bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence of Pulmonary Hypertension (PHTN) in Sickle Cell Disease (SCD) Adolescents with Pulmonary Complications.
Authors: Onyekwere Onyinye C. , Campbell Andrew , Williams James , Gaskin Peter , Rana Sohail , Gordeuk Victor R. , Castro Oswaldo L. 
Published: October 2019

Abstract
Despite the high prevalence of PHTN in adults with SCD, the prevalence in the pediatric population with SCD is not known. We hypothesized that elevated pulmonary artery pressures may be found in SCD adolescents with history of pulmonary complications, such as acute chest syndrome (ACS), obstructive sleep apnea (OSA), asthma, and reactive airway disease. Thirty such sickle cell disease adolescents were screened at Howard University or University of Michigan for PHTN with Doppler echocardiography. We defined PHTN as a tricuspid regurgitant jet velocity (TRV) of at least 2.5 m/sec (corresponding to a pulmonary artery systolic pressure greater than 35 mm Hg). PHTN was found in 16 SCD patients (53.3%) and 5 (16.7%) had TRV > 3.0 m/sec. Clinical findings according to the presences or absence of PHTN are shown in the table.
Potential factors contributing to PHTN in patients with SCD include chronic hemolysis and chronic hypoxia. Our results suggest that PHTN is common among SCD adolescents with a history of pulmonary complications. Consideration should be given to screening such patients for PHTN and exploring treatment options. Further studies are urgently needed to clarify the prevalence and mechanisms of PHTN in adolescents with SCD.
Clinical and demographic data of 30 SCD adolescents with pulmonary findings who underwent echocardiography at Howard University Hospital or University of Michigan
PHTN (N = 16) No PHTN (N = 14) P Age in years (mean +/− SD) 15.9 +/− 3.2 17.4 +/− 2.3 0.17 Females (no. and %) 5 (31.3) 7 (50) 0.5 Hemoglobin SS Phenotype (no and %) 14 (87.5 11 (78.6) 0.5 Hemoglobin concentration (mean +/− SD) 8.0 +/− 2.1 9.3 +/−1.9 0.11 White blood cells (mean +/− SD) 10.9 +/− 2.9 9.7 +/− 3.7 0.4 Platelet (mean +/− SD) 475 +/− 172 364 +/− 240 0.17 Hemoglobin F percent (mean +/− SD) 5.1 +/− 3.5 6.4 +/− 5.5 0.6 Lactate dehydrogenase (mean +/− SD) 505 +/− 162 264 +/− 50 0.002 Total bilirubin (mean +/− SD) 4.1 +/− 2.6 3.4 +/− 2.6 0.5 Creatinine concentration (mean +/− SD) 0.6 +/− 0.2 0.7 +/− 0.2 0.18 Aspartate transaminase (mean +/− SD) 48 +/− 27 36 +/− 16 0.18 Alanine transaminase (mean +/− SD) 51 +/− 37 39 +/− 20 0.3
Detailed Analysis of Neutropenic Risk Factors in Patients with Prostate Cancer Treated with Chemotherapy.
Authors: Laber Elizabeth R. , Laber Damian A. 
Published: October 2019

Abstract
Background: Although thousands of patients (Pts) receive chemotherapy every year in the United States, only few retrospective studies have been done to address the risk factors for chemotherapy (CT) induced neutropenia in patients with cancer. The data in androgen-independent prostate cancer (AIPC) patients is extremely scarce. We decided to perform a retrospective analysis of patients with metastatic AIPC treated with chemotherapy in an open phase II clinical trial looking for predictive factors for neutropenia.
Methods: We reviewed the records of all patients with AIPC who completed at least 2 cycles of CT with cyclophosphamide 50 mg/m2, etoposide 50 mg/m2 and estramustine 280 mg orally every night for 14 days out of a 28 day-cycle. We divided the patients into 2 groups according to neutropenia grade 3–4 (Group 1) versus 0–2 (Group 2). Risk factors reviewed included age, number of organs involved with metastases, number of bone metastasis, prior radiotherapy (RT) to the prostate/pelvis, prior number of areas treated with palliative RT, prior CT regimens, baseline PSA, absolute neutrophil count (ANC) and ECOG performance status (PS).
Results: See table and figures.
Group 1 2 Neutropenia Grade 3–4 0–2 # of Pts 7 11 Age 68 (58–86) 63 (52–74) # organs involved 2.1 1.6 # bone metastases 10.9 9.5 RT prostate/pelvis 0.1 0.4 # palliative RT courses 1 0.6 # prior CT regimens 0.4 0.2 Baseline ANC 3.6 3.8 Baseline PS ECOG 1.3 1.4 Baseline PSA 584 (26–2268) 157 (37–65)
Figure Figure
Conclusions: Average age and PSA were the only risk factors that were different between the patients who developed severe neutropenia and the ones who did not, albeit not statistically significant. Studies with a larger sample size may detect clinically and statistically significant differences.
The Effect of Adenosine on TLR Signaling Pathways in Human Monocytic THP-1 Cells.
Authors: Chen Chin-Fu , Cheng Chun-Huai , Vos Seychelle 
Published: October 2019

Abstract
Adenosine is an important metabolite that serves as a potent regulator of inflammation and mediates various biological functions in different cell types. Adenosine inhibits the proinflammatory actions of inflammatory and immune cells via interaction with its receptors, particularly A2A receptors. Adenosine receptors belong to the seven-transmembrane G-protein coupled receptors and via the different G proteins transfer signals through different effectors including adenyl cyclase, PKA, PKC, PI3K, and MAP kinases. The mechanisms by which the adenosine regulates immune responses and how adenosine receptor pathways interact with other signaling pathways are currently unknown. Toll-like receptors (TLRs) of the innate immune cells recognize conserved microbial structures, such as bacterial lipopolysaccharide and viral double-stranded RNA, and activate signaling pathways that result in innate immune responses against microbial infections. Fcγ receptors of the innate cells play a critical role in the clearance of pathogens, regulation of inflammation and co-ordination of the immune response. We seek to understand the interaction between adenosine (via adenosine receptors) and TLR- and Fcγ R- mediated signaling pathways. We have initiated study on the effect of adenosine and lipopolysaccharide (LPS) on expression of TLR2, TLR4, FcγRI and Fcγ RII receptors in the human monocytic cell line THP-1. We incubated cells with 100μM adenosine for three hours at 37°C and assayed the expression of receptors using flow cytometry. Our results suggest that adenosine increases the expression of TLR2 and TLR4 in both undifferentiated cells and the cells induced to become macrophages by phorbol ester. Incubation with adenosine for 24 hours further increases the expression of TLR2 and TLR4 in both undifferentiated and differentiated THP-1 cells. Similarly, incubation with LPS for three hours increases the expression TLR2 and TLR4 in both undifferentiated and differentiated THP-1 cells. In contrast, the expression level of FcγRI and FcγRII receptors do not change in the presence of either adenosine or LPS. These observations suggest that adenosine specifically enhances expression of TLRs but not Fcγ receptors. To further understand the interaction between adenosine and TLR pathways, we are continuously investigating the effect of adenosine on expression and the protein modification (e.g. phosphorylation) of TLR2, TLR4, and the molecules in the TLR signaling cascades including MyD88, IRAK and MAP kinases using real-time RT-PCR and western blotting.
Recurrent Histiocytosis Evolving to Myelodendritic Leukemia.
Authors: Rubio Araceli , Recasens Valle , Perez-Barrachina Carmen , Orfao Alberto , Giraldo Pilar 
Published: October 2019

Abstract
Background: Langerhans cells histiocytosis (LCH) is a rare disorder caused by proliferation of activated Langerhans cells. Although current therapies are very effective to induce a remission, multiple recurrences are common. Patients: In 1999 a 20-year-old female was admitted in the hospital to study by amenorreha for 5 months. In the exam a tumour located in the cranial base was identified and in lung a nodular infiltration was observed in the CT scan. The histological diagnosis was eosinophilic granuloma. The clinical manifestation was characterised by hypothalamic dysfunction, pituitary failure and diabetes insipidus (DI). Treatment: Telecobaltotherapy in CNS and chemotherapy (DAL HX-83/90). After therapy CNS MRI became normal, and body computed tomography (CT) scan showed minimal residual lung disease. The patient became asymptomatic, under hormonal substitutive therapy. Three years later, the patient was asymptomatic with ECOG 0, but in her peripheral blood a 3% of blast cells was detected (hemoglobin 8.2 g/dL, WBC 3.2x109/L neutrophils 3%, monocytes 8%, lymphocytes 86%, blasts 3%, platelets 213x109/L). Bone marrow: 0.5% blasts: CD45+, CD117+, CD33+, CD13+ weak, CD64++, CD15++, CD3−, CD2−, CD7−, CD79a−, CD19−, MPO−, CD34−, CD56++, HLADR+++, CD36+, CD11b−, CD7.1−/+lisozime+, CD1−/+, CD14 and 77.5% of cells with the same immunophenotype except CD117−, 7.1− and CD45−. One weak later we repeated the bone marrow exam and we found: 88.8% blasts cells with immunophemotype similar to blast as first exam. FISH: 88% translocation in 11q23. CT scan showed small and few nodules in lung and skin lesions were absent. She was diagnosed of leukemia involving progenitors of dendritic Langerhans’/monocytic differentiation cells: FAB AML-M0/M4. The patient has not sibling and she is receiving treatment with 2-Chlorodeoxyadenosine (0.12 mg/kg, days 1–5/28 x 6 courses) associated to epoetin-a. After two courses the patient had normalized her pheripheral blood (hemoglobin 12.5 g/dL, WBC 6.7x109/L with normal distribution and platelets 485 x109/L. The tolerance to therapy was excelent without adverse effects and she has a normal quality of life. Comments: The use of 2-Chlorodeoxyadenosine in LCH is based in its antiproliferative and immunomodulatory effects. CDA has been used in LCH with good results and minimal toxicity. Some cases published have showed a durable complete response in patients with LCH in skin, gastrointestinal, lungs, bone, diabetes insipidus and parenchymal CNS. In our knowledge, it has not been described previously a case of DMCL treated succesfully with CDA. Further studies are needed to determine the role of CDA in this disease, the optimal and schedule of therapy, but we have proved it may be effective even in high-risk patients with LCH. More therapies based on the pathogenesis of LCH are needed to investigate. This study has been supported by a grant from FEHHA
Clinical and Pathological Presentation of T-Cell Large Granular Lymphocyte Proliferations (T-LGL): A Single Institution Experience.
Authors: Battiwalla Minoo , Wallace Paul K. , Ford Laurie A. , Baer Maria R. 
Published: October 2019

Abstract
Proliferations of T-cell large granular lymphocytes (T-LGL) are a rare and heterogeneous disease entity characterized by a chronic course, cytopenias and circulating cytotoxic T lymphocytes. We present the results of a single institution retrospective review of the clinical presentation of T-LGL proliferations. A total of 23 patients evaluated for cytopenias were identified as having T-LGL by flow cytometry, ten male and thirteen female, with a median age of 67 years at diagnosis. Twelve patients had a prior malignancy (non-Hodgkins lymphoma=4, MDS/AML=4, breast cancer=2, squamous cell cancer (SCC) of the skin =2, lung SCC=1, vocal cord SCC=1, uterine cancer=1) and five patients had a history of autoimmune disease (rheumatoid arthritis=2, vasculitis=1, polyarthritis=1, Wegener’s granulomatosis=1), while seven patients had no previous history of autoimmune disease or malignancy. Four patients with prior malignancy had active disease and this led to death in three. Of the twelve patients informative for T-cell receptor gene rearrangements, clonal populations were found in eight. All patients who had cytopenias requiring treatment were initially treated with cyclosporine monotherapy, with the further addition of growth factors if necessary.
Multiparameter flow cytometric analysis of blood or bone marrow aspirates revealed that patients with a prior history of systemic malignancy had the common immunophenotype of CD3+(h), CD8+(h), CD2+, CD5+, CD7(h), CD56(h), CD57+, CD38+, CD16−. In contrast, patients who did not have a prior history of malignancy were CD3+, CD8+, CD2+, CD5+, CD7+, CD56+/−, CD57+, CD38+/(h), CD16+/− (h=heterogeneous). Thus patients with a prior malignancy had more heterogeneous expression of the T-cell markers CD3, CD8 and CD7 and were less likely to express CD16. We conclude that prior malignancy is more common in patients with T-LGL proliferations than previously recognized, may be twice as frequent as autoimmune disease in association with T-LGL and may have a distinct immunophenotype. Our data suggest that malignant cells may induce proliferations of T-LGL.
The Relationship between Systemic Anticoagulation during Cardiac Surgery and Heparin Platelet Factor 4 Antibody Formation.
Authors: Francis John L. , Drexler Alane , Walker Jamie , Rathmann Kristin 
Published: October 2019

Abstract
Heparin-induced thrombocytopenia occurs in approximately 1–3% of patients receiving unfractionated heparin. However, up to 50% of patients receiving heparin for systemic anticoagulation during cardiac surgery with cardiopulmonary bypass develop antibodies to the heparin-platelet factor 4 (HPF4) complex detectable by enzyme-linked immunoassays (ELISA). This high incidence of seroconversion is not diminished by off-pump cardiac surgery (OPCAB), despite significantly lower doses of heparin used for surgical anticoagulation. We tested the hypothesis that HPF4 antibodies develop following cardiac surgery even when heparin is not used for surgical anticoagulation. Patients (n=133) were randomized (2:1) to receive bivalirudin (The Medicines Company, Parsippany, NJ) or heparin for surgical anticoagulation during OPCAB. There were no restrictions on the pre-operative or post operative use of heparin. Blood samples were obtained pre-operatively (baseline), and 7 and 30 days after surgery. Serum samples were stored frozen until tested with a commercially available ELISA for HPF4 antibodies (GTI Inc., WI). An optical density (OD) ≥ 0.4 was considered positive, while an OD >1.0 was deemed strongly positive. The percentage of patients having a positive HPF4 antibody test (OD ≥ 0.4), was similar at baseline (6.7 vs. 6.8%) and at 7 days (27.1 vs. 29.3%) in bivalirudin and heparin-treated patients, respectively. At 30 days, the frequency of HPF4 antibodies was lower in the patients who received bivalirudin for surgical anticoagulation (32.5% vs. 40.9%). The percentage of patients having a strongly positive ELISA (OD > 1.0) was 0% at baseline in both groups, 4.3 vs. 7.3% at 7 days and 4.8 vs. 9.1% at 30 days for bivalirudin vs heparin, respectively. These data suggest that HPF4 antibody formation during hospitalization for cardiac surgery is not dependent only on the heparin used for anticoagulation during surgery. Antibody positivity in baseline samples presumably results from pre-operative heparin use and is consistent with previous reports. Since bivalirudin is not capable of eliciting an HPF4 antibody response, post-operative seroconversion presumably reflects a combination of both pre- and post-operative heparin use. However, when heparin was used for surgical anticoagulation, the number of patients subsequently developing strongly positive HPF4 antibodies was almost twice that seen in the bivalirudin group. This suggests that the use of bivalirudin as a surgical anticoagulant may reduce the incidence and risk of HIT following cardiac surgery.
Inhibitor Incidence in Previously Untreated Patients (PUP) with Hemophilia A and B - a 10-Year-Follow up of the Prospective Multicenter Study.
Authors: Kreuz Wolfhart , Auerswald Guenter K.H. , Budde Ulrich , Lenk Harald 
Published: October 2019

Abstract
The development of neutralizing FVIII-antibodies is one of the most serious complication in the replacement therapy with FVIII and IX concentrates in hemophilia A and B patients. In order to observe different parameters with possible impact on inhibitor development in PUPs with hemophilia A and B a prospective study was started in 1993 by the GTH (German, Swiss and Austrian Society on Thrombosis and Haemostasis Research).
The study protocol provides frequent inhibitor testing particularly during the initial 200 exposure days (ED) according to the modified Bethesda method (central lab Prof. Budde, Hamburg) and correlates inhibitor development with age at first exposure, therapy regimen, dosage, mutation type, type of concentrate and further variables which may have an impact on inhibitor development. Until September 2003, 293 patients with hemophilia A and B have been enrolled in this ongoing study. 206 have been treated (176 hemophilia A, 30 hemophilia B) at least once with plasma derived (pd) or recombinant (r) factor (F) VIII or IX concentrates.
Out of 176 hemophilia A patients 35 developed inhibitors (16 high titer >5 Bethesda Units/BU, 17 low titer >0.6–5 BU, 2 transient low titer inhibitors) after 12 exposure days (ED) in median (range 1–56) at the age of 0.9 years (median, range 0.25–10.8). Inhibitor development was predominantly observed in severe hemophilia A patients (31%) and to a lesser extent in moderate patients (7.7%). Inhibitor incidence was higher in patients receiving recombinant FVIII products than in those treated with plasma derived concentrates (p=0,14). No correlation between age at first exposure and inhibitor development was found. Early prophylaxis resulted in a lower inhibitor incidence than on-demand treatment (p=0.003).
Out of 16 severely affected hemophilia B patients 2 developed inhibitors.
Laboratory Analysis of Abnormal Closure Times with Relation to Low Ristocetin Cofactor Versus Other Causes.
Authors: Arthur Emma , Hassett Andrea Cortese , Bontempo Franklin A. 
Published: October 2019

Abstract
Closure times (CTs) have replaced the limitations of the previous testing methods. However, the clinical utility of detecting abnormal CTs remains poorly defined, with the differential diagnosis including von Willebrand’s disease (vWD), aspirin or NSAIDs, uremia, liver disease, or congenital defects. Ristocetin cofactor (RCoF) measures the functional activity of the vW molecule and when low, most often suggests vWD. CTs are frequently done in patients suspected by history of having vWD with some laboratories preferring to perform the collagen/epinephrine (Col/Epi) CT alone, while others additionally include the collagen/ADP (Col/ADP) CT.
METHODS: We analyzed 1480 consecutive CTs from a large reference laboratory done on a PFA-100 (Dade-Behring) and correlated the CTs with RCoF levels done on a BCS analyzer (Dade-Behring). Normal ranges were: Col/Epi CT 84-175 sec.; Col/ADP CT 65-117 sec.; RCoF 0.5-1.5 U/ml. Calculated means for CT of ≥ 300 sec. used a level of 300.
TABLE
Of the 260 studies with abnormal closure times, 131 (50%) had normal RCoF values, 47 (18%) were high and 18 (32%) were low. All studies with low RCoFs had at least one abnormal CT with 78/82 (95%) having both CTs prolonged, 2/82 (≫2%) with a long Col/EPI only, and 2/82 (≫2%) with a long Col/ADP only. Mean CTs in patients with low RCoFs and both CTs abnormal were 252 seconds for Col/EPI and 174 seconds for Col/ADP, both well above the upper limits of the normal range. Mean CTs in patients with low RCoFs and one abnormal CT were 180 seconds for Col/EPI and 123 seconds for Col/ADP, both just slightly above the upper limits of the normal range.
CONCLUSIONS: These findings suggest that when RCoF is low, both Col/EPI and Col/ADP CTs are prolonged, usually markedly, and the chances that a low RCoF will be missed is low, particularly if both CTs are used.
RESULTS: Total CTs analyzed: 1480 No.≥ 1 Abnormal CT 260/1480 (18%)
Number (%) Both CTs Abnormal Col/Epi ONLY Abnormal Col/ADP ONLY Abnormal Total Abnormal CTs 260 (100%) 203 (78%) 42 (16%) 15 (6%) Total Low RCoFs 82 (100%) 78 (95%) 2 (≈2%) 2 (≈2%)
Childhood ALL Treatment and Protocol Compliance Failure at a Single Institute from Most Developed Area of China.
Authors: Tang JingYan , Xue HuiLiang , Gu Long-Jun , Chen Jing , Pan Ci , Ye Hui 
Published: October 2019

Abstract
Purpose To analyze the main reason of failure in children with ALL at a single institute which is at most developed city of developing country China.
Method All the ALL patients who was diagnosed at our hospital from 1998.10 to 2003.12 were analyzed. The date was created from our department tumor registry database. Patient was divided into 3 groups, high, middle and low risk, depends on 1.Age >=10 year, 2. 50×109/L>WBC<100×109/L, 3. chromosome<45,or DNA index <1.16, 4. t(4;11), 5. T-ALL, 6.CNSL and/or TL, 7. WBC>=100×109/L, 8.t(9;22), 9.<1 year or >12 year, 10. Early response (1) Pred.test day 8,pripherial blast >=1,000/μl, (2) Induction day19–21 or day 35 bone marrow blast >=5%. Anyone from item 1 to 5 was middle risk factor, item 6 to 9 was high risk factor. The patients not receiving any therapy after ALL diagnosis were accounted as early protocol compliance failure, receiving therapy less than 15 days were middle protocol compliance failure, giving up therapy or losing follow-up after 15 day with stable disease or CR were accounted as late compliance failure.
Results Total 224 ALL were diagnosed, of them 38 patients went home with no any therapy. That means early protocol compliance failure was 17%. Of the remained 186 patients, 26 patients(12%) belonged to middle protocol compliance failure and 6 (3%) was late compliance failure. So total protocol compliance failure was 31%. The main reason of compliance failure was lacking financial support. Within the 160 patients who received more than 15 days therapy, 50(31%) was high risk, 51(32%) middle risk, and 52(33%) low risk, another 7 at un-know risk group. Of them, 48 patients relapsed(40) or not reached CR(8), 10 died of complication(mainly infection), total treatment failure was 48(30%).
Conclusion Besides the treatment failure, protocol compliance failure is a important reason for childhood ALL survival failure in developing country.
Aclarubicin and Low Dose Arabinoside Cytosine (Ara-C) in Combination with Granulocyte Colony Stimulating Factor (G-CSF) in Treating Acute Myeloid Leukemia (AML) Patients with Relapsed or Refractory Disease and Myelodysplasia Syndrome (MDS): A Multi-Center Study of 112 Chinese Patients.
Authors: Li J.M. , Shen Y. , Wu D.P. , Liang H. , Jin J. , Chen F.Y. , Song Y.P. , Wang J.M. , Qiu X.F. , Hou M. , Qiu Z.C. , Shen Z.X. 
Published: October 2019

Abstract
112 patients with senile acute myelocytic leukemia (AML), refractory or relapsed AML, and MDS-RAEBt entered this study to receive aclarubicin and low dose Arabinoside Cytosine (Ara-C) in combination with Granulocyte Colony Stimulating Factor (G-CSF) for evaluation of efficacy and tolerance of this CGA regimen. Low dose Ara-C was given at the dosage of 10mg/m2/12h, subcutaneously, D1-14 and aclarubicin 14mg/m2/d, intravenously, D1-4 (regimen A) or 7mg/m2 D1-8 (regimen B). Recombinant G-CSF was given at the dosage of 200μg/m2/d, subcutaneously, D1-14. We proved that overall response rate was 19/26 (73.1%) in senile AML, 48/62 (77.4%) in refractory AML, 12/18 (66.7%) in relapsed AML and 10/13 (76.9%) in MDS-RAEBt; and CR rate was at 8/26 (30.8%) in senile patients, 30/62 (48.4%) in refractory AML, 8/18 (44.4%) in relapsed AML and 5/13 (38.5%) in MDS-RAEBt, which were comparable in four groups of patients. 52 patients were followed up. Median progression free survival (PFS) and overall survival (OS) were 9.0±2.2 months and 11.0±1.6 months, respectively. The Kaplan-Meier estimated PFS and OS rate at 12 months were 40.73±8.15% and 42.85±8.23%, respectively. 1 year OS and PFS rate of the patients with CR were 60%±10.8% and 51.3%±13.7%, respectively, compared with the patients with PR, 17.7%±9.3% and 6.4%±6.1%, respectively. The toxic effects were very rare, mainly manifested as hematological changes, neutropenia and thrombocytopenia due to myelosuppression, which was around 70–80% exceeding NCI grade II. And non-hematological toxicities were not observed in this study. CAG regimen seems to be promising for the treatment of various categories of poor-prognosis AML or MDS-RAEBt, with acceptable toxicity.