bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elevated Expression of IL-17 and IL-23 in Patients with Immune Thrombocytopenic Purpura
Authors: Li Feng , Zou Shanhua , Cheng Yunfeng 
Published: April 2020

Abstract
Introduction: In conjunction with IL-6 and TGF-β, IL-23 stimulates naïve CD4+ T cells to differentiate into Th17 cells. Th17 cells produce IL-17, a pro-inflammatory cytokine that play an important role in the pathogenesis of several autoimmune disorders. However, to date, the role of Th17 cells in immune thrombocytopenic purpura (ITP), a type of autoimmune diseases, has not been clearly established yet.
Methods: Peripheral bloods were obtained from 10 patients with ITP at onset, in remission and from 15 healthy control subjects. The frequencies of IL-17 producing T cells in peripheral blood were analyzed by flow cytometry. Peripheral blood Mononuclear cells (PBMCs) were isolated using Ficoll density-gradient centrifugation and the CD4+ cells were separated by immuno-magnetic microbeads selection. Plasma concentrations of Th17 cell-associated cytokines such as IL-12, IL-17, IL-23, IFN-γ, IL-6 and TGF-β were measured using ELISA. The mRNA expression levels of IL-17, IL-12p40, IFN-γ, IL-23p19 in CD4+ cells were determined by Real-Time PCR.
Results: The frequencies of IL-17-producing T cells were significantly increased in ITP patients at onset, compared to ITP patients in remission (10.7±5.5 % vs 4.1±3.5 %, p &lt; 0.05) and healthy controls (10.7±5.5 % vs 2.1±1.6 %, p &lt; 0.05), however there was no statistical difference between ITP patients in remission and healthy controls. Comparing to healthy subjects, the plasma concentrations of IL-12 (33.3±15.25 pg/ ml vs 12.8±7.24 pg/ml, p&lt;0.05), IL-17 (37.3±12.1 pg/ml vs 5.1±3.6 pg/ml, p &lt; 0.05), IL-23 (30.01±9.33 pg/ml vs 10.42±13.19 pg/ml, p &lt; 0.05) in patients with ITP at onset were found significantly elevated whereas no statistical difference was observed for the levels of IL-12, IL-17 and IL-23 between ITP patients in remission and healthy controls. Furthermore, the expression levels of IL-23p19 mRNA were significantly increased in ITP patients at onset, compared to healthy controls. Changes in IL-23p19 mRNA expression and IL-17 were strongly correlated (R = 0.66, p &lt; 0.05).
Conclusion: Our results support the hypothesis that Th17 cells are involved in the development of ITP and Th17 cells could potentially constitute a novel therapeutic target.
Mild Congenital ADAMTS13 Deficiency in a Patient with Familial Recurrent Ischemic Stroke
Authors: Plaimauer Barbara , Skalicky Susanna , Boehm-Weigert Martina , Scharrer Inge , Scheiflinger Friedrich 
Published: April 2020

Abstract
A severe functional deficiency in the ADAMTS13 protease, characteristic for patients suffering from thrombotic thrombocytopenic purpura (TTP), results in persisting prothrombotic ultra-large von Willebrand factor (ULVWF) multimers, which can lead to systemic microvascular thrombosis. The congenital form of TTP is attributed to the presence of homozygous or double heterozygous mutations in the ADAMTS13 gene leading to impaired secretion and/or a functional defect of the protease. Decreased ADAMTS13 activity has been also described for several physiological and pathological conditions. Emerging evidence indicates mild ADAMTS13 deficiency might also increase risk for arterial thrombosis such as for ischemic stroke. We therefore investigated a possible causal relation between moderate ADAMTS13 deficiency and ischemic stroke in one patient selected with the lowest ADAMTS13 activity amongst a cohort of 70 patients with ischemic stroke. At age 34 and 46 years the patient had suffered from idiopathic ischemic strokes with negative common prothrombotic risk factors. We found slightly elevated VWF antigen (161%), ULVWF multimers and reduced ADAMTS13 activity (17%). Genetic analysis identified five nucleotide exchanges in the ADAMTS13 gene leading to one heterozygous missense mutation P353L and four homozygous amino acid polymorphisms (R7W, Q448E, P618A, A732V). Her asymptomatic son presented with normal VWF antigen (99%) and an ADAMTS13 activity of 58% transmitted by a mutant maternal allele and a paternal allele harboring the single Q448E polymorphism. Recombinant expression studies indicated P353L alone causes an impact on ADAMTS13 secretion that is further pronounced in the context of the four polymorphisms. Secreted ADAMTS13 containing P353L or P353L combined with the four polymorphisms presented with similar binding interaction in a binding assay with immobilized multimeric VWF, however, the binding affinity was slightly less than that of wild-type ADAMTS13 or polymorphic rADAMTS13 proteins containing either Q448E alone or all four polymorphisms combined. ADAMTS13 activity analysis suggested that mainly the secretion process or the protein stability rather than the proteolytic activity was affected by the mutations. Co-transfections mimicking the patient’s genotype indicated homozygosity of the four polymorphisms in the patient led to an attenuation of the adverse effect of the heterozygous P353L point mutation resulting in the moderate ADAMTS13 deficiency in the patient. Our results suggest moderate familial ADAMTS13 deficiency might be causally involved in the pathogenesis of ischemic stroke.
Immune Thrombocytopenic Purpura Due to Passenger Donor Lymphocytes in Liver Transplantation
Authors: Mirza Imran , Almugairi Areej , Nahirniak Susan 
Published: April 2020

Abstract
Introduction: Thrombocytopenia is a frequent complication following solid organ transplant but previous reports suggest that the incidence of immune mediated thrombocytopenic purpura (ITP) following liver transplantation is low (0.7%). Although the mechanisms involved in post transplant thrombocytopenia are complex, the presence of alloantibody derived from passenger donor lymphocytes should be considered when severe thrombocytopenia is identified.
Case presentation: Our case is a 58-year-old gentleman who underwent liver transplantation for end stage cirrhosis and hepatocellular carcinoma. His baseline pre-transplant platelet count was low at 83 ×109/L, but he postoperatively worsened to a platelet count of 5×109/L with bleeding sequelae. The liver donor was a 71-year-old previously healthy man who presented with severe thrombocytopenia (platelet count of 3 ×109/L) and hemorrhagic stroke, but no evidence of hematological pathology on bone marrow examination. As the donor history of presumptive ITP was known to the service, antiplatelet antibody assays on both the donor and recipient were performed using the ELISA based GTI-PAK12 kit (GTI Diagnostics, Waukesha, WI). Although there were no detectable antiplatelet antibodies in the organ recipient’s pre-transplant specimens, the immediate post-transplant specimen demonstrated reactivity in all three GPIIb/IIIa wells, corresponding to a stronger but identical reaction pattern in the organ donor. This suggested that the reactivity and subsequent worsening of the thrombocytopenia were secondary to antibodies produced by passenger donor lymphocytes in the transplanted liver. The transplant recipient was treated with corticosteroids, intravenous immune globulin and platelet transfusion with a return to his baseline platelet count and cessation of bleeding symptomatology five days later. Repeat platelet antibody testing in the organ recipient five weeks post-transplant revealed no detectable antiplatelet antibody reactivity, indicating lack of engraftment of the passenger donor lymphocytes.
Conclusion: Passenger donor lymphocytes producing antiplatelet antibodies may be a contributing factor in post-transplant thrombocytopenia. Close monitoring and high clinical suspicion should be present when there is a history of immune/idiopathic thrombocytopenia in the organ donor.
Pregnancy after Allogeneic Hematopoietic Stem Cell Transplantation in Fanconi Anemia Patients: Multi-Institution Cases Report of Female Fertility Recovery
Authors: Nabhan Samir Kanaan , Bittencourt Marco , Duval Michel , Abecasis Manuel , Dufour Carlo , Boudjedir Karim , Rocha Vanderson , Socié Gérard , Passweg Jakob R. , Pasquini Ricardo , Gluckman Eliane 
Published: April 2020

Abstract
Introduction. Fanconi anemia (FA) is a rare autosomal recessive syndrome characterized by chromosome instability. Main clinical features include progressive bone marrow failure, skeletal defects, increased susceptibility to malignancy and reduced fertility. Moreover, most recipients of allogeneic hematopoietic stem cell transplantation (HSCT) suffer from secondary infertility owing to gonadal damage from myeloablative conditioning. We report a rare clinical situation of FA patients pregnancy after allogeneic HSCT.
Methods. Retrospective analysis of transplanted FA female patients from 1982 to 2008. Five centers participated in this study on behalf of Aplastic Anaemia Working Party-EBMT. Medical records were reviewed and data collected on a standard case report form including detailed information on diagnosis, transplant procedure, gynecological and obstetrics follow-up.
Results. Among 387 transplanted FA patients we identified 202 females who performed a HSCT with a median age of 10,5 years. Five patients became pregnant after the procedure and one of them, twice. They all had their FA diagnosis confirmed by chromosomal breakage test and a bone marrow aspirate with severe hypoplasia/aplasia. Median age at transplantation was 12 years (range 5–17 years). All patients received myeloablative conditioning regimens (cyclophosphamide with or without thoraco-abdominal irradiation) before a bone marrow transplantation, 4 patients from HLA matched sibling donors and 1 from unrelated donor. During follow-up, 4 patients presented signs of ovarian failure (amenorrhea, low levels of FSH/LH and high levels of estradiol). Apart from 1 patient who spontaneously recovered regular menses, the other three received hormonal replacement therapy (HRT) for this purpose. Pregnancy occurred from 3,5 to 17 years after transplant. One patient had an early interruption with a caesarian section at 27 weeks because of an imminent HELLP syndrome. Other pregnancies were uneventful. Among the newborns, there were no FA positive tests, no congenital anomalies and all of them had normal growth and development. Patients remain alive with a median follow-up of 12 years after transplantation with normal hematological status.
Conclusion. Fertility recovery after HSCT can result from incomplete depletion of the ovarian follicle reserve. HRT should begin promptly to prevent the early and late unwanted effects related to oestrogen deficiency after HSCT. Recovery of normal ovarian function and a viable pregnancy, is a realistic possibility even in Fanconi anemia patients following allogeneic SCT.
Successful Use of Recombinant Factor VIIa (rVIIa, NovoSeven) in Two Patients with Bernard Soulier Syndrome and Dental Extraction
Authors: Zotz Rainer B. , Gerhardt Andrea , Scharf Rudiger E. 
Published: April 2020

Abstract
Background: Bernard Soulier syndrome (BSS) is a platelet function disorder that results from partial to complete deficiency or dysfunction of the GP Ib-IX-V receptor. Specific treatment of bleeding episodes or prophylaxis for the prevention of bleeding during surgical procedures is platelet transfusion. Alloimmunization by HLA antigens and antibody formation to the GPIb-IX-V complex frequently occur and, thus limit future responses to platelet transfusions. Recent patient studies have suggested that rVIIa may be an effective therapy for treatment of bleeding in BSS.
Case Reports: We report on our experience with rFVIIa in two patients with BSS and dental extraction. Patient 1 is a 21-year-old woman (extraction of 2 wisdom teeth). In 2000, after a first extraction of one wisdom tooth, which was covered by administration of DDAVP and platelet transfusion, a bleeding episode occurred, requiring resurgery. Patient 2 is a 14 year old boy (extraction of 4 wisdom teeth). rFVIIa was used as first line therapy. An initial dose of rFVIIa (100 μg/kg/bw) was administered 15 min prior to surgery, followed by three doses of 90 μg/kg/bw at 120 min intervals and three doses at 8 hour intervals postoperatively. In the first three days after surgery, 90μg/kg/bw rFVIIa were administered every 12 hours. Tranexamic acid (CyklokapronÒ 3 × 1 g/d) was started postoperatively and continued for 10 days. There were no postoperative bleeding episodes and no platelet transfusion was required.
In conclusion, rFVIIa in combination with tranexamic acid appears to be an effective and safe therapeutic alternative for prophylaxis of bleeding episodes in dental extraction in patients with BSS.
Evolution of Anti-ADAMTS13 Antibodies in a Refractory Case of Thrombotic Thrombocytopenic Purpura with Fatal Outcome
Authors: Plaimauer Barbara , Knoebl Paul , Skalicky Susanna , Ferrari Silvia , Varadi Katalin , Kolovratova Vera , Turecek Peter L. , Rieger Manfred , Scheiflinger Friedrich 
Published: April 2020

Abstract
Thrombotic thrombocytopenic purpura (TTP) is characterized by systemic microvascular thrombosis leading to life-threatening ischemia of multiple organs, and is associated with a severe deficiency of the von Willebrand factor (VWF)-cleaving protease ADAMTS13, which permits highly adhesive ultra-large VWF multimers to accumulate in the circulation. Inhibitory and less frequent non-inhibitory anti-ADAMTS13 autoantibodies have been detected in patients suffering from acquired idiopathic TTP. Current treatment with plasma exchange therapy is considered to remove the autoantibodies while concomitantly supplying plasma with the deficient protease. Plasma therapy greatly reduces mortality, nevertheless, still about 10% of the patients die from refractory TTP. To explore the cause of treatment failure in a fatal case of idiopathic acquired TTP we investigated retrospectively the anti-ADAMTS13 immunological profile of a 70-year-old female patient during the course of disease progression. At admittance, she presented with schistocytes, thrombocytopenia and severe neurological disturbances. ADAMTS13 antigen and activity were borderline low in the presence of initially non-inhibiting anti-ADAMTS13 IgG and IgM antibodies, no ADAMTS13 gene aberrations were detected. She had had no previous episodes of TTP. During treatment, the patient received repeated plasma exchanges, supportive extracorporal immunoadsorption and corticosteroid therapy. Despite ongoing treatment anti-ADAMTS13 antibodies still developed and ADAMTS13 activity remained less than 0.1U/ml. After 5 weeks of therapy, during which time the patient was seriously ill with striking neurological limitations, her platelet count dropped and a splenectomy was performed. The patient’s state improved despite a complicated postoperative phase. During the next 4 weeks, her platelet count increased gradually up to 780 G/L, a moderately low ADAMTS13 activity of 0.24U/ml (0.57ng/ml ADAMTS13 antigen) was detected and ADAMTS13-specific antibodies were not measurable. However, within a few days her platelet count dramatically dropped to 20G/L, anti-ADAMTS13 antibodies reappeared and ADAMTS13 activity again was undetectable. The patient’s state deteriorated and she died 2 days later from multiple organ failure. We show the results of the fluctuating anti-ADAMTS13 antibody profile (functional inhibitors and total IgG, IgG subtypes, IgA and IgM) and the pattern of the ADAMTS13 domain-specific reactivity superimposed with the common clinical laboratory data over the patient’s 9-week clinical course.
Burden of Anemia in Cancer Patients Undergoing Chemotherapy: A Retrospective Database Analysis
Authors: Aravind Suresh , Wu Ying , Ranganathan Gayatri , Nalysnyk Luba 
Published: April 2020

Abstract
Background. Along with neutropenia and thrombocytopenia, anemia is a very common hematological adverse effect in patients undergoing chemotherapy. Prolonged and severe anemia is associated with compromised quality of life. The goal of this study was to evaluate the epidemiology of anemia in cancer patients undergoing chemotherapy in USA.
Methods. Pooled data over the period 2000–07 from a large electronic database of 15 community and 3 hospital-based outpatient oncology clinics in the US was analyzed. Adult patients with a cancer diagnosis were grouped as: lung, breast, ovarian, H&N, colorectal, other solid cancers, hematologic and mixed cancers. Chemotherapies used were grouped into platinum, anthracycline, gemcitabine, taxane-based and other regimens. Presence of anemia (defined as Hb&lt;11 g/dL) was evaluated before and during chemotherapy.
Results. 47,159 patients who met protocol specified inclusion criteria were analyzed (mean age 61 (SD 13) yrs, 42% male). The most common tumor types included breast cancer 19.5%, NSCLC 14.9%, colorectal 11.9%, ovarian 3.1% and H&N 2.5%. 75,243 chemotherapy regimens were administered to these patients. Platinum-based regimens accounted for 27.8% of all regimens and were most common among patients with NSCLC (66.6%), ovarian (60.2%), H&N (76.8%), and colorectal (38.9%). Anthracycline-based chemotherapy predominated in breast (46.5%) and hematological cancers (19.1%). Nearly 21% of all cancer patients were anemic at baseline prior to start of chemotherapy. During the course of chemotherapy about 50% of patients experienced anemia. Development of anemia was most common among those receiving gemcitabine regimens (59%). Percentage of patients with severe anemia were: Hb 9–10g/dL = 12–18%, Hb 8–9 g/dL = 5%, and Hb &lt;8 g/dL = 2%. While on chemotherapy, the incidence of anemia was highest among ovarian cancer patients (56.3%), followed by breast (53.3%) and NSCLC (50.9%). Based on data from one large hospital-based site (8,607 patients), the use of RBC transfusions during this period was relatively low (4% in anthracycline to 12% in platinum-based regimens). About 50% of patients received Erythropoietin Stimulating Agents (ESAs) at some point during chemotherapy.
Conclusions. This large community-based analysis observed that nearly 50% of cancer patients undergoing chemotherapy develop anemia. Anemia continues to be a burden in this patient population.
Changes of Intracellular Signal Pathway of mTOR/S6 in T Cells of Low-Risk Myelodysplastic Syndromes
Authors: Zhang Xiang , He Guangsheng , Depei Wu , Zhu Mingqing , Sun Aining 
Published: April 2020

Abstract
Objects: To explore the state of of intracellular signal pathway of mTOR/S6 in FAB low-risk myelodysplastic syndrome-refractory anemia (RA)/RA with ringed sideroblasts (RAS).
Methods: Samples were collected from 18 MDS-RA/RAS patients. The intracellular percentages of p-mTOR, p-S6 and IFN-γ of CD3+, CD3+CD8+ and CD3+CD8− T cells in bone marrow were detected by flow cytometry (FCM). 10 iron deficiency anemia (IDA) patients [male: 3, female: 7, media age: 44 years (from 31 to 72 years)] were determined as case controls and normal controls respectively.
Results
In normal controls, measurement of p-mTOR, p-S6 and IFN-γ in CD3+, CD3+CD8− and CD3+CD8+ T cells were (1.54±1.51)%, (1.94±1.08)%, (2.04±2.03)%; (0.83±0.82)%, (0.91±0.88)%, (0.95±0.93)%; (4.42±3.55)%, (2.35±1.69)%, (4.73±4.43)%, respectively. By 2.62%) of normal controls, MDS group could be divided into two subgroups: MDS-1 with a higher CD3+p-mTOR+ expression, and MDS-2 with a lower expression. In MDS-1, percentages of p-mTOR, p-S6 and IFN-γ in CD3+, CD3+CD8− and CD3+CD8+ T cells were (20.70±18.02)%, (22.94±19.70)%, (26.03±22.91)%; (2.85±2.36)%, (3.36±2.84)%, (4.91±3.88)%; (13.92±12.87)%, (10.05±9.77)%, (16.38±15.49)%; which were higher than normal controls (P&lt;0.05). In MDS-2, the percentages of CD3+p-mTOR+ [ (0.28±0.28)% ], CD3+CD8−p-mTOR+ [ ( 0.46±0.41 )% ], CD3+CD8+p-mTOR+ [ ( 0.47±0.44 )%], CD3+p-S6+[(0.21±0.21)%] and CD3+CD8−p-S6+[(0.17±0.14)%] were lower than those of normal controls (P&lt;0.05) respectively, whlie there were no significant differences in expression of IFN-γ in T cells [ (12.85±12.47)%, (7.11±7.02)%, (20.29±19.84)%] and p-S6 in CD3+CD8+ cells [0.65±0.64)% ] (P&gt;0.05). Upon RAPA treatment, in CD3+, CD3+CD8− and CD3+CD8+ T cells of MDS-1 group, p-mTOR was inhibited more than 50% in 5of 10 cases; p-S6 was inhibited in 2, 4, and 6 cases, respectively, and IFN-γ was inhibited in 4, 4, 3 cases respectively.
Conclusions
In FAB low-risk MDS, the signal pathway of mTOR/S6 was activated, and it was quiescent in normal controls,. The expression of p-mTOR, p-S6 and IFN-γ of this signal pathway in FAB low-risk MDS was heterogeneous. RAPA could suppress mTOR/S6/IFN-γ in partial patients with low-risk MDS.
Non-Myeloablative Allogeneic Hematopoietic Stem Cell Transplantation (NMHCT) for Patients Relapsing after Autologous Stem Cell Transplantation (autoHCT) for B Cell Non-Hodgkin Lymphoma (NHL)
Authors: Freytes Cesar O , Carreras Jeanette , Zhang Mei-Jie , Laport Ginna G. , Van Besien Koen , Lazarus Hillard M. , Hari Parameswaran 
Published: April 2020

Abstract
The prognosis of patients (pts) with NHL who relapse after autoHCT is poor. Myeloablative allogeneic hematopoietic stem cell transplantation has been utilized in these pts since the allograft is tumor free and may induce a graft-versus-tumor effect. Unfortunately, this approach results in prolonged survival for only a minority of pts. NMHCT is increasingly utilized in this setting since it affords the potential benefits of myeloablative transplantation and may reduce morbidity and treatment-related mortality (TRM). Reports using this approach show conflicting results but are limited by small numbers of pts. The purpose of this study was to determine the outcome of pts with NHL who underwent NMHCT after autoHCT failure including TRM, progression/relapse rate, overall survival (OS) and progression free survival (PFS). The study included 267 pts who underwent NMHCT for relapsed B cell NHL after autoHCT failure, from 1997 to 2006 and reported to the Center for International Blood and Marrow Transplant Research. Patients younger than 21, pts who underwent planned second transplants and recipients of cord blood transplants were excluded. The median age at NMHCT was 52 yrs (range 23–70); 64% were male and 61% had a Karnofsky Performance Score (KPS) of ≥ 90%. Fifty six percent of pts had diffuse large cell lymphoma, immunoblastic or follicular large cell lymphoma; 17% had follicular small or mixed NHL and 27% had mantle cell lymphoma. The time interval from 1st to 2nd transplant was &lt; 1 year in 21% of pts, 1 to 2 years in 30% and &gt; 2 years in 49% of pts. At the time of NMHCT, 63% had chemosensitive NHL, 31% resistant NHL and 6% were untreated after autoHCT. Multiple conditioning regimens were used including most frequently melphalan (25%) busulfan (21%) and fludarabine ± cyclophosphamide (26%). A fourth of the pts received 200 cGy of total body irradiation (TBI) as part of the conditioning regimen. The graft source was peripheral blood in 78% and 90% used unrelated donors. Median follow up of survivors was 37 months. TRM at 3 years was 42%. The cumulative incidence of disease progression at 3 years was 36%. The three-year probabilities of OS (figure 1) and PFS were 33% and 22%, respectively. The incidence of grade II-IV acute graft-versus-host disease (AGVHD) at 100 days was 39% and the incidence of chronic GVHD at 3 years was 41%. The most frequent causes of death were progression of NHL (29%), infection (19%), multiorgan failure (19%) and GVHD (14%). Factors associated with a lower risk of NHL progression or death include KPS ≥ 90%, interval between transplants &gt;24 months, TBI as part of the conditioning regimen and complete remission at the time of NMHCT (figure 2). AGVHD decreased the risk of relapse (RR = 0.59, p=0.036)
Figure 1 Figure 1. Figure 2 Figure 2.