bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relationship Between Myelodysplastic Syndrome and Paroxysmal Nocturnal Hemoglobinuria: Spanish Erythropathology Group and Spanish Paroxysmal Nocturnal Hemoglobinuria Working Group Experience
Authors: Lopez Rubio Montserrat , Gaya Anna , Morado Marta , Carrasco Vicente , Gonzalez Fernandez Ataulfo , Villegas Ana 
Published: October 2019

Abstract

INTRODUCTION
PNH clones appear frequently in patients with myelodysplastic syndrome (MDS) and aplastic anemia (AA) which may even evolve into classic PNH. It has been described isolated cases of clonal evolution from AA, through classic PNH and MDS; and at the end, acute leukemia (AL) has rarely been described. These patients show a progressive replacement of the PNH clone by a dysplastic one carrying a monosomy of chromosome 7.
OBJECTIVE
We designed a retrospective study of patients included in the database of the Spanish PNH Registry in search of patients with a MDS and a PNH clone or those with a classic PNH who evolved into MDS. Our aim was to study the characteristics of patients who showed some of these entities and AA history.
RESULTS
Our search retrieved 6 patients, of whom 3 were MDS cases with a small PNH clone (Table 1). One of the patients had had a previous classic PNH followed by a MDS. The remaining two patients had been diagnosed with AA, developing classical PNH and MDS later; of these, one (patient 2) died with an acute leukemia.
The median follow-up time was 83 (range 56-480) months, while the follow-up time from diagnosis of MDS was 68 (range 6-108) months. The patient characteristics are describe in Table 1.
There are two remarkable features, diagnosis of a RAEB-1 in two cases and the frequency of trisomies of chromosome 8 and 21 and deletion of chromosome 7. These chromosomal abnormalities appeared sequentially as MDS evolved in 3 patients. The PNH clone disappeared in those patients who developed a MDS after an AA/classic PNH and persisted in those MDS cases who showed a PNH clone at diagnosis of MDS.
Table 1. Patients Characteristics Previous diagnosis Follow-up time MDS type Karyotype Case 1 None 70 RARS + 8 Case 2 AA + PNH 56 RCMD -7 evolution to -7, + 21 Case 3 Classical PNH 83 RAEB-1 + 8 Case 4 None 83 RAEB-1 +21 evolution to +21, +8 Case 5 AA + classical PNH 480 RCMD + 8 evolution to +8, -7 Case 6 None 108 RCMD Normal
CONCLUSIONS
Patients with a diagnosis of AA, classic PNH or MDS with a PNH clone must be followed up for life, with bone marrow studies with karyotype and measurements of the PNH clone, to rule out the development of other hematological entities. Our series is a small one and only studies with a larger number of patients will allow us to establish definitive conclusions. The inclusion of these patients in the International PNH Registry is strongly advised.

Disclosures
No relevant conflicts of interest to declare.
Prevalence of Anemia and Treatment Outcomes after Bariatric Surgery-a Retrospective Korean Study
Authors: Kyoung Ha Kim , Min-Young Lee , Kim Han Jo , Kim Se Hyoung , Kim Hyun Jung , Sang-Cheol Lee , Sang Byung Bae , Chan-Kyu Kim , Kyu Taeg Lee , Sung Kyu Park , Won Jong-Ho , Hong Dae Sik , Kim Yong Jin 
Published: October 2019

Abstract

Background
Since the first bariatric surgery was performed in 2003, the number of bariatric surgeries performed in Korea has exponentially escalated along with the trend in Asia and recently surpassed 1,000 cases annually. Sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) are the most common types of bariatric surgery currently performed. Various types of anemia, commonly secondary to iron, folic acid, and vitamin B12 deficiencies, may complicate bariatric surgery in the long term. Thus, we evaluated the clinical course of iron deficiency anemia (IDA) in patients who underwent bariatric surgery.
Methods
A retrospective review of the prospectively established database identified all patients who underwent with RYGB for bariatric surgery between January 2008 and Feb 2014. Bariatric surgery candidates were selected according to international federation for surgery of obesity Asia Pacific Chapter Consensus statements in 2011; patients with a body mass index (BMI) ≥ 30kg/m2 with inadequately controlled obesity-related comorbidities (eg. Diabetes, obstructive sleep apnea, hypertension, or obesity related arthropathy) or with a BMI ≥ 35kg/m2. Anemia was defined as a hemoglobin level <13g/dL in men and <12 g/dL in women. Our institutional guideline of bariatric surgery is
Results
The records of 523 consecutive patients (total 796 bariatric surgeries) who underwent RYGB between January 2011 and 2015 were retrospectively reviewed. The mean preoperative body mass index was 38.0 ± 5.8kg/m2. Female was 419 (80.1%) patients and median age was 38 (range 16-67) years. Of all patients, 17.4 % patients had IDA postoperatively. Median duration from bariatric surgery to time of anemia onset was 13 (3.5-17) months. Oral iron induced 81 % overall response and 13.5% patients were required intravenous iron due to intolerance.
Conclusion
Anemia after bariatric surgery is mainly IDA, iron supplements should be administered to patients in early postoperative periods. Oral iron supplements were effective than expected.

Disclosures
No relevant conflicts of interest to declare.
Predictors of Thalassaemia Carriers in Trinidad and Tobago
Authors: Vuma Sehlule Sinqobile , Mayers Hasina , Legall George 
Published: October 2019

Abstract
Objective: To determine possible predictors of thalassaemia carriers among prospective blood donors in Trinidad and Tobago
Background: Thalassaemias are prevalent in India, South-East Asia, Mediterannean, Middle East and respective migrants. Trinidad ad Tobago (TT) has 1.3million people (34.2% African origin, 35.4% Indian origin, 22.8% mixed heritage, (and the rest include Caucasian, Chinese and indigenous people). DNA analysis for thalassaemia diagnosis/neonatal/population screening is not routinely available. Simple inexpensive thalassaemia predictors are needed. The main indicator is microcytosis, the commonent differential of which is Iron Deficiency Anaemia (IDA). Tiwari(2009), showed 5.4% microcytosis among Indian blood donors. (52%-IDA, 36%-Beta-thalassaemia trait, 8%-mixture of both, 4% neither). Combinations of RBC-parameters improve discriminative powers (Urechaga, 2013). No similar studies have been done in TT.
Design and Methods: 460 prospective blood donors were screened for microcytosis (MCV<83fL) by performing a CBC using a Sysmex XE-2100. Microcytic samples further had blood film analysis, iron studies, haemoglobin electrophoresis, haemoglonin F/A2 quantification, and DNA analysis for thalassaemia mutations. SPSS stastitical analysis was performed to determine predictors of thalassaemia trait. Variables tested were ethnicity, haemoglobin, MCV, MCH, MCHC, RBC (RCC), RDW-SD, and RDW-CV. Mathematical formulae were also used ie the Mentzer, Shine and Lal, Green and King, and Srivastava Indicies.
Results: 86(18.7%) subjects had microcytosis. 44 of these had DNA results. 22(50%) had MCV between 80-83fL. 31(70.5%) had thalassaemia trait: 25(80.6%) with genotype -α/αα, 4(12.9%) α-/α-(all α3.7), one IVS I-5 G/C and one IVSII-666 T/C. The MCV, RDW-SD and RDW-CV were useful in predicting thalassaemia trait. RDW-SD identified 30(96.8%) of the 31 carriers, the Green and King formula identified 27 (87.1%), and Ricerca index identified all 31.
Conclusion: MCV, RDW-SD, Green and King formula and Ricerca index may be useful predictors of thalassaemia trait in Trinidad and Tobago. A higher cut off for MCV (83fL as opposed to the 72fL or 78fL usually used for screening purposes), improves the thalassaemia-trait pick up rate.
(Acknowledgments: aMarie-D Hardy-Dessource, bChristian Saint-Martin, aMarc Romana - (aINSERM S_763, CHU de Pointe-à-Pitre, Pointe-à-Pitre, Guadeloupe: bLaboratoire de l'Unité transversale de la Drépanocytose, CHU de Pointe-à-Pitre, Pointe-à-Pitre, Guadeloupe)

Disclosures
No relevant conflicts of interest to declare.
Total Oxidant and Antioxidant Capacity in Patients with Transfusion Dependent and Nondependent Beta Thalassemia
Authors: Karakas Zeynep , Yilmaz Yasin , Celik Dolay Damla , Annayev Agageldi , Demirel Selcan , Erdem Kuruca Serap 
Published: October 2019

Abstract
Background: The patients with β-thalassemia are usually under oxidative stress due to iron overload as a result of ineffective erythropoiesis and repeated transfusions. The endogen (uric acid, indirect bilirubin) and exogenous (ascorbic acid and vitamin E) antioxidants protect the cells from oxidative damage. The evaluation of antioxidant defense system can be easily done by measuring serum total antioxidant capacity. The aim of this study is to investigate the total oxidant (TOC) and antioxidant capacity (TAC) of patients with transfusion dependent (TDT) and nondependent (NTDT) β -thalassemia.
Methods: Fifty eight patients (age range 3-59; median age 24 years) with β-thalassemia (16 nontransfusion dependent, 42 transfusion dependent) who were followed-up by Istanbul Medical Faculty Thalassemia Center were enrolled in this study. The sex and age matched 25 healthy subjects were used as control group. The total oxidant and antioxidant capacity were measured by Rel Assay Diagnostics, Total Oxidant Status (TOS) kit and Total Antioxidant Status (TAS) kit. The statistics of results were done by SPSS version 21.
Results: 58 patients were included consisting of β thalassemia intermedia (n=16) and β thalassemia major (n=42). The total oxidant capacity was found higher in patients than control group without significant differences. Beside this, the antioxidant capacity of patients was significantly increased (2.75 mmol/l vs 1.94 mmol/l; p=0.001). Within patients group, there was no significant differences in terms of TAC while the TOC level was high in NTDT (2.99 mmol/l vs 1.88 mmol/l; p=0.08). There was no significant relationship between TOC and sex, age (<18 vs >18 years), ferritin and splenectomy status, as the same for TAC.
Conclusions: The oxidative damage in patients with β-thalassemia can trigger the morbidity. The measurement of TOC and TAC status stands a useful, rapid, and simple method to evaluate the complex oxidative mechanism of disease. There are still controversial results about antioxidant status in thalassemia patients. The irregular consume of supportive treatment such as zinc, vitamin C, vitamin E and herbal medicine may affect the TOC and TAC status. The results of this study can guide us to use the antioxidants to decrease the oxidative stress.
Figure 1. Figure 1.

Disclosures
No relevant conflicts of interest to declare.
Nano-Formulated Hydroxyurea Enhances Drug Delivery in K562 Cells
Authors: Mohtar Omar , Tagne Jean Bosco , Klings Elizabeth S 
Published: October 2019

Abstract
The vasculopathy of sickle cell disease (SCD), characterized by a chronic hemolytic anemia, endothelial dysfunction and recurrent vaso-occlusive events, underlies most of the clinical complications. Hydroxyurea (HU), the only FDA approved medication to treat patients with SCD, acts via the induction of fetal hemoglobin (HbF) production. Recent studies suggest that HU increases endothelial nitric oxide (NO) production and reduces adhesion molecule expression as another potential mechanism for the observed reduction in vaso-occlusive events and improved survival in SCD. Despite its benefits, HU is currently under-utilized and we hypothesize that improved targeted drug delivery may increase its usage. The use of nano-emulsions, a class of stable emulsions formed by a monolayer of phospholipids and/or biodegradable material, is a mechanism by which to enhance targeted cellular delivery of therapeutics. We hypothesized that a nano-formulation of HU would enhance drug delivery to the bone marrow and this may be a direct way of impacting HbF expression in SCD. Nano-formulated HU (NHU) was developed using a phospholipid approach and this compound was found to be biologically stable for > 6 months.
Chronic myelogenous leukemia bone marrow (K562) cells were treated with a NHU or HU suspension in concentrations ranging from 25µM to 250µM over a course of 4, 5 and 6 days. Cells were harvested for RNA isolation and qPCR was performed using primers for HbF and basal cell adhesion molecule (BCAM, a cellular adhesion molecule on red and white blood cells. On day 5, when HbF expression in K562 cells peaks, there was a five-fold increase in HbF expression treated with lower concentrations of NHU compared to untreated cells and a two-fold increase in expression compared with HU treated cells. With increasing concentrations of NHU and HU, HbF expression became similar. This suggests that the use of NHU can provide increased HbF expression at a lower concentration with likely less toxicity. Treatment of K562 cells with NHU and HU resulted in decreased BCAM expression on day 6 of treatment. Treatment with NHU produced a four-fold decrease in BCAM expression compared to the same concentration of a HU suspension which supports the concept that NHU can impact gene expression at lower doses than unformulated HU. Nanoformulated HU produces a molecule which is highly stable, and able to achieve higher intracellular concentrations with increased efficacy in K562 cells. This suggests a potential novel therapeutic for patients with sickle cell disease.

Disclosures
Klings: Pfizer: Consultancy; Actelion Pharmaceuticals: Research Funding.
A Meta-Analysis of Gene Expression Studies Highlights the Role of Innate Immunity in the Pathogenesis of Sickle Cell Disease and Reveals Novel Potential Regulators at the Transcriptomic Level
Authors: Hounkpe Bidossessi Wilfried , Fiusa Maiara Marx Luz , Colella Marina Pereira , da Costa Loredana Nilkenes Gomes , Benatti Rafaela Oliveira , Saad Sara Terezinha Olalla , Costa Fernando Ferreira , Santos Magnun Nueldo , De Paula Erich Vinicius 
Published: October 2019

Abstract
Sickle cell disease (SCD) is characterized by chronic inflammation and multisystem tissue damage. Despite the detailed characterization of the inflammatory changes observed in these patients, the precise identity of their critical triggers, as well as the hierarchical relationship between the elements involved in the pathogenesis of this complex disease are yet to be described. Meta-analysis of gene expression studies from public repositories represents a novel strategy, capable to identify key pathogenic mediators and therapeutic targets in complex diseases such as diabetes. The recent development of comprehensive bioinformatics tools further facilitated the identification of relevant genes, pathways and regulatory elements from high-throughput transcriptomic data. Here we performed a meta-analysis of recent gene expression studies with SCD patients, available at the Gene Expression Omnibus public repository. Two databases (GSE35007 and GSE53441) including samples from adults and children with SCD respectively fulfilled our inclusion criteria. We also performed additional meta-analysis comparing the gene expression pattern of these clinical samples with that of heme-stimulated endothelial cells (GSE25014). Meta-analysis was performed with the Inmex bioinformatics tool. Raw data was downloaded, annotated, preprocessed, and submitted to quality check. Differentially expressed genes were identified and ranked based on the RankProd package. Gene set analysis using more than 60 libraries was performed using EnrichR. Transcription factor, kinase enrichment, and pathway cluster analysis were performed using appropriate bioinformatics tools. Only pathways that were identified in more than one library were included. Our results demonstrate that the well-characterized association between innate immunity, hemostasis, angiogenesis and heme metabolism with SCD was also consistently observed at the transcriptomic level, across independent gene expression studies. The enrichment of genes and pathways associated with innate immunity and damage repair-associated pathways supports the model of erythroid danger-associated molecular patterns (DAMPs) as key mediators of the pathogenesis of SCD. In addition, our study generated a novel and large database of candidate genes, pathways, transcription factors and kinases not previously associated with the pathogenesis of SCD, that could be used in future and independent studies in SCD.

Disclosures
No relevant conflicts of interest to declare.
Impact of a Dedicated Sickle Cell Acute Care Observation Unit on Rate of Hospital Admission for Acute Pain Crisis
Authors: Gowhari Michel , Kavoliunaite Laura , Bonnye Johnson , Brown Stephen , Molokie Robert E. , Hsu Lewis L. , Gordeuk Victor R. 
Published: October 2019

Abstract
Introduction: Pain is the top concern of individuals with sickle cell disease (SCD). Acute painful vaso-occlusive episodes are the leading cause of emergency department (ED) encounters and frequent hospital admissions. There are well-documented disparities for patients with SCD, including significant delays in starting therapy and under treatment of pain in the ED. An acute care observation unit (ACOU) staffed with SCD specialists can help to address these disparities. Here we study the service impact of increasing the hours of operation of a dedicated sickle cell ACOU on utilization and hospital admissions at the University of Illinois at Chicago (UIC), a regional sickle cell resource. We hypothesized that increased hours of operations will lead to decreased ED utilization and inpatient hospitalizations.
Methods: The outcomes of individuals >16 years of age presenting with an acute painful episode to the sickle cell ACOU at UIC were assessed for the 12 months before and the 12 months after increasing the hours of operation from 9 hours/day to 15 hours/day Monday through Friday in February 2014. The outcomes of SCD patients presenting to the ED during the 12-month period following expanding hours in the ACOU were also assessed. The main outcome measures were ACOU and ED utilization and hospital admission rates.
Results: There were 344 encounters in the sickle cell ACOU in the 12 months before expansion of service hours compared to 796 in the 12 months after expanding the hours, an increase of 131%. This represents 0.15 patients treated per hour before increasing the hours versus 0.2 per hour after increasing the hours. Seventy-two percent of the patients treated at the sickle cell ACOU were discharged home in the 12 months prior to expanding hours versus 75% after. During the comparative 12-month period following expansion of hours in the ACOU, there were 1074 encounters for SCD acute painful episodes in our ED, representing 0.12 patients treated per hour of operation. Only 35% of SCD patients treated in the ED for an acute painful episode were discharged home.
Conclusion: The sickle cell ACOU at UIC more than doubled its patient volume following the expansion of operation from 9 to 15 hours/day during weekdays. Based on the hours of operation, during a comparative 12-month period the sickle cell ACOU treated twice as many SCD patients with an acute painful compared to the ED while discharging rather than hospitalizing twice as often. These observations suggest that allocating resources to a dedicated sickle cell ACOU can decrease ED utilization and subsequent inpatient hospitalizations.

Disclosures
No relevant conflicts of interest to declare.
Sickle Cell Disease in Central India: High Prevalence of Sickle/Beta Thalassemia and Severe Dsiease Phenotype
Authors: Jain Dipty , Warthe Vinit , Colah Roshan , Serjeant Graham Roger 
Published: October 2019

Abstract
Objectives: To assess the clinical, haematological and molecular features of sickle cell disease in central India where the disease has been reported to be more severe than the mild clinical course usually observed in the Asian haplotype of homozygous sickle cell (SS) disease.
Methods: A cross-sectional assessment of 91 consecutive patients with sickle cell disease attending clinics at the Akola Government Medical College, Akola, Maharastra State, India.
Results: Of the 91 patients, who were predominantly of the scheduled caste community, 49 had SS disease, 6 had sickle cell-HbD Punjab, and 36 had sickle cell-beta thalassaemia. Of the patients with sickle cell-beta thalassaemia, the beta thalassemia mutation was IVS1-5 G>C mutation in 25 patients (69%) while the rest had one of seven other molecular mutations identified (Table1). Contrary to commonly held beliefs, alpha thalassaemia occurred in only 9/90 (10%) of subjects but fetal haemoglobin (HbF) levels were markedly elevated with mean and median levels of 24.4%. All except 3 SS disease patients had the Xmn1(+/+) polymorphism. These patients exhibited many of the severe manifestations of sickle cell disease. Comparison of SS disease and sickle cell-beta thalassaemia showed no differences in the prevalence of dactylitis, bone pain crisis, acute chest syndrome, haemoglobin level, reticulocyte counts or hydroxyurea usage but patients with sickle cell-beta thalassaemia had significantly more hospital admissions, blood transfusions, and greater frequencies of splenomegaly and hepatomegaly.
Conclusions: Many of the patients with sickle cell disease in central India appear to have relatively severe manifestations. This appears to be due to much lower frequencies of alpha thalassaemia and more frequent sickle cell-beta thalassaemia. There is a need for assessment of the indications and policies for blood transfusion and for hydroxyurea.
Table 1. Beta Thalassemia mutations associated with HbS/Beta Thalassemia in Akola Mutation Expression Number IVS 1-5 (G>C) severe b+ 22 IVS 1-1 (G>A) bo 3 Cd 15 (-T) bo 2 Cd 30 (G>C) bo 2 Cd 15 (G>A) bo 1 Cd 39 (C>T) bo 1 Cd 41/42 (-CTTT) bo 1 619 bp deletion bo 1 Total 36

Disclosures
No relevant conflicts of interest to declare.
Coinheritance of Alpha-3.7 Deletion and Hb Questembert [131alpha-2 Tct > CCT](Ser131>Pro)] in an African American Patient Results in an Alpha Thalassemia Phenotype
Authors: Shakir Asiya , Pace Betty , Patel Niren , Kutlar Ferdane , Kutlar Abdullah , Ameri Afshin 
Published: October 2019

Abstract
Patients with Hemoglobin Questembert carry a Ser131Pro mutation in one of their alpha globin chains encoded by a TCT-CCT mutation of one of their alpha 2 globin gene. This mutation usually results in an unstable hemoglobin variant with mild anemia that is rarely symptomatic. Rarely these patients may show increased extravascular hemolysis during stress, due to oxidative membrane damage. Our patient is a 7 year old African American girl that came to medical attention due to severe anemia, reticulocytosis, absent haptoglobin levels, persistent jaundice and hyperbilirubinemia. Over a period of several years the patient progressed to develop marked splenomegaly with progressive anemia. Isoelectric focusing in this patient revealed Hb A, A2 and a variant "S" band which was less than 1% and thus not detectable by HPLC. We speculate that in the presence of limited alpha globin synthesis, due to a deletion of one α-2 gene and in the presence of a highly unstable alpha-2 variant, synthesis of wild-type alpha globin from the remaining alpa-1 gene is not sufficient to allow for normal alpha-globin/ beta-globin assembly. Furthermore the assembly of the alpha-globin Questembert into the hemoglobin tetramer is favored resulting in an extravascular hemolytic disorder.

Disclosures
No relevant conflicts of interest to declare.