Individualized dosing guidelines for PEGasparaginase and factors influencing the clearance: a population pharmacokinetic model.

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Considerable inter- and intra-patient variability exist in serum activity levels of PEGasparaginase, essential for pediatric acute lymphoblastic leukemia treatment. A population pharmacokinetic (popPK) model was developed, identifying patient characteristics explaining […]

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Association of Isolated Diastolic Hypertension as Defined by the 2017 ACC/AHA Blood Pressure Guideline With Incident Cardiovascular Outcomes.

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In the 2017 American College of Cardiology (ACC)/American Heart Association (AHA) guideline, the definition of hypertension was lowered from a blood pressure (BP) of greater than or equal to 140/90 […]

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Effect of Fibrinogen Concentrate vs Cryoprecipitate on Blood Component Transfusion After Cardiac Surgery: The FIBRES Randomized Clinical Trial.

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Abstract: Excessive bleeding is a common complication of cardiac surgery. An important cause of bleeding is acquired hypofibrinogenemia (fibrinogen level <1.5-2.0 g/L), for which guidelines recommend fibrinogen replacement with cryoprecipitate […]

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Preventing Infectious Complications When Treating Non-Malignant Immune-Mediated Hematologic Disorders.

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Abstract: Immunosuppressants, targeted antibody therapies, and surgical splenectomy are amongst the treatment choices for immune-mediated non-malignant hematologic disorders, with infection being the most common non-hematological adverse event from these therapies. […]

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Measurable Residual Disease Monitoring in Acute Myeloid Leukemia with t(8;21)(q22;q22.1): Results of the AML Study Group.

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Abstract: We performed serial measurable residual disease (MRD) monitoring in bone marrow (BM) and peripheral blood (PB) samples of 155 intensively treated patients with RUNX1-RUNX1T1-positive AML using an RT-qPCR-based assay […]

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Stroke and thromboembolism prevention in atrial fibrillation.

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Abstract: Prevention of stroke and systemic thromboembolism remains the cornerstone for management of atrial fibrillation (AF) and flutter. Multiple risk assessment models for stroke and systemic thromboembolism are currently available. […]

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Polypill for Cardiovascular Disease Prevention in an Underserved Population.

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Abstract: Persons with low socioeconomic status and nonwhite persons in the United States have high rates of cardiovascular disease. The use of combination pills (also called “polypills”) containing low doses […]

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Secondary stroke prevention: a population-based cohort study on anticoagulation and antiplatelet treatments, and the risk of death or recurrence.

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Abstract: Using claims databases of a public healthcare program (Quebec) for the years 2010 – 2013, we conducted a cohort study of acute ischemic stroke (AIS) patients to describe secondary […]

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Impact of Multidisciplinary Pulmonary Embolism Response Team Availability on Management and Outcomes.

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Abstract: Treatment strategies for complex patients with pulmonary embolism (PE) are often debated given patient heterogeneity, multitude of available treatment modalities, and lack of consensus guidelines. Although multidisciplinary Pulmonary Embolism […]

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Guidelines from the 2017 European Conference on Infections in Leukaemia for management of HHV-6 infection in patients with hematological malignancies and after hematopoietic stem cell transplantation.

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Abstract: HHV-6B encephalitis is an important cause of morbidity and mortality after allogeneic hematopoietic stem cell transplant. Guidelines for the management of HHV-6 infections in patients with hematological malignancies or […]

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Perioperative care of children with sickle cell disease: a systematic review and clinical recommendations.

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Abstract: Children with sickle cell disease (SCD) require specific perioperative care, and clinical practice in this area remains poorly defined. We aimed to a) conduct a systematic, PRISMA-based review of […]

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Delphi method to identify expert opinion to support children’s cancer referral guidelines.

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Abstract: The National Institute for Health and Care Excellence (NICE) guidance for referral of children with suspected cancer was first published in 2005 and updated in 2015. The updated version […]

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The Russell Viper Venom Time (RVVT) test for investigation of lupus anticoagulant (LA).

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Abstract: Lupus anticoagulants (LAs) represent a laboratory representation of the clinical syndrome of antiphospholipid syndrome (APS), and can also arise in other pathological states. Laboratory testing for LA is complex […]

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Predicting Venous Thromboembolism in Multiple Myeloma: Development and Validation of the IMPEDE VTE Score.

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Abstract: Venous thromboembolism (VTE) is a common cause of morbidity and mortality among patients with multiple myeloma (MM). The International Myeloma Working Group (IMWG) developed guidelines recommending primary thromboprophylaxis in […]

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Consensus Clinical Decision-Making Factors Driving Anticoagulation in Atrial Fibrillation.

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Abstract: Guideline-recommended anticoagulation is frequently omitted in high-risk patients with atrial fibrillation (AF) for reasons not fully understood, which may result in suboptimal care. A nationally representative, expert group of […]

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Which are the most promising targets for minimal residual disease-directed therapy in acute myeloid leukemia prior to allogeneic stem cell transplant?

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Minimal residual disease has emerged as an important prognostic factor for relapse and survival in acute myeloid leukemia. Eradication of minimal residual disease may increase the number of patients with long-term survival; however, to date, strategies that specifically target minimal residual disease are limited. Consensus guidelines on minimal residual disease detection by immunophenotypic and molecular methods are an essential initial step for clinical trials evaluating minimal residual disease. Here, we review promising targets of minimal residual disease prior to allogeneic stem cell transplantation. Specifically, the focus of this review is on the rationale and clinical development of therapies targeting: oncogenic driver mutations, apoptosis, methylation, and leukemic immune targets. We review the progress made in the clinical development of therapies against each target and the challenges that lie ahead.

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Optimization of CSF biological investigations for CNS lymphoma diagnosis.

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Diagnosis of lymphoma leptomeningeal dissemination is challenging and relies on a wide array of methods. So far, no consensus biological guidelines are available. This increases the chance of intra- and interpractice variations, despite the shared concern to perform the minimum amount of tests while preserving clinically relevant results. We evaluated a training cohort of 371 cerebrospinal fluid (CSF) samples from patients with putative lymphomatous CNS localization using conventional cytology (CC), flow cytometry (FCM), molecular clonality assesment by PCR and cytokine quantification (CQ). This led us to propose a biological algorithm, which was then verified on a validation cohort of 197 samples. The samples were classified according to the clinical context and the results of each technique were compared. Using all 4 techniques was not useful for exclusion diagnosis of CNS lymphoma (CNSL), but they proved complementary for cases with suspected CNSL. This was particularly true for CQ in primary CNSL. Overall, diagnosis can be obtained with a two-step approach. The first step comprises CC and FCM, as results are available quickly and FCM is a sensitive method. PCR and CQ can be postponed and performed in a second step, depending on the results from the first step and the clinical context. The proposed algorithm missed none of the CNSL samples of the validation cohort. Moreover, applying this algorithm would have spared 30% of PCR tests and 20% of CQ over a one-year period, without compromising clinical management. This article is protected by copyright. All rights reserved.

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Effect of Systolic and Diastolic Blood Pressure on Cardiovascular Outcomes.

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The relationship between outpatient systolic and diastolic blood pressure and cardiovascular outcomes remains unclear and has been complicated by recently revised guidelines with two different thresholds (?140/90 mm Hg and ?130/80 mm Hg) for treating hypertension.Using data from 1.3 million adults in a general outpatient population, we performed a multivariable Cox survival analysis to determine the effect of the burden of systolic and diastolic hypertension on a composite outcome of myocardial infarction, ischemic stroke, or hemorrhagic stroke over a period of 8 years. The analysis controlled for demographic characteristics and coexisting conditions.The burdens of systolic and diastolic hypertension each independently predicted adverse outcomes. In survival models, a continuous burden of systolic hypertension (?140 mm Hg; hazard ratio per unit increase in z score, 1.18; 95% confidence interval [CI], 1.17 to 1.18) and diastolic hypertension (?90 mm Hg; hazard ratio per unit increase in z score, 1.06; 95% CI, 1.06 to 1.07) independently predicted the composite outcome. Similar results were observed with the lower threshold of hypertension (?130/80 mm Hg) and with systolic and diastolic blood pressures used as predictors without hypertension thresholds. A J-curve relation between diastolic blood pressure and outcomes was seen that was explained at least in part by age and other covariates and by a higher effect of systolic hypertension among persons in the lowest quartile of diastolic blood pressure.Although systolic blood-pressure elevation had a greater effect on outcomes, both systolic and diastolic hypertension independently influenced the risk of adverse cardiovascular events, regardless of the definition of hypertension (?140/90 mm Hg or ?130/80 mm Hg). (Funded by the Kaiser Permanente Northern California Community Benefit Program.).

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Selection of Unrelated Donors and Cord Blood Units for Hematopoietic Cell Transplantation: Guidelines from NMDP/CIBMTR.

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Allogeneic hematopoietic cell transplantation involves consideration of both donor and recipient characteristics to guide the selection of a suitable graft. Sufficient high resolution donor-recipient human leukocyte antigen (HLA) match is of primary importance in transplantation with adult unrelated donors, using conventional graft-versus-host disease prophylaxis. In cord blood transplantation, optimal unit selection requires consideration of unit quality, cell dose and HLA-match. In this summary, the National Marrow Donor Program® (NMDP) and the Center for International Blood and Marrow Transplant Research® (CIBMTR), jointly with the NMDP Histocompatibility Advisory Group, provide evidence-based guidelines for optimal selection of unrelated donors and cord blood units.

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Consensus criteria for diagnosis, staging, and treatment response assessment of T-cell prolymphocytic leukemia (T-PLL).

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T-cell prolymphocytic leukemia (T-PLL) is a rare, mature T-cell neoplasm with a heterogeneous clinical course. With the advent of novel treatment options that will potentially change the management of T-PLL patients it has become necessary to produce consensus guidelines for the design and conduct of clinical trials. The T-PLL International Study group (TPLL-ISG)set out to define standardized criteria for diagnosis, treatment indication, and evaluation of response. These criteria will facilitate comparison of results from clinical trials in T-PLL and will thus support clinical decision making as well as the approval of new therapeutics by healthcare authorities.

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How close are we to incorporating measurable residual disease into clinical practice for acute myeloid leukemia?

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Assessment of measurable residual disease, also called minimal residual disease in patients with acute myeloid leukemia in morphological remission provides powerful prognostic information and complements pretreatment factors such as cytogenetics and genomic alterations. Based on data that low levels of persistent or recurrent residual leukemia is consistently associated with an increased risk of relapse and worse long-term outcomes, its routine assessment has been recommended by some experts and consensus guidelines. In addition to providing important prognostic information, the detection of measurable residual disease may also theoretically help to determine the optimal post-remission strategy for an individual patient. However, the full therapeutic implications of measurable residual disease are uncertain, and thus, controversy exists as to whether it should be routinely incorporated into clinical practice. While some evidence supports the use of allogeneic stem cell transplantation or hypomethylating agents for some subgroups of patients in morphological remission but with detectable residual leukemia, the appropriate use of this information in making clinical decisions remains largely speculative at the present time. To answer this pressing clinical question, several ongoing studies are evaluating measurable residual disease-directed treatments in acute myeloid leukemia and may lead to new, effective strategies for these patients. This review examines the common technologies used in clinical practice and in the research setting to detect residual leukemia, the major clinical studies establishing the prognostic impact of measurable residual disease in acute myeloid leukemia, and the potential ways, both now and in the future, that such testing may rationally guide therapeutic decision-making.

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Multicenter Analysis of Outcomes in Blastic Plasmacytoid Dendritic Cell Neoplasm Offers a Pre-Targeted Therapy Benchmark.

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Abstract: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an uncommon hematologic malignancy with poor outcomes. Existing data on the clinical behavior of BPDCN are limited because reported outcomes are from […]

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Alert-based computerized decision support for high-risk hospitalized patients with atrial fibrillation not prescribed anticoagulation: a randomized, controlled trial (AF-ALERT).

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Abstract: Despite widely available risk stratification tools, safe and effective anticoagulant options, and guideline recommendations, anticoagulation for stroke prevention in atrial fibrillation (AF) is underprescribed. We created and evaluated an […]

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Testing and management for monoclonal gammopathy of uncertain significance and myeloma patients presenting with osteoporosis and fragility fractures.

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Abstract: Multiple myeloma, the second most frequent blood cancer, and its precursor, monoclonal gammopathy of uncertain significance, are associated with an increased risk of fragility fractures. However, current guidelines fail […]

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Low-Dose Alteplase for the Treatment of Submassive Pulmonary Embolism: A Case Series.

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Abstract: Pulmonary embolism (PE) can lead to significant morbidity and mortality. Thrombolytics are currently approved for the treatment of massive PE; however, the CHEST guidelines recommend against systemic thrombolytic use […]

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International myeloma working group consensus recommendations on imaging in monoclonal plasma cell disorders.

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Abstract: Recent advances in the treatment of multiple myeloma have increased the need for accurate diagnosis of the disease. The detection of bone and bone marrow lesions is crucial in […]

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