bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictors of Emergency Room (ER) Visits and Hospitalizations in Patients with Mantle Cell Lymphoma (MCL) Treated with Chemotherapy
Authors: Feinberg Bruce , Schenkel Brad , McBride Ali , Ellis Lorie , Bhor Menaka , Radtchenko Janna , Lal Lincy S 
Published: October 2019

Abstract
Background: Understanding the predictors of increased healthcare resource utilization is essential for better management of patients with MCL, especially as new agents enter the market. This study evaluated predictors for ER visits and hospitalizations in patients with newly diagnosed and relapsed MCL treated with chemotherapy.
Methods: Using claims data (MORE2 Registry®), patients treated with antineoplastics from August 2009-2013 for MCL were retrospectively identified by ICD-9 codes (200.4, 200.40 - 200.48). Patients with secondary malignancies, pregnancy, and age <18 were excluded. Univariate logistic regression analysis was conducted to determine covariates associated with ER visits and hospitalizations. Results for significant variables were reported as odds ratio/p-value. Odds ratio >1 indicates increase in chance of events.
Results: A total of 449 patients with MCL were identified. Median age at diagnosis was 71 years, 70% were male, 61% had Medicare primary insurance, 32% were treated in the relapsed setting, 50% had ER visits, and 53% had hospitalizations throughout their treatment history. Significant increases in ER visits and hospitalizations were associated with the following factors (OR/p-value): chemotherapy duration (ER: 1.001/.046, hospitalization: 1.001/.01), supportive care (ER: 2.249/.014, hospitalization: 2.56/.004), number of MCL related adverse events (ER: 10.571/<.000, hospitalization: 39.282/<.000), and treatment following relapse (ER: 1.771/.005, hospitalization: 2.012/.001). Significant variables associated with a decrease in ER visits were male gender (0.576/.008) and having commercial insurance (0.548/.009). Age was associated with ER increase (1.024/.024). Patients treated in the Northeast region of the US were more likely to be hospitalized (1.897/.005).
Conclusions: This retrospective study shows that older patients with MCL had a higher likelihood of ER visits, while male patients and patients with commercial insurance had a lower likelihood of ER visits. Regional differences impacted hospitalizations. Adverse events, supportive care, and duration of treatment were associated with increases in hospitalizations and ER visits. These data warrant consideration of age and comorbidity-adjusted treatment in MCL patients eligible for treatment with antineoplastics.

Disclosures
Feinberg: Janssen Scientific Affairs, LLC: Consultancy. Schenkel:Janssen Scientific Affairs, LLC: Employment. McBride:Janssen Scientific Affairs, LLC: Consultancy. Ellis:Janssen Scientific Affairs, LLC: Employment. Bhor:Janssen Scientific Affairs, LLC: Consultancy. Radtchenko:Janssen Scientific Affairs, LLC: Consultancy. Lal:Janssen Scientific Affairs, LLC: Consultancy.
The Prevalence of Anemia in Diabetic Patients with Normal Kidney Function
Authors: Mahjoub Ali R. , Patel Eshan , Ali Sami , Webb Kendal , Kalavar Madhumati 
Published: October 2019

Abstract
Background: Anemia, in patients with diabetes, is commonly associated with impaired renal function secondary to diabetic nephropathy. Many studies have analyzed this association of anemia in diabetic patients and have attributed anemia to reduced renal function. However, there has been no known systematic analysis done to evaluate for the prevalence and predictors of anemia in patients with diabetes in the absence of overt nephropathy.
Objective: This retrospective study is designed to measure the prevalence of anemia in diabetic patients with normal renal function of estimated glomerular filtration rate (EGFR) greater than 90 ml/min/1.73m2 and to analyze the presence of other independent risk factors.
Methods: We conducted a retrospective analysis of 200 medical charts of diabetic patients (age > 18) visiting the outpatient endocrine clinic in our institution between January 2015 and June 2015 to identify the prevalence of anemia with and without diabetic nephropathy and any other associated factors.
Results: The prevalence of anemia (defined by the World Health Organization is a Hemoglobin level of less than 13 mg/dl in men and less than 12 mg/dl in women) in our 200 diabetic patients was 22% (44 out of the 200). Out of the 44 anemic patients, 41% had anemia with normal renal function (18 out of 44), 4 men and 14 women aged between 38-80 years old. From the 18 patients with normal renal function, 5 had iron deficiency anemia and 1 had autoimmune disease, while the remaining 12 patients (27% of anemic patients) did not have any known cause of anemia such as renal insufficiency, infection, chronic inflammatory disease, vitamin B12 or folate deficiencies, hemolysis, or acute/chronic blood loss.
Conclusion: Many studies have highlighted an association between anemia and nephropathy in diabetic patients. This retrospective analysis suggests there is a high prevalence of anemia with unidentified etiology in diabetic population. The exact mechanism of such anemia is not fully understood. It is hypothesized to be likely secondary to direct glucose toxicity to erythrocyte precursors in the bone marrow or from oxidative stress to mature erythrocytes. However, further studies are needed to evaluate the underlying pathophysiology of anemia in this particular setting.

Disclosures
No relevant conflicts of interest to declare.
Congenital Dyserythropoietic Anemia Type 1: A New Variant Pathogenic CDAN1 Mutation
Authors: McDaniel Jenny , Cramer Stuart 
Published: October 2019

Abstract
Introduction:
Congenital dyserythropoietic anemia (CDA) is a rare autosomal recessive condition that results in dyserythropoiesis and iron overload. Bone marrow evaluation in these patients demonstrates distinctive abnormalities in red cell precursors including multinucleated erythroblasts and chromatin bridges. Dysmorphisms such as distal limb abnormalities, skin pigmentation defects, vertebral malformations, and short stature may also be present. Mutations in the CDAN1/codanin-1 gene underlie the majority of CDA type I cases. We describe a previously unreported pathogenic variant.
Case report:
The female fetus of a gravida 2 para 1 woman was noted to have hepatomegaly, cardiomegaly, and elevated middle cerebral artery velocity concerning for severe intrauterine anemia at approximately 20 weeks gestation. The parents had one previous pregnancy that resulted in a stillborn male infant with hydrops fetalis and club foot. Given concern for anemia with this pregnancy, percutaneous umbilical cord blood sampling was performed demonstrating a fetal hematocrit of 9%. This severe fetal anemia was initially thought to be secondary to ABO incompatibility as mother was O- with a positive antibody screen and infant was A+. The fetus required four intrauterine transfusions and was delivered at 34 weeks 6 days via cesarean section due to history of previous cesarean. Exam revealed a phenotypically normal female with APGARs of 9/9 and a birth weight of 2130 grams.
Following delivery the infant had serial blood counts performed over a 6-week period, which noted a steady decrease in her hematocrit to 16%. A transfusion was given, and a bone marrow evaluation revealed a cellular marrow with red cell hyperplasia and dyserythropoiesis. Next generation sequencing through PreventionGenetics was performed revealing a novel CDAN1 alteration.
Results:
The patient was found to be heterozygous for two mutations in trans in the CDAN1 gene: c.2072dupT and c.2093A>T.
Discussion:
We present a patient with severe fetal and infant transfusion dependent anemia who has two novel CDAN1 gene variants not previously described. The sequence variant c.2072dupT is predicted to result in a frameshift and premature protein termination and is expected to be pathogenic. The second variant c.2093A>T is predicted to result in an amino acid substitution (p.Glu698Val). Another amino acid substitution (p.Glu698Lys) was previously reported as pathogenic in an individual with congenital dyserythropoietic anemia. Based upon the clinical picture, morphologic characteristics, and genetic findings, we have concluded that this presentation is consistent with a diagnosis of CDA type I. Through the utilization of improved diagnostic techniques we continue to gain knowledge regarding the molecular underpinnings of CDA type I.

Disclosures
No relevant conflicts of interest to declare.
Serum 25- OH Vitamin D and Parathyroid Hormone Levels in Beta Thalassemia Patients
Authors: Türkkan Emine , Tas Burcu Tufan , Ocak Suheyla 
Published: October 2019

Abstract

Introduction: The survival of the patients with thalassemia has progressively improved with advances in therapy, however, increased survival allowed for several complications of disease. Metabolism of vitamin D affected in patients with thalassemia, due to accumulation of iron in the liver as the skin. The aim of this study is to compare vitamin D and parathyroid hormone (PTH) levels between patients with thalassemia and healthy control group.
Methods: In pediatric hematology clinic, 33 patients (23 male, 10 female) with beta thalassemia major and 33 age-sex matched healthy people as a control group were included. Serum 25- OH Vitamin D levels were defined as normal >30 ng/ml, insufficiency between 20-30 ng/ml and deficiency < 20 ng/ml and PTH levels as normal between 10-65 pg/ml, decreased <10 pg/ml, and increased >65 pg/ml.
Results: Mean age was 23.02+8.18 years old in patient group and 23+ 8.16 in control group. %33.3 of the patients had 25-OH vitamin D insufficiency and %30.3 of had 25-OH vitamin D deficiency. In different studies, the 25-OH vitamin D deficiency found between %12-90, and insufficiency between % 24.7-69.8 of the thalassemic patients. %81.8 of the patients had normal PTH levels, %18.2 decreased and none of the patients were found increased. In literature, there were confluent results about PTH levels in thalassemic patients, some of the studies showed hypoparathyroidism, and some of hyperparathyroidism or normal levels of PTH (Vogiatzi Br J Haematol 2009, Moulas Acta Paediatrica 1997, Merchant Indian J Pediatr 2011). In our study we couldn't show hyperparathyroidism in patient group. Also we found parathyroid hormone levels were significantly lower (p<0.001), while 25-OH vitamin D levels were significantly higher (p<0.05), in patients with thalassemia than in control group. This result was interestingly showed that, normal population in our country may be low levels of vitamin D. So we need more studies about PTH and vitamin D levels of healthy people, not only thalassemic patients in our country.

Disclosures
No relevant conflicts of interest to declare.
Hemoglobinopathy- The Old and New Eras in a South-Eastern Nigerian Tertiary Health Center
Authors: Nwabuko Ogbonna Collins , Okoh Dorathy Adaunwa , Nnoli Martin Anazodo 
Published: October 2019

Abstract
BACKGROUND : Hemoglobinopathy is the commonest genetic defect worldwide and sub-Saharan Africa bears the second largest burden of this disorder. The challenges confronting management of hemoglobinopathy in resource-limited settings in Africa are diagnosis, monitoring and prognostication. The old conventional hemoglobin protein electrophoresis test (HbPE) lacks the capacity to make definitive diagnosis of hemoglobin variants (genotype) of an individual, hence, so many diagnosis of hemoglobinopathy have been missed as a result of this defect. This necessitated the need for more reliable technique for screening, diagnosis, monitoring and evaluation of Hemoglobinopathy (High Performance Liquid Chromatography,(HPLC)).
AIMS : This study aimed to compare the old conventional HbPE and the new chromatographic methods (HPLC) of determining variant Hemoglobin in a south-eastern tertiary health institution in Nigeria.
METHODOLOGY : A one-year prospective study of Eight thousand four hundred and seventy eight (8,478) consecutive patients who presented at the Department of Hematology, Federal Medical Centre, Umuahia for HbPE from January to December 2013 (old era) and seventy (70) patients among them who used HPLC to determine their variant hemoglobin (new era). Biomedical data, electrophoretic and chromatographic patterns of their variant hemoglobin were obtained using the conventional alkaline cellulose acetate HbPE machine and the D-10TM HPLC [Bio-Rad Laboratories] respectively. Statistical analysis was done using SPSS.
RESULT: A total of 8,478 patients made up of 1,505(17.8%) males and 5,013(59.1%) females were seen within the study period. The study included both children ( ≥7months) and adult with majority of them (25%) between age of 20-30 years. Three hemoglobin variants were identified viz: [(AA(6447/76%),AS(1876/22.12%),SS(159/1.88%)] using alkaline cellulose acetate HbPE machine in the old era. In the new era, four Hb variants [AA,AS,SS(5.7%) and SD(1.3%)] were obtained using the HPLC. There was a linear increment in quantitative HbF [(AA(31/37),AS(13/20),SS(0/5) had HbF <1%,while AA(0/37),AS(0/20),SS(2/5) had HbF>10%,(Table 1)] and HbA2 [(AA(45/45),AS(8/20),SS(0/5) and AA(0/45),AS(3/20),SS(2/5) had HbA2<3.5% and >10% respectively,(Table 2)] as you move from AA, AS ,to SS Hb variants. The S-window for all HbSS (4/5) was >70% while that of AS and SD ranged between 40-70%.
CONCLUSION : A critical comparison of the old and new methods of diagnosis of hemoglobinopathy showed that the later (HPLC) was superior to the former (HbPE) in the early detection, diagnosis, quantification, monitoring and prognostication of Hemoglobinopathy. Therefore, HPLC is strongly recommended in the policy guidelines for Hemoglobinopathy screening in health institutions in developing countries such as Nigeria where the prevalence is high.
KEYWORDS : Diagnosis, Hemoglobin variants, HbPE, HPLC, Hemoglobinopathy.

Disclosures
No relevant conflicts of interest to declare.
Molecular Genetics Analysis of Von Williebrand Disease: Studies in Cohort Pakistani Patients
Authors: Ahmed Shariq , Naz Arshi , Yadegari Hamideh , Driesen Julia , Shamsi Tahir , Ahmed Nisar , Tariq Shahla , Amanat Samina Tufail , Razik fazal-E- , Nadeem Mohammad , Oldenburg Johannes 
Published: October 2019

Abstract
Introduction: Von Willebrand disease (VWD) type III is the second most common inherited bleeding disorder in Pakistan. It is caused by severe quantitative deficiency of plasma Von Willebrand factor (VWF). Absence of VWF increases the severity of disease and is caused by homozygous/ compound heterozygous mutations in Von Willebrand factor gene.
Objective: The aim of study is to characterize molecular genetics of Von Willebrand type III in Pakistani population.
Setting: NIBD & BMT Karachi, Chughtais lab, Children's Hospital Lahore, PAEC Islamabad and HMC Peshawar.
Material And Method: In this cohort study of Von Willebrand disease (VWD) type III, Blood samples of 48 unrelated patients of type III VWD were collected in National Institute Of Blood Disease & Bone Marrow Transplant (NIBD) Karachi, Chughtais lab, Children's Hospital Lahore, PAEC Islamabad and HMC Peshawar. Genomic DNA was extracted from peripheral blood by QIAamp DNA Blood mini kit (Qiagen) and Exon specific PCR was done for VWF gene and Direct gene sequenced on automated ABI-3130 Genetic Analyzer (Applied Biosystems). Sequence Variations in VWF were checked on ISTH-SSC VWD homepage (http://www.vwf.group.shef.ac.uk/), Ensemble genome browser (http://www.ensembl.org/), VWFdb hemobase and biobase biological database (http://www.hgmd.cf.ac.uk/ac/index.php). We have adopted the nomenclature for numbering amino acids of Human genome variation society (HGVS). Statistics analysis was done SPSSv17.
Results: Sequence analysis detected mutations in 46 (95.83%) out of 48 samples. VWD type III has led to identification of 28 cases (60.8%) homozygous and 18 (39.1%) were compound heterozygous. We have indentified total 31 Mutations distributed as 17 missense mutations (54%), 7 nonsense mutations (22%) 2 small deletions (6%) , 2 insertion mutations (6%) and 3 splice site mutations (9%).19 of these were newly mutations in this cohort study.. Further method multiplex ligation dependent probe amplification (MLPA) is needed for detection of large deletions in two patients. Nonsense c.3931C>T, p.Q1311*was founder mutation in Pakistani patients.
Conclusion: In cohort study, missense mutations are detected as common in among patients and most of the mutations identified in this cohort were homozygous due to Consanguinity in the family of the patients.

Disclosures
Oldenburg: SOBI: Consultancy.
Granulocyte Colony-Stimulating Factor Inhibits CXCR4/SDF-1 Signaling and Overcomes Stromal-Mediated Drug Resistance in Acute Myeloid Leukemia Via Mir-146a
Authors: Zhong Hua , Xu Lan , Li Xin , Sheng Xian-fu , Chen Fang-yuan , Hu Jiong 
Published: October 2019

Abstract
CAG regimen was widely used in the clinical treatment of acute myeloid leukemia (AML). However, the mechanisms of G-CSF in the CAG regimen remain unknown. For the purpose of better elucidating the function of G-CSF, we evidenced that G-CSF could enhance HL60 and primary leukemia cells proliferation in vitro. Meanwhile, transwell migration experiments demonstrated that G-CSF, similar as the CXCR4 antagonist AMD3100, could remarkably inhibit the chemotaxis of HL60 cells induced by the chemokines released from marrow stromal cells (Fig 1). qRT-PCR and Western blotting results showed that the expression of miR-146a was up-regulated after G-CSF treatment, while the expression levels of CXCR4 and smad4 were down-regulated (Fig 2). CXCR4 and Smad4 expression levels in miR-146a over expression lentivirus infected HL60 cells were significantly decreased, which manifested the direct or indirect targeted relationship between miR-146a and CXCR4/Smad4. Our qRT-PCR and Western blotting results also showed an involvement of NF-KB in G-CSF induced up-regulation of miR-146a in AML cells. G-CSF activated NF-KB in the cells. Activated NF-KB induced the up-regulation of miR-146a expression. Sanguinarine, an inhibitor of NF-KB significantly inhibited miR-146a expression. We further demonstrated the involvement of NF-KB in the regulation of G-CSF in CXCR4 and Smad4 expression (Fig 3). Our study demonstrated that G-CSF not only could induce resting leukemia cells into proliferation cell cycle, but also could inhibit chemotaxis of leukemia cells. We elucidated the mechanism of G-CSF/NF-KB/miR-146a/CXCR4 signaling pathway in CAG treatment of AML. The expression levels of MiR-146a /CXCR4 /Smad4 may be selected as the clinical markers for CAG protocol choosing.

Disclosures
No relevant conflicts of interest to declare.
Necroptosis of a Small Subset of Hematopoietic Progenitors Induces Autoimmune Bone Marrow Failure
Authors: Xin Junping , Allen Ni , Gutierrez Rafael , Chen Haiyan , Li Jing , Cannova Joseph , Ng Grace , Schmidt Rachel , Wei Wei , Breslin Peter , Kuo Paul C , Stiff Patrick J. , Zhang Jiwang 
Published: October 2019

Abstract
Acquired aplastic anemia (AAA) is an autoimmune-mediated bone marrow failure (BMF) syndrome. Cryptic clonal genetic lesions were commonly detected in a small subset of hematopoietic stem/progenitor cells (HSPCs) in most patients' BM samples. The mechanism by which the autoimmune reaction is initiated is unknown. Whether and how these cryptic clonal genetic lesions might cause autoimmune BMF have not yet been determined. We found that mice with spontaneous deletion of the TGFβ-activated kinase-1 (Tak1) gene in a small subset of HSPCs (1-3%) developed BMF which resembled the clinical manifestations of AAA patients. BMF in such mice could be reversed by depletion of CD4+ T lymphocytes or treatment with IFN-γ, suggesting a Th1 cell-mediated autoimmune mechanism. Interestingly, the disease onset and progression of BMF in such mice were significantly accelerated by inactivation of TNF-α signaling, indicating that TNF-α might restrict the progression of autoimmune BMF. Furthermore, we determined that the necroptosis of a small subset of hematopoietic cells is the cause of autoimmune BMF because such BMF can be completely prevented by deletion of Rip3, a key necroptotic mediator. Our study suggested that the necroptosis of a small subset of hematopoietic cells induces autoimmune BMF, and that elevated TNF-α restricts the progression of such autoimmune BMF. We believe that, in addition to inhibiting T-cell-mediated autoimmune reactions to induce disease remission, repression of the necroptosis of mutant HSPCs might be necessary to prevent disease relapse and progression of autoimmune BM failure.

Disclosures
Stiff: Gilead: Consultancy, Honoraria, Research Funding; Incyte: Consultancy, Honoraria, Research Funding; Amgen: Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Fate Therapeutics: Research Funding; Plasmacyclics: Consultancy, Honoraria, Research Funding; Eisai: Research Funding.
Utility of Telomere in Diagnosis of Bone Marrow Failure Syndromes
Authors: Abdel-ghaffar Hasan Ahmed , Zaghloul Hosam , El-Waseef Ahmed , El-Naggar Mohamed , Mabed Mohamed , Darwish Ahmad , Al-Dahshan Zainab 
Published: October 2019

Abstract
Background and aim of the work: Bone marrow failure syndromes (BMFS) includes inherited and acquired conditions. Inherited bone marrow failure includes a number of syndromes; with Fanconi anemia (FA) being the most common one of them. Telomeres are eroded with cell division, but in hematopoietic stem cell, maintenance of their length is mediated by telomerase. Short telomeres can result in instability of cell function where diseases occur. Bone Marrow Failure might be developed due to low telomerase activity or short telomeres. Our study is aiming to evaluate the utility of Real Time Quantitative-Polymerase Chain Reaction (RT-qPCR) in measuring the relative telomere length and its significance in diagnosis and prognosis of patients with BMFS.
Materials and methods: The study includes 3 groups: A group of congenital BMF (29 patients), a group of acquired BMF (10 patients) and a third control group (15 cases). The relative telomere length is evaluated for them using RT-qPCR.
Results: We have found that there is a significant difference in relative telomere length between congenital group and controls (p=0.001), also a significant difference between acquired group and controls (p= 0.029). However, there is no significant difference between congenital and acquired groups (p= 0.479). There is no significant correlation between the telomere length and the overall survival or prognosis of the patients of BMFS.
Conclusion: We conclude that the telomere length is significantly altered in patients with BMFS whether being congenital or acquired compared to the control group.

Disclosures
No relevant conflicts of interest to declare.