QOLP-08. THE LANDSCAPE OF EPILEPSY ASSOCIATED WITH DIFFUSELY INFILTRATIVE GLIOMAS

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi184-vi184
Author(s):  
Michael Drumm ◽  
Jessica Templer ◽  
Omar Bushara ◽  
Dusten Unruh ◽  
Jordain Walshon ◽  
...  

Abstract Seizures are among the most prevalent co-morbidities associated with glioma, and pose a serious threat to patients. Our prior work showed that IDH mutation (IDHmut) was associated with much greater seizure frequency at the time of initial glioma diagnosis. However, less is known about the variables that contribute to seizure risk throughout the course of disease. We therefore collected data from 247 patients with grade 2–4 glioma, and determined seizure risk using Kaplan-Meier survival probabilities and multivariable cox regression analyses. Median follow-up of IDH wildtype (IDHwt) and IDHmut glioma patients was 15 months and 36 months, respectively. Incidence of pre-operative seizures for IDHwt and IDHmut patients was 75/168 (45%) and 60/79 (76%), and incidence of post-operative seizures was 70/168 (42%) and 43/79 (54%), respectively. Patients who had a pre-operative seizure had a shorter time to their first post-operative seizure than patients who never had a pre-operative seizure in both IDHwt (P< 0.0001) and IDHmut (P= 0.039) cohorts. Among IDHmut glioma patients, those with subtotal resections developed post-operative seizures faster (median time to first seizure= 9.9 months) than those with gross-total resections (median not reached) (P= 0.0005), but a similar pattern was not observed in IDHwt glioma patients (P= 0.20). Those with IDHmut astrocytomas more quickly developed post-operative seizures (median= 11.1 months), compared to those with IDHwt astrocytomas (24.9 months) or IDHmut oligodendrogliomas (median not reached) (P= 0.033). Tumor progression closely followed post-operative seizures in patients with IDHwt gliomas when either their first post-operative seizure occurred longer than 6 months following resection, or when their post-operative seizures worsened in quality. These data suggest the best predictors of post-operative seizures are as follows: the presence of pre-operative seizures; extent of surgical resection; IDHmut status. These data will help clinicians better manage glioma patients by identifying those at greatest risk of seizures.

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi15-vi15
Author(s):  
Andrew Lassman ◽  
Minhee Won ◽  
J Gregory Cairncross ◽  
Edward Shaw ◽  
Lynn Ashby ◽  
...  

Abstract BACKGROUND Adding intensive-procarbazine, lomustine, and vincristine (iPCV) to radiotherapy (RT) prolonged progression-free (PFS) and overall survival (OS) for patients with 1p19q codeleted anaplastic oligodendroglial tumors (AOTs); some benefit was also observed for IDH-mutant non-codeleted cases (Cairncross et al 2013, 2014, 2016). Now, 25 years after study activation, we updated survival, further assessed IDH as a predictive biomarker, and are exploring the benefit from vincristine. METHODS Eligible adults (KPS ≥ 60, adequate end-organ function) were randomized to pre-RT iPCV (4 cycles x 6 weeks each) vs. RT alone, stratified by age (< or ≥ 50), KPS (60–70 or ≥ 80), and level of anaplasia. Histology (anaplastic oligodendroglioma/oligo-astrocytoma required) and biomarkers (IDH and 1p19q, post-hoc) were determined centrally. Survival was estimated by Kaplan-Meier and Hazard Ratios (HRs) by Cox-regression. RESULTS Overall (n=289), median follow-up was 16.4 years vs. 11.3 years at last report. In codeleted cases, 40% randomized to iPCV remained alive vs. 53% at last report; 5, 10, and 14 year-PFS and -OS rates were 62%, 50%, 41% and 70%, 57%, 46%, respectively; and iPCV unequivocally prolonged PFS (median 9.8 vs. 2.9 years, HR 0.46, 95% CI 0.3–0.7, p< 0.001) and OS (median 13.2 vs. 7.3 years, HR 0.61, 95% CI 0.40–0.94; p=0.02). With IDH mutation but without codeletion (n=66), iPCV prolonged PFS (median 2.8 vs. 1.9 years, HR 0.58, 95% CI 0.34–0.99, p=0.046); OS was longer with a trend for significance (median 5.5 vs. 3.3 years, HR 0.6, 95% CI 0.34–1.03, p=0.06) on this underpowered exploratory post-hoc analysis. CONCLUSION For codeleted AOTs, long-term analyses confirmed that pre-RT iPCV produced meaningful and significant prolongations of PFS and OS. With IDH mutation but without codeletion, iPCV significantly prolonged PFS and showed a trend for prolonged OS. The value of vincristine is being assessed. Supported by NCI grants U10CA180868, U10CA180822, U24CA196067, and UG1CA189867.


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.


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.


Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1738-1738 ◽  
Author(s):  
Ya Zhang ◽  
Xiaosheng Fang ◽  
Na Chen ◽  
Xiao Lv ◽  
Xueling Ge ◽  
...  

Introduction N6-methyladenosine (m6A) RNA methylation is the most abundant epitranscriptomic modification, dynamically installed by the m6A methyltransferases (termed as "writers"), reverted by the demethylases (termed as "erasers"), and recognized by m6A binding proteins (termed as "readers"). Emerging evidence suggests that m6A RNA methylation regulates RNA stability, and participates in the pathogenesis of multiple diseases including cancers. Nevertheless, the role of m6A RNA methylation in chronic lymphocytic leukemia (CLL) remains to be unveiled. Herein, we hypothesized that m6A RNA methylation contributed to the tumorigenesis and maintenance of CLL. Moreover, the risk-prediction model integrated with the m6A regulators could serve as a novel and effective prognostic indicator in CLL. This study aimed to identify robust m6A RNA methylation-associated fingerprints for risk stratification in patients with CLL. Methods A total of 714 de novo CLL patients from 4 cohorts (China, Spain, Germany and Italy) were enrolled with informed consents. EpiQuik m6A RNA methylation colorimetric quantification assay was utilized to assess m6A RNA methylation levels. LASSO Cox regression algorithm was performed to calculate m6A RNA methylation-associated risk score (short for "m6A risk score") in R software. Besides, Kaplan-Meier survival analysis with log-rank test, univariate and multivariate Cox regression analyses and ROC curve analysis of overall survival (OS) were conduct to explore the prognostic value of m6A signature in CLL. Furthermore, RNA-seq, MeRIP-seq, Ribo-seq, functional enrichment analyses in silico and preclinical experiments ex vivo were applied to confirm the biological mechanism of the m6A regulators in CLL. Results In the present study, we performed a comprehensive analysis to dissect the role of m6A RNA methylation regulators in CLL. Compared with normal B cells from healthy donors, obvious decreased level of m6A RNA methylation was observed in primary CLL cells (p<0.01; Figure 1A). In addition, down-regulated m6A RNA methylation was also detected in CLL cell lines MEC1 and EHEB (p<0.05; Figure 1A). Then, we further investigated the association of the m6A RNA methylation regulators with clinical outcomes of CLL patients. By LASSO Cox regression analysis in 486 CLL patients, the m6A risk score was established with the coefficients of fourteen m6A regulators at the minimum lambda value of 0.00892 (Figure 1B-C). Based on the median risk score as the cut-off value, a clear distribution pattern was delineated in CLL patients (Figure 1D). Kaplan-Meier curves showed stratified high-risk patients presented significantly shorter OS versus the low-risk group (HR=4.477, p<0.001; Figure 2A). Besides, m6A risk score also predicts inferior prognosis in stable subgroup (HR=3.097, p=0.037; Figure 2B), and progressed/ relapsed subgroup (HR=3.325, p=0.001; Figure 2C). Moreover, univariate, multivariate cox regression analyses and ROC curve confirmed high m6A risk score as an independent survival predictor in CLL patients (p<0.001; Figure 2D-E). Thereafter, the clinicopathological relevance and underlying mechanism of m6A risk score were explored. Significant elevated m6A risk score was detected in patients with unfavorable treatment responses compared with stable status (p<0.001; Figure 3A). Furthermore, CLL patients with advanced Binet stage, positive ZAP-70 and unmutated IGHV present increased m6A risk score (p<0.05; Figure 3B-C). Intriguingly, we also observed the significantly negative correlation between highrisk score and 13q14 deletion, in accordance with patients' inferior outcome (p=0.047; Figure 3D). Moreover, Pearson correlation analysis, STRING interactive network and functional enrichment analyses deciphered that the m6A regulators exerted crucial roles in CLL progression potentially via modulating RNA metabolism and oncogenic pathways (Figure 4A-C). Conclusion To date, our study provides evidence for the first time that reduced m6A RNA methylation contributes to the tumorigenesis of CLL. Distinct m6A risk scoreis demonstrated as an efficient tool facilitating prognosis evaluation in CLL patients. However, validation of the signature in more independent cohorts are warranted. Further interrogations will be elucidated on the biological mechanism of m6A regulators, highlighting insights into pathogenesis and therapy strategy of CLL. Disclosures No relevant conflicts of interest to declare.


2020 ◽  
Author(s):  
Liang Jin ◽  
Ting-shuai Zhai ◽  
Zhen Zhou ◽  
Xiang Liu ◽  
Jia-xin Zhang ◽  
...  

Abstract Background: We aimed to evaluate the impact of nephron sparing surgery (NSS) on survival in upper urinary tract urothelial carcinoma (UTUC) patients stratified by tumor grade and stage compared to radical nephroureterectomy (RNU) or no surgery. Methods: Overall, 10319 UTUC patients between 2004 and 2015 were extracted from the SEER database. Patients were divided into no surgery group, NSS group and RNU group. Kaplan-Meier plots illustrated survival rates according to surgical method. Multivariable Cox regression analyses assessed the effect of different surgical methods on survival rates. Result: Among the 10319 UTUC patients. Kaplan-Meier plots showed that NSS was associated with a higher overall survival (OS) and cancer-specific survival (CSS) in grade Ⅲ and Ⅳ and AJCC stage Ⅳ patients (all p <0.05). In multivariable Cox regression analyses, NSS was prone to a higher OS or CSS in grade Ⅲ ( p > 0.05). Moreover, NSS predisposed to a higher OS only in AJCC stage Ⅳ ( p <0.05). Conclusion: The beneficial effect of NSS was evident in grade Ⅲ or AJCC stage Ⅳ. NSS can be considered in grade Ⅲ or stage Ⅳ, for other grades or stages remains to be seen, both of which will be verified by further prospective research.


Author(s):  
Zeming Liu ◽  
Di Hu ◽  
Jinpeng Li ◽  
Qing Xia ◽  
Yan Gong ◽  
...  

BackgroundCoronavirus disease 2019 (COVID-19) has evolved into a pandemic. We hypothesized that biochemical indicators of liver function may help determine the prognosis of COVID-19 patients.MethodsPatient information was collected from the Wuhan-Leishenshan hospital. Logistic and Cox regression analyses, Kaplan-Meier curves, and Curve fitting were used to determine the correlation between elevated levels of aspartate transaminase (AST), alanine transaminase (ALT), and AST/ALT and severity of disease/mortality.ResultsLogistic and Cox regression analyses and Kaplan-Meier survival curves showed that COVID-19 progression correlated with elevated levels of AST and AST/ALT. The odds ratios for elevated levels of AST and AST/ALT in patients were 0.818 (95% confidence interval [CI]: 0.274-2.441, P = 0.035) and 2.055 (95% CI: 1.269-3.327, P = 0.003), respectively; the hazard ratios were 4.195 (95% CI: 1.219-14.422, P = 0.023) and 3.348 (95% CI: 1.57-7.139, P = 0.002), respectively. The Kaplan-Meier survival curves demonstrated that patients with elevated AST and AST/ALT levels had a higher risk of developing severe COVID-19.ConclusionElevated AST and AST/ALT levels correlated with severity of COVID-19 and mortality. Liver function tests may help clinicians in determining the prognosis of patients undergoing treatment for COVID-19.


2021 ◽  
Author(s):  
Bence Beres ◽  
Maria Yusenko ◽  
Lehel Peterfi ◽  
Gyula Kovacs ◽  
Daniel Banyai

Abstract Purpose Approximately 15% of clinically localised conventional renal cell carcinomas (cRCC) develop metastases within 5 years of follow-up. Sarcomatous cRCC is a highly malignant cancer of the kidney. The aim of our study was to identify biomarkers for estimating the postoperative progression of cRCCs. Methods Global microarray-based gene expression analysis of RCCs with and without sarcomatous changes revealed that a high MMP12 expression was associated with a sarcomatous histology. Additionally, we analysed MMP12 expression using a multi-tissue array comprising 736 cRCC patients without metastasis at the time of surgery. The median follow-up time was 66 ± 29 months. Results Immunohistochemistry revealed MMP12 expression in 187 of 736 cRCCs with good follow-up data. Subsequent Kaplan–Meier analysis revealed that patients with MMP12 positive tumours exhibited a significantly shorter tumour-free survival (p < 0.001). In multivariate Cox regression analysis a weak to strong MMP12 expression indicated a 2.4–2.8 times higher risk of postoperative tumour relapse (p < 0.001; p < 0.003, respectively). Conclusions MMP12 may serve as a biomarker to estimate postoperative cRCC relapse and as a possible target for penfluridol therapy.


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