Neurological event prediction for patients with symptomatic cerebral cavernous malformation: the BLED2 score

2021 ◽  
pp. 1-8

OBJECTIVE Retrospective patient cohort studies have identified risk factors associated with recurrent focal neurological events in patients with symptomatic cerebral cavernous malformations (CCMs). Using a prospectively maintained database of patients with CCMs, this study identified key risk factors for recurrent neurological events in patients with symptomatic CCM. A simple scoring system and risk stratification calculator was then created to predict future neurological events in patients with symptomatic CCMs. METHODS This was a dual-center, prospectively acquired, retrospectively analyzed cohort study. Adult patients who presented with symptomatic CCMs causing focal neurological deficits or seizures were uniformly treated and clinically followed from the time of diagnosis onward. Baseline variables included age, sex, history of intracerebral hemorrhage, lesion multiplicity, location, eloquence, size, number of past neurological events, and duration since last event. Stepwise multivariable Cox regression was used to derive independent predictors of recurrent neurological events, and predictive accuracy was assessed. A scoring system based on the relative magnitude of each risk factor was devised, and Kaplan-Meier curve analysis was used to compare event-free survival among patients with different score values. Subsequently, 1-, 2-, and 5-year neurological event rates were calculated for every score value on the basis of the final model. RESULTS In total, 126 (47%) of 270 patients met the inclusion criteria. During the mean (interquartile range) follow-up of 54.4 (12–66) months, 55 patients (44%) experienced recurrent neurological events. Multivariable analysis yielded 4 risk factors: bleeding at presentation (HR 1.92, p = 0.048), large size ≥ 12 mm (HR 2.06, p = 0.016), eloquent location (HR 3.01, p = 0.013), and duration ≤ 1 year since last event (HR 9.28, p = 0.002). The model achieved an optimism-corrected c-statistic of 0.7209. All factors were assigned 1 point, except duration from last event which was assigned 2 points. The acronym BLED2 summarizes the scoring system. The 1-, 2-, and 5-year risks of a recurrent neurological event ranged from 0.6%, 1.2%, and 2.3%, respectively, for patients with a BLED2 score of 0, to 48%, 74%, and 93%, respectively, for patients with a BLED2 score of 5. CONCLUSIONS The BLED2 risk score predicts prospective neurological events in symptomatic CCM patients.

2017 ◽  
Vol 25 (1) ◽  
pp. 81-88 ◽  
Author(s):  
Damianos G. Kokkinidis ◽  
Prio Hossain ◽  
Omar Jawaid ◽  
Bejan Alvandi ◽  
T. Raymond Foley ◽  
...  

Purpose: To examine whether laser atherectomy combined with drug-coated balloons (laser + DCB) can improve the outcomes of femoropopliteal (FP) in-stent restenosis (ISR). Methods: A dual-center retrospective study was conducted of 112 consecutive patients (mean age 70.3±10.6 years; 86 men) with Tosaka class II (n=29; diffuse stenosis) or III (n=83; occlusion) FP-ISR lesions. Sixty-two patients (mean age 68.5±10 years; 51 men) underwent laser + DCB while the other 50 patients (mean age 72.5±10.8 years; 35 men) had laser atherectomy plus balloon angioplasty (laser + BA). Critical limb ischemia was the indication in 33% of the interventions. The average lesion length was 247 mm. A Cox regression hazard model was developed to examine the association between laser + DCB vs laser + BA; the results are presented as the hazard ratio (HR) and 95% confidence interval (CI). One-year target lesion revascularization (TLR) and reocclusion were estimated using the Kaplan-Meier method. Results: Overall procedure success was 98% and was similar between groups. Bailout stenting was less often required in the laser + DCB group (31.7% vs 58%, p=0.006). The combination of laser + DCB was associated with improved 12-month estimates for freedom from TLR (72.5% vs 50.5%, p=0.043) and freedom from reocclusion (86.7% vs 56.9%, p=0.003). Among patients with Tosaka III FP-ISR, combination therapy with laser + DCB was also associated with increased freedom from reocclusion (87.1% vs 57.1%, p=0. 028). On multivariable analysis, treatment with laser + DCB was associated with a significantly reduced risk of reocclusion (HR 0.08, 95% CI 0.17 to 0.38; p=0.002). Conclusion: When used for treatment of complex FP-ISR lesions, DCB angioplasty combined with laser atherectomy is associated with significantly reduced 1-year TLR and reocclusion rates.


2019 ◽  
Vol 8 (6) ◽  
pp. 661-671 ◽  
Author(s):  
Shuang Ye ◽  
Yuanyuan Xu ◽  
Jiehao Li ◽  
Shuhui Zheng ◽  
Peng Sun ◽  
...  

The role of G protein-coupled estrogen receptor 1 (GPER) signaling, including promotion of Ezrin phosphorylation (which could be activated by estrogen), has not yet been clearly identified in triple-negative breast cancer (TNBC). This study aimed to evaluate the prognostic value of GPER and Ezrin in TNBC patients. Clinicopathologic features including age, menopausal status, tumor size, nuclear grade, lymph node metastasis, AJCC TNM stage, and ER, PR and HER-2 expression were evaluated from 249 TNBC cases. Immunohistochemical staining of GPER and Ezrin was performed on TNBC pathological sections. Kaplan–Meier analyses, as well as logistic regressive and Cox regression model tests were applied to evaluate the prognostic significance between different subgroups. Compared to the GPER-low group, the GPER-high group exhibited higher TNM staging (P = 0.021), more death (P < 0.001), relapse (P < 0.001) and distant events (P < 0.001). Kaplan–Meier analysis showed that GPER-high patients had a decreased OS (P < 0.001), PFS (P < 0.001), LRFS (P < 0.001) and DDFS (P < 0.001) than GPER-low patients. However, these differences in prognosis were not statistically significant in post-menopausal patients (OS, P = 0.8617; PFS, P = 0.1905; LRFS, P = 0.4378; DDFS, P = 0.2538). There was a significant positive correlation between GPER and Ezrin expression level (R = 0.508, P < 0.001) and the effect of Ezrin on survival prognosis corresponded with GPER. Moreover, a multivariable analysis confirmed that GPER and Ezrin level were both significantly associated with poor DDFS (HR: 0.346, 95% CI 0.182–0.658, P = 0.001; HR: 0.320, 95% CI 0.162–0.631, P = 0.001). Thus, overexpression of GPER and Ezrin may contribute to aggressive behavior and indicate unfavorable prognosis in TNBC; this may correspond to an individual’s estrogen levels.


2017 ◽  
Vol 398 (7) ◽  
pp. 765-773 ◽  
Author(s):  
Shuo Zhao ◽  
Julia Dorn ◽  
Rudolf Napieralski ◽  
Axel Walch ◽  
Sandra Diersch ◽  
...  

Abstract In serous ovarian cancer, the clinical relevance of tumor cell-expressed plasmin(ogen) (PLG) has not yet been evaluated. Due to its proteolytic activity, plasmin supports tumorigenesis, however, angiostatin(-like) fragments, derived from PLG, can also function as potent anti-tumorigenic factors. In the present study, we assessed PLG protein expression in 103 cases of advanced high-grade serous ovarian cancer (FIGO III/IV) by immunohistochemistry (IHC). In 70/103 cases, positive staining of tumor cells was observed. In univariate Cox regression analysis, PLG staining was positively associated with prolonged overall survival (OS) [hazard ratio (HR)=0.59, p=0.026] of the patients. In multivariable analysis, PLG, together with residual tumor mass, remained a statistically significant independent prognostic marker (HR=0.49, p=0.009). In another small patient cohort (n=29), we assessed mRNA expression levels of PLG by quantitative PCR. Here, elevated PLG mRNA levels were also significantly associated with prolonged OS of patients (Kaplan-Meier analysis; p=0.001). This finding was validated by in silico analysis of a microarray data set (n=398) from The Cancer Genome Atlas (Kaplan-Meier analysis; p=0.031). In summary, these data indicate that elevated PLG expression represents a favorable prognostic biomarker in advanced (FIGO III/IV) high-grade serous ovarian cancer.


Neurology ◽  
2018 ◽  
Vol 90 (10) ◽  
pp. e856-e863 ◽  
Author(s):  
Sepide Kashefiolasl ◽  
Markus Bruder ◽  
Nina Brawanski ◽  
Eva Herrmann ◽  
Volker Seifert ◽  
...  

ObjectiveDespite the low annual risk of hemorrhage associated with a cavernous malformation (CM) (0.6%–1.1% per year), the risk of rehemorrhage rate and severity of neurologic deficits is significantly higher; therefore, we aimed to evaluate the rupture risk of CMs depending on various factors.MethodsWe retrospectively analyzed medical records of all patients with CM admitted to our institution between 1999 and April 2016. Cavernoma volume, location of the lesion, existence of a developmental venous anomaly (DVA), number of cavernomas, and patient characteristics (sex, age, hypertension, and antithrombotic therapy) were assessed.ResultsOne hundred fifty-four patients with CM were included; 89 (58%) ruptured CMs were identified. In statistical univariable analysis, the existence of a DVA was significantly higher in the ruptured cavernoma group (p < 0.001; odds ratio [OR] 4.6). A multivariable analysis of all included independent risk factors designated young age (<45 years) (p < 0.05; OR 2.2), infratentorial location (p < 0.01; OR 2.9), and existence of a DVA (p < 0.0001; OR 4.7) with significantly higher risk of rupture in our patient cohort. A separate analysis of these anatomical locations, supratentorial vs infratentorial, indicated that the existence of a DVA (p < 0.01; OR 4.16) in ruptured supratentorial cases and CM volume (≥1 cm3) (p < 0.0001; OR 3.5) in ruptured infratentorial cases were significant independent predictors for hemorrhage.ConclusionsYoung age (<45 years), infratentorial location, and the presence of a DVA are associated with a higher hemorrhage risk. CM volume (≥1 cm3) and the existence of a DVA were independently in accordance with the anatomical location high risk factors for CM rupture.


2020 ◽  
Author(s):  
Tianwei Wang ◽  
Yunyan Wang

Abstract Objectives: In this study, we want to combine GATA3, VEGF, EGFR and Ki67 with clinical information to develop and validate a prognostic nomogram for bladder cancer.Methods: A total of 188 patients with clinical information and immunohistochemistry were enrolled in this study, from 1996 to 2018. Univariable and multivariable cox regression analysis was applied to identify risk factors for nomogram of overall survival (OS). The calibration of the nomogram was performed and the Area Under Curve (AUC) was calculated to assess the performance of the nomogram. Internal validation was performed with the validation cohort., the calibration curve and the AUC were calculated simultaneously.Results: Univariable and multivariable analysis showed that age (HR: 2.229; 95% CI: 1.162-4.274; P=0.016), histology (HR: 0.320; 95% CI: 0.136-0.751; P=0.009), GATA3 (HR: 0.348; 95% CI: 0.171-0.709; P=0.004), VEGF (HR: 2.295; 95% CI: 1.225-4.301; P=0.010) and grade (HR: 4.938; 95% CI: 1.339-18.207; P=0.016) remained as independent risk factors for OS. The age, histology, grade, GATA3 and VEGF were included to build the nomogram. The accuracy of the risk model was further verified with the C-index. The C-index were 0.65 (95% CI, 0.58-0.72) and 0.58 (95% CI, 0.46-0.70) in the training and validation cohort respectively. Conclusions: A combination of clinical variables with immunohistochemical results based nomogram would predict the overall survival of patients with bladder cancer.


2019 ◽  
Vol 74 (9) ◽  
pp. 2774-2783 ◽  
Author(s):  
Eun-Jeong Yoon ◽  
Dokyun Kim ◽  
Hyukmin Lee ◽  
Hye Sun Lee ◽  
Jeong Hwan Shin ◽  
...  

Abstract Background To assess the mortality dynamics of patients with Pseudomonas aeruginosa bloodstream infections (BSIs) and the influence of OprD deficiencies of the microorganism on early mortality. Methods A prospective multicentre observational study was conducted with 120 patients with P. aeruginosa BSIs occurring between May 2016 and April 2017 in six general hospitals in South Korea. PCR and sequencing were carried out to identify the alterations in oprD and the presence of virulence factors. Cox regression was used to estimate the risk factors for mortality at each timepoint and Kaplan–Meier survival analyses were performed to determine the mortality dynamics. Results During the 6 week follow-up, 10.8% (13/120) of the patients with P. aeruginosa BSIs died in 2 weeks, 14.2% (17/120) in 4 weeks and 20.0% (24/120) in 6 weeks, revealing a steep decrease in cumulative survival between the fourth and sixth weeks. ICU admission and SOFA score were risk factors for mortality in any weeks after BSI onset and causative OprD-defective P. aeruginosa had a risk tendency for mortality within 6 weeks. Among the 120 P. aeruginosa blood isolates, 14 were XDR, nine produced either IMP-6 or VIM-2 MBL, and 21 had OprD deficiency. Conclusions BSIs caused by OprD-defective P. aeruginosa resulted in a 2-fold higher 6 week mortality rate (33.3%) than that of BSIs caused by OprD-intact P. aeruginosa (17.2%), likely due to the decreased susceptibility to carbapenems and bacterial persistence in clinical settings.


eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Wenna Guo ◽  
Liucun Zhu ◽  
Rui Zhu ◽  
Qihan Chen ◽  
Qiang Wang ◽  
...  

Cutaneous melanoma (CM) is a life-threatening form of skin cancer. Prognostic biomarkers can reliably stratify patients at initial melanoma diagnosis according to risk, and may inform clinical decisions. Here, we performed a retrospective, cohort-based study analyzing genome-wide DNA methylation of 461 patients with CM from the TCGA database. Cox regression analyses were conducted to establish a four-DNA methylation signature that was significantly associated with the overall survival (OS) of patients with CM, and that was validated in an independent cohort. Corresponding Kaplan–Meier analysis displayed a distinct separation in OS. The ROC analysis confirmed that the predictive signature performed well. Notably, this signature exhibited much higher predictive accuracy in comparison with known biomarkers. This signature was significantly correlated with immune checkpoint blockade (ICB) immunotherapy-related signatures, and may have potential as a guide for measures of responsiveness to ICB immunotherapy.


2020 ◽  
Author(s):  
Jesper Ryg ◽  
Henriette Engberg ◽  
Pavithra Laxsen Anru ◽  
Solvejg Gram Henneberg Pedersen ◽  
Martin Gronbech Jorgensen ◽  
...  

Abstract Background Predicting expected survival time in acutely hospitalised older patients is a clinical challenge. Objective To examine if activities of daily living (ADL) assessed by Barthel-Index-100 (Barthel-Index) at hospital admission adds useful information to clinicians on expected survival time in older patients. Methods A nationwide population-based cohort study was used. All patients aged ≥65 years in the National Danish Geriatric Database from 2005 to 2014 were followed up until death, emigration or study termination (31 December 2015). Individual data were linked to national health registers. Barthel-Index was categorised into five-point subcategories with a separate category of Barthel-Index = 0. Kaplan–Meier analysis was used to assess crude survival proportions (95% CI) and Cox regression to examine association of Barthel-Index and mortality adjusting for age, Charlson comorbidity index, medication use, BMI, marital status, prior hospitalisations and admission year. Results In total, 74,589 patients (63% women) aged (mean (SD)) 82.5(7.5) years with Barthel-Index (median (IQR)) 54(29-77) were included. In patients with Barthel-Index = 100-96 crude survival was 0.96(0.95-0.97) after 90-days, 0.88(0.87-0.89) after 1-year, and 0.79(0.78-0.80) after 2-years. Corresponding survival in patients with Barthel-Index = 0 was 0.49(0.47-0.51), 0.35(0.34-0.37) and 0.26(0.24-0.27). Decreasing Barthel-Index was associated with increasing mortality in the multivariable analysis. In women with Barthel-Index = 0, the mortality risk (HR (95% CI)) was 14.74(11.33-19.18) after 90-days, 8.40(7.13-9.90) after 1-year and 6.22(5.47-7.07) after 2-years using Barthel-Index = 100-96 as reference. In men, the corresponding risks were 11.36(8.81-14.66), 6.22(5.29-7.31) and 5.22(4.56-5.98). Conclusions ADL measured by Barthel-Index provides useful, easily accessible and independent information to clinicians on expected survival time in patients admitted to a geriatric department.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
G Benetos ◽  
M Goncalves ◽  
E Von Felten ◽  
G Rampidis ◽  
O Clerc ◽  
...  

Abstract Background Coronary computed tomography angiography (CCTA) provides incremental prognostic information over traditional risk factors in patients with suspected coronary artery disease. However, little is known about the long-term predictive performance of CCTA-derived coronary volumes and mid-diastolic left ventricular (LV) mass. Purpose To assess long-term prognostic value of coronary volumes and mid-diastolic LV mass as novel potential imaging predictors derived from low-dose prospectively ECG-triggered CCTA. Methods Consecutive patients with suspected or known coronary artery disease, referred for low-dose CCTA, were included. Patients with previous revascularization were excluded. The following parameters were evaluated: calcium score, segment involvement score (SIS: 1 point for each coronary segment with presence of plaque), coronary volume, mid-diastolic LV mass and coronary volume indexed to LV mass. Major adverse cardiovascular events (MACE) were defined as all-cause death, non-fatal myocardial infarction and revascularization (PCI or CABG). The association between CCTA measures and the occurrence of events was quantified using cox regression hazard and Kaplan Meier analysis. Results A total of 147 consecutive patients were included in the study. Of them, 93 (63.3%) were male and 79 (53.7%) hat one or more traditional cardiovascular risk factors. There was a weak but statistical significant inverse correlation between indexed coronary volume and both calcium score (R=-0.3, p=0.01) and SIS (R=-0.24, p=0.005). After a median follow-up of 5.8 years 30 MACE occurred in 25 patients, including 3 deaths, 26 revascularizations and 1 non-fatal myocardial infarction. In univariate cox regression hazard analysis calcium score (HR=12.69, 95% CI 2.99–53.83, p<0.001), SIS (HR=1.66, 95% CI 1.43–1.94, p<0.001), LV mass (HR=1.02, 95% CI 1.01–1.03, p=0.007) and indexed coronary volume (HR=0.89, 95% 0.82–0.96, p=0.004) were associated with outcome. In multivariate analysis, indexed coronary volume, remained an independent predictor for MACE when adjusted for traditional risk factors and SIS (HR=0.93, 95% CI 0.87–1.00, p=0.05), while LV mass did not reach statistical significance (p=0.46). By ROC curve analysis, a value of 21.85 mm3/gr was defined as optimal cutoff for indexed coronary volume. In Kaplan Meier plots, patients with low indexed coronary volume (<21.85 mm3/gr) showed higher event rates (log rank p<0.001) compared to high indexed coronary volume (≥21.85 mm3/gr). Conclusions Indexed coronary volume, derived from low-dose CCTA, independently predicts cardiovascular events. Larger studies are mandated to confirm the predictive value of this potential new biomarker.


2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Sirui Ma ◽  
Soumon Rudra ◽  
Jian L Campian ◽  
Sonika Dahiya ◽  
Gavin P Dunn ◽  
...  

Abstract Background We aimed to evaluate the clinical outcomes of molecular glioblastoma (mGBM) as compared to histological GBM (hGBM) and to determine the prognostic impact of TERT mutation, EGFR amplification, and CDKN2A/B deletion on isocitrate dehydrogenase (IDH)-wildtype GBM. Methods IDH-wildtype GBM patients treated with radiation therapy (RT) between 2012 and 2019 were retrospectively analyzed. mGBM was defined as grade II-III IDH-wildtype astrocytoma without histological features of GBM but with one of the following molecular alterations: TERT mutation, EGFR amplification, or combination of whole chromosome 7 gain and whole chromosome 10 loss. Overall survival (OS) and progression-free survival (PFS) were calculated from RT and analyzed using the Kaplan–Meier method. Multivariable analysis (MVA) was performed using Cox regression to identify independent predictors of OS and PFS. Results Of the 367 eligible patients, the median follow-up was 11.7 months. mGBM and hGBM did not have significantly different OS (median: 16.6 vs 13.5 months, respectively, P = .16), nor PFS (median: 11.7 vs 7.3 months, respectively, P = .08). However, mGBM was associated with better OS (hazard ratio [HR] 0.50, 95% CI 0.29–0.88) and PFS (HR 0.43, 95% CI 0.26–0.72) than hGBM after adjusting for known prognostic factors on MVA. CDKN2A/B deletion was associated with worse OS (HR 1.57, 95% CI 1.003–2.46) and PFS (HR 1.57, 95% CI 1.04–2.36) on MVA, but TERT mutation and EGFR amplification were not. Conclusion Criteria for mGBM may require further refinement and validation. CDKN2A/B deletion, but not TERT mutation or EGFR amplification, may be an independent prognostic biomarker for IDH-wildtype GBM patients.


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