A randomized trial of blood donor iron repletion on red cell quality for transfusion and donor cognition and well-being.

Although altruistic regular blood donors are vital for the blood supply, many become iron deficient from donation-induced iron loss. The effects of blood donation-induced iron deficiency on red cell transfusion quality or donor cognition are unknown. In this double-blind, randomized trial, adult iron-deficient blood donors (n = 79; ferritin < 15 µg/L and zinc protoporphyrin >60 µMol/mol heme) who met donation qualifications were enrolled. A first standard blood donation was followed by the gold-standard measure for red cell storage quality: a 51-chromium posttransfusion red cell recovery study. Donors were then randomized to intravenous iron repletion (1 g low-molecular-weight iron dextran) or placebo. A second donation ∼5 months later was followed by another recovery study. Primary outcome was the within-subject change in posttransfusion recovery. The primary outcome measure of an ancillary study reported here was the National Institutes of Health Toolbox-derived uncorrected standard Cognition Fluid Composite Score. Overall, 983 donors were screened; 110 were iron-deficient, and of these, 39 were randomized to iron repletion and 40 to placebo. Red cell storage quality was unchanged by iron repletion: mean change in posttransfusion recovery was 1.6% (95% confidence interval -0.5 to 3.8) and -0.4% (-2.0 to 1.2) with and without iron, respectively. Iron repletion did not affect any cognition or well-being measures. These data provide evidence that current criteria for blood donation preserve red cell transfusion quality for the recipient and protect adult donors from measurable effects of blood donation-induced iron deficiency on cognition. This trial was registered at www.clinicaltrials.gov as NCT02889133 and NCT02990559.

Effects of Daily Posttraumatic Stress Disorder Symptoms on Heart Rate Variability.

OBJECTIVE: Posttraumatic stress disorder (PTSD) is common, debilitating, and associated with an increased risk of health problems, including cardiovascular disease. PTSD is related to poor autonomic function indicated by reduced heart rate variability (HRV). However, very little work has tested the timescale or direction of these effects, given that most evidence comes from cross-sectional studies. Documentation of when effects occur and in what direction can shed light on mechanisms of cardiovascular disease risk and inform treatment. The present study of 169 World Trade Center responders, oversampled for PTSD, tested how daily PTSD symptoms were associated with autonomic function as reflected through HRV. METHODS: Participants ( N = 169) completed surveys of PTSD symptoms three times a day at 5-hour intervals for 4 days while also wearing ambulatory monitors to record electrocardiograms to derive HRV (i.e., mean absolute value of successive differences between beat-to-beat intervals). RESULTS: HRV did not predict PTSD symptoms. However, PTSD symptoms during a 5-hour interval predicted reduced HRV at the next 5-hour interval ( ß = -0.09, 95% confidence interval = -0.16 to -0.02, p = .008). Results held adjusting for baseline age, current heart problems, and current PTSD diagnosis. CONCLUSIONS: Findings underscore growing awareness that PTSD symptoms are not static. Even their short-term fluctuations may affect cardiovascular functioning, which could have more severe impacts if disruption accumulates over time. Research is needed to determine if momentary interventions can halt increases in PTSD symptoms or mitigate their impact on cardiovascular health.

Prospective Bidirectional Relationship Between Sleep Duration and Posttraumatic Stress Disorder Symptoms After Suspected Acute Coronary Syndrome.

OBJECTIVE: Sleep disturbance is a "hallmark" symptom of posttraumatic stress disorder (PTSD). Poor sleep (including short sleep) after combat-related trauma can also predict subsequent PTSD. Less is known about the association between sleep duration and PTSD symptoms when PTSD is induced by acute coronary syndrome (ACS). We examined the bidirectional relationship between sleep duration and PTSD symptoms over the year after hospital evaluation for ACS. METHODS: Participants were enrolled in this observational study after emergency department evaluation for ACS. Sleep duration ("During the past month, how many hours of actual sleep did you get at night?") and cardiac event or hospitalization-induced PTSD symptoms (PTSD Checklist) were assessed at 1, 6, and 12 months after hospital discharge. Cross-lagged path analysis was used to model the effects of sleep duration and PTSD symptoms on each other. Covariates included age, sex, race/ethnicity, cardiac severity, baseline depression symptoms, and early acute stress disorder symptoms. RESULTS: The sample included 1145 participants; 16% screened positive for probable PTSD (PTSD Checklist score ≥33). Mean sleep duration across time points was 6.1 hours. Higher PTSD symptoms predicted shorter sleep duration at the next time point (i.e., 1-6 and 6-12 months; B = -0.14 hours/10-point difference, SE = 0.03, p < .001). Shorter sleep duration was associated with higher PTSD symptoms at the next time point (B = -0.25 points/hour, SE = 0.12, p = .04). CONCLUSIONS: Short sleep duration and PTSD symptoms are mutually reinforcing across the first year after ACS evaluation. Findings suggest that sleep, PTSD symptoms, and their relationship should be considered in the post-ACS period.

Handling the different requirements for commercial and investigational MNC collections by apheresis.

BACKGROUND: With the success of chimeric antigen receptor T-cell (CAR-T) and similar cellular-based therapies, the demand for collection of autologous mononuclear cells by apheresis (MNC(A)) from blood by apheresis has increased. From an apheresis technical standpoint, the collection of MNC(A) is relatively straightforward, especially when compared with collection of hematopoietic progenitor cells (HPC(A)). Most of the collection for MNC(A) are performed for the commercial entities, who use the product for manufacturing cellular therapeutics. We have noticed discrepancies in the handling and apheresis processes required by different companies in obtaining essentially the same product (all companies in the study manufacture CAR-T-based products). We have analyzed the MNC collection requirements from all FDA-approved CAR-T cellular products and some investigational products collected at University of Nebraska Medical Center. We identified discrepancies in the process and suggested mitigation strategies. METHODS: Step-by-step analysis of the collection requirements. Review of the current guidelines and recommendations on this issue. RESULTS: Multiple discrepancies in the collection process have been identified, even in the products collected for the same company. Practical approach of satisfying all the requirements based on University of Nebraska Medical Center experience has been suggested. CONCLUSION: The current recommendations from multiple sources were reviewed in discussion.

A multi-institutional survey of apheresis services among institutions in the United States.

INTRODUCTION: Apheresis practices in the United States (US) have not been comprehensively characterized to date. This study aimed to address this gap by evaluating apheresis therapy through a national survey. METHODS: A multi-institutional survey was conducted between April and July 2023. The survey, comprising 54 questions, focused on institutional demographics, procedures, equipment, staffing, training, and impacts of the Coronavirus Disease 2019 (COVID-19) pandemic. Responses from 22 institutions, primarily academic medical centers, were analyzed. RESULTS: Therapeutic plasma exchange (TPE) was the most common procedure, followed by hematopoietic progenitor cell collection (HPC-A) and red blood cell exchange (RCE). CAR-T cell collections were widespread, with some institutions supporting over 30 protocols concurrently. Most sites used the Spectra Optia Apheresis System, were managed by a transfusion medicine service, and employed internal apheresis providers. Insufficient staffing levels, exacerbated by the COVID-19 pandemic, were common and most often addressed using overtime. DISCUSSION: The survey highlighted the ubiquity of TPE, expanding cellular collections and staffing challenges. The role of apheresis in supporting cellular therapy, particularly in newly developing cell and gene therapies and clinical trials, was evident. Staffing issues during the pandemic emphasized the need for innovative recruitment strategies. CONCLUSION: This nationwide survey provides the most comprehensive analysis to date of apheresis practices in large US academic centers.

Use of a Single-Item Ecological Momentary Assessment to Measure Daily Exercise: Agreement with Accelerometer-Measured Exercise.

Accelerometers have been used to objectively quantify physical activity, but they can pose a high burden. This study was conducted to determine the feasibility of using a single-item smartphone-based ecological momentary assessment (EMA) in lieu of accelerometers in long-term assessment of daily exercise. Data were collected from a randomized controlled trial of intermittently exercising, otherwise healthy adults (N = 79; 57% female, mean age: 31.9 ± 9.5 years) over 365 days. Smartphone-based EMA self-reports of exercise entailed daily end-of-day responses about physical activity; the participants also wore a Fitbit device to measure physical activity. The Kappa statistic was used to quantify the agreement between accelerometer-determined (24 min of moderate-to-vigorous physical activity [MVPA] within 30 min) and self-reported exercise. Possible demographic predictors of agreement were assessed. Participants provided an average of 164 ± 87 days of complete data. The average within-person Kappa was κ = 0.30 ± 0.22 (range: -0.15-0.73). Mean Kappa ranged from 0.16 to 0.30 when the accelerometer-based definition of an exercise bout varied in duration from 15 to 30 min of MVPA within any 30 min period. Among the correlates examined, sex was significantly associated with agreement; mean agreement was higher among women (κ = 0.37) than men (κ = 0.20). Agreement between EMA self-reported and accelerometer-measured exercise was fair, suggesting that long-term exercise monitoring through a single-item EMA may be acceptable.

Apheresis medicine education during the early phase of the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic introduced challenges and disruption across healthcare, including apheresis medicine (AM). In this study, we report findings from a survey conducted among American Society for Apheresis Physician Committee (ASFA-PC) members to describe the impact of the COVID-19 pandemic on AM education practices. STUDY DESIGN AND METHODS: A voluntary, anonymous, 24-question, institutional review board-approved survey regarding AM teaching during the pandemic was distributed to ASFA-PC members in the United States between December 1, 2020, and December 15, 2020. Descriptive analyses were reported as number and frequency of respondents for each question. Free text responses were summarized. RESULTS: Responses were received from 14/31 (45%) of ASFA-PC members, of whom 12 practiced at academic institutions. Among these, 11/12 (92%) transitioned to virtual platform for AM trainee conferences during the pandemic. A variety of resources were employed to support independent AM learning. While 7/12 (58%) respondents did not change the informed consent process for AM procedures, others delegated this process or introduced remote alternatives. The most common method respondents used to conduct AM patient rounding was a hybrid in-person/virtual model. CONCLUSION: This survey describes the adaptations and changes AM practitioners made to trainee education in response to the early phase of the COVID-19 pandemic. The transition to virtual and/or hybrid trainee learning and AM rounds underscores the importance of digital AM resources. Further study of the effects of the pandemic and its impact on AM trainee education, as well as patient care is warranted.

Assessing deviations for HPCs obtained during COVID-19 (ADHOC): Evaluating impact of the COVID-19 pandemic on cellular therapy products and processes, the BEST collaborative study.

BACKGROUND: The success of allogeneic hematopoietic stem cell transplantation is dependent on a world-wide network of collection centers providing donations that predominantly have been infused as fresh cells. The logistics chain that supports the just-in-time delivery model for stem cell and immunotherapy products was severely stressed by the COVID pandemic, and in early 2020 a number of national and international bodies recommended that cells should be cryopreserved at the collection or transplant center to avoid interruptions in their acquisition or delivery to patients who had started conditioning. STUDY DESIGN: To assess the potential consequences of such pandemic-related deviations to normal practice, we surveyed nine international laboratories to determine if the characteristics or transplant outcomes of allogeneic stem cell donations differed in the immediate periods before and after the switch to routine cryopreservation. RESULTS: Nine centers on two continents provided data for 72 HSC donations just before, and 71 just after, switching to cryopreservation for allogeneic HSC products. No statistically significant differences between the period before and after cryopreservation were noted for time from product collection to receipt, product temperature at receipt, or CD34+ cell viability at receipt. There was an indication of slower absolute neutrophil count recovery after cryopreservation was required (mean time of 15 vs. 17.6 days). DISCUSSION: While there were no apparent changes to most parameters studied, there was an indication of slower neutrophil engraftment that will need to be examined in larger, longer term studies.

The Perceived Stress Scale as a Measure of Stress: Decomposing Score Variance in Longitudinal Behavioral Medicine Studies.

BACKGROUND: The Perceived Stress Scale (PSS) is a widely used measure designed to assess perceptions of recent stress. However, it is unclear to what extent the construct assessed by the PSS represents factors that are stable versus variable within individuals, and how these components might vary over time. PURPOSE: Determine the degree to which variability in repeated PSS assessments is attributable to between-person versus within-person variance in two different studies and populations. METHODS: Secondary analyses utilized data from two studies with up to 13 PSS assessments: An observational study of 127 patients with heart failure followed over 39 months (Study 1), and an experimental study of 73 younger, healthy adults followed over 12 months (Study 2). Multilevel linear mixed modeling was used to estimate sources of variance in the PSS total and subscale scores across assessments. RESULTS: Between-person variance accounted for a large proportion of the total variance in PSS total scores in Study 1 (42.3%) and Study 2 (51.1%); within-person variance comprised the remainder. Between-person variance was higher for shorter assessment periods (e.g., 1 week), and was comparable when examining only the first 12 months of assessments in each study (52.9% vs. 51.1%). CONCLUSIONS: Within two samples differing in age and health status, between-person variance accounted for approximately half of the total variation in PSS scores over time. While within-person variance was observed, the construct assessed by the PSS may substantially reflect a more stable characteristic of how an individual perceives stressful life circumstances than previously appreciated.

The Perceived Stress Scale (PSS) is a widely used questionnaire designed to assess how an individual perceives recent stress in their life. It is unclear, however, the degree to which the PSS is measuring factors that are consistent within individuals versus those that fluctuate, and how these components might change when the PSS is administered repeatedly over time. To address this knowledge gap, data from two studies were used­a study of 137 patients with heart failure followed for 39 months and a study of 73 younger, healthy adults followed for 12 months. In each, participants completed up to 13 PSS assessments, with 2,880 total PSS assessments completed across the studies. Multilevel linear mixed modeling was used to examine sources of score variance across assessments. Between-person variance (i.e., score variability that is relatively stable over time but differs between individuals) accounted for approximately half of the total variation in PSS scores over time, and was higher over shorter assessment periods. While within-person variance was observed (i.e., score variability that fluctuates within the same individual over time), these results suggest that the PSS may assess a substantially more stable characteristic of how an individual perceives stressful life circumstances than previously appreciated.

Anhedonic Depression Is Not Associated With Risk of Recurrent Major Adverse Cardiac Events and All-Cause Mortality in Acute Coronary Syndrome Patients.

BACKGROUND: Depression after acute coronary syndrome (ACS) is common and increases risks of adverse outcomes, but it remains unclear which depression features are most associated with major adverse cardiac events (MACE) and all-cause mortality (ACM). PURPOSE: To examine whether a subtype of depression characterized by anhedonia and major depressive disorder (MDD) predicts 1-year MACE/ACM occurrence in ACS patients compared to no MDD history. We also consider other depression features in the literature as predictors. METHODS: Patients (N = 1,087) presenting to a hospital with ACS completed a self-report measure of current depressive symptoms in-hospital and a diagnostic interview assessing MDD within 1 week post-hospitalization. MACE/ACM events were assessed at 1-, 6-, and 12-month follow-ups. Cox regression models were used to examine the association of the anhedonic depression subtype and MDD without anhedonia with time to MACE/ACM, adjusting for sociodemographic and clinical covariates. RESULTS: There were 142 MACE/ACM events over the 12-month follow-up. The 1-year MACE/ACM in patients with anhedonic depression, compared to those with no MDD, was somewhat higher in an age-adjusted model (hazard ratio [HR] = 1.63, p = .08), but was not significant after further covariate adjustment (HR = 1.24, p = .47). Of the additional depression features, moderate-to-severe self-reported depressive symptoms significantly predicted the risk of MACE/ACM, even in covariate-adjusted models (HR = 1.72, p = .04), but the continuous measure of self-reported depressive symptoms did not. CONCLUSION: The anhedonic depression subtype did not uniquely predict MACE/ACM as hypothesized. Moderate-to-severe levels of total self-reported depressive symptoms, however, may be associated with increased MACE/ACM risk, even after accounting for potential sociodemographic and clinical confounders.

Skin Conductance Reactivity as a Predictor of Stroke-induced Posttraumatic Stress Disorder Symptoms: A Dimensional Approach.

Background: Posttraumatic stress disorder (PTSD) symptoms can develop following acute, life-threatening medical events. This study explores a potential biomarker of PTSD risk that is novel to a medical trauma population: a noninvasive, mobile skin conductance (SC) measurement. Methods: Participants (N=64) were enrolled in-hospital following a stroke or transient ischemic attack (TIA). Mobile measurement of SC reactivity to recalling the stroke/TIA traumatic event was conducted at hospital bedside in the days following the stroke/TIA. PTSD symptoms that developed in response to the stroke/TIA were measured at 1-month follow-up. We tested the association between SC reactivity and total 1-month PTSD symptoms, as well as PTSD symptom dimensions of fear and dysphoria. Results: In unadjusted analyses, there were significant positive associations between in-hospital SC reactivity to recalling the stroke/TIA traumatic event and higher-order fear-related symptoms (r=.30, p=.016), as well as lower-order fear-related symptoms of anxious arousal (r=.27, p=.035) and avoidance (r=.25, p=.043) at 1 month. Associations between SC reactivity and the fear, anxious arousal, and avoidance symptom dimensions remained significant in multivariable regression models that adjusted for relevant covariates including age, gender, stroke severity, medical comorbidity, and psychosocial factors. Although there was a positive association observed between SC reactivity to recalling the stroke/TIA event and total PTSD symptom severity at 1-month follow-up, it did not reach the level of statistical significance (r=.23, p=.070). Further, no significant association was detected for dysphoria-related symptoms (r=.11, p=.393). Conclusions: This is the first study to test the prospective association of SC reactivity with PTSD symptom development following a medical trauma. The findings indicate that mobile measures of SC reactivity may be useful for in-hospital identification of individuals at risk for fear-related PTSD symptom development following a medical event and highlight the potential mechanisms involved in the development of these symptoms following a medical event.

Social Support as a Protective Factor for Alcohol Use Disorders: Results from a Nationally Representative Family History Study.

AIMS: The current study examined the buffering effect of social support on the relationship between family history and alcohol use disorder symptoms (AUDsx). METHODS: The current study analyzes data from Waves 1 and 2 of the National Epidemiologic Survey of Alcohol and Related Conditions (N = 34,653). Count of AUDsx were measured using the Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-IV Version, the independent variable was a weighted density measure of family history of AUDsx and the moderating variable was social support measured using the 12-item Interpersonal Support Evaluation List (ISEL-12). Negative binomial regression models were used to estimate the association between (1) family history and AUDsx and (2) social support and AUDsx. Average marginal effects were estimated to explore the buffering effect of social support on the association between family history and AUDsx. RESULTS: Family history was positively associated with AUDsx (incidence rate ratio (IRR) = 1.46, 95% CI = 1.39-1.54) and social support was negatively associated with AUDsx (IRR = 0.80, 95% CI = 0.74-0.86). The marginal effects of family history decreased at higher levels of social support, indicating a buffering influence of social support on the association between family history and AUDsx. CONCLUSIONS: Results reveal a buffering effect of social support, where greater levels of social support reduce the association between family history and AUDsx. These results indicate that the social context, and social support specifically, may be important for diminishing the risk of AUDsx.

Race/Ethnicity, Spirometry Reference Equations, and Prediction of Incident Clinical Events: The Multi-Ethnic Study of Atherosclerosis (MESA) Lung Study.

Rationale: Normal values for FEV1 and FVC are currently calculated using cross-sectional reference equations that include terms for race/ethnicity, an approach that may reinforce disparities and is of unclear clinical benefit. Objectives: To determine whether race/ethnicity-based spirometry reference equations improve the prediction of incident chronic lower respiratory disease (CLRD) events and mortality compared with race/ethnicity-neutral equations. Methods: The MESA Lung Study, a population-based, prospective cohort study of White, Black, Hispanic, and Asian adults, performed standardized spirometry from 2004 to 2006. Predicted values for spirometry were calculated using race/ethnicity-based equations following guidelines and, alternatively, race/ethnicity-neutral equations without terms for race/ethnicity. Participants were followed for events through 2019. Measurements and Main Results: The mean age of 3,344 participants was 65 years, and self-reported race/ethnicity was 36% White, 25% Black, 23% Hispanic, and 17% Asian. There were 181 incident CLRD-related events and 547 deaths over a median of 11.6 years. There was no evidence that percentage predicted FEV1 or FVC calculated using race/ethnicity-based equations improved the prediction of CLRD-related events compared with those calculated using race/ethnicity-neutral equations (difference in C statistics for FEV1, -0.005; 95% confidence interval [CI], -0.013 to 0.003; difference in C statistic for FVC, -0.008; 95% CI, -0.016 to -0.0006). Findings were similar for mortality (difference in C statistics for FEV1, -0.002; 95% CI, -0.008 to 0.003; difference in C statistics for FVC, -0.004; 95% CI, -0.009 to 0.001). Conclusions: There was no evidence that race/ethnicity-based spirometry reference equations improved the prediction of clinical events compared with race/ethnicity-neutral equations. The inclusion of race/ethnicity in spirometry reference equations should be reconsidered.

Investigating the Content of #UequalsU on Twitter.

Undetectable = Untransmittable (U = U) is the scientific fact that HIV cannot be transmitted when an individual is virally suppressed. This breakthrough discovery has the potential to greatly reduce HIV stigma and its negative effects. However, U = U is not widely known. Given that Twitter has the potential to raise awareness of health issues, the purpose of this study was to analyze the content of the #UequalsU on Twitter. The results showed that mentioning sex and mentioning love were strong predictors that a tweet would be liked and retweeted. This information could help to spread the message of U = U more widely and potentially lessen HIV stigma.

Lung function impairment and risk of incident heart failure: the NHLBI Pooled Cohorts Study.

AIMS: The aim is to evaluate associations of lung function impairment with risk of incident heart failure (HF). METHODS AND RESULTS: Data were pooled across eight US population-based cohorts that enrolled participants from 1987 to 2004. Participants with self-reported baseline cardiovascular disease were excluded. Spirometry was used to define obstructive [forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) <0.70] or restrictive (FEV1/FVC ≥0.70, FVC <80%) lung physiology. The incident HF was defined as hospitalization or death caused by HF. In a sub-set, HF events were sub-classified as HF with reduced ejection fraction (HFrEF; EF <50%) or preserved EF (HFpEF; EF ≥50%). The Fine-Gray proportional sub-distribution hazards models were adjusted for sociodemographic factors, smoking, and cardiovascular risk factors. In models of incident HF sub-types, HFrEF, HFpEF, and non-HF mortality were treated as competing risks. Among 31 677 adults, there were 3344 incident HF events over a median follow-up of 21.0 years. Of 2066 classifiable HF events, 1030 were classified as HFrEF and 1036 as HFpEF. Obstructive [adjusted hazard ratio (HR) 1.17, 95% confidence interval (CI) 1.07-1.27] and restrictive physiology (adjusted HR 1.43, 95% CI 1.27-1.62) were associated with incident HF. Obstructive and restrictive ventilatory defects were associated with HFpEF but not HFrEF. The magnitude of the association between restrictive physiology and HFpEF was similar to associations with hypertension, diabetes, and smoking. CONCLUSION: Lung function impairment was associated with increased risk of incident HF, and particularly incident HFpEF, independent of and to a similar extent as major known cardiovascular risk factors.

Development and preliminary validation of a scale to assess physicians' emotional distress intolerance in end-of-life care communication.

CONTEXT: End-of-life care (EOLC) communication is beneficial but underutilized, particularly in conditions with a variable course such as chronic obstructive pulmonary disease (COPD) and congestive heart failure (CHF). Physicians' emotional distress intolerance has been identified as a barrier to EOLC communication. However, studies of emotional distress intolerance in EOLC have largely relied on anecdotal reports, qualitative data, or observational studies of physician-patient communication. A free-standing measure of multiple dimensions of distress tolerance is warranted to enable the identification of individuals experiencing distress intolerance and to facilitate the effective targeting of interventions to improve distress tolerance. OBJECTIVES: This study provides preliminary data on the reliability and validity of the Physician Distress Intolerance (PDI) scale. We examine potential subdimensions of emotional distress intolerance. METHOD: Family medicine and internal medicine physicians completed the PDI, read vignettes describing patients with COPD or CHF, and indicated whether they initiated or delayed EOLC communication with their patients with similar conditions. RESULTS: Exploratory and confirmatory factor analyses were performed on separate samples. Confirmatory factor analysis confirmed that a three-factor solution was superior to a two- or one-factor solution. Three subscales were created: Anticipating Negative Emotions, Intolerance of Uncertainty, and Iatrogenic Harm. The full scale and subscales had adequate internal consistency and demonstrated evidence of validity. Higher scores on the PDI, indicating greater distress intolerance, were negatively associated with initiation and positively associated with delay of EOLC communication. Subscales provided unique information. SIGNIFICANCE OF RESULTS: The PDI can contribute to research investigating and addressing emotional barriers to EOLC communication.

Considerations for immune effector cell therapy collections: a white paper from the American Society for Apheresis.

BACKGROUND AIMS: This white paper was developed to provide leukapheresis guidance for the collection of mononuclear cells from adult and pediatric patients who are destined for immune effector cell (IEC) therapies for commercial and research applications. Currently, there is considerable variability in leukapheresis processes and limited published information regarding best practices relevant to new cellular therapies, especially IECs. Herein the authors address critical leukapheresis questions in five domains to help guide consistent collection processes and ensure high-quality products. The first four domains are onboarding, pre-collection, collection and post-collection, with protocol feasibility, preparation, care and follow-up of the patient/donor at each step, respectively, and technical considerations during collection. The fifth domain of quality assurance focuses on ensuring product potency, purity, safety and auditing. METHODS: The American Society for Apheresis (ASFA) Clinical Applications Committee (IEC Therapy Subcommittee) was charged by the society's board of directors with working collaboratively with other ASFA committees and organizations, including the Foundation for the Accreditation of Cellular Therapy, Association for the Advancement of Blood and Biotherapies, American Society for Transplantation and Cellular Therapy, National Marrow Donor Program and International Society for Cell & Gene Therapy, to develop guidelines regarding leukapheresis collection of cells destined for the manufacture of IEC therapies. After a review of the literature and discussion with members of the involved committees and various institutions, a draft guidance was created and circulated for comment and revision. RESULTS: Critical aspects of apheresis that could affect the quality and quantity of the leukapheresis product were identified. These areas were then discussed and reviewed. After consensus, the best practice guidelines were proposed and accepted. CONCLUSIONS: In the current era of rapid growth of IEC therapies, it is important to address critical leukapheresis steps to provide high-quality products and more consistent practices and to eliminate redundant efforts.

Multicenter evaluation of the IL-3-pSTAT5 assay to assess the potency of cryopreserved stem cells from cord blood units: The BEST Collaborative study.

BACKGROUND: The IL-3-pSTAT5 assay, a new, rapid, and standardized flow-cytometry-based assay may compensate for several limitations of the colony-forming unit (CFU) assay typically used for stem cell potency assessments of cord blood units (CBU). We performed an inter-laboratory evaluation of the performance of this new assay. STUDY DESIGN AND METHODS: This Biomedical Excellence for Safer Transfusion (BEST) Collaborative multicenter, international study included 15 participants from public cord blood banks (CBBs), CBB-supporting research laboratories, and stem cell laboratories. To perform the IL-3-pSTAT5 assay, participating centers received reagents, instructions, and 10 blind CBU samples, including eight normal samples and two samples exposed to a transient warming event. We measured inter-laboratory agreement qualitatively (proportion of correctly classified samples) and quantitatively (coefficient of variation [CV], correlation coefficients, receiver operating characteristics (ROC) curve, and intraclass correlation coefficient [ICC]). RESULTS: The qualitative agreement was 97.3% (i.e., 107/110; Fleiss' kappa = 0.835). The average CV on a per-sample basis was 11.57% among all samples, 8.99% among normal samples, and on a per-center basis was 9.42% among normal samples. In a correlation matrix that compared results across centers, the mean Pearson's correlation coefficient was 0.88 (standard deviation = 0.04). The ICC was 0.83 (95% confidence interval = 0.68-0.95). The area under the curve (AUC) from the ROC curve was 0.9974. DISCUSSION: Excellent qualitative and quantitative agreement was exhibited across laboratories. The IL-3-pSTAT5 assay may therefore be implemented in flow cytometry laboratories to rapidly and reliably provide standardized measures of stem cell potency in CBUs.

Transfusion therapy of neonatal and paediatric patients: They are not just little adults.

Patient blood management (PBM) strategies are needed in the neonate and paediatric population, given that haemoglobin thresholds used are often higher than recommended by evidence, with exposure of children to potential complications without meaningful benefit. A literature review was performed on the following topics: evidence-based transfusions of blood components and pharmaceutical agents. Other topics reviewed included perioperative coagulation assessment and perioperative PBM. The Transfusion and Anaemia Expertise Initiative (TAXI) consortium published a consensus statement addressing haemoglobin (Hb) transfusion threshold in multiple subsets of patients. A multicentre trial (PlaNeT-2) reported a higher risk of bleeding and death or serious new bleeding among infants who received platelet transfusion at a higher (50 000/µl) compared to a lower (25 000/µl) threshold. Recent data support the use of a restrictive transfusion threshold of 25 000/µl for prophylactic platelet transfusions in preterm neonates. The TAXI-CAB consortium mentioned that in critically ill paediatric patients undergoing invasive procedures outside of the operating room, platelet transfusion might be considered when the platelet count is less than or equal to 20 000/µl and there is no benefit of platelet transfusion when the platelet count is more than 50 000/µl. There are limited controlled studies in paediatric and neonatal population regarding plasma transfusion. Blood conservation strategies to minimise allogenic blood exposure are essential to positive patient outcomes neonatal and paediatric transfusion practices have changed significantly in recent years since randomised controlled trials were published to guide practice. Additional studies are needed in order to provide practice change recommendations.

Therapeutic plasma exchange practices in immune thrombocytopenia related hospitalizations: Results from a nationally representative sample.

Per the American Society for Apheresis, therapeutic plasma exchange (TPE) is a Category III indication in the management of immune thrombocytopenia (ITP). This nationally representative study evaluates TPE utilization in hospitalized adults with a primary admission diagnosis of ITP. Hospitalizations with ITP as the primary admitting diagnosis were analyzed from the 2010 to 2014 National Inpatient Sample, the largest all-payer inpatient database in the United States. Univariate and multivariable logistic regressions were used to determine clinical outcomes in ITP patients undergoing TPE. Sampling weights were applied to generate nationally representative estimates. From 2010 to 2014, there were a total of 56,149 admissions with a primary admitting diagnosis of ITP, of which 0.66% admissions (n = 372) also coded TPE. Most subjects undergoing TPE were the highest disease severity class: major (34.6%) and extreme severity (31.0%), by all-patients refined diagnoses-related groups severity of illness subclass. After multivariable analysis, underlying severity of illness remained the most significant predictor of TPE (P < .001). ITP admissions with TPE had a high rate of comorbidities (50%) and significantly longer mean length of hospital stay than those without (P < .001). TPE was reported in ~0.6% of hospitalizations with ITP as the primary diagnosis in this nationally representative sample from 2010 to 2014. TPE was performed in patients with the highest severity of underlying illness, and higher rates of comorbidities.