scholarly journals Endothelial Activation and Stress Index (EASIX) as an Early Predictor for Mortality and Overall Survival in Hematological and Non-Hematological Patients with COVID-19: Multicenter Cohort Study

2021 ◽  
Vol 10 (19) ◽  
pp. 4373
Author(s):  
Elżbieta Kalicińska ◽  
Monika Biernat ◽  
Justyna Rybka ◽  
Aleksander Zińczuk ◽  
Justyna Janocha-Litwin ◽  
...  
Keyword(s):  
Overall Survival ◽  
Hematological Malignancies ◽  
Strong Predictor ◽  
Endothelial Activation ◽  
Stress Index ◽  
Multicenter Cohort Study ◽  
Hematological Cancer ◽  
Hematological Patients ◽  
Multiple Organs ◽  
First Time

COVID-19, as a disease involving the endothelium of multiple organs, is characterized by high mortality rates among hospitalized patients. Patients with hematological malignancies are particularly at risk of an unfavorable course of COVID-19. The endothelial activation and stress index (EASIX) score has been used as a simple predictor of overall survival (OS) in specific groups of hematological cancer patients. EASIX, as a biomarker of endothelial dysfunction, might play a prognostic role in patients with COVID-19. Here, we performed a comprehensive retrospective analysis of the EASIX score in 523 hospitalized COVID-19 patients with or without coexisting hematological cancer. Hematological cancer COVID-19 patients had higher EASIX scores compared to the overall population with COVID-19. In hematological patients, EASIX was a strong predictor of the occurrence of sepsis during COVID-19. Our findings demonstrated EASIX as a strong predictor of intensive care unit admission, in-hospital mortality, the occurrence of acute renal failure and the need for hemodialysis, both in hematological and non-hematological COVID-19 patients. Patients with a high EASIX score on COVID-19 diagnosis had significantly inferior OS compared to patients with low EASIX. We showed for the first time that EASIX might serve as a simple, universal prognostic tool of OS in both hematological and non-hematological COVID-19 patients.

scholarly journals Endothelial activation and stress index (EASIX) is a reliable predictor for overall survival in patients with multiple myeloma

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Ga-Young Song ◽  
Sung-Hoon Jung ◽  
Kihyun Kim ◽  
Seok Jin Kim ◽  
Sang Eun Yoon ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Endothelial Activation ◽  
Stress Index ◽  
Reliable Predictor

scholarly journals EASIX for Prediction of Outcome in Hospitalized SARS-CoV-2 Infected Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Thomas Luft ◽  
Clemens-Martin Wendtner ◽  
Florentina Kosely ◽  
Aleksandar Radujkovic ◽  
Axel Benner ◽  
...  
Keyword(s):  
Hospital Admission ◽  
Health Care Systems ◽  
Strong Predictor ◽  
Multivariable Analysis ◽  
Endothelial Activation ◽  
Fold Change ◽  
Public Health Care ◽  
Stress Index ◽  
Soluble Thrombomodulin ◽  
Care Systems

BackgroundThe coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and has evoked a pandemic that challenges public health-care systems worldwide. Endothelial cell dysfunction plays a key role in pathophysiology, and simple prognosticators may help to optimize allocation of limited resources. Endothelial activation and stress index (EASIX) is a validated predictor of endothelial complications and outcome after allogeneic stem cell transplantation. Aim of this study was to test if EASIX could predict life-threatening complications in patients with COVID-19.MethodsSARS-CoV-2-positive, hospitalized patients were enrolled onto a prospective non-interventional register study (n=100). Biomarkers were assessed at hospital admission. Primary endpoint was severe course of disease (mechanical ventilation and/or death, V/D). Results were validated in 126 patients treated in two independent institutions.ResultsEASIX at admission was a strong predictor of severe course of the disease (odds ratio for a two-fold change 3.4, 95%CI 1.8-6.3, p<0.001), time to V/D (hazard ratio (HR) for a two-fold change 2.0, 95%CI 1.5-2.6, p<0.001) as well as survival (HR for a two-fold change 1.7, 95%CI 1.2-2.5, p=0.006). The effect was retained in multivariable analysis adjusting for age, gender, and comorbidities and could be validated in the independent cohort. At hospital admission EASIX correlated with increased suppressor of tumorigenicity-2, soluble thrombomodulin, angiopoietin-2, CXCL8, CXCL9 and interleukin-18, but not interferon-alpha.ConclusionEASIX is a validated predictor of COVID19 outcome and an easy-to-access tool to segregate patients in need for intensive surveillance.

scholarly journals Early Administration of Convalescent Plasma Improves Survival in Patients with Hematological Malignancies and COVID-19

Viruses ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 436
Author(s):  
Monika Maria Biernat ◽  
Anna Kolasińska ◽  
Jacek Kwiatkowski ◽  
Donata Urbaniak-Kujda ◽  
Paweł Biernat ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Hematological Malignancies ◽  
Treated Group ◽  
Viral Clearance ◽  
Early Administration ◽  
Improved Outcomes ◽  
Historical Group ◽  
High Risk Populations ◽  
Diagnosis Of Infection

The use of convalescent plasma in the treatment of COVID-19 may lead to a milder course of infection and has been associated with improved outcomes. Determining optimal treatments in high risk populations is crucial, as is the case in those with hematological malignancies. We analyzed a cohort of 23 patients with hematological malignancies and COVID-19 who had received plasma 48–72 h after the diagnosis of infection and compared it with a historical group of 22 patients who received other therapy. Overall survival in those who received convalescent plasma was significantly higher than in the historical group (p = 0.03460). The plasma–treated group also showed a significantly milder course of infection (p = 0.03807), characterized by less severe symptoms and faster recovery (p = 0.00001). In conclusion, we have demonstrated that convalescent plasma is an effective treatment and its early administration leads to clinical improvement, increased viral clearance and longer overall survival in patients with hematological malignancies and COVID-19. To our knowledge, this is the first report to analyze the efficacy of convalescent plasma in a cohort of patients with hematological malignancies.

scholarly journals Early bilirubinemia after allogeneic stem cell transplantation—an endothelial complication

2021 ◽  
Author(s):  
Hao Dai ◽  
Olaf Penack ◽  
Aleksandar Radujkovic ◽  
David Schult ◽  
Joshua Majer-Lauterbach ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Serum Levels ◽  
Endothelial Activation ◽  
Stress Index ◽  
Clinical Correlations ◽  
Angiopoietin 2 ◽  
The Impact

AbstractHyperbilirubinemia occurs frequently after allogeneic stem cell transplantation. Causes include primary liver damage and endothelial complications as major contributors. Here, we have investigated the impact of early bilirubinemia (EB) on posttransplant outcomes. Maximum total bilirubin levels (days 0–28) were categorized using maximally selected log rank statistics to identify a cut off for the endpoint non-relapse mortality (NRM) in a training cohort of 873 patients. EB above this cut off was correlated with NRM and overall survival (OS) and with pre- and posttransplant Angiopoietin-2, interleukin (IL)18, CXCL8 and suppressor of tumorigenicity-2 (ST2) serum levels, and the endothelial activation and stress index (EASIX). Clinical correlations were validated in a sample of 388 patients transplanted in an independent institution. The EB cut off was determined at 3.6 mg/dL (61.6 µM). EB predicted OS (HR 1.60, 95% CI 1.21–2.12, p < 0.001), and NRM (CSHR 2.14; 1.28–3.56, p = 0.004), also independent of typical endothelial complications such as veno-occlusive disease, refractory acute graft-versus-host disease, or transplant-associated microangiopathy. However, EB correlated with high Angiopoietin-2, EASIX-pre and EASIX-day 0, as well as increased levels of posttransplant CXCL8, IL18, and ST2. In summary, EB indicates a poor prognosis. The association of EB with endothelial biomarkers suggests an endothelial pathomechanism also for this posttransplant complication.

scholarly journals PATH-13. PLEOMORPHIC XANTHOASTROCYTOMA INTEGRATED GENOMIC CHARACTERIZATION - WHAT HAVE WE LEARNED?

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii426-iii427
Author(s):  
Rachael Vaubel ◽  
Valentina Zschernack ◽  
Alissa Caron ◽  
Dragana Milosevic ◽  
Robert Jenkins ◽  
...  
Keyword(s):  
Overall Survival ◽  
Strong Predictor ◽  
Progression Free Survival ◽  
Genetic Alterations ◽  
Pleomorphic Xanthoastrocytoma ◽  
Who Grade ◽  
Targeted Next Generation Sequencing ◽  
Genomic Characterization ◽  
Promoter Mutations ◽  
Methylation Profiling

Abstract Pleomorphic xanthoastrocytoma (PXA) is a rare astrocytoma occurring predominantly in children and young adults. It is characterized histologically by large pleomorphic, spindled and lipidized cells with frequent eosinophilic granular bodies and pericellular reticulin deposition. BRAF p.V600E mutation and CKDN2A/B deletion are the most common genetic alterations. We report the integrated genomic characterization of a cohort of 67 patients (37 F, 30 M; median age 20.3 years (interquartile 13.4–32.9) with histologically defined PXA (52, 78%) or anaplastic PXA (A-PXA) (15, 22%), using genome-wide cytogenetic (ThermoFisher Oncoscan, n=67), methylation profiling (Illumina EPIC array, n=43), and targeted next generation sequencing (n=32). BRAF p.V600E mutation (n=51, 76.1%) and CDKN2A/B deletion (n=63; 94%) were the most frequent alterations. Of 16 BRAF p.V600E negative cases, 7 showed an alternative BRAF activating mutation (n=2), NF1 (n=3) mutation or ATG7-RAF1 fusion (n=2). Targeted TERT analysis found promoter mutations in 3 (of 58) cases, but TERT amplification was absent. Supervised and unsupervised methylation profiling against a comprehensive reference cohort demonstrated consensus grouping with the PXA class in 36 of 43 cases; while the minority grouped with a ganglioglioma class (n=3), with reactive brain or had no resolvable subgroup (n=4). Follow-up was available in 61 patients (91.0%) (median 63 months). Overall survival was significantly different between PXA and A-PXA (5-year:80.4% vs. 55.1%; p=0.001), but not progression-free survival (5-year:61.7% vs. 39.8%; p=0.128). Our data confirm the high frequency of MAP-K abnormalities and CDKN2A/B deletion in PXA. WHO grade remains a strong predictor of patient overall survival.

scholarly journals Serum CEACAM1 Elevation Correlates with Melanoma Progression and Failure to Respond to Adoptive Cell Transfer Immunotherapy

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
R. Ortenberg ◽  
S. Sapoznik ◽  
D. Zippel ◽  
R. Shapira-Frommer ◽  
O. Itzhaki ◽  
...  
Keyword(s):  
Strong Predictor ◽  
Xenograft Model ◽  
Tumor Burden ◽  
Adoptive Cell Transfer ◽  
Screening Tools ◽  
Response To Treatment ◽  
Tumor Biomarker ◽  
Melanoma Patients ◽  
First Time

Malignant melanoma is a devastating disease whose incidences are continuously rising. The recently approved antimelanoma therapies carry new hope for metastatic patients for the first time in decades. However, the clinical management of melanoma is severely hampered by the absence of effective screening tools. The expression of the CEACAM1 adhesion molecule on melanoma cells is a strong predictor of poor prognosis. Interestingly, a melanoma-secreted form of CEACAM1 (sCEACAM1) has recently emerged as a potential tumor biomarker. Here we add novel evidences supporting the prognostic role of serum CEACAM1 by using a mice xenograft model of human melanoma and showing a correlation between serum CEACAM1 and tumor burden. Moreover, we demonstrate that serum CEACAM1 is elevated over time in progressive melanoma patients who fail to respond to immunotherapy as opposed to responders and stable disease patients, thus proving a correlation between sCEACAM1, response to treatment, and clinical deterioration.

scholarly journals Age-Adjusted Endothelial Activation and Stress Index for Coronavirus Disease 2019 at Admission Is a Reliable Predictor for 28-Day Mortality in Hospitalized Patients With Coronavirus Disease 2019

2021 ◽  
Vol 8 ◽  
Author(s):  
Felipe Pérez-García ◽  
Rebeca Bailén ◽  
Juan Torres-Macho ◽  
Amanda Fernández-Rodríguez ◽  
Maria Ángeles Jiménez-Sousa ◽  
...  
Keyword(s):  
Positive Predictive Value ◽  
Receiver Operating Characteristic ◽  
Negative Predictive Value ◽  
Predictive Value ◽  
Operating Characteristic ◽  
Predictive Performance ◽  
Endothelial Activation ◽  
Stress Index ◽  
Reliable Predictor ◽  
Receiver Operating

Background: Endothelial Activation and Stress Index (EASIX) predict death in patients undergoing allogeneic hematopoietic stem cell transplantation who develop endothelial complications. Because coronavirus disease 2019 (COVID-19) patients also have coagulopathy and endotheliitis, we aimed to assess whether EASIX predicts death within 28 days in hospitalized COVID-19 patients.Methods: We performed a retrospective study on COVID-19 patients from two different cohorts [derivation (n = 1,200 patients) and validation (n = 1,830 patients)]. The endpoint was death within 28 days. The main factors were EASIX [(lactate dehydrogenase * creatinine)/thrombocytes] and aEASIX-COVID (EASIX * age), which were log2-transformed for analysis.Results: Log2-EASIX and log2-aEASIX-COVID were independently associated with an increased risk of death in both cohorts (p &lt; 0.001). Log2-aEASIX-COVID showed a good predictive performance for 28-day mortality both in the derivation cohort (area under the receiver-operating characteristic = 0.827) and in the validation cohort (area under the receiver-operating characteristic = 0.820), with better predictive performance than log2-EASIX (p &lt; 0.001). For log2 aEASIX-COVID, patients with low/moderate risk (&lt;6) had a 28-day mortality probability of 5.3% [95% confidence interval (95% CI) = 4–6.5%], high (6–7) of 17.2% (95% CI = 14.7–19.6%), and very high (&gt;7) of 47.6% (95% CI = 44.2–50.9%). The cutoff of log2 aEASIX-COVID = 6 showed a positive predictive value of 31.7% and negative predictive value of 94.7%, and log2 aEASIX-COVID = 7 showed a positive predictive value of 47.6% and negative predictive value of 89.8%.Conclusion: Both EASIX and aEASIX-COVID were associated with death within 28 days in hospitalized COVID-19 patients. However, aEASIX-COVID had significantly better predictive performance than EASIX, particularly for discarding death. Thus, aEASIX-COVID could be a reliable predictor of death that could help to manage COVID-19 patients.

scholarly journals CRP and ferritin in addition to the EASIX score predict CAR-T–related toxicity

2021 ◽  
Vol 5 (14) ◽  
pp. 2799-2806
Author(s):  
Uri Greenbaum ◽  
Paolo Strati ◽  
Rima M. Saliba ◽  
Janet Torres ◽  
Gabriela Rondon ◽  
...  
Keyword(s):  
Cumulative Incidence ◽  
B Cell Lymphoma ◽  
Risk Groups ◽  
Endothelial Activation ◽  
Stress Index ◽  
Cell Transplant ◽  
T Cell Therapy ◽  
Hematopoietic Stem ◽  
Laboratory Parameters ◽  
Car T

Abstract The Endothelial Activation and Stress Index (EASIX) score, defined as [(creatinine × lactate dehydrogenase [LDH])/platelets], is a marker of endothelial activation that has been validated in the allogeneic hematopoietic stem cell transplant setting. Endothelial activation is one of the mechanisms driving immune-mediated toxicities in patients treated with chimeric antigen receptor-T (CAR-T)-cell therapy. This study’s objective was to evaluate the association between EASIX and other laboratory parameters collected before lymphodepletion and the subsequent onset of cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS) those patients. Toxicity data were collected prospectively on 171 patients treated with axicabtagene ciloleucel (axi-cel) for large B-cell lymphoma (LBCL). CRS grades 2 to 4 were diagnosed in 81 (47%) patients and ICANS grades 2 to 4 in 84 (49%). EASIX combined with ferritin (EASIX-F) identified 3 risk groups with CRS grades 2 to 4 cumulative incidence of 74% (hazards ratio [HR], 4.8; 95% confidence interval [CI], 2.1-11; P &lt; .001), 49% (HR, 2.3; 95% CI, 1.02-5; P = .04), and 23% (reference), respectively. EASIX combined with CRP and ferritin (EASIX-FC) identified 3 risk groups with an ICANS grade 2 to 4 cumulative incidence of 74% (HR, 3.6; 95% CI, 1.9-6.9; P &lt; .001), 51% (HR, 2.1; 95% CI, 1.1-3.9; P = .025), and 29% (reference). Our results indicate that common laboratory parameters before lymphodepletion correlate with CAR-T–related toxicities and can help support clinical decisions, such as preemptive toxicity management, hospitalization length, and proper setting for CAR-T administration.

scholarly journals Nomogram to predict overall survival for patients with pseudomyxoma peritonei of appendiceal origin: A retrospective cohort study

2020 ◽  
Author(s):  
Mingjian Bai ◽  
Shilong Wang ◽  
Ruiqing Ma ◽  
Ying Cai ◽  
Yiyan Lu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Pseudomyxoma Peritonei ◽  
Roc Analysis ◽  
Prediction Models ◽  
Radical Surgery ◽  
Individual Risk ◽  
Good Discrimination ◽  
Internal Validation ◽  
Discrimination Ability ◽  
First Time

Abstract Background Pseudomyxoma peritonei (PMP) is a rare disease, the prognosis of overall survival (OS) is affected by many factors, present study aim to define independent prediction indicators and establish a nomogram for PMP patients.Methods 119 PMP patients received cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in our center for the first time were included between 01/06/2013 and 22/11/2019 . The log-rank test was used to compare the OS rate among groups, subsequently, variables with P<0.10 were subjected to multivariate Cox model for defining independent prediction indicators. Finally, the nomogram prediction models will be established and for internal validation.Results Multivariate analysis showed Sex, D-Dimer, CA125, CA19-9, PCI, and degree of radical surgery were independently associated with OS in PMP patients. A nomogram was plotted based on the independent predictive factors and undergone internal validation, ROC analysis was performed to calculate discrimination ability of the nomogram, the C-index was 0.880 (95%CI: 0.806- 0.933) and calibration plots showed good performance. Conclusions Six independent prognostic factor for predicting survival in PMP patients were difined, the nomogram has a good discrimination ability for individual risk predition, more researches are needed to verify and improve the prediction model.

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