bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Optimal Cut-Off Level for Hemoglobin A2 to Differentiate between Sickle Cell Disease Genotypes
Authors: Al Shueili Fayiz , Al-Khabori Murtadha K. , Al-Kindi Salam , Wali Yasser , Al-Zadjali Shoaib 
Published: October 2019

Abstract
Objectives: Hemoglobin A2 (HbA2) is elevated in the presence of beta thalassemia trait and it is used as an indicator of its presence. High-Performance Liquid Chromatography (HPLC) overestimates HbA2 in patients with Sickle Cell Disease (SCD) due to the co-elution of HbS in HbA2 column. The optimal cut-off level of HbA2 to indicate the presence of beta thalassemia trait has not been well established in patients with SCD. We aim to define the optimal cut-off level of HbA2 to differentiate between SS and S/Beta SCD genotype variants.
Methods: In this cross-sectional study, we included 241 patients with SCD who have either SS or S/Beta genotype based on their HPLC and the Sickledex test®. The diagnoses were confirmed by the direct sequencing of PCR amplified products of all exons, exon-intron junctions and promoter region of the beta globin gene. We retrieved the following clinical and laboratory variables from the electronic health records: age, gender, Hemoglobin (Hb), Mean Corpuscular Volume (MCV), Red Blood Cell (RBC) count and HbA2. We used the receiver operating curve (ROC) analysis to obtain the optimal cut-off level of HbA2 using the maximum sensitivity and specificity (Youden criteria). All descriptive and analytical statistics were performed using R program. The ROC analysis was performed with the "OptimalCutpoints" package available in R program.
Results: Among the 241 patients included in the analysis, SS and S/Bthal patients were 81% and 19% respectively. Male to female ratio was 126:115. Fifty-two percent were using hydroxyurea. The median HbA2 level was 4.5% (Range: 0.0-6.5) in the SS group and 6.5% (Range: 3.5-8.2) in the S/Bthal group. The median Hb, MCV and RBC count was 9.4 g/dL (Range: 5.3 - 15.0), 75 fL (55 - 111) and 3.8 *1012/L (1.9 - 6.3) respectively for the SS group; while it was 9.7 g/dL (6.6 - 12.3), 68 fL (57 - 86) and 4.2 *1012/L (2.5 - 5.4) respectively for the S/Bthal group. The optimal cut-off level for HbA2 was estimated to be 5.7% using a sensitivity of 91% and a specificity of 92%. The positive and negative predictive values were 75% and 98% respectively. The discrimination estimated using the Area Under the Curve (AUC) was 0.936 (95% Confidence Interval: 0.878-0.994).
Conclusions: The optimal cut-off HbA2 level to differentiate SCD with the S/Bthal genotype from the SS genotype is 5.7% with a high sensitivity, specificity and discrimination. The unexpected overlap in the MCV and the RBC count is likely related to the high rate of Alpha thalassemia trait in the analyzed population. Incorporation of the presence of alpha thalassemia trait in the analysis may improve the discrimination of MCV and RBC count.

Disclosures
No relevant conflicts of interest to declare.
Proteomics Analysis Reveals Protein Panels That Are Associated with Prediction to Tyrosine Kinase Inhibitors Response, Bone Marrow Transplant, Survival and Disease Outcome of Chronic Myeloid Leukemia Patients
Authors: Alaiya Ayodele , Aljurf Mahmoud , Shinwari Zakia , Alsharif Fahad Z. , Alzahrani Hazza A. , Ahmed Syed Osman , Owaidah Tarek , Hanbali Amr Suleiman , Shaheen Marwan , Al Fraih Feras , Elfakih Riad , Alhayli Saud , Hashmi Shahrukh , Rasheed Walid , Almhareb Fahed , Chaudhri Naeem A. 
Published: October 2019

Abstract
Clinical and molecular diagnosis of most hematological malignancies including Chronic Myeloid Leukemia (CML) can be accurately made. However, prediction of treatment response and estimation of disease survival period eludes the currently available tools for patient care. Quantitative expression proteomics can potentially be developed as effective tool to monitor therapy response towards achieving personalized medicine for CML patients.
We have over 10 years follow up period for some of the CML patients, and the majorities of them are alive and doing well on Imatinib. On the other hand, a small fraction of the patients were switched to alternative Tyrosine Kinase Inhibitors (TKI) and some underwent bone marrow transplants (BMT).
Our follow up results stratified all 37 analyzed newly diagnosed CP-CML patients into 5 distinct cohorts including 52% on Imatinib, 12% on Nilotinib, 9% on Dasatinib, and 15% BMT, while 12% of the patients had disease-related mortality. Kaplan-Meier survival curve showed no significant difference between all patients on TKI and BMT that were alive under a follow up period of 4-11 years compared. On the other hand 3 of 4 patients had disease related deaths less than 2 years of diagnosis. Only one patient survived for almost 10 years (Figure 1). Besides survival analysis, peripheral blood samples obtained from the patients at time of diagnosis were subjected to expression proteome analysis using label-free quantitative liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). A subset of significantly differentially expressed proteins was able to distinctively discriminate samples into their respective treatment response and disease outcome groups based on unique protein expression signatures (P<0.05 and > 2- ∞- fold change, (Figure 2). Some of the identified proteins were implicated in hematological diseases including CML as potential biomarkers using Ingenuity Pathway Analysis.
These protein signatures once validated in larger sample cohorts might be capable of prediction of molecular response, choice of therapy and disease outcome for CML patients. Therefore; allowing for identification of would be high risk patients that might potentially benefit from aggressive treatment at point of diagnosis pre initiation of conventional therapy. Altogether our findings indicate that analysis of panel of protein markers have the potential of clinical utility for prediction of response to therapy, disease survival and objective prognostication of disease outcome, thus bringing personalized medicine closer to CML patients.

Disclosures
No relevant conflicts of interest to declare.
Assisted Administration of Subcutaneous Rituximab to the Patient's Home. Significant Reduction of Indirect Costs Incurred By Care Recipients and Unpaid Caregivers Together with a Total Adherence to the Treatment Schedule and Same Safety
Authors: Iuliano Francesco , Iuliano Eleonora , Rossi Marco 
Published: October 2019

Abstract

Dec 2018, 7 consecutive patients, ( CLL n = 1; FL n = 3; DLBCL n= 1 AEA n=1,ITP n=1), were enrolled in the study. Median age of the patients was 68 years (range, 28-87). The pharmacoeconomic analysis included assessment of direct costs ( hospital inpatient, physician inpatient, physician outpatient, emergency department nursing home care, specialists' and other health professionals' care, diagnostic tests, prescription drugs and drug sundries, and medical supplies),indirect costs incurred by care recipients and unpaid caregivers, including time, productivity and travel cost.
Results Rituximab subcutaneous formulation was administered at a fixed dose of 1400 mg with a frequency related to the type and the phase of the treated disease. Before starting MabThera subcutaneous injections, all patients received beforehand, a full dose of Rituximab by intravenous infusion. Premedication with an anti-pyretic an antihistaminic and prednisone , was given orally in the evening before and the morning of the subcutaneous administration the infusion was carried out by the staff of the home care unit together with a doctor. All the procedure was controlled by the hospital specialist through a smart-phone. Median age of the patients was 58 years (range, 32-83). Median number of courses delivered to each patient was 6 (range, 4- 12) .Adherence to treatment was 100%.No Infusion related adverse reactions have been observed.
Conclusion
In our experience, despite the high percentage of elderly patients of whom 36% living in rural area, it was possible to give treatment to all patients with high adherence and satisfaction. There has been a reduction in direct medical costs due to less use of hospitalization, a reduction of indirect costs by 70% due to the lower number of working days lost and a drastic reduction of travel costs, with the same safety of administration.

Disclosures
No relevant conflicts of interest to declare.
Therapeutic Disassembly of Leukemogenic Enhancer Complexes
Authors: Forbes Lauren , Isaac Krasnopolsky , Minuesa Dinares Gerard , Kharas Michael G. , Kentsis Alex 
Published: October 2019

Abstract
Despite a detailed understanding of the genetic mechanisms of acute myeloid leukemia (AML), treatments remain deeply inadequate. Aberrant activity of hematopoietic transcription factors and their co-activators has been implicated in the expression of leukemogenic genes, providing a compelling therapeutic target. Hematopoietic transcription factor MYB and its co-activator CREB-binding protein/P300 (CBP/P300) are required for the initiation and maintenance of a variety of acute leukemias. Using protein engineering methods, we have developed cell-penetrant peptidomimetic inhibitors that interfere with this interaction by targeting the KIX domain of CBP/P300. A second-generation inhibitor based on the chimeric interaction of MYB and CREB, termed CRYBMIM, binds CPB/P300 KIX with 10-fold higher affinity and exhibits logarithmic cell killing of most leukemia subtypes, while sparing healthy human hematopoietic progenitor cells (Figure 1). Comparative gene expression, chromatin mapping, and protein-protein interaction mapping elucidate the molecular mechanisms by which CRYBMIM dismantles oncogenic enhanceosomes, leading to the downregulation of leukemogenic gene expression in leukemia but not normal cells. Finally, we have developed a peptide-protein conjugation strategy for in vivo delivery of peptidomimetics by polyvalent reversible conjugation to transferrin (TF). We found that TF-peptide conjugates are readily taken up by AML cells and accumulate in AML nuclei, supporting their translation into new therapeutic strategies for patients. Taken together, this work advances an effective therapeutic strategy for therapeutic disruption of leukemogenic enhancer complexes, and defines mechanisms of aberrant gene expression control in AML.

Disclosures
No relevant conflicts of interest to declare.
Efficacy of Maintenance Therapy after Autologous Hematopoietic Stem Cell Transplantation in High-Risk Aggressive Lymphoma: A Single-Center Prospective Non-Randomized Study
Authors: Chen Yongquan , Zheng Zhihong , Luo Xiaofeng , Ren Jinhua , Geng Haili , Issa Hajji Ally , Chen Zhizhe , Hu Jianda , Yang Ting 
Published: October 2019

Abstract
OBJECTIVE: Relapse after autologous hematopoietic stem cell transplantation (ASCT) is still challenging for high-risk aggressive lymphoma. This study was to investigate the efficacy and safety of maintenance therapy post-ASCT.
METHODS: From June 2009 to March 2018, patients with high-risk aggressive lymphoma in our hospital were treated with maintenance therapy post-ASCT according to the patient's wishes, and then assigned to maintenance group or observation group. The end point of follow-up was disease progression or death. The 3-year overall survival (OS) and disease-free survival (DFS) were compared between these two groups.
RESULTS: A total of 79 patients were enrolled, with a median age of 38 years (8-64 years), 50 males and 29 females. IPI score ≥2 points in 28 cases, stage III-IV in 58 cases, B symptoms in 21 cases, Extranodal lesions ≥ 2 in 17 cases, bone marrow infiltration in 15 cases, and 24 cases with partial remission (PR) prior to ASCT. In addition to 2 cases of early death, the remaining 77 patients with lymphoma were underwent successfully transplantation and achieved CR post-ASCT. 54 patients were assigned to the observation group, and 23 patients to the maintenance group, including 17 with rituximab and 6 with DPP/DCEP-G alternation regimen. There were no s ignificant differences in gender, age, pre-transplant disease status, and hematopoietic reconstitution between the two groups. The main causes of death were disease recurrence. No serious adverse reactions occurred during the maintenance treatment period. After a median follow-up of 616 days (12-2854 days), the relapse rates of the observation group and the maintenance group were 49.1% vs 12.9%, and the DFS of the 1st, 2nd, and 3rd years were 62.8% VS 93.8%, 48.1% VS 87.1%, and 45.3% VS 87.1% (P = 0.007), respectively. The OS of the 1st, 2nd, and 3rd years were 89.3% VS 100%, 83.2% VS 92.9%, and 76.2% VS 92.9% (P=0.212), respectively.
Conclusion: Maintenance therapy post-ASCT could reduce the risk of relapse and promote disease-free survival, which deserves further investigation.

Disclosures
No relevant conflicts of interest to declare.
Contribution of Flow Cytometry Immunophenotyping in Diagnostic of Acute and Chronic Leukemias
Authors: Paiva Aldair Sousa , Paiva Hugo Diogenes De Oliveira , Cavalcanti Geraldo Barroso , Silveira Lenilton Silva , Silva Lorena KF , Gil Erica Aires , Vasconcelos Roberto C , Bahia Frank , Freitas Rodrigo Villar , Silva Dany GKC , Sales Valéria SF , Jardim Alessandra Suelen , Soares Victor lima , Marciel James Farley 
Published: October 2019

Abstract
BACKGROUND: Today immunophenotyping by flow cytometry is an useful adjunct to cytomorphologyc analysis to correct diagnostic of leukemias. It provides objective and quantitative data allowing for a high level of sensitivity detection and better characterization of acute and chronic leukemias. The purpose of this study was to demonstrate the contribution of the immunophenotyping by monoclonal antibodies (Mo.Ab.) in leukemic cells from patients with acute and chronic leukemias. METHODS: Analyzed 76 patients with leukemias before the treatment. The diagnostic of leukemias was based on the morphological and immunophenotyping analysis of leukemic cells from peripheral blood and bone morrow. The cytomorphologycal analysis was based on French - American - Britsh criteria (FAB classification) in blood and bone marrow films stain by leishmann and the immunophenotyping by flow cytometry with a panel of Mo.Ab. specific to acute leukemias as: CD1a, CD2, CD3, CD4, CD5, CD8, CD7, CD10, CD13, CD19, CD20, CD103, CD22, CD33, CD34, CD117, CD38, HLADR, TdT, anti-mieloperoxidase, anti-IgM and anti-kappa and lambda light chain. Further clinical and laboratory information as age, sex, presence of tumoral mass, lymphadenopathy, hepatosplenomegaly, hemoglobin determination, total and specific white cell count and cytomorphological analysis of blood film and bone morrow smear. RESULTS: Thirty four patients presented acute myeloid leukemia (AML), twenty acute lymphoblastic leukemia (ALL), nineteen B-cell chronic lymphocytic leukemia (B-CLL), two T-cell chronic lymphocytic leukemia and one case was hairy cell leukemia (HCL). Males were more frequently found in all types of leukemias. ALL were more observed in children (age < 15 years old) and in AML however were more frequently in adults patients. The chronic leukemias were presented in patients with 50 years old or more in all cases. The correlation between the immunophenotyping and clinical pathological profile of these leukemias demonstrated that ALL were more associated to lymphadenopathy, AML to hepatosplenomegaly, and CLL to lymphadenopathy and high count of white cells in peripheral blood. The thrombocytopenia and anemia were found in more cases of acute leukemia. CONCLUSION: This date suggest that today the immunophenotyping by flow cytometry is an important methodology to diagnostic and classification of leukemias.

Disclosures
No relevant conflicts of interest to declare.
Direct Oral Anticoagulant Vs Vitamin K Antagonist As Anticoagulant Therapy in Patients with Inherited and Acquired Thrombophilia
Authors: Olivera Pável E , Campoy Desirée , Velasquez César A , Flores Katia , Ene Gabriela S , Canals Tania , Artaza Gonzalo , Subira Maricel , Vila Sofía , Sierra Jorge , Salinas Ramón 
Published: October 2019

Abstract
BACKGROUND
The patients with venous thromboembolism (VTE) and thrombophilia have historically been treated with vitamin K antagonist (VKA) therapy. Nowadays, direct oral anticoagulants (DOAC) are broadly used in the treatment and prevention of VTE. However, the use of DOAC in the treatment of inherited and acquired thrombophilia remains unclear.
AIMS
To assess the safety and effectiveness in both cohorts according to DOAC or VKA treatment in a cohort of patients with VTE and thrombophilia.
METHODS
We included adult patients with VTE and thrombophilia treated with DOAC or VKA (2016-2018) from the beginning of treatment. Patients in the VKA group received acenocoumarol. Demographic, laboratory, thrombophilia diagnosis data and clinical presentation of VTE were collected. All patients with history of at least one VTE episode were included. The diagnosis of VTE was established by a positive finding of duplex sonography. Pulmonary embolism was diagnosed based on positive results of high resolution computed tomography. Inherited trombophilia included homozygous and heterozygous Factor V Leiden and prothrombin G20210A, natural anticoagulant deficiencies (protein C, protein S, or antithrombin) or combined defects. Patients with antiphospholipid syndrome (APS) were considered to have acquired thrombophilia. Bleeding events were classified according to ISTH criteria.
RESULTS
Among 181 patients, 96 (45.5%) were treated with DOAC (6 Dabigatran, 45 Rivaroxaban, 12 Apixaban and 33 Edoxaban) and 85 were treated with VKA. Among patients receiving VKA, the time in therapeutic range was 58.5%. Mean Follow - Up (FU) were 8.1 and 6.8 months (DOAC vs VKA, p:0.77). Demographic characteristics, thrombophilia subtypes and clinical features of VTE are summarised in table 1. The most frequent previous anticoagulant treatment was low molecular weight heparin (DOAC 71.6% vs VKA 98%, p:0.15). During FU, 9 recurrent VTE episodes were reported: 2 (2.1%) vs 5 (5.9%) [DOAC vs VKA, p: 0.57] and 5 (5.2%) vs 17 (20%) major and clinically relevant non-major bleeding events [DOAC vs VKA, p: 0.001] occurred. There were 2 arterial thromboembolic events in the VKA group (APS and antithrombin deficiency patient's in the periprocedural setting).
CONCLUSIONS
In our study, the effectiveness of DOAC treatment for VTE in patients with thrombophilia had a similar profile to VKA and caused significantly less major and clinically relevant non-major bleeding. This suggests that DOAC could be a good treatment option in this clinical setting. However, additional evaluation of DOAC use in patients with thrombophilia is necessary in order to provide more evidence.

Disclosures
No relevant conflicts of interest to declare.
Bimonthly Medical Visits Reduce Sickle Cell Admissions
Authors: Imahiyerobo Allison A , Billings Daniel D , Mora Erika , Eisenberger Andrew , Diuguid David L. 
Published: October 2019

Abstract
Background: Sickle cell disease (SCD) is a chronic medical disease that in some patients is characterized by frequent vasoocculsive crisis (VOC). A minority of sickle cell patients comprises a majority of hospital VOC admissions, and the transition to adult care is a particularly high risk time period. We sought to identify if increased frequency of outpatient medical care led to a reduction of hospital days following intervention and if there were improvements in daily function, and reduction of premature requests for opiate refills.
Methods: Retrospective review of 11 patients, average age of 25 (range 19-37 years old), 63% were female. Genotype of SCD included 8/11 with SS, 2/11 with SC and 1/11 with SBeta Thal. Sickle cell standard of care medical visits were monthly at our institution. Two nurse practitioners and 2 hematologists at the medical center implemented the intervention of increased frequency of medical visits to bimonthly follow up for between 5 and 48 weeks, with a mean length of 12 weeks of increased frequency of medical visits.
Results: In the 6 months preceding intervention there were a total of 300 hospital days of admission for VOC (2 patients <10 hospital days, 6 patients with 10-20 hospital days, 3 patients with over 20 hospital days; range 27-111 days). During the intervention 7/11 patients had no hospitalizations, 2/11 were discharged from the emergency department and never admitted. Another patient had 7 days of admission over 34 weeks of bimonthly medical visits and 1 patient had increase to days 37 days over 22 weeks of bimonthly medical visits. The average length of follow up after the intervention was 25 weeks: 4/11 had reduction of hospital days, 2/11 had the same number of hospital days and 4/11 had more hospital days. Secondary benefits were 3/11 patients were able to restart and maintain employment, 2/11 were able to re-enroll in educational programs, and 3/11 had a reduction in premature requests for opiate refills.
Conclusions: Increased frequency of outpatient medical visits leads to reduced hospital admission time for some patients and subjective improvement in daily function as measured by the ability to work or go to school. Future research is needed address the small subset of young adults who had an increase in hospital admission.
Figure. Figure.

Disclosures
No relevant conflicts of interest to declare.
The Predictive Value of Thromboelastogram in the Evaluation of Patients with Suspected Acute Venous Thromboembolism
Authors: Abu Assab Tareq , Raveh-brawer David , Abramowitz Julia , Naamad Mira , Rowe Jacob M. , Ganzel Chezi 
Published: October 2019

Abstract
The diagnosis of venous thromboembolism (VTE) is being done by imaging studies but can be ruled out by clinical probability assessment together with a D-dimer blood test. Thromboelastogram (TEG) is usually used for the evaluation of bleeding tendency but can demonstrate also hypercoagulable states. Our hypothesis was that TEG may estimate the presence of VTE more accurately than D-dimer. This prospective study recruited patients that presented to the emergency room or to the vascular laboratory with signs/ symptoms that raise the suspicion of acute VTE. TEG parameters that were examined were: Reaction time(R), Clot time formation (K), Alpha angle (α), Maximal amplitude (MA), Clot viscoelasticity (G), Coagulation Index (CI) and Clot lysis at 30 minutes (LY30). The expected values for hypercoagulable state include: short R and K and high α, MA, G, LY30 and CI.
Between April and October 2016, a total of 109 patients were enrolled in the study with a median age of 55.7 (21-89) years. Their characteristics are summarized in table 1. Forty-eight percent of the patients had at least one risk factor for development of VTE. According to the Well's criteria, 54 (49.5%) patients had low probability, 46 (42.2%) - moderate and 9 (8.3%) - high probability for developing VTE. Eighteen patients were diagnosed with VTE; 12 with DVT, 7 with PE and one with both.
Analyzing the different TEG parameters, both as continuous (table 2) or categorical variables (according to their normal range), did not reveal a statistically significant difference between VTE positive and negative patients. Combining different TEG parameters or dividing the cohort according to: gender, clinical suspicion of VTE based on the Well's criteria or different levels of D-dimer did not change the results of the analysis.
In conclusion, the current study could not demonstrate a significant value of any TEG parameter as a predictor of VTE in a general population of patients who came to the emergency room or vascular laboratory with signs/ symptoms that raise the suspicion of VTE.

Disclosures
No relevant conflicts of interest to declare.