bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tigecycline Was a Promising Candidate for Febrile Neutropenic and Carbapenem-Resistant Patients with Hematologic Malignancy
Authors: Xu Bing , He Lingli , Shi Pengcheng , Guo Xutao , Li Jie , Wang Yan , Deng Manman , Zhou Yong , Li Yin , Liang Jiabao 
Published: October 2019

Abstract

Background: To investigate the efficacy and safety of tigecycline (TGC) in febrile neutropenic and carbapenem-resistant patients with hematologic malignancy.
Methods: The clinical data of 71 patients with hematologic malignancy, febrile neutropenia (FN) were retrospectively analyzed. They are unresponsive to carbapenem for 3~5 days before receiving TGC. The loading dose of tigecyclin was 100 mg at the first time, and 50 mg every 12 hours as maintenance therapy. The efficacy was evaluated according to the Ministry of Health issued in 2007, meanwhile, the drug side effects were also evaluated.
Result: The median duration of neutropenia was 14 days (ranged from 1 to 83d). 61 out of 71 patients (84.5%) suffered from Respiratory infection, and 21 patients (35.2%) suffered from bloodstream infection. Microbiological evidence was got in 55 patients. Among 124 isolated species, Gram-negative microorganism (40.7%) was more commonly observed compared with Gram-positive microorganism (37.3%). The total effective rate of tigecycline was 64.8%. The bacterial clearance rates and bacterial hypothetical clearance were 20.8% and 22.6%, respectively. The media time for temperature come back to nomal was 3 days ( ranged from 1 to 10d). The clinical effective rate was 86.7% when tigecycline was administered for more than 9 days, while just 50.0% when administered for less than 9 days ( P = 0.02) . Patients with bloodstream infection got a worse efficacy than those without bloodstream infection ( 50% vs 67.8%, P=0.038). As a second-line anti-infective therapy, the clinical effective rate of tigecycline (70.8%) was mildly higher than those third-line or fourth-line therapy (61.7%) (P= 0.446)). The most common side effects were mild gastrointestinal symptoms including nausea,vomiting and diarrhea. No lethal adverse events was observed.
Conclusions: ur results demonstrated tigecycline was effective and safety for patients unresponsive to carbapenem with febrile neutropenia. A further study with larger number of cases was needed.

Disclosures
No relevant conflicts of interest to declare.
Granulocyte Transfusion in Febrile Neutropenia
Authors: Aydogan Gonul , Keskindemirci Gonca , Tugcu Deniz , Akici Ferhan , Salcioglu Zafer , Akcay Arzu , Sen Hulya , Gokce Muge , Bayram Cengiz , Aycicek Ali , Aktay Ayaz Nuray 
Published: October 2019

Abstract

Background: Over last 30 years cure rates are increasing among oncology patients. As the therapy intensifies, infectious complications become more common. Neutropenia is defined as neutrophil counts of <500/mm³ and it is one of the most frequent and severe complications of pediatric cancer therapy. In 12-17% of patients with febrile neutropenia, there are proven bacteremia and fungal infections. Pediatric oncology patients have a frequency of 30 morbidity and 1% mortality due to infections. Granulocyte transfusions (GTX) were found to be an effective protective and therapeutic strategy in prolonged neutropenia. GTX had been shown to be limiting the duration and complications of neutropenic period, maximum levels of CRP and duration of antibiotic usage especially after myeloablative therapy.
Materials and methods: In this study that was performed at Kanuni Sultan Süleyman Education and Research Hospital pediatric hematology-oncology unit, 170 granulocyte transfusions applied to 37 high risk febrile neutropenia attack of 23 patients were evalauted retrospectively. Granulocyte transfusions were done when the neutrophile counts were between 0 to 300 /mm³ by taking account the general status, physical examination and cultures of patients. Donors were selected according to blood types and their informed cosent were taken. The donors came to the unit one night before, 8 mg intramuscular dexamethasone and 480 mcg of G-CSF were applied. After 12 hours, granulocytes were taken from the donors by intermittent flow technique and given to patients intraveneously. The time needed for getting away from neutropenia, number of febrile days and observed adverse effects were recorded.
Results: For 23 high risk febrile neutropenic patients, granulocyte transfusion was performed at an average of 1-27 times per attack, totally 170 times in 37 attack. Eight of the patients were girls and 15 were boys, ages were ranging between 6 months to 16 years. Product quality qas found to be 1.41 x 1010; 2,14 x 1010/m2. Mean days for subsiding of fever was 6.45 days, mean time for getting rid of neutropenia was 8.15 days. Three patients died during neutropenia attacks. Two of them had both infections and uncontrolled progressive primary disease. Only one patient was lost from infection even though he had antibiotic, antifungal and supportive therapy. Only upper respiratory disease symptoms were noted at 3 of the donors. In one of the patients, transfusion was stopped due to allergic reactions. No other adverse reactions were noted.
Conclusion: Our results were similar to the literature and it shows that granulocyte transfusions after myeloablative therapy limits the neutopenic period, decrease complications of neutropenia, maximum level of CRP and the duration and number of antibiotic usage. But stil controlled studies done at larger cohorts are needed.

Disclosures
No relevant conflicts of interest to declare.
Quantification of Marrow Plasmacytosis in HIV Patients
Authors: O'Brien Timothy , Bowman Lynda 
Published: October 2019

Abstract
Introduction:
A reactive, polyclonal increase in marrow plasma cells in pts with HIV is relatively common, reported to occur in 25% of cases in one series (1) and recently noted to be "usually seen" (2). However, quantification of the degree of marrow plasmacytosis has not been well described.
Methods:
Pts with a diagnosis of HIV and who had a bone marrow aspirate and biopsy performed at our institution over a 10 year period (2/2004-9/2014) were reviewed. Pts with a diagnosis of myeloma were excluded. A 500 cell count was performed on each marrow aspirate and plasma cell percentage determined.
Results:
65 pts were identified; 9 were excluded due to dry taps, so there were 56 evaluable marrow aspirates. Reasons for performing the aspirate and biopsy included: lymphoma staging (NHL in 11/65, HL in 4/65); abnormal SPEP (2/65); abnormal MRI (1/65); FUO (14/65), Kaposi's sarcoma/fevers (3/65), pancytopenia (15/65), thrombocytopenia (6/65), neutropenia (2/65) and anemia (10/65). The average marrow plasma cell percentage was 4.6%, with a range from 0- 21% (median 4%). Only 7/56 (12.5%) had >10% plasma cells. Of these 7 cases, only one had an identifiable cause (multicentric Castleman's) for the plasmacytosis. The 6 others had no neoplastic or infectious etiology, except for HIV itself (including one with 21% plasma cells). All had polyclonal plasmacytosis.
Conclusions:
In this small series of HIV marrows the degree of plasmacytosis was generally mild (average of 4.6%, which is barely above the upper limit of normal range of 3.5%). However, there were a minority of cases which exhibited significant plasmacytosis (as high as 21%) without any cause other than HIV. This suggests that, while significant marrow polyclonal plasmacytosis is usually not seen in HIV, it may occur as a result of HIV itself without any other identifiable cause.
1) Karchen DS and Frost AR. The bone marrow in HIV-related disease: Morphology and clinical correlation. Am J Clin Path. 1991; 95(1): 63-71.
2) Leibman HA and Tulpule A. "Hematologic manifestations of HIV/AIDS". Chapter 159. Hematology: Basic Principles and Practice, 6th edition. 2013.

Disclosures
No relevant conflicts of interest to declare.
First Report from the Saudi Bleeding Screening Study: Are Platelet Disorders More Common in Arabs?
Authors: Owaidah Tarek , Al-Momen Abdul Kareem M , Alzahrani Hazza A , Albanyan Abdulmajeed , Alsulaiman Ayman , Khawar Siddiqui , Alzahrani ALI , al-Madani Mohammad , AlSaleh Khalid , Mahsin Saleh 
Published: October 2019

Abstract
Inherited platelet disorders (IPDs) are a heterogeneous group of diseases affecting platelet production and function with variable clinical severity. The prevalence is estimated to be less than 1:1000,000 worldwide in most common types. There are no population based epidemiological studies in Arab ethnicity to estimate the prevalence of IPD.
Over 2 years we had conducted questioner-based survey among high school and 1st year university students in Riyadh city, Saudi Arabia. We had interviewed 3881 students (1901 (49%) male and 1980 (51%) female). Out of these students 1849(47.6%) had answered yes for any of the questions in first questioner which was followed by a detailed questioner based on MCMDM1 - VWD. Only 323 agreed to have blood testing to investigate for the bleeding tendency. Each positive case was tested for CBC, PT, PTT, ABO and PFA 100 according to standard technique. Any positive screening test for coagulation or platelet screening test was followed by more testing for relevant coagulation factor level. Those were positive only for PFA100 had been tested for platelet aggregation, electronmicroscopy, PB morphology and a sample for DNA and proteomics been collected.
The most common bleeding symptom was epistaxis found in 19.7% (3881) of all interviewed students students and was more in the positive cases 229 (43.6%) students from a total of 525 with more boys (147 out of 296, 49.7%) than the girls (82 out of 229, 35.8%, P-value= 0.002). The cutaneous symptoms were reported by 29.3% (154/525), more common in girls (102/229, 44.5%) than boys (52, 296, 17.6%, p-value<0.001). Out of the investigated cases,( 47 out of 323, 14.5 %) had high PFA100-EPI and (57 out of 323, 17.6%) Had high PFA100-ADP and 22 of these had both cartilage prolonged. We had tested 37 of the suspected cases for platelet disorders for platelet aggregation, only one case had typical features of Glanzmann's disease and 20 cases were abnormal with no clear pattern for known platelet disorders and were labeled as probable platelet disorders. We had diagnosed 8 cases with vWD.
Conclusion: The early results from our bleeding survey indicate that platelet disorders probably more common in our population than been reported els where. We are waiting the final result of laboratory tests which includes ultrastructural features, proteomics and genotyping of these cases with probable platelet diorders

Disclosures
Owaidah: King abdulaziz city for science, Novo Nordisk, Bayer: Honoraria, Research Funding.
Platelet Features from ITP Patients Responders to Different Therapeutic Treatments
Authors: Butta Nora , Rivas Pollmar María Isabel , Álvarez Román María Teresa , Martín Salces Monica , Fernandez Bello Ihosvany , Canales Miguel , Jiménez Yuste Victor 
Published: October 2019

Abstract
Background: Patients with ITP have a wide variation in the presentation of the disease, platelet count and their clinical course.
The decision to begin treatment is based on the hemorrhagic symptoms and platelet count. Intravenous immunoglobulin (IVIG) is usually associated with glucocorticoid administration in patients with severe bleeding or platelet counts <20x109/L and a quick response is required. Agonists of thrombopoietin receptor (TPO-AR) and splenectomy are other therapeutic tools for these patients.
Materials and Methods: We recruited patients with ITP before and after responding to treatment with IVIG (n = 11) and AR-TPO (4 patients with romiplostim and 10 with eltrombopag), 5 splenectomized patients and 82 healthy controls.
The percentage of reticulated platelets, platelet activation and binding of annexin-V were evaluated by flow cytometry. Plasma levels of TPO and "a proliferation-inducing ligand" (APRIL) were determined by ELISA. Procoagulant activity associated microparticles (MP) and the ability of plasma to generate thrombin were determined, respectively, with Zymuphen kit and calibrated automated thrombinography (CAT) triggered by 1 pM tissue factor and 4 micromolar phospholipid (PPP-low reagent, Diagnostica Stago, Spain).
Results: Patients with ITP that respond to IGIV and AR-TPO treatments recovered platelet counts without reaching the levels of the control group, whereas the platelet count in splenectomized patients did not differ from it. Plasma levels of TPO and the number of immature platelets in the first two groups were higher than in controls before responding to treatment. Despite recovering platelet count, platelet capacity of being activated by agonists such as TRAP (thrombin receptor agonist for PAR-1) was less than that of the controls in all groups. This decrease was not due to a reduction in the expression of the fibrinogen receptor on platelets from ITP patients.
Platelets from ITP patients before and after responding to all treatments studied, showed more phosphatidylserine exposure and greater microparticles-associated and plasma-associated procoagulant activity.
Plasma levels of APRIL, a factor that stimulates B cells and antibody production, decreased in ITP patients who responded to the AR-TPO, reaching the levels observed in the control group. In the group of splenectomized patients a decrease of APRIL was also observed, but still remained higher than in healthy controls.
Conclusions: ITP patients who respond to treatment with IVIG and AR-TPO and undergoing splenectomy recovered platelet count but not its function. The treatments did not modify the microparticles- and plasma-associated thrombogenic capacity. Among all the treatments studied, AR-TPO and splenectomy had an addittional benefical effect reducing APRIL plasma levels

Disclosures
No relevant conflicts of interest to declare.
Mod-5014, a Long-Acting FVIIa-CTP, Proposing a Novel Prophylactic Treatment Supporting Less Frequent Subcutaneous or Intravenous Injections with a Similar Mechanism of Action to rFVIIa: Proof-of-Concept in Hemophilic Animal Models
Authors: Binder Lior , Bar-Ilan Ahuva , Hoffman Malka , Hart Gili 
Published: October 2019

Abstract
Introduction:
OPKO Biologics is a clinical-stage public company developing bio-better long-acting versions of existing therapeutic proteins, utilizing a technology termed CTP. The technology involves fusion of the C-terminal peptide of hCG to a target protein. The aim of this work was to comprehensively assess the feasibility of intravenous (IV) or subcutaneous (SC) administration of FVIIa-CTP (MOD-5014) utilizing the most relevant in vivo pre-clinical models, and to characterize the FVIIa-CTP mechanism of action in preparation for an on-going clinical study.
Methods:
FVII-CTP was expressed in CHO cells, purified and activated utilizing a CTP-specific purification process. FVIIa-CTP's pharmacokinetics (PK), pharmacodynamics (PD), long-term hemostatic effect and safety parameters were extensively characterized following SC and IV administration in transient FVII-/- rats and FVIII-/- mice. In addition, the long-term hemostatic effect of FVIIa-CTP was evaluated following a bleeding challenge and compared to commercial rFVIIa. Finally, interaction with co-factors, activity, and the off-target effect of FVIIa-CTP was comprehensively characterized.
Results:
The studies demonstrated that FVIIa-CTP provides long-term exposure (AUC) and half-life that are significantly superior to those of rFVIIa, and consistent with the prolonged half-life of FVIIa-CTP (at an average of 3- and 5-fold, respectively) when compared to IV or SC administration of FVIIa. In addition, a 30% increase in bioavailability was observed relative to commercial FVIIa. A profound improvement in clotting parameters and survival rate following TVT, as well as a reduction of bleeding duration and intensity in tail-clip studies were obtained for both routes of administration for up to 48 hours. Moreover, the safety profile of FVIIa-CTP was further confirmed.
Conclusion:
Attachments of CTP to FVIIa led to a pronounced enhancement of PK and PD, increased exposure as reflected by AUC, elevated half-life, and improved recovery in mice, rats and pigs following SC and IV administration. FVIIa-CTP injection resulted in an improved bioavailability that translated to a marked in vivo hemostatic effect. Our data suggest that CTP-fused FVIIa can potentially provide a novel approach for IV or SC prophylactic treatment of hemophilic patients (both pediatric and adult), with the major benefit of significant improvement in quality of life.

Disclosures
No relevant conflicts of interest to declare.
Evaluation of Triton X-100 Effect on Coagulation Tests
Authors: Nadeau Marchand Sarah , Khalaf Daniel , Nadeau Chantal , Blais Normand 
Published: October 2019

Abstract
CONTEXT:
Triton X-100 is a non-ionic surfactant that has been proposed as a virus inactivator in a laboratory setting for it causes cell lysis through lipid membrane disruption without denaturing proteins. Very few studies have tried to evaluate its effect on laboratory tests, especially on coagulation tests that require a phospholipid subtract.
METHOD:
Plasma samples were collected. Triton X-100 was spiked at a concentration of 0,25% and specimens were incubated for an hour. We performed international normalized ratio (INR), activated partial thromboplastin time (aPTT), thrombin time (TT), fibrinogen dosing and D-Dimer dosing, comparing the standard plasma with the triton X-100 exposed plasma. We also dosed coagulation factors, and performed dilution and lupus anticoagulant studies. Finally, we compared prothrombin time and aPTT using reagents from various manufacturers.
RESULTS:
We observed an important difference for the INR and the aPTT with addition of triton x-100. A slight decrease of an average of 6.6 to 16.4% was also found in factor assays. Differences in the INR and the aPTT were dependent respectively on the ISI and the phospholipids content of the reagent.
CONCLUSION:
The addition of triton x-100 significantly modifies INR and aPTT results with every reagent tested. The impact on TT and fibrinogen is not clinically relevant, and the D- Dimer dosage is not affected. The slight decrease in all coagulation factors does not explain those results. The interference could result from an interaction with phospholipids, calcium or some enzymatic reactions caused by the presence of triton x-100 in the analyzed specimen.
Table. Test Mean Mean Mean of difference p-value (paired t-test) without Triton with Triton INR 1,59 2,87 68,80% p<0,001 aPTT 31,59 sec 61,80 sec 86,10% p<0,001 TT 16,82 sec 17,42 sec 3,50% p<0,001 Fibrinogen 3,27 g/L 3,21 g/L -0,70% p=0,001 D-Dimer 2897 mcg/L 2905 mcg/L 4,30% p=0,697

Disclosures
No relevant conflicts of interest to declare.
Carbohydrate Glycosylation Deficiency Disorder Secondary to Absence of Phosphomannose Mutase Confers Both a Hemorrhagic and Thrombotic Phenotype
Authors: Gleditsch Katrina , Ameri Afshin 
Published: October 2019

Abstract
Congenital disorders of glycosylation are a group of inherited disorders affecting the addition of a carbohydrate moiety to a protein. A defect in this pathway can cause adverse effects in most organ systems, often presenting early in life. The most common of these disorders is CDG type 1a / PMM2-CDG). In this disorder the loss of the enzyme phosphomannomutase-2 prevents the conversion of mannose-6-phosphate to mannose-1-phosphate. This has previously been associated with deficiencies of protein C, protein S, antithrombin III, factor IX and factor XI and a subsequent imbalance of coagulation pathways leading to thrombotic events.
We present the case of a 14-year-old male with known history of CDG1a and previous bleeding complications following left orchiopexy at age 3, at that time coagulation screening showed a normal PT/PTT and surgery was deemed safe. The patient now presented to our pediatric hematology/oncology clinic for further evaluation of coagulation abnormalities prior to pediatric surgery performing right orchiopexy. Laboratory values at this time showed coagulation deficiencies, of ATIII, Factor XI, Protein C and Protein S, PT/ PTT , F VIII, FIX and vWF where normal. Prior to surgery, patient was given fresh frozen plasma and ATIII concentrate the patient underwent a successful Stage One Fowler-Stephen Procedure with adequate hemostasis. Several months later the patient developed leg swelling and was diagnosed right femoral DVT. This resolved with ATIII substitution and anticoagulation with LMW heparin. The patient's immediate family was tested for bleeding/clotting disorders and results were found to be normal. This report not only supports the association of bleeding but also thrombosis with CDG1a. We propose that in patients with known CDG routine PT/PTT will not uncover a hemostatic abnormality but further screening isolated factor deficiency need to be performed and prophylactic factor substitution be performed prior to any surgical interventions. Also an awareness of the highly procoagulant state in these patients that predispose to DVT and central nervous system vascular thrombosis need to be present.

Disclosures
No relevant conflicts of interest to declare.