bluuebunny/crossref_metadata_2025_split huggingface dataset:
Engraftment Syndrome Following Unrelated Cord Blood Transplant in Pediatric Patients.
Authors: Domm Jennifer , Wang Li , Calder Cassie , Manes Becky , Frangoul Haydar 
Published: April 2020

Abstract
Engraftment syndrome or hyper-acute graft versus host disease like syndrome describes a constellation of symptoms that occur prior or during neutrophil recovery after both allogeneic and autologous stem cell transplant. The usual symptoms are high grade fever and diffuse erythematous rash. There are no prior published reports describing the incidence and clinical implications of engraftment syndrome in recipients of unrelated cord blood transplant. There were 326 patients ≤ 18 years of age with malignant (N=229) or non-malignant (N=97) diseases enrolled on a prospective National Heart Lung Blood Institute (NHLBI) sponsored cord blood transplant study between 1999 and 2003. Dataset was abstained after signed agreement with the NHLBI and local IRB approval. All patients received myeloablative preparative regimen with either total body irradiation or busulfan based regimens with cyclosporine and prednisone GVHD prophylaxis. All patients received anti-thymocyte globulin as part of their conditioning regimen. ES was defined as high grade fever and diffuse erythematous rash without documented infections. The median age was 4.65 years (range 0.04 – 17.90) with 127 (60%) male, 264 (81%) had a performance status of ≥ 90. Two hundred twenty eight (70%) of the patients had malignant diseases and 179 (55%) received a cord blood unit matched at 3/6 or 4/6 HLA antigens and 147 (45%) received a cord blood unit matched at 5/6 or 6/6 HLA antigens. The median total nucleated cell dose per kg infuses was 6.94 x 107/kg (range 0.08–809.4 x 107/kg). Sixty-four patients (20%) developed engraftment syndrome at a median of 10 days (range 5–24) post transplant. All patients developed engraftment syndrome prior to engraftment and were treated with high dose steroids. Patients who developed engraftment syndrome had a median age of 2.47vs. 5.57 years, 48% had nonmalignant disease versus 25%, compared to those who did not develop engraftment syndrome respectively. The median pre-cyopreserved total nucleated cells infused was 8.58x107/kg (range 1.54x107 to 27.49 x107) in those who developed engraftment syndrome compared to 6.68x107/kg (range 0.08 x107 to 80.91x107) to those who did not. A multivariable analysis using Cox regression analysis using engraftment syndrome as a time dependent co-variable was performed including patients age, sex, performance status (&lt;90 versus ≥ 90), disease (malignant versus non malignant), HLA match (3–4/6 versus 5–6/6 HLA match), and total nucleated cell count per kg infused. Overall survival was significantly worse in female recipients (HR 1.78, CI 1.31–2.41, p=0.0002), those with malignant diseases (HR 1.75, CI 1.15–2.66, p=0.009), patients with performance status &lt;90 (HR 1.66, CI 1.15–2.40, p=0.007) and those who developed engraftment syndrome (HR 1.61, CI 1.15–2.28, p=0.006). Engraftment syndrome is a common complication following unrelated cord blood transplant in pediatric patients that increases the risk of overall mortality.
Acute Treatments and Early Outcomes of Childhood Arterial Ischemic Stroke: First Analysis of the International Pediatric Stroke Study.
Authors: Goldenberg Neil A , Bernard Timothy J. , Gordon Anne , Fullerton Heather J. , deVeber Gabrielle A. 
Published: April 2020

Abstract
Background: In pediatric arterial ischemic stroke (AIS) clinical treatment trials are lacking and treatment practices variable. Factors determining treatment selection and outcomes are important to delineate.
Objective: We aimed to (1) describe acute treatments and outcomes in childhood AIS, and (2) test putative variables for treatment selection, and outcome in a prospective-retrospective multicenter international study.
Methods: We evaluated treatments and early outcomes of children enrolled in the International Pediatric Stroke Study with AIS diagnosed at &gt;28 days and &lt;18 years of age from 2003 to 2007. Putative predictor variables for antithrombotic treatment selection included age, clinical AIS subtypes, geographic region (Asia, Australia, Canada, Europe, South America, and U.S.), and diagnosis pre- versus post-2004 (when pediatric AIS guidelines published).
Results: Among 676 children with acute AIS, anticonvulsants and antibiotics were administered acutely in 57% and 40%, respectively; use of each decreased with age (P&lt;0.001). Acute anticoagulants (AAC; with/without concomitant anti-platelet therapy) were selected more frequently than either acute anti-platelet agents (AAP) alone or no acute antithrombotic treatment (NAAT) (43% AAC vs. 28% AAP alone and 29% NAAT). NAAT decreased with increasing age. AAC was most frequent in cerebral/cervical arterial dissection (n=52; 75% AAC vs. 6% AAP) and least frequent with moyamoya syndrome (n=72; 31% AC vs. 43% AAP). AAC was most common in Europe and Canada, AAC vs. AAP relatively balanced in the U.S., and AAP most common in Asia and South America. AAC use was similar pre- versus post-2004. At hospital discharge 71% had neurological deficits independent of age, subtype, or geographical region. Mortality at discharge was 3%.
Conclusions: Acute anticoagulation is frequently but not uniformly employed in childhood AIS. With current treatment, the prevalence of neurological deficit at hospital discharge is high. These findings reflect disparity in published guidelines and highlight the need for clinical trials to reduce adverse outcomes.
Figure 1. Acute antithrombotic therapy in childhood AIS, by geographic region. Figure 1. Acute antithrombotic therapy in childhood AIS, by geographic region.
Platelet Responsiveness to Aspirin Loading in Patients with ST Elevation MI Undergoing Primary Percutaneous Intervention Is Associated with Myocardial Reperfusion and Clinical Outcome.
Authors: Varon Davi d , Matetzky Shlomi , Fefer Paul , Shenkman Boris , Shechter Michael , Levi Nitza , Savion Naphtali , Hod Hanoch 
Published: April 2020

Abstract
Background: In patients with stable coronary artery disease, and patients undergoing elective percutaneous coronary intervention (PCI), laboratory resistance to aspirin is associated with a higher incidence of adverse events. Nevertheless, the responsiveness to aspirin in acute myocardial infarction (AMI) and its implications have not yet been investigated.
Methods: The study comprised 76 aspirin naïve patients who underwent primary PCI (PPCI) for ST-elevation MI (STEMI). Platelet reactivity was assessed 30–60 mins after a loading dose of 300mg chewable aspirin, by conventional aggregometry and Impact R, where platelet reactivity to arachidonic acid (AA) was expressed by platelet deposition under flow conditions.
Results: Patients were stratified using the median value of AA-induced platelet aggregation (PA) (49%) to good responders to aspirin (n=38), who had a median AA-induced PA of 33% (25–41), and poor responders to aspirin (n=38), who had a median AA-induced PA of 77% (70–84). Similarly, good compared with poor responders had higher surface coverage by Impact R (3.9±2.6 vs. 2.2±1.3, p=0.003). Good versus poor responders were similar regarding baseline demographic, clinical and angiographic characteristics. However, good responders were more likely to demonstrate early ST-segment resolution ≥ 70% after PPCI (84% vs 54%, p &lt;0.01), suggestive of better myocardial reperfusion. Good compared to poor responders had a lower incidence of adverse cardiovascular events (re-infarction, need for re-intervention, congestive heart failure and/or death) throughout a 6-month follow-up (11% vs 24%, respectively; p&lt;0.05).
Conclusions: Ex vivo poor platelet responsiveness to aspirin loading in STEMI patients is associated with a worse prognosis in patients
Predictive Factors for Poor Outcome in Danaparoid-Treated HIT-Patients: A French Multicentre Case-Control Study.
Authors: Elalamy IsmaïL. , Tardy-Poncet B. , Mulot A. , DeMaistre E. , Pouplard Claire , Nguyen Philippe , Trossaert M. , Blanloeil Y. , Cleret B. , Gruel Yves , Lecompte T. , Tardy B. 
Published: April 2020

Abstract
Objective: to identify predictive factors of complications and mortality in danaparoid-treated HIT-patients.
Patients and Methods: case-control study involving HIT-patients defined by a relative decrease in platelet count of over 40% with or without thrombosis at presentation and positive laboratory testing (functional assay +/− ELISA). A patient presenting a complication 48 hours after heparin replacement with danaparoid (thrombosis, DIC, amputation, haemorrhage, death) was considered as a case.
Results: 49 cases and 65 controls were included (mean age 67±14 y; 51% women), from cardiovascular (53%) or orthopaedic (5%) surgery, intensive care (6%) or medicine (8%) units. Mean duration to complication was 7 days (D): death (n=26); thromboses (n=23); DIC (n=6); amputations (n=4); and haemorrhages (n=8).
In univaried analysis, compared to controls, cases presented:
an earlier HIT (7.9±3.5 versus 10.1±7.1 D; p=0.03) a lower platelet nadir (53±37 versus 70±37 G/L ; p=0.01), a more frequent thrombosis at HIT diagnosis (59% versus 32%, p=0.004), a later heparin withdrawal after HIT diagnosis (2.8 versus 1.3 d; p=0.01), a delayed heparin replacement (3.7 versus 1.9 d ; (p=0.001), an inadequate dosage of replacement therapy (44% versus 19% ; p=0.004).
In multivaried analysis, predictive factors leading for poor outcome were:
an initial thrombosis at HIT diagnosis (OR=3.2 [1.3–8]), a delay greater than 48 h for replacement therapy with danaparoid (OR=6.6 [2.5–17.3]), insufficient doses of danaparoid (OR=4.3 [1.5–12]).
Conclusion: this study confirms the mandatory need for a prompt replacement therapy and strict adherence to recommended doses for HIT-patients.
Prothrombin Complex Concentrate for Warfarin Reversal: A Single Dose Is Effective for All INRs &gt;4.5.
Authors: Gatt Alexander , Riddell Anne , van Veen Joost J , Kitchen Steve , Tuddenham Edward , Makris Michael 
Published: April 2020

Abstract
Introduction: 1% of patients of warfarin experience life-threatening bleeding per year and require emergency reversal of their anticoagulation. This is usually done by using a combination of vitamin K and prothrombin complex concentrate (PCC), FVIIa or FFP. Algorithms for warfarin reversal commonly use INR thresholds to guide the PCC dose. However, the INR system has only been validated for values up to 4.5.
Aim: To compare the ability of PCC, FVIIa and FFP to reverse the warfarin effects on the INR and thrombin generation (TG) as measured by the calibrated automated thrombography (CAT). We hypothesised that INRs greater than 4.5 would not correlate with TG and in which case one concentration of reversal agents would be suitable to reverse warfarin in all these patients.
Methods and Results: A pool of plasma from patients on warfarin (final INR 4.8) was spiked with Beriplex P/N (25Units/kg), FVIIa (~140μg/kg) and FFP (~20ml/kg). The INR normalised with Beriplex and FVIIa and was reduced to 1.4 with FFP. However, only Beriplex completely normalised TG parameters. In view of this Beriplex was used for subsequent reversal experiments. We analysed 48 plasma samples with INR &gt;4.5 (median 5.5; range 4.6–8.0) and measured TG at 5pM tissue factor. We found a significant moderate correlation between the INR and the endogenous thrombin potential (ETP) which is the maximum amount of thrombin generated (r=−0.59; P= &lt;0.0001). The mean ETP was 279.4nM.min (95%CI 240 – 318.9; SD 135.9). 2 plasma samples with INR &gt;8.0 were spiked with 5 concentrations of Beriplex P/N (7.5, 15, 25, 35 & 50Units/kg) in order to decide which is the ideal concentration of this PCC to reverse warfarin effects on the CAT. Both samples showed that a concentration between 25 and 35Units/kg could normalise TG without producing hypercoagulability. Hence we chose 30Units/kg to spike another 10 samples with INR &gt;4.5 (mean 6.4; range 4.7–8.0). The INR, TG and FII, VII, IX and X were tested after the addition of Beriplex P/N. The INR normalised in all samples (median 1.2; range 1.08–1.3) as did the ETP (median 1942nM.min; range 1546–2753nM.min), FII (mean 114U/dl; range 76–126U/dl), FIX (mean 127U/dl; range 106–154U/dl) and FX (mean 131U/dl; range 120–140U/dl). FVII increased to a mean 52U/dl (range 20–68U/dl). A lower concentration of Beriplex (25U/ kg) did not satisfactorily normalise the INR and TG in all samples tested.
Conclusion: PCCs fully reverse the effects of warfarin when compared to standard doses of FFP and FVIIa. INRs &gt;4.5 still correlate with TG but the amount of thrombin generated was comparatively low making the use of one dose of PCC (30U/kg) suitable for reversing the effect of all INRs &gt;4.5. This not only simplifies the reversal algorithms but reduces cost since doses up to 50U/kg are sometimes advocated for INRs &gt;6.0.
High Sensitivity Detection of Bacillus Cereus in Plasma Samples.
Authors: Rao Shilpakala Sainath , Mohan Ketha V. K. , Atreya Chintamani D 
Published: April 2020

Abstract
Microbial contamination of blood and blood products remains a major concern in transfusion medicine. Detection of bacterial contamination has been traditionally carried out by inoculating the contaminated blood/blood products into a liquid or solid nutrient medium followed by 18–24 h incubation period to observe any bacterial colony formation (growth). Although this technique is highly sensitive and specific, the test requires at least 24 hours for accurate diagnosis, which is a limitation Nucleic acid-based and antigen-based assays that have been recently in use also have limitations either with regard to time, sensitivity or specificity. In the present study we utilized Bacillus cereus and bacteriolysin (PlyG) derived from its g-phage virus as a model system for high sensitivity detection of this B. cereus in plasma. Six overlapping synthetic peptides in the bacterial binding C-terminal region of PlyG were tested in the study. The length of the synthetic peptides ranged from 20 to 10-mer and were biotinylated for subsequent detection. Peptide binding to bacteria was detected using either Streptavidin-conjugated horse radish peroxidase (HRP) on a nitrocellulose membrane or by using streptavidin-conjugated fluorescent Q-dots (liquid nano crystals) and analyzing under a fluorescence microscope. Various dilutions of log-phase cultures of B. cereus were spiked into plasma samples and incubated with the peptides for 1 hour followed by detection using either the streptavidin-HRP or streptavidin-Q-dots. Results revealed that two out of six peptides bound strongly to Bacillus in both the assays, while the rest of the peptides were either non-binders or weakly-binding. The membrane-based assay demonstrated an assay sensitivity of 102 colony forming units (CFU)/ml whereas the Q dots-based fluorescence assay was able to detect even a single bacterium. Overall, our findings suggest that both these assays are rapid and sensitive and results could be achieved within 2–3 hours. Quantitation of the fluorescent signal by fluorometry in a 96-well plate format is in progress.
The findings and conclusions in this abstract have not been formally disseminated by the Food and Drug Administration and should not be construed to represent any Agency determination or policy.
Front-Line Chemo-Immunotherapy Rituximab-FC + Rituximab Maintenance in Patients with Untreated Advanced Stage Non Follicular Lymphoma (INFL): Preliminary Results of a Prospective Study of the Intergruppo Italiano Linfomi and Roche (ML18324).
Authors: Baldini Luca , Pulsoni Alessandro , Rossi Giuseppe , Vitolo Umberto , Morra Enrica , Olivero Barbara , Cavalieri Elena , Merli Francesco , Rigacci Luigi , Nobile Francesco , Orsucci Lorella , Brugiatelli Maura , Musto Pellegrino , Deliliers Giorgio Lambertenghi , Gamba Enrica 
Published: April 2020

Abstract
Fludarabine in combination with cyclophosphamide (FC) plus rituximab (R) is an effective treatment for newly diagnosed as well as relapsed low-grade non-Hodgin’s lymphoma (NHL), including chronic lymphocytic leukemia (TAM 2006 and 2008, Keating 2005, Sacchi 2007). Maintenance treatment with R improves overall and progression-free survival in patients both with and without rituximab during induction, with relapsed/resistant follicular NHL (Van Oers 2006). We investigated efficacy and safety of the chemo-immunotherapy FCR followed by rituximab maintenance treatment in patients with advanced untreated indolent B-cell non follicular lymphomas (INFL). Patients and methods: from July 2005 to May 2007, 47 pts whit untreated advanced stage INFL (23 lymphocytic, 20 limphoplasmacytic and 4 nodal marginal zone NHL) were enrolled in an open label, single arm, multicenter phase II study, consisting with 6 courses of FC (Fludarabine, 25 mg/m2 i.v. plus Cyclophosphamide, 250 mg/m2, days 2–4) plus 8 doses of R (375 mg/m2, day 1 every FC cycle and day 14 of cycles 4 and 5) followed by R maintenance (375 mg/m2 every two months for 4 doses). Prophylactic antibiotic treatment with cotrimoxazole (two tablets three times a week) and antifungal profilaxis with itraconazole was planned from the beginning of chemotherapy to three months later or until normalization of CD4 count. The primary endpoint of this study is the percentage of failure free patients after two years from the treatment start. Results: 46/47 pts were evaluable for therapeutic response: median age 59 years (31–68), M/F ratio 28/18; stage III/ IV 44; B symptoms and splenomegaly 11 and 14 pts respectively; FLIPI scores were: 0–1, 16 pts (34.8%), score 2, 19 pts (41.3%) and score ≥ 3, 11 pts (23.9%). Forty-five patients received all the 6 courses of treatment and 1 patient 3 courses only. The ORR was 96% (44/46 pts) with 28 complete (61%) and 16 (35%) partial responses; 2 pts were in MR/SD. A total of 274 courses of FRC were given to 47 patients. The most frequent serious toxicity (NCI-CTC grade 3–4) was neutropenia that was reported in 55% of the courses. Three cases of Herpes zoster infection were reported. All the patients are still alive. Conclusions: in a series of INFL at diagnosis, FCR regimen is safe and effective with a very high CR rate. The whole study will provide insights on the role of R maintenance after R-chemotherapy in a particular subset of low-grade NHLs.
The Role of the P1 Residue of Protease Nexin 2 and Basic Pancreatic Trypsin Inhibitor in the Mechanism of Factor XIa Inhibition.
Authors: Navaneetham Duraiswamy , Sinha Dipali , Walsh Peter N. 
Published: April 2020

Abstract
Factor XIa (FXIa), a plasma serine protease that activates FIX, is regulated by protease nexin 2 (PN2), a Kunitz-type protease inhibitor (KPI) secreted on platelet activation. The Kunitz protease inhibitor domain of protease nexin 2 (PN2KPI) is highly homologous (45% primary sequence identity) to basic pancreatic trypsin inhibitor (BPTI, another Kunitz-type protease inhibitor) and their backbone tertiary structures are nearly identical (J Biol Chem280: 36165, 2005; J Mol Biol230: 919, 2005). However, PN2KPI (Ki 1 nM) is 600-fold more potent as a FXIa inhibitor than bovine basic pancreatic trypsin inhibitor (BPTI; Ki 630 nM). The present study is aimed at examining why these two structurally similar inhibitors are so different in their affinities and specificities in FXIa inhibition and analyzing the mechanisms of FXIa inhibition by these two inhibitors. Reasoning that the P1 residue (Arg15 in PN2KPI and Lys15 in BPTI) might play a crucial role in determining the affinity and specificity for FXIa we expressed BPTI-K15R (mimicking PN2KPI at the P1 site) and PN2KPI-R15K (mimicking BPTI at the P1 site) and examined their inhibitory properties. BPTI-K15R was found to inhibit FXIa with a Ki (10 nM) ~60-fold tighter than BPTI (Ki 630 nM), whereas PN2KPI-R15K inhibited FXIa with a Ki (32 nM) that was 32- fold impaired compared with PN2KPI (Ki 1 nM). Progress curves of peptidyl fluorogenic substrate (Boc-Glu-Ala-Arg-AMC) hydrolysis by FXIa in the presence of all the inhibitors except BPTI clearly demonstrated higher initial rates that continuously decreased until reaching a steady state, typical of slow inhibition. Progress curves obtained using BPTI, on the other hand, were found to be linear at all concentrations of the inhibitor. Analysis using steady state kinetics clearly demonstrated that BPTI is a competitive inhibitor in FXIa hydrolysis of the peptidyl chromogenic substrate, pyro-Glu-Pro-Arg-pNA. Analysis of progress curves using kinetic equations for slow, tight-binding inhibitors confirmed that the formation of the FXIa:PN2KPI complex occurs in a single step that is slow, whereas formation of FXIa:PN2KPI-R15K, FXIa:BPTI and FXIa:BPTI-K15R complexes do not conform to the same kinetic mechanism. Thus PN2KPI and BPTI inhibit FXIa by distinctly different mechanisms and the Arg at the P1 site of PN2KPI confers specificity and high affinity for FXIa inhibition and in part determines the mechanism of PN2KPI as a slow, tight binding inhibitor.
Characteristics and Clinical Outcomes of Adult Aplastic Anemia with Abnormal Cytogenetics at Diagnosis.
Authors: Kim Sung-Yong , Kim Myungshin , Han Kyungja , Lee Seok , Lee Mark Hong , Lee Jong-Wook , Min Woo-Sung , Kim Chun-Choo 
Published: April 2020

Abstract
Background and methods Occasionally, patients with acquired aplastic anemia (AA) present with abnormal cytogenetics in bone marrow cells at diagnosis. The diagnosis and treatment of such patients have not been established and have been center-dependent. We have treated adult AA patients with abnormal cytogenetics in a same way as those with normal cytogenetics. Presently, the characteristics and clinical outcomes of 600 adult AA patients who had successful cytogenetics at diagnosis were retrospectively evaluated. Our aim was to determine the characteristics and clinical courses of AA patients with cytogenetic abnormalities at diagnosis who were treated as those with normal cytogenetics.
Results Characteristics : Of the evaluable patients, 572 (95.3 %) had normal cytogenetics and 28 (4.7 %) had abnormal cytogenetics at diagnosis. The most frequent abnormality was trisomy 8 (n=15) followed by monosomy 7/deletion 7q (n=5) and deletion 1q (n=5). Other chromosome abnormalities were isochromosome 17q (n=1), trisomy 15 (n=1) and monosomy 21 (n=1). There was no significant statistical difference in gender (P=0.562), Hepatitis B or C infection (P=0.402), paroxysmal nocturnal hemoglobinuria (P=0.709) and severity of AA (P=0.325) between patients displaying normal cytogenetics and abnormal cytogenetics. The age of abnormal cytogenetics patients was significantly lower than normal cytogenetics patients (P&lt;0.001).
Immunosuppressive therapy : A total of 334 patients received immunosuppressive therapy using antithymocyte globulin and cyclosporine. Six months after commencement of therapy, 165 (50.9 %) patients responded partially or completely. Multivariate analysis revealed abnormal cytogenetics (HR=0.250; 95% CI=0.077–0.808; P=0.021), absence of paroxysmal nocturnal hemoglobinuria and age (≥ 67) as independent predictors for the poor response to immunosuppressive therapy.
Leukemic transformation : Kaplan-Meier modeling revealed that abnormal cytogenetics was also associated with higher cumulative leukemic transformation rate (P&lt;0.001) and lower leukemia-free survival (P=0.021). Of note, the cause of all deaths in non-severe AA patients with abnormal cytogenetics was leukemic transformation.
Conclusion: Patients with abnormal cytogenetics at diagnosis of AA tend to respond poorly to immunosuppressive therapy and present with a high leukemic transformation risk, which suggests that cytogenetic abnormalities should be emphasized more than morphological features in diagnosis and treatment decision in AA.