Leveraging Graph Models to Design Acute Kidney Injury Disease Research Data Warehouse

Author(s):  
Ahmad Baghal
2018 ◽  
Vol 2018 ◽  
pp. 1-16 ◽  
Author(s):  
Anubhav Chakraborty ◽  
Pragasam Viswanathan

Over the years, the epigenetic landscape has grown increasingly complex. Until recently, methylation of DNA and histones was considered one of the most important epigenetic modifications. However, with the discovery of enzymes involved in the demethylation process, several exciting prospects have emerged that focus on the dynamic regulation of methylation and its crucial role in development and disease. An interplay of the methylation-demethylation machinery controls the process of gene expression. Since acute kidney injury (AKI), a major risk factor for chronic kidney disease and death, is characterised by aberrant expression of genes, understanding the dynamics of methylation and demethylation will provide new insights into the intricacies of the disease. Research on epigenetics in AKI has only made its mark in the recent years but has provided compelling evidence that implicates the involvement of methylation and demethylation changes in its pathophysiology. In this review, we explore the role of methylation and demethylation machinery in cellular epigenetic control and further discuss the contribution of methylomic changes and histone modifications to the pathophysiology of AKI.


Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3782-3782
Author(s):  
Nan Xinyu ◽  
Srivastava Pallavi ◽  
Mamta Puppala ◽  
Sai Ravi Pingali ◽  
Ibrahim Ibrahim ◽  
...  

Abstract Background: Hyperleukocytosis is complication of leukemia and is defined as peripheral white blood cell (WBC) count greater than 100, 000/mm^3. The high WBC count can increase blood viscosity and lead to leukostatsis, which is a medical emergency most commonly seen in acute leukemias. The use of Leukapheresis, is controversial and there are few guidelines. We performed a retrospective review of outcomes in patients with hyperleukocytosis who received leukapheresis in Houston Methodist Hospital between 2006 and 2015. Methods: The patient data was queried from METEOR (Methodist Environment for Translational Enhancement and Outcomes Research), a clinical data warehouse and analytics environment that integrates existing business data warehouse with internal and external research databases and national registries to support clinical research and outcome studies for improving patient care cost-effectively. METEOR data warehouse contains records dating back to January 1, 2006 with over 1 million unique patients and over 4 million unique patient encounters. We queried for the diagnosis of leukemia and those that received at least one course of leukapheresis and also obtained baseline demographics, and overall outcomes. Results: We reviewed 5585 of whom 42 patients who meet the criteria-patients, 29 of them have diagnosis of AML, 6 with CLL, 4 with ALL, and 3 with CML. The baseline demographics included 29 males and 13 females, whose median age was 52.5; 19 were Caucasians while 10 were African Americans, 5 Hispanic, 5 Asian and 3 reportedly as others. As shown in Table 1, the population is divided into 3 groups according to WBC before leukapheresis. Group 1 has 7 patients with WBC <100,000, median of 80.460. Group 2 has 17 patients with WBC range from 100,000 to 200,000, median of 150,740. Group 3 has 18 patients with WBC above 200,000, median of 252,200. In group 1, the average leukostatsis symptom grade is 1.43, average % decrease of WBC is 34.54%, ( blast-84%). In group 2, the average leukostatsis symptom grade is 1.88, average % decrease of WBC is 48.25%, ( blast- 69%). In group 3, the average leukostatsis symptom grade is 1.06, average % decrease of WBC is 42.81%, (blast-59.5%). In terms of complications, in group 1, 42.86% presented with acute kidney injury (AKI), 28.57% with tumor lysis syndrome, 28.57% with disseminated intravascular coagulation (DIC), 28.57% with sepsis, 14.29% with pneumonia, 42.86% with respiratory failure, 14.29% and with acute coronary syndrome (ACS). In group 2, 17.65% presented with AKI, 47.06% with TLS, 47.06 % with DIC, 23.53% with sepsis, 11.76% with pneumonia, 41.18% with respiratory failure, and 5.88% with acute coronary syndrome. In group 3 11.10 % presented with acute kidney injury, 44.44% with TLS, 38.89 % with DIC, 22.22% with sepsis, 11.11% with pneumonia, 27.78 % with respiratory failure, and 5.56 % with ACS. The 4 weeks mortality rate are 42.86% for group 1, 29.41% for group 2, and 22.22% for group 3. Conclusions: We have validated the Hyperleukocytosis grading schema and usefulness of leukapheresis. Our data indicates comparable mortality in pts with WBC between 100 -200,000 and > 200,000. Further statistical review of this data set will be presented at the ASH Meeting, Orlando 2015 Table 1. Group 1 Group 2 Group 3 WBC range <100,000 100,000 to 200,000 >200,000 Number of patients 7 17 18 Average leukostasis symptom grade 1.43 1.88 1.06 % Lymphoid leukemia 14.29% 17.65% 33.33% Median WBC before leukapheresis 80,460 150,740 252,200 Average % decrease of WBC 34.54% 48.25% 42.81% Median % of blast before leukapheresis 84% 69% 59.5% Average % change in %blast 5.35% 11.23% -6.55% Average Creatinine after Leukapheresis 2.39 1.47 1.38 Average uric acid after leukapheresis 8.77 6.52 6.75 Average Fibrinogen after leukapheresis 424.25 336.78 300.56 % Acute kidney injury 42.86% 17.65% 11.10% % Tumor lysis syndrome 28.57% 47.06% 44.44% % DIC 28.57% 47.06% 38.89% % Sepsis 28.57% 23.53% 22.22% % Pneumonia 14.29% 11.76% 11.11% % Respiratory failure 42.86% 41.18% 27.78% % Acute Coronary Syndrome 14.29% 5.88% 5.56% % 4 weeks Mortality 42.86% 29.41% 22.22% References: 1. Novotny JR, Müller-Beissenhirtz H, Herget-Rosenthal S, Kribben A, Dührsen U. Grading of symptoms in hyperleukocytic leukaemia: a clinical model for the role of different blast types and promyelocytes in the development of leukostatsis syndrome. Eur J Haematol 2005:74:501-510 Disclosures No relevant conflicts of interest to declare.


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