Publications by authors named "Cassandra D Josephson"

Objective: To evaluate if hematologic thresholds for red blood cell (RBC) and platelet transfusions changed over time following publication of new evidence from randomized trials in a multicenter cohort of extremely low birth weight (ELBW) infants.

Study Design: We analyzed data from the National Heart Lung and Blood Institute Recipient Epidemiology and Donor Evaluation Study-IV-Pediatrics (REDS-IV-P) study from April 2019 through December 2023. We compared pre-transfusion hemoglobin and platelet counts closest to each transfusion within 24 hours by year using linear mixed models and used model interaction terms to determine if trends over time differed by postnatal weeks.

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Introduction: Patients with sickle cell disease (SCD) are transfused phenotypically-matched red blood cells (RBCs) for various indications. While screening for units that are sicklenegative is standard practice, the transfusion of RBCs containing other hemoglobin variants can be of concern to transfusion services and clinicians due to possible adverse events. Thus, this study aimed to review possible adverse events in patients with SCD with transiently acquired hemoglobin variants.

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Identifying critically ill patients who are likely to improve their respiratory physiology following RBC transfusion is dynamic and difficult. Current decision tools are over-reliant on hemoglobin transfusion thresholds, without considering respiratory measures that may reflect physiologic effects of anemia and functional responses to RBC transfusion. Further, routine clinical measures to determine transfusion efficacy beyond hemoglobin increment are lacking to identify patients as responders or non-responders.

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Background: Variability in blood donors, components, and recipients are known to affect transfusion outcomes, yet the combined effects of these factors remains unclear.

Materials And Methods: The Red Blood Cell - Improving Transfusions for Chronically Transfused Recipients (RBC-IMPACT) study was a multi-center longitudinal study conducted in the United States (US) and Brazil over two years to investigate RBC survival after transfusion (Aim 1) and acute increase in iron post transfusion (Aim 2) (see https://clinicaltrials.gov/study/NCT05255445).

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Introduction: Life-threatening hemorrhage (LTH) is a significant cause of mortality in pediatrics. Timing of mortality in children with LTH is important for future trials.

Methods: In a secondary analysis of the prospective observational massive transfusion in children (MATIC) study, time-to-event analysis was performed to determine timing of death based on etiology of LTH and cause of death.

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Background: Therapeutic plasma exchange (TPE) is the primary intervention for treating symptomatic hyperviscosity from hypergammaglobulinemia, yet its efficacy for treating hyperviscosity related to hyperfibrinogenemia is unclear.

Objectives: Define the safety and efficacy of TPE for critically ill COVID-19 patients with elevated blood viscosity from hyperfibrinogenemia.

Methods: We performed a prospective randomized controlled trial in critically ill COVID-19 patients in a single US healthcare system.

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Background And Objectives: Cold-stored whole blood (CS-WB) in paediatric cardiac surgery is making a resurgence, given its identified benefits compared to conventional blood component therapy (CT).

Study Design And Methods: A single-centre retrospective study was conducted from January 2018 to October 2018 by including children <18 years of age undergoing cardiac surgery requiring cardiopulmonary bypass. ABO-compatible CS-WB from non-directed random donors was leukoreduced with platelet-sparing filters and compared with CT.

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Red blood cell (RBC) antigen matching beyond ABO and RhD is commonly recommended for patients with sickle cell disease (SCD) and thalassaemia. We present an updated systematic literature review to inform evidence-based guidelines on RBC matching. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) tool was used to develop recommendations.

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Blood transfusions, crucial in managing anemia and coagulopathy in intensive care unit (ICU) settings, require accurate prediction for effective resource allocation and patient risk assessment. However, existing clinical decision support systems have primarily targeted a particular patient demographic with unique medical conditions and focused on a single type of blood transfusion. This study aims to develop an advanced machine learning-based model to predict the probability of transfusion necessity over the next 24 h for a diverse range of non-traumatic ICU patients.

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Objectives: To assess sex-specific differences in the association between pre-transfusion haemoglobin values and early neurodevelopmental function.

Design: Observational follow-up of infants with birth weights <1000 g and gestational ages 22-28 weeks who were enrolled in the NICHD Neonatal Research Network Transfusion of Prematures (TOP) Trial at 19 U.S.

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Importance: Observational studies often report that anemia and red blood cell (RBC) transfusions are associated with a higher risk of necrotizing enterocolitis (NEC) among extremely low-birthweight (ELBW) infants.

Objective: To evaluate whether there is a temporal association between 72-hour hazard periods of exposure to RBC transfusions and NEC among ELBW infants randomized to either higher or lower hemoglobin transfusion thresholds.

Design, Setting, And Participants: This post hoc secondary analysis of 1690 ELBW infants who survived to postnatal day 10 enrolled in the Transfusion of Prematures (TOP) randomized multicenter trial between December 1, 2012, and April 12, 2017, was performed between June 2021 and July 2023.

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Article Synopsis
  • Post-transfusion survival of donor red blood cells (RBCs) is crucial for effective treatment in conditions like sickle cell disease (SCD) and can be measured using biotin labeling.
  • An observational study tested the survival of biotin-labeled RBCs in pediatric SCD patients receiving chronic transfusions, revealing one donor unit with microcytosis and alpha-thalassemia.
  • The findings indicated that RBCs from donors with alpha-thalassemia may have a shorter survival post-transfusion, suggesting a need for more research on how these traits affect overall transfusion effectiveness.
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Article Synopsis
  • The study aimed to develop automated tools for actively monitoring errors in pediatric blood management (PBM) rather than relying on passive methods.
  • An expert panel identified 28 triggers for errors, leading to the creation of 5 automated tools, which were tested using electronic health record data over four years.
  • Findings showed that first transfusions without patient identification were common near misses, and over-transfusions were identified as a significant source of harm in pediatric care.
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Article Synopsis
  • Transfusion can elevate the risk of organ failure due to its impact on the immune system, leading to concerns about acute kidney injury (AKI) and acute respiratory distress syndrome (ARDS) in children with severe bleeding.
  • In a study of 449 children aged around 7.3 years, AKI developed in 18.5% and ARDS in 20.3% within five days after a bleeding incident, with a notable association between higher platelet-to-red blood cell transfusion ratios and increased AKI risk.
  • The findings suggest that while higher platelet transfusions may raise AKI risk, they are not linked to ARDS, indicating a need for further research to explore the underlying mechanisms involved.
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Background: Recent data suggest female sex imparts a survival benefit after trauma in adults. The independent associations between patient sex and age with outcomes have not been examined in children with life-threatening hemorrhage (LTH) from all etiologies.

Study Design And Methods: In a secondary analysis of a multicenter prospective observational study of children with LTH, Massive Transfusion in Children (MATIC), we analyzed if patient sex and age were associated with differences in severity of illness, therapies, and outcomes.

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Background: Red blood cell (RBC) antibodies are common in multiply transfused patients with sickle cell disease (SCD). Unlike RBC alloantibodies, the potential of autoantibodies to cause post-transfusion hemolysis may be uncertain. Biotin-labeling provides a direct measurement of red cell survival (RCS) over time, thus can be used to assess the clinical significance of RBC antibodies.

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There is little formal guidance to direct neonatal blood banking practices and, as a result, practices vary widely across institutions. In this vulnerable patient population with a high transfusion burden, considerations for blood product selection include freshness, extended-storage media, pathogen inactivation, and other modifications. The authors discuss the potential unintended adverse impacts in the neonatal recipient.

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Red blood cell (RBC) transfusion is a common clinical intervention used to treat patients with acute and chronic anemia. The decision to transfuse RBCs in the acute setting is based on several factors but current clinical studies informing optimal RBC transfusion decision making (TDM) are largely based upon hemoglobin (Hb) level. In contrast to transfusion in acute settings, chronic RBC transfusion therapy has several different purposes and is associated with distinct transfusion risks such as iron overload and RBC alloimmunization.

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Purpose: Balanced blood product resuscitation with red blood cells, plasma, and platelets can be achieved using whole blood (WB) or component therapy (CT). However, balanced resuscitation of younger children with severe traumatic hemorrhage may be complicated by delays in delivering all blood components and concerns regarding multiple product exposures. We hypothesized that WB achieves balanced resuscitation faster than CT, with fewer product exposures and improved clinical outcomes.

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The optimal use of prophylactic platelet transfusion remains uncertain in a number of clinical scenarios. Platelet count thresholds have been established in patients with hematologic malignancies, yet thresholds backed by scientific data are limited or do not exist for many patient populations. Clinical scenarios involving transfusion thresholds for thrombocytopenic patients with critical illness, need for surgery or invasive procedures, or those involving specials populations like children and neonates, lack clear evidence for discerning favorable outcomes without undue risk related to platelet transfusion.

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Background: Anemia in very low birth weight (VLBW) infants is common and frequently managed with red blood cell (RBC) transfusions. We utilized a linked vein-to-vein database to assess the role of blood donors and component factors on measures of RBC transfusion effectiveness in VLBW infants.

Study Design And Methods: We linked blood donor and component manufacturing data with VLBW infants transfused RBCs between January 1, 2013 and December 31, 2016 in the Recipient Epidemiology Donor Evaluation Study-III (REDS III) database.

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Among the risk factors for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), ABO(H) blood group antigens are among the most recognized predictors of infection. However, the mechanisms by which ABO(H) antigens influence susceptibility to COVID-19 remain incompletely understood. The receptor-binding domain (RBD) of SARS-CoV-2, which facilitates host cell engagement, bears significant similarity to galectins, an ancient family of carbohydrate-binding proteins.

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Antibodies against fetal red blood cell (RBC) antigens can cause hemolytic disease of the fetus and newborn (HDFN). Reductions in HDFN due to anti-RhD antibodies have been achieved through use of Rh immune globulin (RhIg), a polyclonal antibody preparation that causes antibody-mediated immunosuppression (AMIS), thereby preventing maternal immune responses against fetal RBCs. Despite the success of RhIg, it is only effective against 1 alloantigen.

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Background: Firearm injury (FI) is the leading cause of death in children and adolescents in the United States (US). We describe the epidemiology of pediatric FI-associated emergency department (ED) visits and hospitalizations in the US stratified by race and ethnicity.

Methods: Data on pediatric (0-17-year-olds) FI were analyzed using the 2019 Nationwide Emergency Department Sample (NEDS) and Kids' Inpatient Database (KID), the largest all-payer databases in the US for ED visits and pediatric hospitalizations, respectively.

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