, non-invasive assessment of hemodynamic parameters using SphygmoCor tonometer (Atcor Med., Australia), HDL subfraction distribution using Lipoprint (Quantimetrix) as well as measurements of selected biomarkers. Follow-up was 12 months. Results At 12-month follow-up 9% of patients had died, and recurrent ischemic stroke also occurred in 9% of patients - only in the ESUS group (Figure). Patients who died had significantly lower levels of LDL and HDL cholesterol (included HDL-8 and -9 subfractions) and higher level of triglicerides (p=0.01, p=0.01, and p=0.02; respectively), lower level of adiponectin (p=0.01), lower value of mean early diastolic (E') mitral annular velocity (p=0.04) and lower diastolic blood pressure (p=0.04). The atrial fibrillation (AF) occurred in 10% of pts during the 12 months (log-rang, p=0.254) (Figure). The log-rank test showed that ESUS group had a significantly poorer outcome of AF in the first 2 months after hospitalization compared to reference group (11% vs 5%, p=0.041). Based on a Kaplan-Meier analysis, the outcome of re-hospitalizationin the 1st year was 28% (18/64) in the ESUS group and 17% (6/36); log-rank, p=0.058. In the multivariate analysis mean early diastolic (E') mitral annular velocity (odds ratio [OR] 0.75, 95% confidence interval [CI]: 0.6–0.94; p=0.01) was significantly associated with CV hospitalizations assessed at 12-month follow-up. The only independent predictor of AF occurrence in the 12-month follow-up was lower value of Tissue Doppler-derived right ventricular systolic excursion velocity S' (OR 0.65, 95% Cl 0.45–0.93; p=0.01). The only independent predictor of recurrent stroke was the ratio of peak velocity of early diastolic transmitral flow to peak velocity of early diastolic mitral annular motion as determined by pulsed wave Doppler (E/E') (OR 0.75, 95% CI: 0.6–0.94; p=0.01). E/E' ratio was also independently associated with composite endpoint consisting of death, hospitalization and recurrent stroke (OR 1.90, 95% CI 1.1–3.2, p=0.01). Kaplan-Meier Analysis - survival and AF Conclusions The indices of diastolic dysfunction are significantly associated with unfavourable prognosis after ESUS. There is a robust role for outpatient cardiac monitoring especially during first 2 months after ESUS to detect potential AF. Acknowledgement/Funding The study was financed by research grants no. 502-03/5-139-02/502-54-229-18 of the Medical University of Lodz


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.


Open Heart ◽  
2021 ◽  
Vol 8 (1) ◽  
pp. e001440
Author(s):  
Shameer Khubber ◽  
Rajdeep Chana ◽  
Chandramohan Meenakshisundaram ◽  
Kamal Dhaliwal ◽  
Mohomed Gad ◽  
...  

BackgroundCoronary artery aneurysms (CAAs) are increasingly diagnosed on coronary angiography; however, controversies persist regarding their optimal management. In the present study, we analysed the long-term outcomes of patients with CAAs following three different management strategies.MethodsWe performed a retrospective review of patient records with documented CAA diagnosis between 2000 and 2005. Patients were divided into three groups: medical management versus percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG). We analysed the rate of major cardiovascular and cerebrovascular events (MACCEs) over a period of 10 years.ResultsWe identified 458 patients with CAAs (mean age 78±10.5 years, 74.5% men) who received medical therapy (N=230) or underwent PCI (N=52) or CABG (N=176). The incidence of CAAs was 0.7% of the total catheterisation reports. The left anterior descending was the most common coronary artery involved (38%). The median follow-up time was 62 months. The total number of MACCE during follow-up was 155 (33.8%); 91 (39.6%) in the medical management group vs 46 (26.1%) in the CABG group vs 18 (34.6%) in the PCI group (p=0.02). Kaplan-Meier survival analysis showed that CABG was associated with better MACCE-free survival (p log-rank=0.03) than medical management. These results were confirmed on univariate Cox regression, but not multivariate regression (OR 0.773 (0.526 to 1.136); p=0.19). Both Kaplan-Meier survival and regression analyses showed that dual antiplatelet therapy (DAPT) and anticoagulation were not associated with significant improvement in MACCE rates.ConclusionOur analysis showed similar long-term MACCE risks in patients with CAA undergoing medical, percutaneous and surgical management. Further, DAPT and anticoagulation were not associated with significant benefits in terms of MACCE rates. These results should be interpreted with caution considering the small size and potential for selection bias and should be confirmed in large, randomised trials.


2021 ◽  
pp. 1-20
Author(s):  
Diego Santos García ◽  
Teresa de Deus Fonticoba ◽  
Carlos Cores ◽  
Ester Suárez Castro ◽  
Jorge Hernández Vara ◽  
...  

Background: There is a need for identifying risk factors for hospitalization in Parkinson’s disease (PD) and also interventions to reduce acute hospital admission. Objective: To analyze the frequency, causes, and predictors of acute hospitalization (AH) in PD patients from a Spanish cohort. Methods: PD patients recruited from 35 centers of Spain from the COPPADIS-2015 (COhort of Patients with PArkinson’s DIsease in Spain, 2015) cohort from January 2016 to November 2017, were included in the study. In order to identify predictors of AH, Kaplan-Meier estimates of factors considered as potential predictors were obtained and Cox regression performed on time to hospital encounter 1-year after the baseline visit. Results: Thirty-five out of 605 (5.8%) PD patients (62.5±8.9 years old; 59.8% males) presented an AH during the 1-year follow-up after the baseline visit. Traumatic falls represented the most frequent cause of admission, being 23.7% of all acute hospitalizations. To suffer from motor fluctuations (HR [hazard ratio] 2.461; 95% CI, 1.065–5.678; p = 0.035), a very severe non-motor symptoms burden (HR [hazard ratio] 2.828; 95% CI, 1.319–6.063; p = 0.008), falls (HR 3.966; 95% CI 1.757–8.470; p = 0.001), and dysphagia (HR 2.356; 95% CI 1.124–4.941; p = 0.023) was associated with AH after adjustment to age, gender, disease duration, levodopa equivalent daily dose, total number of non-antiparkinsonian drugs, and UPDRS-IIIOFF. Of the previous variables, only falls (HR 2.998; 95% CI 1.080–8.322; p = 0.035) was an independent predictor of AH. Conclusion: Falls is an independent predictor of AH in PD patients.


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.


2021 ◽  
Author(s):  
Bertrand Baussart ◽  
Chiara Villa ◽  
Anne Jouinot ◽  
Marie-Laure Raffin-Sanson ◽  
Luc Foubert ◽  
...  

Objective: Microprolactinomas are currently treated with dopamine agonists. Outcome information on microprolactinoma patients treated by surgery is limited. This study reports the first large series of consecutive non-invasive microprolactinoma patients treated by pituitary surgery and evaluates the efficiency and safety of this treatment. Design: Follow-up of a cohort of consecutive patients treated by surgery. Methods: Between January 2008 and October 2020, 114 adult patients with pure microprolactinomas were operated on in a single tertiary expert neurosurgical department, using an endoscopic endonasal transsphenoidal approach. Eligible patients were presenting a microprolactinoma with no obvious cavernous invasion on MRI. Prolactin was assayed before and after surgery. Disease-free survival was modeled using Kaplan-Meier representation. A cox regression model was used to predict remission. Results: Median follow-up was 18.2 months (range: 2.8 to 155). In this cohort, 14/114 (12%) patients were not cured by surgery, including 10 early surgical failures, and 4 late relapses occurring 37.4 months (33 to 41.8) after surgery. From Kaplan Meier estimates, 1-year and 5-year disease free survival were 90.9% (95% CI, 85.6%-96.4%) and 81% (95% CI,71.2%-92.1%) respectively. The preoperative prolactinemia was the only significant preoperative predictive factor for remission (P<0.05). No severe complication was reported, with no anterior pituitary deficiency after surgery, one diabetes insipidus, and one postoperative cerebrospinal fluid leakage properly treated by muscle plasty. Conclusions: In well selected microprolactinoma patients, pituitary surgery performed by an expert neurosurgical team is a valid first-line alternative treatment to dopamine agonists.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 11548-11548
Author(s):  
Olga Vornicova ◽  
Jay Wunder ◽  
Peter W. M. Chung ◽  
Abha A. Gupta ◽  
Rebecca Anne Gladdy ◽  
...  

11548 Background: The mainstay therapy of operable STS remains surgery, which may include (neo)adjuvant therapies. Within the TSP, marginally inoperable STS are often treated with sequential chemo (CTX) and radiation (RT) therapy, followed by surgery (SX). Herein we present our experience of multi-modality therapies for marginally inoperable STS patients (pts). Methods: This was a dual-center, single program, retrospective review. Pts were included if deemed to have marginally inoperable primary or recurrent STS, as determined at the TSP tumor board. Pts included must have had CTX with the intent of having RT and SX after. Pts demographics, treatment details and clinical outcomes data were collected. Relapse free survival (RFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Multivariate analysis of the influence of disease characteristics and treatment on outcomes was assessed using Cox regression. Results: From June 2005 to May 2019, 75 pts were identified. Median age was 52 years (range 16-72). Pts were predominantly male (55%). Histological subtypes included dedifferentiated liposarcoma (29%), leiomyosarcoma (27%), synovial sarcoma (19%) and others (25%). Primary tumor was located in the retroperitoneum (48%), extremity (23%), pelvis (12%), thorax (9%), and other sites (8%). All pts had doxorubicin and ifosfamide CTX (median 4 cycles; range 1-6), while RT dose delivered was 50.4Gy/28 fractions in 58 (77%) of cases. Twenty three pts (31%) achieved partial response, 40 pts (53%) had stable disease and 12 pts (16%) had progression of disease (PD) on CTX, of which half (8%) did not undergo further treatment. Nine pts (12%) underwent CTX followed by SX due to significant response, 9 pts (12%) underwent CTX and RT without SX due to persistent tumor unresectability or PD. The final 50 pts (67%) completed multi-modality treatment (CTX, RT & SX). Overall, 59 pts (79%) had SX; negative margins were achieved in 53 (71%). 19 pts (25%) had postoperative complications, causing death in 2 pts (2.7%). With a median follow-up of 72 months, median RFS and OS were 26.9 months (95% CI: 0-86.0), and 65 months (95% CI: 13.5-116.4). Extremity location was associated with superior RFS (median not reached [NR], HR 0.28 95% CI 0.09-0.83, p = 0.022), and OS (median NR, HR 0.29 95% CI 0.09-0.90, p = 0.032). Receipt of RT was associated with superior RFS (median NR, HR 0.23 95% CI 0.10-0.52, p < 0.001); and OS (median NR, HR 0.21 95% CI 0.09-0.50, p < 0.001). Pts who had PD after CTX were associated with poor outcomes - RFS (median 4.7 months, HR 2.03 95% CI 0.61-6.76, p = 0.24); and OS (median 21.9 months, HR 2.48 95% CI 0.73-8.47, P = 0.144). Conclusions: Multi-modality approach resulted in successful resection for most pts with marginally inoperable STS. Extremity location and RT administration were associated with better RFS and OS, while progression on CTX confers worse survival outcomes.


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