Plasma cell-free RNA signatures of inflammatory syndromes in children.

Inflammatory syndromes, including those caused by infection, are a major cause of hospital admissions among children and are often misdiagnosed because of a lack of advanced molecular diagnostic tools. In this study, we explored the utility of circulating cell-free RNA (cfRNA) in plasma as an analyte for the differential diagnosis and characterization of pediatric inflammatory syndromes. We profiled cfRNA in 370 plasma samples from pediatric patients with a range of inflammatory conditions, including Kawasaki disease (KD), multisystem inflammatory syndrome in children (MIS-C), viral infections, and bacterial infections. We developed machine learning models based on these cfRNA profiles, which effectively differentiated KD from MIS-C-two conditions presenting with overlapping symptoms-with high performance [test area under the curve = 0.98]. We further extended this methodology into a multiclass machine learning framework that achieved 80% accuracy in distinguishing among KD, MIS-C, viral, and bacterial infections. We further demonstrated that cfRNA profiles can be used to quantify injury to specific tissues and organs, including the liver, heart, endothelium, nervous system, and the upper respiratory tract. Overall, this study identified cfRNA as a versatile analyte for the differential diagnosis and characterization of a wide range of pediatric inflammatory syndromes.

Radiofrequency identification tracking system (RFID) significantly improves blood bank inventory management and decreases staff work effort.

BACKGROUND: Before implementation of the radio frequency identification (RFID) system, there was a high loss rate of 4.0%-4.3% of red blood cell (RBC) units every year expiring on the shelf in our transfusion service laboratory. We introduced RFID technology to improve inventory management and the burden of work on the staff. The goal of this study was to evaluate the impact of RFID technology on the inventory management of RBC units and the staff workload in a transfusion service laboratory. STUDY DESIGN AND METHODS: Using an RFID system involves encoding RBC units with an RFID tag capturing information such as donor identification number, product code, blood type, expiration date, product volume, and negative antigen(s). Tag information is collected through retrofitted storage shelves linked to the RFID server. The study analyzed RBC usage by unit and by volume (mL) and staff work effort to carry out inventory management tasks before and after the implementation of the RFID system. RESULTS: Implementation of the RFID technology reduced the loss, or discard, of RBC units to less than 1% annually (a statistically significant change, p < .001). The RFID computer dashboard provides a constant visual update of the inventory, allowing technologists to have accurate product counts and reducing their work burden. DISCUSSION: Implementation of RFID technology substantially reduced RBC product loss, improved inventory management, and lessened staff work burden.

A global analysis of the use of immunoglobulin, shortages in supply, and mitigating measures: A survey of hospital providers (a BEST Collaborative study).

BACKGROUND: Immunoglobulin (IG) therapy is widely used to treat primary and secondary immune deficiencies and as immunomodulatory agent for various disorders. There is great concern that shortages of IG may rise, potentially affecting medical treatment options. STUDY DESIGN AND METHODS: An international survey was developed to study how intravenous immunoglobulins (IVIGs) are used and managed within hospitals in case of shortages. Study data were collected and managed using REDCap electronic data capture tools hosted by the Biomedical Excellence for Safer Transfusion (BEST) Collaborative. The survey was directed to hospital pharmacists and blood bank transfusion professionals and disseminated through members of the BEST Collaborative network. RESULTS: Survey respondents from institutions in the USA, Canada, Europe, Japan, and Australia (n = 13) confirmed that the primary specialties utilizing IG are neurology, hematology, and immunology. More than 60% of respondents reported IG supply shortages, but mitigation strategies were not well developed. DISCUSSION: As IG is the leading driver in plasma demand, more studies are needed to understand current and future demand for IG from the clinical perspective. Necessity lies in establishing clinical guidance to address shortages.

Use of group A thawed plasma in emergency transfusions at a pediatric quaternary care center.

BACKGROUND: Balanced plasma/red blood cell transfusions have shown survival benefit in emergency scenarios. To improve plasma availability, we implemented 5-day group A thawed plasma at our pediatric hospital in February 2021. STUDY DESIGN AND METHODS: We maintain thawed group A plasma units (5-day shelf-life) ready for immediate issue in the blood bank (since February 2021) and trauma code room (since August 2022). Group A plasma (un-titered) is issued for patients with unknown blood type during emergencies. We retrospectively reviewed records and laboratory results of recipients to assess safety and identify possible adverse events related to incompatible plasma. RESULTS: Between February 2021 and December 2023, 173 emergency plasma requests occurred for 161 patients. Ninety-one occurred with massive transfusion protocol activations. Thirty-six patients (22.4%) were blood group B or AB, and 23 received incompatible plasma (age 0-21.3 years, weight 0.74-149.8 kg, incompatible plasma dose 4.0-428.4 mL/kg). These patients did not have any differences in survival outcomes or hospital lengths of stay (LOS) compared with compatible plasma recipients, mirroring the adult experience. None experienced adverse events related to group A plasma. No transfusion reactions were reported. No increase in wastage/outdate occurred upon thawed plasma implementation (2020 versus 2021 to 2023, 7.73% [133/1721] vs. 8.58% [497/5792], p = .284). CONCLUSIONS: We implemented 5-day group A thawed plasma. Units are rapidly available from the blood bank and trauma code room without increased wastage. We did not identify any transfusion-associated adverse events in pediatric recipients of incompatible group A plasma.

Results of clinical effectiveness of conventional versus Mirasol-treated Apheresis Platelets in Patients with Hypoproliferative Thrombocytopenia (MiPLATE) trial.

BACKGROUND: The Mirasol® Pathogen Reduction Technology System was developed to reduce transfusion-transmitted diseases in platelet (PLT) products. STUDY DESIGN AND METHODS: MiPLATE trial was a prospective, multicenter, controlled, randomized, non-inferiority (NI) study of the clinical effectiveness of conventional versus Mirasol-treated Apheresis PLTs in participants with hypoproliferative thrombocytopenia. The novel primary endpoint was days of ≥Grade 2 bleeding with an NI margin of 1.6. RESULTS: After 330 participants were randomized, a planned interim analysis of 297 participants (145 MIRASOL, 152 CONTROL) receiving ≥1 study transfusion found a 2.79-relative rate (RR) in the MIRASOL compared to the CONTROL in number of days with ≥Grade 2 bleeding (95% confidence interval [CI] 1.67-4.67). The proportion of subjects with ≥Grade 2 bleeding was 40.0% (n = 58) in MIRASOL and 30.3% (n = 46) in CONTROL (RR = 1.32, 95% CI 0.97-1.81, p = .08). Corrected count increments were lower (p < .01) and the number of PLT transfusion episodes per participant was higher (RR = 1.22, 95% CI 1.05-1.41) in MIRASOL. There was no difference in the days of PLT support (hazard ratio = 0.86, 95% CI 0.68-1.08) or total number of red blood cell transfusions (RR = 1.12, 95% CI 0.91-1.37) between MIRASOL versus CONTROL. Transfusion emergent adverse events were reported in 119 MIRASOL participants (84.4%) compared to 133 (82.6%) participants in CONTROL (p = NS). DISCUSSION: This study did not support that MIRASOL was non-inferior compared to conventional platelets using the novel endpoint number of days with ≥Grade 2 bleeding in MIRASOL when compared to CONTROL.

A review and analysis of outcomes in randomized clinical trials of plasma transfusion in patients with bleeding or for the prevention of bleeding: The BEST collaborative study.

BACKGROUND: Previous systematic reviews have revealed an inconsistency of outcome definitions as a major barrier in providing evidence-based guidance for the use of plasma transfusion to prevent or treat bleeding. We reviewed and analyzed outcomes in randomized controlled trials (RCTs) to provide a methodology for describing and classifying outcomes. STUDY DESIGN AND METHODS: RCTs involving transfusion of plasma published after 2000 were identified from a prior review (Yang 2012) and combined with an updated systematic literature search of multiple databases (July 1, 2011 to January 17, 2023). Inclusion of publications, data extraction, and risk of bias assessments were performed in duplicate. (PROSPERO registration number is: CRD42020158581). RESULTS: In total, 5579 citations were identified in the new systematic search and 22 were included. Six additional trials were identified from the previous review, resulting in a total of 28 trials: 23 therapeutic and five prophylactic studies. An increasing number of studies in the setting of major bleeding such as in cardiovascular surgery and trauma were identified. Eighty-seven outcomes were reported with a mean of 11 (min-max. 4-32) per study. There was substantial variation in outcomes used with a preponderance of surrogate measures for clinical effect such as laboratory parameters and blood usage. CONCLUSION: There is an expanding literature on plasma transfusion to inform guidelines. However, considerable heterogeneity of reported outcomes constrains comparisons. A core outcome set should be developed for plasma transfusion studies. Standardization of outcomes will motivate better study design, facilitate comparison, and improve clinical relevance for future trials of plasma transfusion.

Prophylactic Transfusion Strategies in Children Supported by Extracorporeal Membrane Oxygenation: The Pediatric Extracorporeal Membrane Oxygenation Anticoagulation CollaborativE Consensus Conference.

OBJECTIVES: To derive systematic-review informed, modified Delphi consensus regarding prophylactic transfusions in neonates and children supported with extracorporeal membrane oxygenation (ECMO) from the Pediatric ECMO Anticoagulation CollaborativE. DATA SOURCES: A structured literature search was performed using PubMed, EMBASE, and Cochrane Library (CENTRAL) databases from January 1988 to May 2020, with an update in May 2021. STUDY SELECTION: Included studies assessed use of prophylactic blood product transfusion in pediatric ECMO. DATA EXTRACTION: Two authors reviewed all citations independently, with a third independent reviewer resolving conflicts. Thirty-three references were used for data extraction and informed recommendations. Evidence tables were constructed using a standardized data extraction form. MEASUREMENTS AND MAIN RESULTS: The evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation system. Forty-eight experts met over 2 years to develop evidence-informed recommendations and, when evidence was lacking, expert-based consensus statements or good practice statements for prophylactic transfusion strategies for children supported with ECMO. A web-based modified Delphi process was used to build consensus via the Research And Development/University of California Appropriateness Method. Consensus was based on a modified Delphi process with agreement defined as greater than 80%. We developed two good practice statements, 4 weak recommendations, and three expert consensus statements. CONCLUSIONS: Despite the frequency with which pediatric ECMO patients are transfused, there is insufficient evidence to formulate evidence-based prophylactic transfusion strategies.

Optimizing electronic blood ordering and supporting administration workflows to improve blood utilization in the pediatric hospital setting.

BACKGROUND: Red blood cell wastage occurs when blood is discarded rather than transfused, and ineffective ordering results in unnecessary crossmatch procedures. We describe how a multimodal approach to redesigning electronic ordering tools improved blood utilization in a pediatric inpatient setting and how using innovative application of time series data analysis provides insights into intervention effectiveness, which can guide future process improvement cycles. METHODS: A multidisciplinary team used best practices and Toyota Production System methodology to redesign electronic blood ordering and improve administration processes. We analyzed crossmatch to transfusion ratio and red blood cell wastage time series data extracted from our laboratory information system and electronic health record. We used changepoint analysis to identify statistically discernible breaks in each time series, compatible with known interventions. We performed causal impact analysis on red blood cell wastage time series data to estimate blood wastage avoided due to the interventions. RESULTS: Changepoint analysis estimated an 11% decrease in crossmatch to transfusion ratio and a 77% decrease in red blood cell monthly wastage rate during the intervention period. Causal impact analysis estimated a 61% reduction in expected wastage compared to the scenario if the interventions had not occurred. DISCUSSION: Our results show that electronic health record design is an important factor in reducing waste and preventing unnecessary crossmatching, and that time series analysis can be a useful tool for evaluating the long-term impact of each stage of intervention in a longitudinal process redesign effort for the purpose of effectively targeting future improvement efforts.

Multi-institutional experience with COVID-19 convalescent plasma in children.

BACKGROUND AND OBJECTIVES: Convalescent COVID-19 plasma (CCP) was developed and used worldwide as a treatment option by supplying passive immunity. Adult studies suggest administering high-titer CCP early in the disease course of patients who are expected to be antibody-negative; however, pediatric experience is limited. We created a multi-institutional registry to characterize pediatric patients (<18 years) who received CCP and to assess the safety of this intervention. METHODS: A REDCap survey was distributed. The registry collected de-identified data including demographic information (age, gender, and underlying conditions), COVID-19 disease features and concurrent treatments, CCP transfusion and safety events, and therapy response. RESULTS: Ninety-five children received CCP: 90 inpatients and 5 outpatients, with a median age of 10.2 years (range 0-17.9). They were predominantly Latino/Hispanic and White. The most frequent underlying medical conditions were chronic respiratory disease, immunosuppression, obesity, and genetic syndromes. CCP was primarily given as a treatment (95%) rather than prophylaxis (5%). Median total plasma dose administered and transfusion rates were 5.0 ml/kg and 2.6 ml/kg/h, respectively. The transfusions were well-tolerated, with 3 in 115 transfusions reporting mild reactions. No serious adverse events were reported. Severity scores decreased significantly 7 days after CCP transfusion or at discharge. Eighty-five patients (94.4%) survived to hospital discharge. All five outpatients survived to 60 days. CONCLUSIONS: CCP was found to be safe and well-tolerated in children. CCP was frequently given concurrently with other COVID-19-directed treatments with improvement in clinical severity scores ≥7 days after CCP, but efficacy could not be evaluated in this study.

Proceedings of the 2022 NHLBI and OASH state of the science in transfusion medicine symposium.

BACKGROUND: State of the Science (SoS) meetings are used to define and highlight important unanswered scientific questions. The National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health, and the Office of the Assistant Secretary for Health (OASH), Department of Health and Human Services held a virtual SoS in transfusion medicine (TM) symposium. STUDY DESIGN AND METHODS: In advance of the symposium, six multidisciplinary working groups (WG) convened to define research priorities in the areas of: blood donors and the supply, optimizing transfusion outcomes for recipients, emerging infections, mechanistic aspects of components and transfusion, new computational methods in transfusion science, and impact of health disparities on donors and recipients. The overall objective was to identify key basic, translational, and clinical research questions that will help to increase and diversify the volunteer donor pool, ensure safe and effective transfusion strategies for recipients, and identify which blood products from which donors best meet the clinical needs of specific recipient populations. RESULTS: On August 29-30, 2022, over 400 researchers, clinicians, industry experts, government officials, community members, and patient advocates discussed the research priorities presented by each WG. Dialogue focused on the five highest priority research areas identified by each WG and included the rationale, proposed methodological approaches, feasibility, and barriers for success. DISCUSSION: This report summarizes the key ideas and research priorities identified during the NHLBI/OASH SoS in TM symposium. The report highlights major gaps in our current knowledge and provides a road map for TM research.

Using trends and outliers in managing delayed transfusions.

OBJECTIVES: To investigate if time to initiate a blood transfusion after an informative laboratory test could feasibly be used by the transfusion medicine service as a metric to monitor for transfusion delays. BACKGROUND: Delayed transfusions may result in patient morbidity and mortality, but no standards for timely transfusion have been developed. Information technology tools could be implemented to identify gaps in provision of blood and to recognise areas of improvement. MATERIALS AND METHODS: Data obtained from a children's hospital's data science platform and time from the release of laboratory results to the initiation of transfusions were calculated and weekly medians were used for trend analyses. Outlier events were obtained using locally estimated scatterplot smoothing and generalised extreme studentized deviate test. RESULTS: Overall, the number of outlier events on the timing of transfusions based on patients' haemoglobin level and platelet count were small (n = 1 and n = 0 for 139 weeks, respectively). Investigation of these events for adverse clinical outcomes was non-significant. CONCLUSIONS: Herein, we propose that the trends and outlier events could be further investigated and used to make decisions and implement protocols to improve patient care.

International guidelines regarding the role of IVIG in the management of Rh- and ABO-mediated haemolytic disease of the newborn.

Haemolytic disease of the newborn (HDN) can be associated with significant morbidity. Prompt treatment with intensive phototherapy (PT) and exchange transfusions (ETs) can dramatically improve outcomes. ET is invasive and associated with risks. Intravenous immunoglobulin (IVIG) may be an alternative therapy to prevent use of ET. An international panel of experts was convened to develop evidence-based recommendations regarding the effectiveness and safety of IVIG to reduce the need for ETs, improve neurocognitive outcomes, reduce bilirubin level, reduce the frequency of red blood cell (RBC) transfusions and severity of anaemia, and/or reduce duration of hospitalization for neonates with Rh or ABO-mediated HDN. We used a systematic approach to search and review the literature and then develop recommendations from published data. These recommendations conclude that IVIG should not be routinely used to treat Rh or ABO antibody-mediated HDN. In situations where hyperbilirubinaemia is severe (and ET is imminent), or when ET is not readily available, the role of IVIG is unclear. High-quality studies are urgently needed to assess the optimal use of IVIG in patients with HDN.

Current state and positive impact of hospital-based blood donor centers in the United States.

BACKGROUND: The COVID-19 pandemic has brought tremendous challenges to the United States blood supply. Decreased collections have caused blood product shortages. The number of hospital-based donor centers (HBDCs) has decreased in the past decades, but they provide important support to their hospital systems. MATERIALS/METHODS: We identified 79 active HBDCs through an information request to the FDA. These centers were invited to participate in a survey about their activities, blood product collections, and perceived value. RESULTS: Thirty-six centers responded (46% response rate). The centers represented a wide range of states and geographic settings. Whole blood collection was most common, but some respondents also prepared specialized products such as COVID-19 convalescent plasma and pathogen-reduced platelets. Positive impacts of HBDCs included inventory availability, cost-effectiveness/savings, community outreach, supporting special patient populations, and collecting specialty products. All respondents anticipate at least stable operations, if not growth, in the future. CONCLUSION: HBDCs continue to be valuable assets in addressing emerging patient transfusion needs. Their unique offerings are tailored to the populations their hospitals support, and demonstrate the value in having the collection infrastructure in place to rapidly respond to critical shortages. This survey provides benchmark data about a broad group of HBDCs including products prepared, inventory self-sufficiency levels, and reasons for positive impact.

Rate of D-alloimmunization in trauma does not depend on the number of RhD-positive units transfused: The BEST collaborative study.

BACKGROUND: Evidence indicates the life-saving benefits of early blood product transfusion in severe trauma resuscitation. Many of these products will be RhD-positive, so understanding the D-alloimmunization rate is important. METHODS: This was a multicenter, retrospective study whereby injured RhD-negative patients between 18-50 years of age who received at least one unit of RhD-positive red blood cells (RBC) or low titer group O whole blood (LTOWB) during their resuscitation between 1 January, 2010 through 31 December, 2019 were identified. If an antibody detection test was performed ≥14 days after the index RhD-positive transfusion then basic demographic information was collected, including whether the patient became D-alloimmunized. The overall D-alloimmunization rate, and the rate stratified by the number of units transfused, were calculated. RESULTS: Data were collected from nine institutions. Five institutions reported fewer than 10 eligible patients each and were excluded. From the remaining four institutions, all from the USA, there were 235 eligible patients; 77 (random effects estimate: 32.7%; 95% CI: 19.1-50.1%) became D-alloimmunized. Three of the institutions reported D-alloimmunization rates ≥38.6%, while the remaining institution's rate was 12.2%. In both random and fixed-effects models, the rate of D-alloimmunization was not significantly different between those who received one RhD-positive unit and those who received multiple RhD-positive units. CONCLUSION: In this large, multicenter study of injured patients, the overall rate of D-alloimmunization fell within the range previously reported. The rate of D-alloimmunization did not increase as the number of transfused RhD-positive units increased. These data can help to inform RhD type selection decisions.

The BLOODSAFE program: Building the future of access to safe blood in Sub-Saharan Africa.

BACKGROUND: The supply of blood in many low- and middle-income nations in Sub-Saharan Africa (SSA) does not meet the patient care needs. Lack and delay of blood transfusion cause harm to patients and slow the rate of progress in other parts of the health system. Recognizing the power of implementation science, the BLOODSAFE Program was initiated which supports three SSA research study teams and one data coordinating center (DCC) with the goal to improve access to safe blood transfusion in SSA. STUDY DESIGN AND METHODS: The study team in Ghana is focusing on studying and decreasing iron deficiency in blood donors and evaluating social engagement of blood donors through different approaches. The study team in Kenya is building a "vein to vein" workflow model to elucidate and devise strategies to overcome barriers to blood donation and improve infrastructural components of blood product production and use. The Malawi team is studying the infectious disease ramifications of blood donation as well as blood donor retention strategies aimed at blood donors who commence their donation career in secondary schools. RESULTS AND DISCUSSION: Together the project teams and the DCC work as a consortium to support each other through a shared study protocol that will study donor motivations, outcomes, and adverse events across all three countries. The BLOODSAFE Program has the potential to lead to generalizable improvement approaches for increasing access to safe blood in SSA as well as mentoring and building the research capacity and careers of many investigators.

What Laboratory Tests and Physiologic Triggers Should Guide the Decision to Administer a Platelet or Plasma Transfusion in Critically Ill Children and What Product Attributes Are Optimal to Guide Specific Product Selection? From the Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding.

OBJECTIVES: To present consensus statements and supporting literature for plasma and platelet product variables and related laboratory testing for transfusions in general critically ill children from the Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding. DESIGN: Systematic review and consensus conference of international, multidisciplinary experts in platelet and plasma transfusion management of critically ill children. SETTING: Not applicable. PATIENTS: Critically ill pediatric patients at risk of bleeding and receiving plasma and/or platelet transfusions. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A panel of 10 experts developed evidence-based and, when evidence was insufficient, expert-based statements for laboratory testing and blood product attributes for platelet and plasma transfusions. These statements were reviewed and ratified by the 29 Transfusion and Anemia EXpertise Initiative - Control/Avoidance of Bleeding experts. A systematic review was conducted using MEDLINE, EMBASE, and Cochrane Library databases, from inception to December 2020. Consensus was obtained using the Research and Development/University of California, Los Angeles Appropriateness Method. Results were summarized using the Grading of Recommendations Assessment, Development, and Evaluation method. We developed five expert consensus statements and two recommendations in answer to two questions: what laboratory tests and physiologic triggers should guide the decision to administer a platelet or plasma transfusion in critically ill children; and what product attributes are optimal to guide specific product selection? CONCLUSIONS: The Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding program provides some guidance and expert consensus for the laboratory and blood product attributes used for decision-making for plasma and platelet transfusions in critically ill pediatric patients.

Research Priorities for Plasma and Platelet Transfusion Strategies in Critically Ill Children: From the Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding.

OBJECTIVES: To present a list of high-priority research initiatives for the study of plasma and platelet transfusions in critically ill children from the Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding. DESIGN: Systematic review and consensus conference of international, multidisciplinary experts in platelet and plasma transfusion management of critically ill children. SETTING: Not applicable. PATIENTS: Critically ill pediatric patients at risk of bleeding and receiving plasma and/or platelet transfusions. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A panel of 13 experts developed research priorities for the study of plasma and platelet transfusions in critically ill children which were reviewed and ratified by the 29 Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding experts. The specific priorities focused on the following subpopulations: severe trauma, traumatic brain injury, intracranial hemorrhage, cardiopulmonary bypass surgery, extracorporeal membrane oxygenation, oncologic diagnosis or stem cell transplantation, acute liver failure and/or liver transplantation, noncardiac surgery, invasive procedures outside of the operating room, and sepsis and/or disseminated intravascular coagulation. In addition, tests to guide plasma and platelet transfusion, as well as component selection and processing, were addressed. We developed four general overarching themes and 14 specific research priorities using modified Research and Development/University of California, Los Angeles methodology. CONCLUSIONS: Studies are needed to focus on the efficacy/harm, dosing, timing, and outcomes of critically ill children who receive plasma and/or platelet transfusions. The completion of these studies will facilitate the development of evidence-based recommendations.

Executive Summary of Recommendations and Expert Consensus for Plasma and Platelet Transfusion Practice in Critically Ill Children: From the Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding (TAXI-CAB).

OBJECTIVES: Critically ill children frequently receive plasma and platelet transfusions. We sought to determine evidence-based recommendations, and when evidence was insufficient, we developed expert-based consensus statements about decision-making for plasma and platelet transfusions in critically ill pediatric patients. DESIGN: Systematic review and consensus conference series involving multidisciplinary international experts in hemostasis, and plasma/platelet transfusion in critically ill infants and children (Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding [TAXI-CAB]). SETTING: Not applicable. PATIENTS: Children admitted to a PICU at risk of bleeding and receipt of plasma and/or platelet transfusions. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A panel of 29 experts in methodology, transfusion, and implementation science from five countries and nine pediatric subspecialties completed a systematic review and participated in a virtual consensus conference series to develop recommendations. The search included MEDLINE, EMBASE, and Cochrane Library databases, from inception to December 2020, using a combination of subject heading terms and text words for concepts of plasma and platelet transfusion in critically ill children. Four graded recommendations and 49 consensus expert statements were developed using modified Research and Development/UCLA and Grading of Recommendations, Assessment, Development, and Evaluation methodology. We focused on eight subpopulations of critical illness (1, severe trauma, intracranial hemorrhage, or traumatic brain injury; 2, cardiopulmonary bypass surgery; 3, extracorporeal membrane oxygenation; 4, oncologic diagnosis or hematopoietic stem cell transplantation; 5, acute liver failure or liver transplantation; 6, noncardiac surgery; 7, invasive procedures outside the operating room; 8, sepsis and/or disseminated intravascular coagulation) as well as laboratory assays and selection/processing of plasma and platelet components. In total, we came to consensus on four recommendations, five good practice statements, and 44 consensus-based statements. These results were further developed into consensus-based clinical decision trees for plasma and platelet transfusion in critically ill pediatric patients. CONCLUSIONS: The TAXI-CAB program provides expert-based consensus for pediatric intensivists for the administration of plasma and/or platelet transfusions in critically ill pediatric patients. There is a pressing need for primary research to provide more evidence to guide practitioners.

Results of Testing Children for Severe Acute Respiratory Syndrome Coronavirus-2 Through a Community-based Testing Site.

OBJECTIVE: To describe the demographics, clinical features, and test results of children referred from their primary provider for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in the community setting. STUDY DESIGN: Retrospective cross-sectional study of children ≤22 years of age who were tested for SARS-CoV-2 at a community-based specimen collection site in Washington, DC, affiliated with a large children's hospital between March 21 and May 16, 2020. RESULTS: Of the 1445 patients tested at the specimen collection site for SARS-CoV-2 virus, 408 (28.2%) had a positive polymerase chain reaction test. The daily positivity rate increased over the study period, from 5.4% during the first week to a peak of 47.4% (Ptrend < .001). Patients with fever (aOR, 1.7; 95% CI, 1.3-2.3) or cough (aOR, 1.4; 95% CI, 1.1-1.9) and those with known contact with someone with confirmed SARS-CoV-2 infection (aOR, 1.6; 95% CI, 1.0-2.4.) were more likely have a positive test, but these features were not highly discriminating. CONCLUSIONS: In this cohort of mildly symptomatic or well children and adolescents referred to a community drive-through/walk-up SARS-CoV-2 testing site because of risk of exposure or clinical illness, 1 in 4 patients had a positive test. Children and young adults represent a considerable burden of SARS-CoV-2 infection. Assessment of their role in transmission is essential to implementing appropriate control measures.

Multisystem Inflammatory Syndrome of Children: Subphenotypes, Risk Factors, Biomarkers, Cytokine Profiles, and Viral Sequencing.

OBJECTIVE: To assess demographic, clinical, and biomarker features distinguishing patients with multisystem inflammatory syndrome in children (MIS-C); compare MIS-C sub-phenotypes; identify cytokine biosignatures; and characterize viral genome sequences. STUDY DESIGN: We performed a prospective observational cohort study of 124 children hospitalized and treated under the institutional MIS-C Task Force protocol from March to September 2020 at Children's National, a quaternary freestanding children's hospital in Washington, DC. Of this cohort, 63 of the patients had the diagnosis of MIS-C (39 confirmed, 24 probable) and 61 were from the same cohort of admitted patients who subsequently had an alternative diagnosis (controls). RESULTS: Median age and sex were similar between MIS-C and controls. Black (46%) and Latino (35%) children were over-represented in the MIS-C cohort, with Black children at greatest risk (OR 4.62, 95% CI 1.151-14.10; P = .007). Cardiac complications were more frequent in critically ill patients with MIS-C (55% vs 28%; P = .04) including systolic myocardial dysfunction (39% vs 3%; P = .001) and valvular regurgitation (33% vs 7%; P = .01). Median cycle threshold was 31.8 (27.95-35.1 IQR) in MIS-C cases, significantly greater (indicating lower viral load) than in primary severe acute respiratory syndrome coronavirus 2 infection. Cytokines soluble interleukin 2 receptor, interleukin [IL]-10, and IL-6 were greater in patients with MIS-C compared with controls. Cytokine analysis revealed subphenotype differences between critically ill vs noncritically ill (IL-2, soluble interleukin 2 receptor, IL-10, IL-6); polymerase chain reaction positive vs negative (tumor necrosis factor-α, IL-10, IL-6); and presence vs absence of cardiac abnormalities (IL-17). Phylogenetic analysis of viral genome sequences revealed predominance of GH clade originating in Europe, with no differences comparing patients with MIS-C with patients with primary coronavirus disease 19. Treatment was well tolerated, and no children died. CONCLUSIONS: This study establishes a well-characterized large cohort of MIS-C evaluated and treated following a standardized protocol and identifies key clinical, biomarker, cytokine, viral load, and sequencing features. Long-term follow-up will provide opportunity for future insights into MIS-C and its sequelae.