bluuebunny/crossref_metadata_2025_split huggingface dataset:
Psychological, Physical and Functional Importance of Patient Reported Outcomes Among Cancer Outpatients
Authors: Shrotriya Shiva , Walsh Declan , Sharma Mukta , Rayamajhi Supratik 
Published: October 2019

Abstract
Introduction:
There has been increased interest in patient-reported outcomes (PROs) as they allow consistent monitoring of patients' symptoms and quality of life. We evaluated the prevalence of PROs among cancer outpatients. Our objective was to look at the association of ET components with demographic and disease characteristics.
Methods:
PROs were prospectively collected cross sectional data which were later mixed with retrospectively obtained clinical data from the EMR. Predictors of ET components were determined by linear regression analysis. The predictors of those who required Help was determined by logistic regression.
Results:
The mean age was 58 (±14) years. 54% were male. The common cancer diagnoses were breast 17%, hematological (Leukemia) 17% and lymphoma 12%. Only a minority (7%) of participants required help (N = 1076) with the tablet-based surveys. Age categories ≤ 30 and 51-70 scored lower in mean depression ET. African Americans had a higher mean ET Anger scale. African Americans scored higher in mean need of Help -ET. Age 31-50 years was at 13% lower risk and 51-70 years was at 72% lower risk. Those with self-care problems were at higher risk of requiring Help with tablet computer.
Conclusions:
Many cancer patients visiting the cancer center had high pain/discomfort, anxiety/depression, problems with usual activities and mobility problems. Younger patients (31-50 years) had more distress and depression (ET). African Americans reported more problems with mobility, self-care, usual activities, pain/discomfort and anxiety/depression (EQ5D). Those with self-care problems were at risk to require help with tablet-based surveys.

Disclosures
No relevant conflicts of interest to declare.
When to Suspect Systemic Mastocytosis?
Authors: Kaplan Sibel , Kuskonmaz Baris , Soyer özge Ulusoy , Aytaç Selin , Gümrük Fatma 
Published: October 2019

Abstract
Background : Mastocytosis is a rare disease in children and it usually resolves by adolesence.However; it causes anxiety in parents and should be taken into consideration in patients with cutaneous eritematous lesions.
Aim: To find out the systemic mastocytosis patients who apply to pediatric hematology , pediatric allergy and dermatology policlinics.
Material and Methods: The files of 24 patients diagnosed with mastocytosis between January 2018 and August 2018 in our clinic were retrospectively analyzed.
Results: All patients had cutaneous mastocytosis, 14 patients had urticaria pigmentosa and 9 patients had solitary mastocytoma and one patient had diffuse cutaneous mastocytosis. The male-female ratio was: 2/1. The median age for onset of disease was 7,2 (0-48 months )months. The patients had different types of skin findings such as macules (n=16), plaques(n=6), papules(n=4) and bullae(n=3). None of the patients had anaphylaxis but two patients had angioedema. The diagnosis was confirmed with skin biopsy in 8 patients. The other were diagnosed due to typical history and physical examination.
None of the patients had cytopenia, hepatosplenomegaly.Only one patient triptase level >20 ug/l. The bone marrow aspiration and biopsy was done to 3 patients and all were normal.The patients were treated with H2 antihistaminics, local moisturizing creams and topical corticosteroid drugs in case of undesirable pruritus.
Conclusions: Most cases of childhood mastocytosis are observed in the form of cutaneous mastocytosis and ıt usually resolves by adolescence. If the patients have cytopenia, hepatosplenomagaly or triptase level >20 ug/l the bone marrow aspiration and biopsy is recommended.

Disclosures
No relevant conflicts of interest to declare.
Treatment of Unresectable Unicentric Castleman Disease with Therapeutic Embolization
Authors: Mohan Meera , Meek James C , Meek Mary Elizabeth , Broadwater Ralph Lynn , Stone Katie , Greenway Amy , Alapat Daisy , van Rhee Frits 
Published: October 2019

Abstract
Introduction: Unicentric Castleman disease (UCD) is a rare non-clonal lymphoproliferative disorder affecting one lymph node station. UCD can be an incidental finding on radiologic studies, whilst other patients have symptomatology due to compression of vital structures. Surgical extirpation is the preferred therapy and is usually curative, but unresectable UCD can represent a therapeutic challenge. Castleman lymph nodes are often highly vascularized, which offers the opportunity for therapeutic embolization. We report a series of 6 patients with unresectable UCD who were treated with embolization either as sole therapy or supplemented by cryoablation and surgery.
Methods: CT rotational angiography was performed to localize the arterial supply of UCD masses. Feeding vessels were selectively embolized using a 50:50 mixture of lipiodol and alcohol or 300-500 micron embospheres. A second arteriography was performed 2 to 3 months later to identify and embolize any new arterial channels.
Results: Data is summarized in Table 1. Of a cohort of 47 patients with UCD, 6 (13%) were found to have symptomatic, unresectable disease. All patients were HIV and human herpesvirus-8 negative. The median patient age was 34 years (range: 28-34); five patients were male and one was female. Disease was localized to the pelvis (n=3), mediastinum (n=2), and axilla (n=1). In all but one case, the histology was of the hyaline vascular variety. Four patients had failed R-CHOP, rituximab/steroids, or both. In 2 patients, embolization was done as primary therapy, while 3 underwent additional surgery. In 5 patients, embolization was performed twice to ablate secondary arterial channels that had appeared after the first procedure. Adjunctive cryoablation at the time of embolization was applied in 2 patients. All treated patients had major reduction in their lymph node mass. The median reduction in tumor bulk was from 274cc (range:13-969) to 21cc (range: 3-394). One patient with an axillary mass involving the brachial plexus failed therapy and received radiation. A second patient had regrowth of the UCD and responded to combination lenalidomide and obinituzumab. Responses were sustained for at least 2 years in the remaining patients.
Conclusion: A small number of case reports have been described UCD patients treated with arterial embolization as an immediate preoperative adjunct to surgery to limit intraoperative bleeding. In the present series, we utilized embolic devascularization to achieve cytoreduction rather than merely prevent surgical hemorrhage. Embolization was complemented by cryoablation and rendered surgery feasible. This case series highlights that effective disease control can be obtained of unresectable UCD using a multimodality approach in which vascular embolization plays a crucial role.

Disclosures
No relevant conflicts of interest to declare.
The Efficacy of Ultrasound Joint Examination for the Management in Patients with Hemophilia
Authors: Nishimura Shiho , Tomioka Keita , Shimomura Maiko , Mizoguchi Yoko , Sasaki Shinobu , Tani Chihiro , Matsubara Yoshiko , Awai Kazuo , Nakashima Yuko , Adachi Nobuo , Kobayashi Masao 
Published: October 2019

Abstract
The regular prophylactic replacement therapy with clotting factors has significantly reduced the arthropathy in patients with hemophilia. Early detection of the signs of joint damage is important to prevent the progressive joint damage. For the early detection, we have introduced the regular ultrasound (US) joint examination in patients with hemophilia from 2014 based on the hemophilia early arthropathy detection with ultrasound (Head-US) scanning protocol. US examination has been performed at the time of annual comprehensive clinic in Hiroshima University Hemophilia Center. Forty-five patients aged 1 to 33 years were enrolled and more than 280 joints were evaluated in this study. US joint examination was performed within 30 minutes without the sedation in all aged children. Abnormal findings, such as cartilage changes, subchondral bone erosion, synovial hypertrophy and/or joint effusion were observed in 8 out of 45 patients. The replacement therapy with clotting factors of all 8 patients aged 13 to 33 years was an insufficient prophylaxis during early childhood. The residual 37 patients aged less than 15 years have relatively followed the prophylactic treatment. The prophylactic regimen has been individually determined based on the trough levels of factor IX concentration in plasma for hemophilia B and pharmacokinetics of factor VIII using MyPKFitR for hemophilia A patients, respectively. The result suggests the importance of the careful prophylactic replacement therapy considering the factor concentration in plasma.
Four patients aged 4, 5, 18, and 19 years, respectively, suffered from painful and/or swollen joint episodes from 2014 to 2018. Urgent US examination without the use of any sedatives revealed ankle, knee, or hip joint bleeding in each case. According to the replacement therapy for breakthrough bleeding, hemoarthropathy was accessed by consecutive examination of US. These results suggest that US joint examination could be necessary for the early detection of joint damage and for appropriate treatment of hemoarthropathy. Collectively, utilization of US examination would be essential for the management through the life in patients with hemophilia.

Disclosures
No relevant conflicts of interest to declare.
Next Generation Flow for Multiple Myeloma Minimal Residual Disease: Igh Rearrangement NGS Is Complement to the NGF
Authors: Kim Sung-Min , Kim Jung-Ah , Jeong Dajeong , Yun Jiwon , Lim Kyu Min , Hwang Sang Mee , Yoon Sung-Soo , Lee Dong Soon 
Published: October 2019

Abstract
Background: Detection of leukemia-associated aberrant immuno-phenotype is used to assess minimal residual disease (MRD) by multi-parameter flow cytometry (MFC). However, detection of MRD by MFC remains to be a challenging due to the possible change in aberrant immunophenotype during disease progress. In our present study, we compared International Myeloma Working group (IMW) treatment response and NGF MRD, including BM PC% and cytogenetics. Thereon, we conducted IgH rearrangement study by NGS in cases showing discrepant results.
Methods: A total of 35 BM (35 myeloma patients at follow-up) was enrolled. We performed NGF using 8-color antibody panel using Navios flow cytometer and Infinicyt. Linearity of NGF was validated with myeloma cell line (U266) and BM specimen at initial diagnosis in myeloma patient. IgH rearrangement NGS was performed using Immunoseq assay (Adaptive Biotechnologies, Seattle, WA, USA). Paired specimen at initial diagnosis BM and follow-up BM were subjected to NGS study.
Results: Detection sensitivity of NGF was <0.001%. Patients who achieved CR or sCR showed MRD negativity in 63.6% (7/11). Twenty-three patients showed neoplastic PCs above LLOQ and their response criteria were 1 sCR, 3 CR, 2 VGPR, 3 PR, 1 MR, 5 SD, 3 progressive disease, 3 relapse, and 2 with unavailable response. Four patients who did not achieve CR (1 VGPR, 1 PR, 1 MR, and 1 SD) showed MRD negativity by NGF. In 4 patients with discrepancy between IMW treatment response and NGF, we compared the results of IgH NGS at initial BM with those after treatment. NGS revealed a persistence of residual clone in 1 patient and an acquisition of new clone after treatment. One patient had same dominant clone both initial diagnosis BM (95.2%; proportion of clone) and follow-up BM (45.8%). The other patient had newly appeared clones in follow-up BM (6.12%, 5.63%, 3.42%, 3.11%, 3.09%) which clones were absent in initial diagnosis BM. The other 2 patients showed heterogeneous clones without dominant clone at follow-up BM by NGS. Results of FISH and immunofixation are summarized in Table 1. This results show IgH rearrangement NGS can detect malignant clone that could not be identified by using NGF.
Conclusions: Thirty-six percent of patients who did not achieve CR showed NGF MRD negativity and NGS revealed residual clones in half of them. Switching of immunophenotypes of neoplastic PC can escape monitoring of NGF, and complementary NGS test is needed to catch such drifting clones for monitoring of MRD in MM.

Disclosures
No relevant conflicts of interest to declare.
Single-Cell Mutational Profiling Describes the Molecular Heterogeneity of Clonal Evolution in MDS during Therapy and Relapse
Authors: Aleshin Alexey , Durruthy-Durruthy Robert , Medeiros Bruno C. , Eastburn Dennis J. , Greenberg Peter L 
Published: October 2019

Abstract
Background: Myelodysplastic syndromes (MDS) are a collection of clonal diseases of dysfunctional hematopoietic stem cells, characterized by ineffective hematopoiesis, cytopenias, and dysplasia. Increased understanding of the mutational landscape of MDS has led to initial improvements in prognostic models based on clinical and cytogenetic variables. However, bulk sequencing techniques are limited in their ability to delineate clonal complexity and identify rare drug resistant subclones. To better understand clonal heterogeneity and clonal evolution of MDS we applied a high-throughput single cell sequencing technique to both diagnostic and longitudinal MDS samples.
Methods: Samples were examined for 5 patients with MDS at diagnosis and, when available, progression. Mutational bulk sequencing was performed by NGS panel sequencing and exon sequencing was available in select cases. Single cell processing was performed using the Tapestri (Mission Bio) platform. Briefly, individual cells were isolated using a microfluidic approach, followed by barcoding and genomic DNA amplification for individual cancer cells confined to droplets. Barcodes are then used to reassemble the genetic profiles of cells from next generation sequencing data. We applied this approach to individual MDS samples, genotyping the most clinically relevant loci across upwards of 10,000 individual cells.
Results: Single-cell sequencing was able to be performed successfully on all samples tested and recapitulated bulk sequencing data. We observed high concordance between bulk variant allele frequencies (VAFs) and sample level VAFs derived from single cell sequencing data (r2 = 0.98). Additionally, single cell analysis allowed for resolution of subclonal architecture and tumor phylogenetic evolution beyond what was predicted from bulk sequencing alone. Single-cell SNVs were able to resolve host and donor cell populations after bone marrow transplant and accurately predict chimerism and disease relapse. Furthermore, we were able to resolve the co-occurance of molecular alterations within subclones and establish zygosity of individual mutations at a single cell level. Rare subclones associated with disease relapse, were able to be identified in initial diagnostic samples that were frequently under the limit of detection of bulk NGS.
Conclusions: Our results suggest more molecular complexity in MDS tumor samples than implied from bulk sequencing methods alone and indicates utility of single-cell sequencing for identification of resistant clones and longitudinal therapy monitoring.

Disclosures
Aleshin: Mission Bio, Inc.: Consultancy; Natera, Inc.: Employment. Durruthy-Durruthy:Mission Bio, Inc.: Employment, Equity Ownership. Medeiros:Genentech: Employment; Celgene: Consultancy, Research Funding. Eastburn:Mission Bio, Inc.: Employment, Equity Ownership.
Correlation of Circulating Microparticles with Coagulation and Fibrinolysis Is Healthy Individuals
Authors: Albert Venencia , Subramanian Arulselvi , Pati Hara Prasad 
Published: October 2019

Abstract
Introduction
Microparticles (MPs) are small membrane blebs that are released in response to cellular activation or apoptosis from the cell surface by proteolytic cleavage of the cytoskeleton. Previous studies have reported low levels of naturally produced cell-derived microparticle in healthy individuals. This study was conducted to assess whether circulating microparticles induce thrombin generation leading to low grade activation of the coagulation system in healthy individuals.
Materials & Methods
Flow cytometry analysis of three phenotypes of Platelet derived (PMP), Endothelial derived (EMP) and TF bearing (TFMP) microparticles was done in in the 20 healthy individuals. Triple gating strategy (i) particle size(<0.5µm) (ii) expression of cell surface markers (PMP, CD42a+; EMP, CD62E+; TF bearing MP(TFMP), CD142+) and (iii) phosphatidylserine(Annexin V+) was used. Plasma concentrations of thrombomodulin (TM), Tissue Factor (TF), Tissue factor pathway inhibitor (TFPI), Protein C (PC), Free Protein S (PS), Thrombin antithrombin (TAT) complexes, soluble fibrin monomer (sFM) was done assess the status of coagulation system. Spearman's rank correlation was done examine the role of cell-derived microparticles as critical effectors of thrombosis.
Results: the study group comprised of 75% males of the age group (mean±SD27.3±4.32. Total Microparticles (Annexin V+) enumerated in plasma was 1125±355 (count/µl). 52.8% were TFMP [median (IQR)] [380.3(301.8-710.1) (count/µl)]. Highest number of MP originated from activated platelets [249.1(198.9-404.5) (count/µl)], followed by endothelial cells [140.9(124.9-286.0) (count/µl)]. A statistically significant and inverse correlation of EMP's with TAT complex was observed [12.7(6.8-20.1) ng/ml] (r = -0.46, p = 0.01), PS (93.4±20.6 %) (r = -0.52, p = 0.01) and TM (11.4±4.47 ng/ml) (r = -0.56, p = 0.008). Also, TFMP significantly correlated with TF [3.9(3.0-5.0)] (r = 0.46, p = 0.03) and PC (90.4±17.7) (r=-0.42, p=0.04). No correlation was observed between PMP numbers and coagulation pathway markers.
Conclusion: Sub optimal degree of coagulation and natural anticoagulation pathway are occurring in healthy individuals. Microparticles moderately correlated with TF levels. Low EMP's levels correlated with the anticoagulation markers and thrombin generation, suggesting that EMPS may have a role in inhibition of thrombosis. The impact of endothelial vesiculation on basal coagulation should be studied further.

Disclosures
No relevant conflicts of interest to declare.
Ectopic expression of Delta4 impairs hematopoietic development and leads to lymphoproliferative disease
Authors: Dorsch Marion , Zheng Gang , Yowe David , Rao Prakash , Wang Yanjun , Shen Qiong , Murphy Curran , Xiong Ximing , Shi Qiuju , Gutierrez-Ramos Jose-Carlos , Fraser Chris , Villeval Jean-Luc 
Published: October 2019

AbstractNotch signaling plays a critical role in cell fate determination in many developmental systems, including the hematopoietic system. We and others have recently cloned a novel Notch ligand called Delta4. In this study, we show the effect of retrovirus-mediated ectopic expression of Delta4 in hematopoietic cells. Lethally irradiated mice transplanted with bone marrow cells expressing Delta4 initially suffered from leukopenia and thrombocytopenia. Although all lineages were affected, the deficit in B cells and platelets was the most durable and profound. A rapid expansion of CD4+CD8+ cells occurred shortly after transplantation. CD4+CD8+ cells progressively invaded all tissues analyzed except the thymus, which surprisingly was atrophic. CD4+CD8+cells were mainly non–Delta4-transduced cells, strongly suggesting that the disease was not cell autonomous. Around 15 weeks after transplantation, mice died from this severe lymphoproliferative disorder, which was not transplantable in late-stage disease into secondary recipients. Mice transduced with a soluble form of Delta4 behaved like control mice. Characterization of early hematopoietic development revealed that Delta4 expression impaired formation of day-12 spleen colony-forming units (CFU-Ss) and, to a greater extent, pre–CFU-Ss. No effect was observed on myeloid colony-forming cells (CFU-Cs), indicating that Delta4 specifically acted on the earliest hematopoietic stem cell compartment. These results show that constitutive expression of Delta4 in hematopoietic cells impairs the development of B cells, platelets, and early stem cells and induces a lethal lymphoproliferative disease.
Acute thrombocytopenia after treatment with tirofiban or eptifibatide is associated with antibodies specific for ligand-occupied GPIIb/IIIa
Authors: Bougie Daniel W. , Wilker Peter R. , Wuitschick Elizabeth D. , Curtis Brian R. , Malik Mohammad , Levine Stewart , Lind Richard N. , Pereira Jaime , Aster Richard H. 
Published: October 2019

AbstractAcute thrombocytopenia is a recognized complication of treatment with GPIIb/IIIa inhibitors whose cause is not yet known. We studied 9 patients who developed severe thrombocytopenia (platelets less than 25 × 109/L) within several hours of treatment with the GPIIb/IIIa inhibitors tirofiban (4 patients) and eptifibatide (5 patients). In each patient, acute-phase serum contained a high titer (range, 1:80-1:20 000) IgG antibody that reacted with the glycoprotein IIb/IIIa complex only in the presence of the drug used in treatment. Four patients had been previously treated with the same drug, but 5 had no known prior exposure. Pretreatment serum samples from 2 of the latter patients contained drug-dependent antibodies similar to those identified after treatment. No tirofiban- or eptifibatide-dependent antibodies were found in any of 100 randomly selected healthy blood donors, and only 2 of 23 patients receiving tirofiban or eptifibatide who did not experience significant thrombocytopenia had extremely weak (titer, 1:2) tirofiban-dependent antibodies. In preliminary studies, evidence was obtained that the 9 antibodies recognize multiple target epitopes on GPIIb/IIIa complexed with the inhibitor to which the patient was sensitive, indicating that they cannot all be specific for the drug-binding site. The findings indicate that acute thrombocytopenia after the administration of tirofiban or eptifibatide can be caused by drug-dependent antibodies that are “naturally occurring” or are induced by prior exposure to drug. These antibodies may be human analogs of mouse monoclonal antibodies that recognize ligand-induced binding sites (LIBS) induced in the GPIIb/IIIa heterodimer when it reacts with a ligand-mimetic drug.
Normal Arp2/3 complex activation in platelets lacking WASp
Authors: Falet Hervé , Hoffmeister Karin M. , Neujahr Ralph , Hartwig John H. 
Published: October 2019

AbstractArp2/3 complex is believed to induce de novo nucleation of actin filaments at the edge of motile cells downstream of WASp family proteins. In this study, the signaling pathways leading to Arp2/3 complex activation, actin assembly, and shape change were investigated in platelets isolated from patients with Wiskott-Aldrich Syndrome (WAS), that is, who lack WASp, and in WASp-deficient mouse platelets. WASp-deficient human and mouse platelets elaborate filopodia, spread lamellae, and assemble actin, identical to control WASp-expressing platelets. Human platelets contain 2 μM Arp2/3 complex, or 8600 molecules/cell. Arp2/3 complex redistributes to the edge of the lamellae and to the Triton X-100–insoluble actin cytoskeleton of activated WASp-deficient platelets. Furthermore, the C-terminal CA domain of N-WASp, which sequesters Arp2/3 complex, inhibits by half the actin nucleation capacity of octylglucoside-permeabilized and activated WAS platelets, similar to its effect in WASp-expressing cells. Along with WASp, platelets express WAVE-2 as a physiologic activator of Arp2/3 complex and a small amount of N-WASp. Taken together, our findings show that platelets activate Arp2/3 complex, assemble actin, and change shape in the absence of WASp, indicating a more specialized role for WASp in these cells.