bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Randomized, Double-Blind Trial of the Interaction between Cranberry Juice and Warfarin.
Authors: Ansell Jack , McDonough Maryellen , Harmatz Jerold S. , Greenblatt David J. 
Published: April 2020

Abstract
Therapeutic warfarin therapy is highly influenced by concomitant drug therapy or dietary factors by effecting warfarin metabolism or vitamin K status. Cranberry juice (CJ) was recently implicated to influence the INR in patients on warfarin based on a number of brief anecdotal or case reports. This study was designed to determine what influence, if any, daily cranberry juice consumption has on INR levels and plasma warfarin concentrations in patients stably anticoagulated with warfarin. Patients on warfarin for a variety of indications from a population of anticoagulation clinic patients were selected because of their past history of stable anticoagulation and willingness to participate in the study. Major inclusion criteria required a therapeutic INR range of 2.0 – 3.0, no hepatic or renal dysfunction, a stable INR (1.7 – 3.3) on at least 2 measurements within 8 weeks prior to study entry, and informed consent. The study consisted of a 2 week lead-in phase (with weekly INRs in range); a 2 week intervention phase (double-blind daily consumption of an 8 oz glass of cranberry juice or placebo); and a one week follow-up phase (35 day total). Any patient with an out of range INR during the intervention phase ceased the intervention but continued through follow-up. 30 patients were randomized, 14 to CJ and 16 to placebo. 28.6% (4/14) in the CJ group developed a minimally elevated INR and 7.1%(1/14) developed a low INR during the intervention phase. 25% (4/16) in the control group developed a minimally elevated INR during the intervention. There was no significant difference in the mean INRs from each group on each day of measurement except for day 11 of the intervention phase when the CJ group was significantly higher than the placebo group (p&lt;0.02), although on day 15 (end of intervention) the mean INRs from both groups were identical. Plasma warfarin levels are currently pending and should be helpful in identifying any effect on warfarin clearance or warfarin plasma protein binding. A daily 8 oz glass of cranberry juice appears to have no consistent effect on the INR in patients on warfarin therapy compared to placebo.
Cost-Consequences of Fondaparinux Use for Treatment of Heparin-Induced Thrombocytopenia.
Authors: Kanaan Abir O. , Donovan Jennifer L. , Belliveau Paul P. , Roy Tara , Al-Homsi Ahmad-Samer 
Published: April 2020

Abstract
Heparin-induced thrombocytopenia (HIT) is a severe complication of therapy with heparin and low molecular-weight heparins and is associated with increased morbidity and mortality. Furthermore, HIT constitutes an economic burden on health care systems. Direct thrombin inhibitors (DTIs) lepirudin and argatroban; the approved agents for HIT treatment; are expensive and require intravenous administration with substantial use of resources and increased duration of hospital stay. Indeed, the cost of management of HIT utilizing DTIs in heart surgery has been estimated to range from over $100 to $300 million dollars nationwide. Published case reports, abstracts, and our own data support the use of fondaparinux, a pentasaccharide, in the management of HIT as an effective and safe alternative to DTIs. We evaluated the cost associated with fondaparinux use in a series of patients with HIT treated at our tertiary care teaching institution. We performed a retrospective review of 18 patients with HIT receiving fondaparinux during study period from January 2002 through June 2006. HIT diagnosis was found in 77.7% of patients during their hospital stay and in 22.2% at admission. Ten patients were initially treated with argatroban (9) or lepirudin (1) before switching to fondaparinux due to concerns of increased risk of bleeding mandating the use of an anticoagulant with short half-life or to renal failure prohibiting the use of fondaparinux. The total cost for the group including actual direct variable (room, pharmacy, lab, and supplies), actual direct fixed, and indirect costs was $1,484,297 and the mean was $82,462±70,153. The actual direct variable cost was $888,461 with a mean of $49,359±43,047 per patient. The actual direct fixed cost was $344,563 with a mean of $19,142±15,257. The indirect cost was $251,273 with a mean of $13,960±12,094. In this series, the daily cost of anticoagulant per patient based on average wholesale price (AWP) $407. This compared favorably to a daily cost per patient of $1093.76 for argatroban and $1732.8 for lepirudin. The total cost of drug for all patients was $70,414 as opposed to an estimated cost of $189,220 or $299,774 should argatroban or lepirudin have been used, respectively. This translated into an estimated savings from $129,000 to $229,000. In summary, the utilization of fondaparinux in HIT treatment at our institution resulted in a dramatic drug cost reduction. Coupled with its subcutaneous route of administration and the absence of need for laboratory monitoring, allowing reduction in hospital stay and spared resources, fondaparinux would represent an attractive alternative to DTIs in the management of HIT pending further clinical studies to confirm its safety and efficacy.
Irradiation of Cellular Blood Components with Cobalt 60 Is Very Efficient and Safe in the Prevention of Transfusion Associated Graft Versus Host Disease (TA-GVHD) in the Allogeneic Transplant Setting.
Authors: Karduss Amado J. , Leon Eduardo , Buitrago Lina , Gomez Luis R. , Jimenez Alejo , Reyes Pedro , Coll Yadira , De Ossa Hilda 
Published: April 2020

Abstract
For the prevention of TA-GHVH in patients who received a allogeneic stem cell transplant is mandatory the gamma irradiation of the all cellular blood components. This irradiation is usually done with Cesium 137 and with a special blood bank irradiators. However these devices are expensive; because that, in developing countries, is frequent the utilization of Cobalt 60 and the same device that is used in the radiotherapy department, instead of blood bank irradiators. We present our experience with this technique.
From Dec 2002 to Dec 2005 thirty patients received a allogeneic stem cell transplant and 28 were analysed. The stem cells source was: peripheral blood 25, unrelated cord blood 2, and bone marrow 1. The irradiation of the blood was performed with Cobalt 60–1.24 Mev- (theratron 780 C); the irradiation field was calculated for covering all of the bag surface and a dose of 3.5 Gy was administered to the mild plane of the bag.
158 blood concentrates were transfused, 68 red cell (X:2.5 per patient), and 90 platelets (3.2 per patient). The pre transfusion median hemoglobin and platelet levels were 7.63 g/dl and 12.000/ul; after transfusion was a median increase of 2.3 gm/dl (0.6–4.7) in hemoglobin and 18.000/ul (0–140.000) in platelets.
There was no any case of TA-GVHD. Four patients developed pos transplant aGVHD, in all of the cases the disease began 50 days or more after the last transfusion, there were no pancytopenia and the aGVHD was resolved completely with the treatment.
Conclusion
In receptors of allogeneic stem cell transplant the gamma irradiation of blood components with Cobalt 60 and with the same device which is used for patients radiotherapy is 100% effective and safe in the prevention of TA-GVHD. This is a good alternative in centers without blood bank irradiator
Review of Serologically Confirmed Cases of Transfusion-Related Acute Lung Injury Reported to a Blood Center.
Authors: Houseworth Julie L. , Rhamy Jennifer , Yarnell Vicki , Parks Jodi A. , Smith Daniel S. , White Linda , Waxman Dan A. 
Published: April 2020

Abstract
We reviewed 13 cases of serologically confirmed Transfusion-Related Acute Lung Injury (TRALI) reported to our blood center over a five-year period. Cognate antigen-antibody pairs were noted, as well as product transfused, indication for transfusion, onset of symptoms related to transfusion and time to resolution. All patients demonstrated bilateral pulmonary edema on CXR. Onset of symptoms for all cases occurred during transfusion of implicated product, or within one hour post-transfusion. All donors of implicated products were multiparous females. The majority of implicated products (77%) were FFP. There were 3 TRALI deaths, all resulted from transfusion of FFP. Anti-neutrophil, HLA Class I and/or Class II antibodies were identified in all fatal cases. Platelets comprised 15% of implicated products, and RBC’s only a single case (7 %). Among patients with TRALI receiving FFP, the most common indication was reversal of anticoagulation (50%). Chart review in two cases indicated Vitamin K in lieu of FFP may have been appropriate.
Comparison of Serologically Confirmed TRALI Cases Patient Product Reason for Tx Time to Resolution Neutrophil Antibody HLA I HLA II HLA PRA 1 FFP Reverse anticoag. Death @ 7 hours HNA-3a Neg. Neg. 0 2 Platelet Thrombocytopenia &lt;1 day + Neg. Neg. 0 3 FFP Reverse anticoag. 2 days + Neg. Neg. 0 4 Platelet Pancytopenia &lt;1 day + Neg. Neg. 0 5 FFP Reverse anticoag. 4 days + A2 B3 DR 52 I - 90% II - 56% 6 FFP Not available unknown + Neg. Neg. 0 7 FFP Periop. Bleeding unknown Not tested A2 Neg. 40% 8 FFP Reverse anticoag. 2 weeks Not tested Neg. DR 17 63% 9 Cryopoor plasma TTP 4 days Not tested Neg. DR 52 41% 10 FFP Reverse anticoag. Death @ 4 hours Not tested B 50 DR 16 I - 95% II - 89% 11 RBC Bleeding 2 days Not tested Neg. DR 52 60% 12 FFP GI Bleed Death Not tested Neg. DR 53 DQ 5 60% 13 FFP GI Bleed 2 days Not tested Neg DR 52 60%
In our small series, the majority of implicated products were FFP, and all products were from multiparous females. Production of FFP exclusively from male donors is currently under consideration. Although male donor plasma can be expected to reduce the risk of TRALI associated with transfusion of FFP, it will not eliminate it entirely. Therefore, the risk of TRALI should be factored into the decision to transfuse all products. FFP should be administered cautiously for all indications, including reversal of anticoagulation.
False Positive Pregnancy Test Resulting from Passive Transfusion of beta-Human Chorionic Gonadotropin (bHCG) from Donor Red Blood Cells.
Authors: Shelat Suresh G. , Friedman David F. , Smith-Whitley Kim , Meny Geralyn 
Published: April 2020

Abstract
Blood products may contain donor-derived soluble factors such as allergens or antibodies, which when transfused, may cause pathology in the recipient or unexpected test results.
Case: We describe a 16 year old female with hemoglobin SC disease who was referred for erythrocytapheresis to reduce the level of sickle hemoglobin prior to a surgical procedure that required general anesthesia. The patient was exchanged with five units of packed red blood cells (PRBC). The following day, routine pre-operative laboratory testing revealed an unexpected positive result in assays for beta subunit of human chorionic gonadotropin (bHCG), an early indicator of pregnancy. The patient denied sexually activity. The result caused postponement of the elective surgical procedure and prompted an abdominal ultrasound study to identify the source of bHCG, which was normal.
Methods: Immunoassay was used to determine the bHCG level in the patient (Table 1) and in the residual plasma in each of the transfused units (Table 2).
Conclusion: One blood donor, who was unaware of her pregnancy status at the time of donation, harbored a high bHCG level which caused the positive test results in the recipient patient’s serum and urine. If an unexpected result is detected in a recipient of a blood transfusion, it is important to consider the possibility of passive transfusion of the analyte.
Table 1: bHCG test results from recipient’s blood following transfusion. Test Result Negative cut-off Qualitative bHCG (serum) Positive &lt; 10 mIU/ml Qualitative bHCG (urine) Positive &lt; 20 mIU/ml Quantititative bHCG (serum) 9 mIU/ml &lt; 5 mIU/ml Table 2: bHCG levels in the segments from the PRBC units transfused. Unit number bHCG, mIU/ml* *Negative cut-off, &lt;5 mIU/ml; **Exceeds the dynamic range (0–1000 mIU/ml) of qualitative bHCG assay. 1 0.39 2 0.71 3 &gt;1000** 4 0.18 5 0.24
Fetal Liver Hematopoiesis Becomes Sensitive to Estrogen after Transplantation to Adult Mice.
Authors: Chang Ko-Tung , Pelichovska Tereza , Sefc Ludek , Broulik Petr , Necas Emanuel 
Published: April 2020

Abstract
The hematopoietic stem/progenitor cells from fetal liver (FL) of the mouse do not express estrogen receptors in contrast to the cells from adult bone marrow (BM) [Igarashi H et al: Proc Natl Acad Sci USA (2001) 98, 15131–15136]. Since estrogen had been shown to suppress B-lymphopoiesis in vivo [Medina KL et al: Blood (2000) 95, 2059–2067; Erlandsson MC: Immunology (2003) 108, 346–351], we investigated estrogen action on B-lymphopoiesis derived from FL cells transplanted to adult mice. FL cells from E14.5 embryos of C57Bl/6 mice (Ly5.1), or a mixture of FL cells (Ly5.1) with BM cells (Ly5.2), were transplanted either into sublethally (7 Gy) or into lethally (11 Gy) irradiated male Ly5.2 recipients, respectively. Half of the recipients were kept on a diet containing estradiol (estimated intake of 100 micrograms/day). Peripheral blood obtained from the retrobulbar venous plexus was analyzed for presence of Ly5.1 (FL origin) or Ly5.2 (BM origin) WBCs using flow cytometry (FACS Calibur, Becton Dickinson) from 2 weeks up to 16 weeks after transplantation. The WBCs were also stained with anti-mouse CD45R/B220 antibody to detect B-lymphocytes. Numbers of repopulating B-lymphocytes of FL origin were little affected by estrogen 2 and 4 weeks after transplantation while those of BM origin were significantly suppressed. However, the difference between responses of FL or BM origin B-lymphopoiesis to estrogen became much smaller after 8 weeks and was not evident after 16 weeks. The chimeric bone marrow was further transplanted to secondary lethally irradiated recipients and effect of estrogen on B-lymphopoiesis of either FL or BM origin was studied for another 20 weeks. In this case B-lymphopoiesis of FL origin was suppressed by estrogen immediately after transplantation similarly as that of BM origin. The results provide a functional confirmation of previously reported molecular differences between FL and adult BM stem/progenitor cells dwelling in lack of the expression of estrogen receptors in the FL cells. They also conclusively demonstrate that FL stem/progenitor cells become invariably sensitive to estrogen after being exposed to the environment of the adult organism for a long enough time.
Mortalin-2 (mthsp70/PBP74/Grp75) Mediates the Erythropoietin Signal To Stimulate Growth of Purified Human Erythroid Progenitor Cells.
Authors: Ohtsuka Rie , Abe Yasunobu , Fujii Tomomi , Nishimura Junji , Muta Koichiro 
Published: April 2020

Abstract
Erythropoietin (EPO) stimulates erythroid growth by enhancing the proliferation, maturation and survival of late stage erythroid progenitor cells. Intracellular signaling molecules such as Janus kinase 2 (JAK2) and phosphoinositide-3 kinase (PI-3K)/Akt are considered mediators of the EPO signal; however, the entire process of EPO stimulation remains undetermined. Previously, we used siRNA to show that mortalin-2, which is a member of the heat shock protein 70 family of chaperones, mediates EPO signaling to stimulate the growth of human erythroid colony forming cells (ECFCs). In the present study, we examined the relationship between cell growth and mortalin-2 overexpressed in ECFCs, and analyzed the gene expression pattern of ECFCs treated with mortalin-2 siRNA using a DNA microarray, to further clarify the intracellular mechanism by which EPO and mortalin-2 interact. In the presence of different concentrations of EPO (0–1.0 U/ml), the effect of mortalin-2 overexpression on ECFC growth was determined by MTT assay. There was tendency to better viability of ECFCs treated with mortalin-2 expression vectors than control cells, especially in the EPO 0 U/ml group (p=0.08). BrdU ELISA, used to investigate the effects of mortalin-2 on the DNA synthesis of ECFCs, revealed that when ECFCs were treated with mortalin-2 expression vectors, the cells showed an increase in the amount of BrdU incorporation into DNA without EPO. Next we analyzed the gene expression pattern using mRNA obtained from ECFCs cultured with or without EPO after treatment with mortalin-2 siRNA or control siRNA. When ECFCs were cultured with EPO after treatment with mortalin-2 siRNA, the expression of 19 genes was suppressed to less than 0.6 fold, and these genes included those involved in cell growth, apoptosis or transport, such as interleukin 6 receptor, ATP-binding cassette, Mdm2, BCL2 interacting protein and interleukin 10 receptor alpha. Furthermore, the expression of 8 genes was upregulated to over 1.5 fold, and these genes included transcription or signal transmission related genes, such as ubiquitin A-52 residue ribosomal protein fusion product 1 and serum/glucocorticoid regulated kinase 2. There were also some genes whose expressions overlapped with genes obtained from ECFCs cultured without EPO after treatment with control siRNA. Our data suggests that mortalin-2 expression depends on various pathways, and that one of these pathways mediates EPO signaling to stimulate mortalin-2 expression, which is related to the growth of erythroid progenitor cells.
A Novel Role of Complement Components C1q and C5a in Hematopoietic Stem/Progenitor Cell Migration.
Authors: Jalili Ali , Marquez-Curtis Leah , Montano Jencet , Shirvaikar Neeta , Ratajczak Mariusz Z. , Janowska-Wieczorek Anna 
Published: April 2020

Abstract
The complement protein C1q primarily provides a recognition and activation signal that triggers the classical pathway of complement, but it also has multiple immune functions including acting as a chemoattractant for neutrophils, eosinophils, mast and monocyte-derived dendritic cells. Moreover, hematopoietic stem cells have recently been shown to express the C1q receptor, C1qRp. C5a also strongly chemoattracts monocyte/macrophages to inflammatory sites. Recently we showed that G-CSF mobilization activates complement by a classical IgM-dependent pathway (Blood2005;106:1976a). In this study we examined the possible roles of C1q and C5a in hematopoietic stem/progenitor cells (HSPC) migration. We found that C5aR was expressed at the mRNA level on mobilized peripheral blood (mPB) and cord blood (CB) CD34+ cells but at the protein level only on mPB CD34+ cells. Flow cytometry revealed high C1qRp expression on both mPB and CB CD34+ cells. When the expression of C5aR and C1qRp was examined on the CB CD34+ cells expanded towards myeloid, megakaryocytic and erythroid lineages (at days 0, 3, 6, 11 and 14 of expansion), we found that C5aR expression increased with cell maturation (days 3–14) in both myeloid and megakaryocytic progenitors. In contrast, C1qRp was highly expressed on day 0, stayed constant in myeloid and megakaryocytic cells (days 3–11), and was down-regulated by day 14 in megakaryocytic cells. C1qRp was down-regulated in erythroid precursors during their maturation. We also found that C5a but not C1q is a chemoattractant for mPB CD34+ cells. In chemotaxis assays towards an SDF-1 gradient,
C5a primed chemotactic responses of both mPB and CB CD34+ cells to a low (10 ng/mL) gradient of SDF-1 (up to 80% of their response to a high (200 ng/mL) SDF-1 gradient); C1q primed the chemotactic responses of both types of CD34+ cells (up to 100% of the response to a high SDF-1 gradient), and the priming effect of C1q on SDF-1-induced chemotaxis of expanded myeloid and megakaryocytic precursors decreased, consistent with down-regulation of C1qRp on these cells by day 14.
Hence these results indicate that HSPC and progenitor cells express functional C5a and C1q receptors and that both the C5a-C5aR and C1q-C1qRp axes sensitize the responses of these cells to SDF-1 and thus could play a role in HSPC homing/mobilization to bone marrow. Further studies in animal models are needed to elucidate the roles of C5a and C1q in HSPC trafficking.
Myeloid Lineage Restriction Is Prior to and Independent of Lymphoid Lineage Restriction.
Authors: Matsubara Azusa , Ooehara Jun , Yamazaki Yuji , Takano Hina , Nakauchi Hiromitsu , Ema Hideo 
Published: April 2020

Abstract
It has been widely accepted that hematopoietic stem cells (HSCs) exclusively give rise to either myeloid or lymphoid lineage along their differentiation. Phenotypically defined as FcRloCD34+IL-7R−Sca-1−Kit+Lin− cells, common myeloid progenitors (CMPs) are supposedly at the first branched point for myeloid lineage commitment. Phenotypically defined as Thy1.1−IL-7R+KitloSca-1loLin− cells, common lymphoid progenitors are supposedly at the first branched point for both B- and T-lymphoid lineage commitment. Contradicting this model, we previously made observations of the myeloid lineage restriction in very early stages of HSC differentiation. We therefore decided to compare the myeloid and lymphoid differentiation potentials in long-term HSCs, short-term HSCs, multipotent progenitors (MPPs), CMPs, granulocyte/macrophage progenitors (GMPs), megakaryocyte/erythrocyte progenitors (MEPs), and CLPs at the single cell level. Because any available assays are not so sensitive enough for detection of lymphoid lineage differentiation potential, we primarily focused on myeloid differentiation potentials in this study. Here we provide data indicative of the absence of CMPs in the adult mouse bone marrow. Long-term HSCs (CD34−Kit+Sca-1+Lin− cells), short-term HSCs (Flt-3−CD34+Kit+Sca-1+Lin− cells), MPPs (Flt-3+CD34+Kit+Sca-1+Lin− cells), CMPs (FcRloCD34+IL-7R−Sca-1−Kit+Lin− cells), GMPs (FcRhiCD34+IL-7R−Sca-1−Kit+Lin− cells), MEPs (FcRloCD34−IL-7R−Sca-1−Kit+Lin− cells), and CLPs (IL-7R+KitloSca-1loLin− cells) were purified from adult B6 mice by flow cytometry. Single cell cultures were performed in the presence of SCF+TPO+IL-3+EPO. All colonies made by single cells were subjected to Cytospin preparations, followed by May-Gruenwald-Giemsa staining, for morphological classifications of colony cells: neutrophil (n), macrophage (m), erythroblast (E), or megakaryocyte (M). Cells with all n, m, E, M differentiation potentials (nmEM cells) were detected in on average 31%, 5%, and fewer than 1 % of long-term HSCs, short-term HSCs, and MPPs, repectively. Notably, none of a total of over 800 CMPs showed the full nmEM differentiation potential. These CMPs instead showed potentials belonging to members of GMPs and MEPs, suggesting CMPs are mostly an overlaping population of GMPs and MEPs rather than a distinct population. Single cell transplantation experiments revealed the coexistence of cells with the myleoid and B-lymphoid potentials or cells with the myeloid and T-lymphoid potentials among CD34−Kit+Sca-1+Lin− long-term HSC population. These progentiors are likely to be immediate progeny of HSCs. Together, these data support our view that myeloid lineage restriction takes place prior to and independent of lymphoid lineage restriction.