bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prothrombin Complex Concentrate in the Management of Major Bleeding Induced By Oral Anticoagulant Therapy: Experience of a Tertiary Care Center
Authors: Alsheef Mohammed Abdullah , Zaidi Abdul Rehman Z. , Kullab Ghaydaa Juma 
Published: November 2019

Background
In patients taking oral anticoagulants and presenting with major bleeding, a rapid, effective, and safe reversal agent is urgently required. There are limited data of 4-factor prothrombin complex concentrate (4F-PCC) in the management of oral anticoagulant associated major bleeding.
Aims
The purpose of this study is to provide clinical experience regarding the effectiveness of 4F-PCC in the management of major bleeding induced by warfarin, dabigatran, and rivaroxaban.
Methods
A retrospective study of 43 patients who were admitted to our tertiary care center with major bleeding induced by oral anticoagulants and received 4F-PCC. The effectiveness of PCCs was assessed by using the International Society of Thrombosis and Hemostasis criteria. Descriptive statistics were utilized for analysis.
Results
Forty-three patients were screened for inclusion into the study; notably, 21% of patients were excluded from further analysis. Of those included in this analysis (n=22), gastrointestinal bleeding accounted for (45.5%), followed by musculoskeletal bleeding (18.2%). The indication for anticoagulation was stroke prevention atrial fibrillation and VTE in the majority of the patients (45.5%), (45.5%) respectively. Patients received a mean of 2085.2 IU of PCC. Before and after 24 hours of PCC administration, the median INR resulted in a significant reduction (P;<0.001), with median aPTT (P;0.018). After final adjudication, the hemostatic effectiveness of PCC was assessed as effective in 19 patients (86.4%) and ineffective in three patients (13.6%). No major complications occurred during treatment or any serious adverse events.
Conclusions
PPC immediately and effectively reversed the effect of warfarin and rivaroxaban in patients with major bleeding and partial effect on the reversal of dabigatran.
Figure

Disclosures
No relevant conflicts of interest to declare.
Characteristics and Trends of Sickle Cell Disease Patients Once Presented to the Emergency Department, Reflecting on a Possible Burden: United States (2010-2015)
Authors: Haykal Tarek , Al-Dulaimi Ragheed , Kerbage Josiane , Samji Varun , Goranta Sowmya , Deliwala Smit , Bachuwa Ghassan 
Published: November 2019

Background: Sickle cell disease (SCD) is an autosomal recessive, multisystem disorder, characterized by chronic hemolytic anemia, painful episodes of vaso-occlusion, progressive organ failure and a reduced life expectancy. SCD is the most common monogenetic disease, with millions affected worldwide. It is estimated that there are 100,000 people living with SCD in the United States (US). Patients with SCD often use emergency department (ED) services to obtain medical care. Limited nationwide information in the recent years is available about ED use among patients with SCD.
Methods: Data from the National Hospital Ambulatory Medical Care Survey (NHAMCS) for the years 2010-2015 were analyzed, to examine the prevalence and care of SCD patients in the EDs across the US. The NHAMCS is a survey of hospital ED and outpatient visits. Cases were identified using ICD 9 codes and all analyses accounted for complex survey structure of the data.
Results: On average, approximately 1.4 million ED visits were estimated to have occurred between the years 2010 and 2015 with SCD as one of the diagnoses listed, where 860,000 were attributed to sickle cell crises. 37.29% were of female sex while 62.71% were males. 11.62% were under 15 years of age, 28.22% were between 15 and 24 years of age, 51.15% were between the ages of 25 and 44 years and 9.02% were older than 45 years. The chief complaint for the majority of cases was pain. The expected source of payment were Medicare and Medicaid at 30.45% and 41.98% respectively, while private insurance coverage and self-pay were only at 11.71% and 5.81% respectively. Of all SCD ED visits, 68.5% were considered as initial presentations and up to 23.37% were considered as follow-up. 33.31% of the visits ended up needing a hospital admission while 66.69% got discharged from the ED.In 43.39% of the visits, a form of imaging was ordered, compared to 56.61% where it was not. Upon getting triaged in the ED, 67.62% of all SCD visits needed either emergent or urgent medical attention, while the rest were either none-urgent, or a regular check-up.
Conclusion: In well-resourced countries, like the US, comprehensive care programs have increased life expectancy of sickle cell disease patients, with almost all infants surviving into adulthood. However unfortunately with poor control of the disease due to limited therapeutic options and with growing morbidity for the aging SCD patients, the burden on the medical system becomes extremely high. Our study highlights the significant burden SCD creates in the EDs across the US based on data collected from a national database.

Disclosures
No relevant conflicts of interest to declare.
Preoperative Transfusion in Pediatric Patient with Sickle Cell Disease
Authors: Al Darwish Mohamed , Alabkary Sukainah , Al deabel Hajer , Alqatari Fatimah , AlDubaisy Wafa 
Published: November 2019

Background: Sickle cell disease (SCD) is associated with perioperative complications. Red cell transfusion has been recommended in the management of SCD undergoing elective procedure to minimize perioperative complications. The aim of this study was to retrospectively review our experience in the management of children patients with SCD with the Arab-Indian (AI) haplotype undergoing elective and emergency surgery, and to determine blood transfusion requirement and surgery-related perioperative complications.
Patients and Methods: A total number of 173 SCD patients undergoing surgery at Qatif Central Hospital, Qatif, Eastern province, Saudi Arabia was conducted between February 2007 and June 2019. children less than 14 years and above one year were included (111 boys and 62 girls). Patients were divided into two groups: Group A did not receive transfusion and Group B had top-up transfusion. The medical records were reviewed to define the perioperative risks and the postoperative complications in relation to the type of transfusion modality selected.
Two surgical procedures were analyzed: a low and medium risk group including laparoscopic cholecystectomy, laparoscopic splenectomy, tonsillectomy, adenotonsillectomy, herniotomy and dental procedure.
Results: eighty-three (n:83) patients (Group A) did not received transfusions (Group B) while . There were 15 (17.2%) postoperative complications; seven (8.4%) occurred in group A patients who did not received transfusion and eight (8.8%) occurred in group B patients who received top-up transfusion. Sickle cell disease-related complications consisted of acute painful vaso-occlusive crises in three patients (3.5%). Six patients (3.9%) had acute chest syndrome, 4 (4.5%) had hepatic crises and one had subclinical pancreatitis. Only one (1.2%) patient in group B (top up) had a mild hemolytic transfusion reaction. Moreover, there was no significant difference in the complications between the transfusion and none transfusion subgroups.
Conclusion: Surgery in SCD patients is safe without a preoperative blood transfusion. Moreover, there was no significant difference in the complications between the transfusion and none transfusion subgroups. To conclude, blood transfusion or exchange blood transfusion should be individualized based on genotype, haplotype and type of surgery.

Disclosures
No relevant conflicts of interest to declare.
Stat3 Is Activated By ROS to Uniquely Regulate Primitive Erythropoiesis
Authors: Murphy Zachary C. , McGrath Kathleen E. , Palis James 
Published: November 2019

The mammalian embryo requires the sequential circulation of primitive and definitive erythroid cells for survival and growth. The central cytokine regulator of primitive and definitive erythropoiesis is erythropoietin (EPO). We have previously determined that primitive erythroid progenitors, unlike their definitive (CFU-E) counterparts, do not require EPO for survival. However, the mechanisms regulating the EPO-independent emergence of primitive erythropoiesis in the yolk sac remains poorly understood. Interestingly, maturing primitive erythroblasts in the murine embryo, unlike definitive erythroblasts in the fetal liver and adult bone marrow, express not only STAT5 but also STAT3, which is tyrosine phosphorylated at baseline and in response to EPO. These initial findings led is to hypothesize that STATs 5 and 3 differentially regulate terminal differentiation of primitive erythroid cells. To analyze the function of these two STATs in primary erythroid cells, we developed an imaging flow cytometry-based methodology to quantitate total and phosphorylated levels of STAT proteins in small numbers of cells isolated from staged murine embryos. We found that STAT5 plays conserved roles in primitive and definitive erythroblast survival and surface CD71 expression. In contrast, STAT3 regulates cell cycle progression and mitochondrial polarization specifically in primitive erythroblasts. In addition, STAT3, unlike STAT5, was phosphorylated in the absence of cytokine stimulation. We asked if reactive oxygen species (ROS) may be activating STAT3, since primary primitive erythroblasts, unlike definitive erythroblasts, specifically express Aquaporins 3 and 8, which can transport hydrogen peroxide, as well as water. Indeed, hydrogen peroxide exposure increased endogenous ROS, as well as phosphorylated STAT3, levels both in wild-type and EPOR-null primitive erythroblasts. Consistent with these findings, inhibition of aquaporin channel transport prevented STAT3 phosphorylation by exogenous hydrogen peroxide, but not by EPO. Taken together, our data support the concept that the primitive erythroid lineage, emerging in the hypoxic and EPO-low environment of the yolk sac in the pre-circulation murine embryo, uniquely integrates ROS-mediated STAT3 activation to regulate key aspects of terminal erythroid maturation.

Disclosures
Palis: Rubies Therapeutics: Consultancy.
A Randomized Phase 3 Clinical Trial of the Combination of Plinabulin (plin) + Pegfilgrastim (peg) Versus (vs) Peg Alone for Tac (docetaxel, doxorubicin, cyclophosphamide) Induced Neutropenia (cin)
Authors: Blayney Douglas W. , Huang Lan , Mohanlal Ramon 
Published: November 2019

Trial in Progress:
Granulocyte colony stimulating factors (G-CSFs) (including Peg) reduce, but do not completely ameliorate CIN. Plinabulin is a novel, small molecule, single-dose-per cycle therapy, with equal activity against docetaxel CIN vs. Peg, but with several advantages: Plin has 1. Less bone pain, 2. Anticancer effects, and 3. Dosing 30 min after chemotherapy (chemo). The CIN nadir with Plin occurs in week 2 and with Peg in week 1 of the chemo cycle. All these features suggest a mechanism of action (MoA) with Plin that is different from Peg (Blayney, ASCO 2018; IASLC 2018). Neutrophil demargination with Plin and a reduced neutrophil transit time consistent with IL-6 signaling, and reversal of a LSK block in bone marrow, suggest protective rather than a stimulatory MoA for Plin in CIN (Blayney, SLB 2018; Ghosh, AACR 2018, Suwa, Am J Physiol 2000). Due to their differences in MoA, there is a strong rationale to combine Plin and Peg, as this offers the potential of better protection against CIN in both week 1 and 2 in the chemo cycle. In the Phase II portion of study BPI2358-106 (Study 106., NCT03294577), we evaluated the effects of the Plin combined with Peg on CIN and Bone Pain. Study 106 treated breast cancer (BC) patients with TAC with 6 mg Peg alone (Peg6), or Peg6+Plin. Plin dose was 20 mg/m2. Grade (Gr) 3 and 4 neutropenia frequency, duration of Gr 3 and 4 neutropenia (DSMN), and neutrophil nadir was based on absolute neutrophil counts, obtained on days 0, 1, 3, 6, 7, 8, 9, 10, 11, 12, 13, 15. Bone pain was assessed by a validated questionnaire on days 1, 2, 3, 4, 6, 7, 8, 9, and expressed as % of patients reporting bone pain.
Phase II Results.
The confirmatory phase 3 portion of study 106 will test addition of Plin to Peg6, which may offer superior protection against TAC CIN vs Peg alone without bone pain. The Plin/Peg combination is a novel CIN approach with the potential to optimize chemotherapy, by minimizing chemotherapy dose modifications due to CIN or bone pain.*p&lt;0.05; **p&lt;0.001; ***P&lt;0.01 Peg+Plin vs Peg 6mg
Table

Disclosures
Blayney: BeyondSpring Pharmaceuticals: Research Funding. Huang:BeyondSpring Pharmaceuticals: Employment. Mohanlal:BeyondSpring Pharmaceuticals: Employment.
Portal Vein Thrombosis: A Single Institution Experience
Authors: Pichardo Rayli , Katiyar Vatsala , Vohra Ishaan , Abu Omar Yazan , Patel Sanjay 
Published: November 2019

Background: Portal vein thrombosis (PVT) is a common complication of liver cirrhosis but can also be seen in non-cirrhotic patients. In this context, we present a single institution experience of PVT in our patient population contrasting the difference of presentation between both groups of PVT.
Methods: We retrospectively analyzed electronic medical records of patients with PVT (confirmed with radiographic criteria) from 2009 to 2018. We collected data regarding the demographics, characteristics of PVT, liver cirrhosis, presence of malignancy, treatment and laboratory investigations done at the time of diagnosis. Clinical endpoints of 90-death mortality, admission to intensive care unit and length of stay were also collected.
Results: a total of 162 patients fulfilled inclusion criteria. 104 (64.2%) male patients, mean age of 56.4, predominantly African American patients 75 (46.3%). 81 (50.0%) patients had cirrhotic PVT and 85 (52.5%) had malignant PVT. Most patients presented with abdominal pain 102 (63%), with an acute onset 51 (31.5%). 111 (68.5%) patients were not treated with anticoagulation. 28 (17.3%) patients died within 90 days of diagnosis and 22 (13.6%) patients were admitted to intensive care unit during same admission. When comparing Malignant with non-malignant PVT, patients with malignancy had a higher death rate 22 (30.1%) vs 6 (8.8%), p value <0.05. When comparing cirrhotic vs non-cirrhotic PVT, patients with cirrhosis had a higher MICU admission, history of HCC and they were treated with anticoagulation more.
Conclusion: In terms of etiology, PVT patients with malignancy seem to be doing worse than patients without malignancy while patients with cirrhosis except for higher rates for MICU admission; they seem to be doing similarly. Reasons for this discrepancy could be attributed to the fact that malignancies associated with high rates of PVT seem to be more aggressive in terms of mortality. Other studies need to be conducted in order to further clarify what we know about malignant and cirrhotic PVT.
Table

Disclosures
No relevant conflicts of interest to declare.
Efficacy and Safety of DAC Combined with CAG Regimen (decitabine in combined with aclacinomycin, cytarabine and G-CSF) As a Second Induction Regimen Compared with Non-DAC Regimen for Acute Myeloid Leukemia Who Failed the First Course of Standard Induction IA Chemotherapy
Authors: Chen Yili , Dai Min , Liu Qifa 
Published: November 2019

BACKGROUND: Acute myeloid leukemia (AML) patients who failed the first course of standard induction chemotherapy remain a challenge owing to poor response to the second induction regimen. We retrospectively compared the efficacy and safety of DAC+CAG regimen with non-DAC regimen in AML patients who failed the first course of standard induction regimen.
MATERIALS AND METHODS: The three regimens consisted of (1) DAC combined with CAG regimen (decitabine, cytarabine, aclarubicin and granulocyte colony stimulating factor, n=25) ; (2) the repeated first course (IA 3+7, n=30); (3) Intermediate-dose AraC -based chemotherapy including IA 3+3 (idarubicin, Ara-C n=14) or CLAG (cladribine, aclarubicin and granulocyte colony stimulating factor, n=15).
RESULTS: Our data indicate that after the second course, the overall response (OR, complete remission [CR]+partial remission [PR]) rates in DAC+CAG group was higher than the Intermediate-dose AraC -based group (80% vs 48.3%, P= 0.049), whereas the CR rates among 3 groups were not statistically different (P = 0.09). The overall survival (OS) of DAC+CAG group is longer than IA 3+7 group and Intermediate-dose AraC -based group with significance (21 months VS 18.5 months, P=0.038 and 21 months VS 10 months, P=0.023, respectively), the relapse-free survival (RFS) of DAC+CAG group is longer than Intermediate-dose AraC-based group (16 months VS 8.5 months, P=0.016), though there was no significant difference in overall survival (OS) of the transplanted patients among the 3 groups (P = 0.064). The median duration of thrombocytopenia in the DAC+CAG group is shorter than IA 3+7 group and Intermediate-dose AraC-based group (10 days vs 12 days, P<0.001 and 10 days vs 14 days P=0.023, respectively). Fewer incidence of lung infection and febrile neutropenia in the DAC+CAG group than other two groups (P=0.018 and P=0.025, respectively) were observed, no patients died within 4 weeks after initiating the second induction course in the DAC+CAG group whereas 2 patients died in the Intermediate-dose AraC -based group.
CONCLUSION: Our data indicate that DAC combined with CAG regimen may represent a better alternative option with good response and safety for AML patients who failed the first course of standard induction chemotherapy.

Disclosures
No relevant conflicts of interest to declare.
Anaemia in Labour: A Prospective Assessment of Women in Rivers State University Teaching Hospital, Nigeria
Authors: Kua Paul L , Omunakwe Hannah E , Okafor Afam C , Williams George Monima 
Published: November 2019

Background: Anemia in any phase of pregnancy is associated with much morbidity and risk of mortality to the mother and the fetus, it is a global health concern and is quite prevalent in Africa. About 58% of pregnant women in Nigeria are said to be anemic and earlier reports from this study site showed that 69.6% of women initiating antenatal care were anemic, it was commoner in women of teen-age and the hematocrit was lower as the gestational age at booking increased.
Methods: We assessed 464 consenting consecutive pregnant women who presented to our labour ward between November 2017 and July 2018 to know their age, booking status, haematocrit at late pregnancy and followed on to know the mode of delivery as well as the occurrence of postpartum bleeding. The data were analysed using IBM Statistical Package for Social Sciences version 23.
Results: A total of 462 consenting women were included in the study, majority of study participants were between the age of 26-35 years 299 (64.7%) with a minimum age of 15 years and maximum age of 47 years and mean age was 31.2 ± 5.2 years. The majority had moderate to severe anemia 335 (70.3%) and were booked for antenatal care with trained personnel 402 (87.2%) and 47 (10.2%) of them developed post-partum haemorrhage.
A significantly higher proportion of the study participants who were un-booked presented with severe anemia (χ2 =14.3; p=0.001); developed PPH (χ2 =13.9; p<0.001) Table 1. The highest proportion of persons who developed postpartum hemorrhage was found in persons with severe anaemia. This difference was significant. (χ2 =87.1; p<0.001).
Hematocrit was found to be the strongest determinant of the occurrence of postpartum hemorrhage among the study participants. The adjusted regression analysis showed that for every one-unit increase in hematocrit of study participants, there was a 16% reduction in the probability of occurrence of PPH and this probability was statistically significant (p<0.001). Booking status was also found to be a predictor of PPH such that un-booked women were 2.3 times more likely to experience PPH than booked women in the study population. This was found to be significant (p=0.04). Table 2
This data supports earlier findings that anaemia worsens the outcome of pregnancy. Unbooked mothers are more at risk of dire outcomes such as postpartum haemorrhage which is the leading cause of maternal mortality. There is a need for guidelines and enforcement of such at all levels of healthcare delivery especially in unorthodox centres where women go for care, as is common in developing countries. The need for health education and active prevention and management of anaemia in the early stages of pregnancy is advocated.

Disclosures
No relevant conflicts of interest to declare.
Splanchnic Venous Thrombosis (SVT) Case Series at a Tertiary Care Hospital: Exploring Clinical Presentation, Diagnosis, Etiology, Thrombophilia, Treatment, and Outcome
Authors: Alsheef Mohammed Abdullah , Alomar Mukhtar , Kullab Ghaydaa Juma , AlTwaijri Abdurahman , Maymani Hassan , Zaidi Abdul Rehman Z. 
Published: November 2019

Background
Splanchnic vein thrombosis (SVT) is an uncommon, but potentially life-threatening disease.
Aims
The aim was to gather more information on most common clinical presentations, risk factors, and treatment outcomes with anticoagulant therapy of SVT patients.
Methods
A retrospective study for 100 patients diagnosed with SVT confirmed by radiological imaging. Variables about demographics and history, signs and symptoms, risk factors, and treatment were collected from patients medical charts.
Results
The age group and the age of diagnosis of the patients was mainly 26-40 (40% and 46% respectively). 19% of patients had positive family history. The most affected veins were multiple veins (42%), followed by portal vein (34%), and then the superior mesenteric vein (11%). Recurrence was seen in 12% of patients. SVT was unprovoked in 48% of our patients and provoked in 52% commonly associated with significant trauma (29%), surgery (18%) in which bariatric surgery was the main culprit (11%) followed by colon/small intestine surgery (9%). 56% of the patients presented with abdominal pain, and 21% had abdominal distension, 9% had melena and 9% had splenomegaly. Thrombophilia was seen in 19% of the patients. Maintenance of anticoagulation was mostly by Warfarin (89%) and Rivaroxaban (9%). Duration of anticoagulation was extended (more than one year) in 72% of patients. 12% of patients had mesenteric ischemia and required bowel resection.
Conclusions
Anticoagulant therapy, in addition to surgery, showed excellent outcome in most patients with SVT. The most common provoking factors were trauma and bariatric surgery. Rivaroxiban demonstrated good safety and efficacy profile and can offer an alternative to traditional therapy in SVT patients.

Disclosures
No relevant conflicts of interest to declare.
Extended Half-Life of the Double-Chain Recombinant Factor VIII-Fc Fusion Protein (FRSW107) in Hemophilia a Patients
Authors: Xue Feng , Sun Jing , Chen Yun , Zhang Xinsheng , Sun Haiyan , Wang Yali , Yang Renchi 
Published: November 2019

Objective:To determine pharmacokinetics (PK), safety and tolerability of a double-chain recombinant human factor VIII-Fc fusion protein (FRSW107) in previously treated patients (PTPs) in clinical trial which was registered at www.clinicaltrials.gov as NCT03747653 and scheduled to finish at end of July, 2019. Methods:At least 12 PTPs (12 to 60 years old) with FVIII:C<2% and without history of FVIII inhibitors received a single dose of rFVIII (Advate) at 25 or 65 IU/kg followed by an equal dose of FRSW107. Results: Up-on the data from 7 subjects received 25 IU/kg , the geometric mean t1/2 of FRSW107 was 26.23 hours. This represents a 1.98-fold improvement over that of rFVIII (13.34 hours) at equivalent doses. All adverse events were unrelated to study drug. None of the study subjects developed FVIII inhibitors. Conclusion:According to the preliminary data from this phase 1 clinical trial, FRSW107 shows a significantly extended half- life compared to control FVIII while no safety issue identified.

Disclosures
No relevant conflicts of interest to declare.