High CD34-positive cell dose in matched unrelated donor allogeneic hematopoietic stem cell transplant is not associated with graft-versus-host disease or mortality.

BACKGROUND: CD34+ stem cells serve as the primary graft source for allogeneic transplants, with a minimum of 2-4 × 106 cells/kg needed for engraftment. There are conflicting data on outcomes at high stem cell doses, with studies limited by few patients receiving doses far above the minimum target. STUDY DESIGN AND METHODS: In this retrospective, single-center study of patients with hematologic malignancies who underwent matched unrelated donor transplants, we assessed outcomes for engraftment, survival, relapse, and graft-versus-host disease (GVHD) for the highest CD34+ dose quintile (>13 × 106 cells/kg, n = 36) compared to the remaining patients (n = 139). Similar analysis was performed correlating T cell dose and outcomes. RESULTS: There was no difference between the groups in neutrophil engraftment, with a trend toward faster platelet engraftment. There was no significant difference in mortality (adjusted risk ratio [aRR] = 1.02, 95% confidence interval [CI] = 0.85-1.22), relapse (aRR = 1.10, 95% CI = 0.85-1.42), or overall survival by Kaplan-Meier analysis (p = .44). High CD34+ dose was not associated with higher incidence of acute GVHD (aRR = 0.99 grades II-IV, aRR = 1.18 grades III-IV) or chronic GVHD (aRR = 0.87 overall, RR = 1.21 severe). There was limited correlation between CD34+ and T cell dose (R2 = .073), and there was no significant difference in survival, relapse, or GVHD in the highest T cell dose quintile (n = 33) compared to the remaining quintiles (n = 132). DISCUSSION: We found no difference in survival, relapse, or GVHD incidence or severity in patients receiving CD34+ doses above prior cutoffs reported in the literature. These data do not support the routine use of graft CD34+ dose reduction.

Examining Injustices: Transfusion Medicine and Race.

Race and ethnicity are sociopolitical and not biological constructs, and assertions that these population descriptors have scientific meaning has caused significant harm. A critical assessment of the transfusion medicine literature is an important aspect of promoting race-conscious as opposed to race-based medicine. Utilizing current definitions and health equity frameworks, this review will provide a critical appraisal of transfusion medicine studies at the intersection of race and healthcare disparities, with a focus on larger methodological challenges facing the transfusion medicine community. Moving forward, risk modelling accounting for upstream factors, patient input, as well as an expert consensus on how to critically conduct and evaluate this type of literature are needed. Further, when using race and ethnicity in research contexts, investigators must be aware of existing guidelines for such reporting.

Blood Group Serology and "Race": Looking Back to Move Forward.

Less than a decade after the discovery of the ABO antigens as a Mendelian inherited trait, blood group antigen frequencies were first used to define racial groups. This approach, known as seroanthropology, was the basis for collecting large amounts of blood group frequency data in different populations and was also sometimes used for racist purposes. Ultimately, population geneticists used these data to disprove race as a biological construct. Through understanding the history of seroanthropology, and recognizing the harms of its lingering presence, healthcare providers can better practice race-conscious, as opposed to race-based, transfusion medicine.

Current advances in 2022: A critical review of selected topics by the Association for the Advancement of Blood and Biotherapies (AABB) Clinical Transfusion Medicine Committee.

BACKGROUND: The Association for the Advancement of Blood and Biotherapies Clinical Transfusion Medicine Committee (CTMC) composes a summary of new and important advances in transfusion medicine (TM) on an annual basis. Since 2018, this has been assembled into a manuscript and published in Transfusion. STUDY DESIGN AND METHODS: CTMC members selected original manuscripts relevant to TM that were published electronically and/or in print during calendar year 2022. Papers were selected based on perceived importance and/or originality. References for selected papers were made available to CTMC members to provide feedback. Members were also encouraged to identify papers that may have been omitted initially. They then worked in groups of two to three to write a summary for each new publication within their broader topic. Each topic summary was then reviewed and edited by two separate committee members. The final manuscript was assembled by the first and senior authors. While this review is extensive, it is not a systematic review and some publications considered important by readers may have been excluded. RESULTS: For calendar year 2022, summaries of key publications were assembled for the following broader topics within TM: blood component therapy; infectious diseases, blood donor testing, and collections; patient blood management; immunohematology and genomics; hemostasis; hemoglobinopathies; apheresis and cell therapy; pediatrics; and health care disparities, diversity, equity, and inclusion. DISCUSSION: This Committee Report reviews and summarizes important publications and advances in TM published during calendar year 2022, and maybe a useful educational tool.

The next phase in patient safety education: Towards a standardized, tools-based pathology patient safety curriculum: A call to action from the Association of Pathology Chairs' Residency Program Directors Section Training Residents in Patient Safety Workgroup.

Patient safety education is a mandated Common Program Requirement of the Accreditation Council for Graduate Medical Education and for the Royal College of Physicians and Surgeons of Canada in all medical residency and fellowship programs. Although many hospitals and healthcare environments have general patient safety education tools for trainees, few to none focus on the unique training milieu of pathologists, including a mix of highly automated and manual error-prone processes, frequent multiplicity of events, and lack of direct patient relationships for error disclosure. We established a national Association of Pathology Chairs-Program Directors Section Workgroup focused on patient safety education for pathology trainees entitled Training Residents in Patient Safety (TRIPS). TRIPS included diverse representatives from across the United States, as well as representatives from pathology organizations including the American Board of Pathology, the American Society for Clinical Pathology, the United States and Canadian Academy of Pathology, the College of American Pathologists, and the Society to Improve Diagnosis in Medicine. Objectives of the workgroup included developing a standardized patient safety curriculum, designing teaching and assessment tools, and refining them with pilot sites. Here we report the establishment of TRIPS as well as data from national needs assessment of Program Directors across the country, who confirmed the need for a standardized patient safety curriculum.

RND Pump-Mediated Efflux of Amotosalen, a Compound Used in Pathogen Inactivation Technology to Enhance Safety of Blood Transfusion Products, May Compromise Its Gram-Negative Anti-Bacterial Activity.

Pathogen inactivation is a strategy to improve the safety of transfusion products. The only pathogen reduction technology for blood products currently approved in the US utilizes a psoralen compound, called amotosalen, in combination with UVA light to inactivate bacteria, viruses, and protozoa. Psoralens have structural similarity to bacterial multidrug efflux pump substrates. As these efflux pumps are often overexpressed in multidrug-resistant pathogens, we tested whether contemporary drug-resistant pathogens might show resistance to amotosalen and other psoralens based on multidrug efflux mechanisms through genetic, biophysical, and molecular modeling analysis. The main efflux systems in Enterobacterales, Acinetobacter baumannii, and Pseudomonas aeruginosa are tripartite resistance-nodulation-cell division (RND) systems, which span the inner and outer membranes of Gram-negative pathogens, and expel antibiotics from the bacterial cytoplasm into the extracellular space. We provide evidence that amotosalen is an efflux substrate for the E. coli AcrAB, Acinetobacter baumannii AdeABC, and P. aeruginosa MexXY RND efflux pumps. Furthermore, we show that the MICs for contemporary Gram-negative bacterial isolates for these species and others in vitro approached and exceeded the concentration of amotosalen used in the approved platelet and plasma inactivation procedures. These findings suggest that otherwise safe and effective inactivation methods should be further studied to identify possible gaps in their ability to inactivate contemporary, multidrug-resistant bacterial pathogens. IMPORTANCE Pathogen inactivation is a strategy to enhance the safety of transfused blood products. We identify the compound, amotosalen, widely used for pathogen inactivation, as a bacterial multidrug efflux substrate. Specifically, experiments suggest that amotosalen is pumped out of bacteria by major efflux pumps in E. coli, Acinetobacter baumannii, and Pseudomonas aeruginosa. Such efflux pumps are often overexpressed in multidrug-resistant pathogens. Importantly, the MICs for contemporary multidrug-resistant Enterobacterales, Acinetobacter baumannii, Pseudomonas aeruginosa, Burkholderia spp., and Stenotrophomonas maltophilia isolates approached or exceeded the amotosalen concentration used in approved platelet and plasma inactivation procedures, potentially as a result of efflux pump activity. Although there are important differences in methodology between our experiments and blood product pathogen inactivation, these findings suggest that otherwise safe and effective inactivation methods should be further studied to identify possible gaps in their ability to inactivate contemporary, multidrug-resistant bacterial pathogens.

Clinical consequences of a 30-day interval between antibody identifications.

BACKGROUND: While studies have shown that antibody detection may be delayed if an antibody identification (ABID) is not performed every 3 days, little data exist on the potential major risk of an acute hemolytic transfusion reaction (aHTR). STUDY DESIGN AND METHODS: At our institution, if no change in the screen, or a positive crossmatch, ABIDs are performed every 30 days. Between January 1, 2015 and May 31, 2019, all new antibodies detected within 28 days of a prior transfusion were identified. Testing results and patient charts were reviewed for evidence of hemolysis. The $211 patient charge was used to determine the cost for ABIDs performed during the studied time period. RESULTS: For 36 patients, a new clinically significant alloantibody was detected within 28 days of an antigen-positive transfusion. Only one of these patients had a history of prior alloimmunization and put at possible risk due to the ABID policy. For this patient, while there was less than the expected increment to an antigen-positive unit, there was no clinical or laboratory evidence of an aHTR. During this same time, 6095 ABIDs were performed, at a cost of approximately $1.29 million, and 72,665 red cell transfusions occurred. CONCLUSION: With an ABID every 30 days, only one patient, over 4.5 years, was put at potential risk for hemolysis from one transfusion (0.001% of the total units transfused during the time period). While antibody detection may be delayed, performing ABIDs every 30 days saves money and medical laboratory scientist time and should be balanced against potential patient harm.

Pathology trainees rarely report safety incidents: A review of 13,722 safety reports and a call to action.

Reporting and understanding patient safety incidents is a cornerstone of improving patient care quality and safety. The Accreditation Council for Graduate Medical Education specifically mandates that physician trainee education include participation in the recognition, reporting, and root cause analysis of patient safety incidents. Studies on safety event reporting, however, have consistently shown that attending physicians submit few safety reports, and trainees submit even fewer. We undertook a study to assess the rate at which pathology trainees report patient safety events relative to the rates at which trainees in other medical specialties do. We performed a retrospective analysis of 13,722 safety reports submitted to our medium-sized Academic Medical Center's incident reporting system. We then analyzed those reported by trainees (residents and fellows), and then further drilled down on the subset of trainee-reported safety events reported by pathology trainees. Despite accounting for over 5% of all types of trainees at the enterprise level, pathology trainees accounted for only 0.5% of all trainee safety reports. Our findings represent a call to action for pathology training programs to engage their residents and fellows in quality and safety initiatives, to understand and remove barriers to safety event reporting for vulnerable populations such as trainees, and to empower trainees to confidently report safety risks as valued frontline care providers.

An international genomics health workforce education priorities assessment.

Aim: Global implementation of genomic medicine will require education of healthcare providers. There are limited international needs assessment data to guide curriculum development. Materials & methods: Genomics education experts developed and distributed a survey to individuals with knowledge of country-specific needs: 113 completed surveys (19% response rate) from 34 countries. A high percentage of respondents ranked non genetics physicians as the #1 target for genetics education. Over 70% indicated a need for moderate/extensive modification in physician training. The majority considered germline and somatic topics and targeting primary care and specialist providers equally important. Conclusion: Regardless of country economic level, there is a clear need for genomics education of healthcare providers. The study results can be used to focus future genomic medicine education efforts.

Anesthesiology Resident Knowledge of Transfusion Medicine: Results From the Anesthesiology Transfusion Education Study.

BACKGROUND: Transfusion of blood products is a common practice in anesthesiology. Inadequate transfusion medicine knowledge may lead to inappropriate transfusion practices and patient risk. Using a validated assessment tool modified for anesthesiology, we conducted a survey of anesthesiology residents in the United States to assess transfusion medicine knowledge. METHODS: A validated transfusion medicine examination and accompanying survey were forwarded by program directors to residents for anonymous completion on May 5 and closed on June 30, 2021. The outcome of interest was the mean examination score. Secondary areas of interest were performance by year of training and previous educational experience in transfusion reported by the trainees. Rasch analysis was performed on the examination quality and individual question performance. Kruskal-Wallis H tests were used to identify differences between mean scores. Post hoc comparisons were used to assess specific pairwise differences between mean test scores by survey variable. RESULTS: Four hundred twenty-three anesthesiology residents in 37 programs completed the examination. The mean score was 45.5% ± 12.6%. There was a significant difference in mean cumulative examination scores between different resident training levels (P < 0.001). There was a significant difference in scores between clinical anesthesia (CA)-1 and CA-2 residents (P = 0.011) and CA-1 and CA-3 residents (P = 0.012). No significant difference in examination scores was observed between CA-2 and CA-3 residents (P = 0.95). All these subgroups scored below 50% on the examination. Significant differences between the residency training programs and cumulative scores were identified (P < 0.001). CONCLUSIONS: This examination highlights gaps in transfusion medicine knowledge within US anesthesiology residents. Targeted education may improve knowledge in this area and patient care.

Pediatric resident knowledge of transfusion medicine: Results from the BEST-TEST3 international education needs assessment.

BACKGROUND: Transfusions are a common intervention within pediatrics and require unique considerations to optimize patient care. Poor knowledge of evidence-based transfusion practice can lead to misuse of transfusion therapy and harm. While there have been assessments of transfusion medicine knowledge of physicians caring for adult patients, there is little data regarding pediatricians. STUDY DESIGN AND METHODS: Using a published transfusion medicine knowledge exam for internal medicine physicians as a backbone, pediatric transfusion medicine experts, using an iterative process, developed a pediatric-specific examination. Pilot testing and Rasch analysis, a method used in high-stakes testing, was used to validate the exam. The exam and a previously validated survey on transfusion medicine training, attitudes, and perceived ability were administered to pediatric residents. Analysis consisted of descriptive statistics as well as comparisons of exam scores based on survey responses. RESULTS: 330 pediatric residents from 19 sites in 6 countries participated in the study. The vast majority (91%) of residents had obtained blood product consent. The mean exam score was 37.1% (range 9.5%-71.4%) with no statistical differences based on amount or perceived quality of transfusion medicine education or perceived ability. DISCUSSION: A rigorously validated exam has now been developed that can be used to assess pediatric transfusion medicine knowledge. A large international group of pediatric residents performed poorly on the exam demonstrating a pressing need for improved transfusion medicine education to ensure safe and appropriate administration of blood components to infants and children.

Hospital Medicine Providers' Transfusion Knowledge: A Survey Study.

Blood transfusion is one of the most common procedures performed in the inpatient setting. Although ordering a transfusion is a component of routine practice for most hospitalists, prior literature has shown that non-transfusion medicine physicians have poor to intermediate transfusion medicine knowledge (TMK). No recent study has evaluated TMK among hospitalists, including both attending hospitalists and advanced practice providers (APPs). Using a validated exam and a truncated version of a validated survey, we obtained an initial impression of attitudes, perceived and actual TMK. A total of 183 hospital medicine providers nation-wide completed the 12-question online survey and 20 question exam, including 155 attending hospitalists and 28 APPs. The overall mean score was 52% (range 20%-85%). Forty-one percent of participants reported less than 1 hour of training in transfusion medicine. Five of the seven questions with the worst performance (<25% correct) were on transfusion reactions. Almost all respondents reported consenting a patient for blood transfusion and 60% believed that TMK was very or extremely important in order to provide appropriate care for patients. More than 80% believed that having additional transfusion medicine education would be at least moderately helpful. Although routinely consenting patients for transfusion, hospital medicine providers may have insufficient TMK particularly as it pertains to transfusion reactions. The majority of hospitalists rated TMK important to clinical practice and had an interest in additional training, thus continuing medical education has the potential to improve TMK and patient care.

Call for improvement in medical school training in genetics: results of a national survey.

PURPOSE: To assess, from the student perspective, medical school training in genetics and genomics. METHODS: In 2019, the Undergraduate Training in Genomics (UTRIG) Working Group developed genetics-related survey and knowledge questions for the RISE-FIRST, an exam administered to postgraduate year 1 (PGY1) pathology residents in the United States during their first months of training. Survey questions focused on perceived knowledge in genetics and the structure and quality of training with responses compared with those in control areas. RESULTS: There were 401 PGY1 pathology residents who took the 2019 RISE-FIRST (65% of those in the United States). There was significantly lower perceived understanding of genetics compared with nongenetics topics. Respondents also reported less time spent learning genetics and lower quality training compared with control areas. Only 53% indicated an interaction during medical school with a medical geneticist. Residents also did not perform as well on the UTRIG-developed knowledge questions than those in other areas of pathology. CONCLUSION: The RISE-FIRST is a useful tool in assessing the current state of medical school training in genetics. This needs assessment may serve as a call to action to improve medical school genetics education and promote greater understanding of the role of genetics professionals in patient care.

Development of a Validated Exam to Assess Pathologist Knowledge of Genomic Oncology.

CONTEXT.­: There is a clear need to educate health professionals in genomic medicine. Pathologists, given their critical role in cancer diagnostics, must understand core concepts in genomic oncology. Although high-quality evaluation is a cornerstone of medical education, to our knowledge a rigorously validated genomic oncology assessment tool has not been published. OBJECTIVE.­: To develop and validate a genomic oncology exam. DESIGN.­: A previously developed exam was updated and validated using 3 approaches: pretesting/posttesting in relation to a live genomic pathology workshop; comparison of scores of individuals at a priori defined knowledge levels; and use of Rasch analysis. This last approach is used in high-stakes testing, such as licensing exams. The exam included both knowledge-based as well as skills-based questions related to the use of online genomics tools. RESULTS.­: There was a significant difference in exam scores preworkshop and postworkshop (37.5% to 75%; P < .001). Individuals at a priori defined beginner, intermediate, and expert levels scored 35%, 58%, and 89%, respectively (P < .001). Rasch analysis demonstrated excellent fit and reliability and led to further exam refinement with the removal of 2 questions deemed unnecessary for assessment. CONCLUSIONS.­: A rigorously validated exam has now been created to assess pathologist genomic oncology knowledge and skills. The exam can be used to assess both individual learners as well as educational interventions. The exam may also be applicable to other specialties involved in genomic-based cancer care.

Integration of Genomic Medicine in Pathology Resident Training.

OBJECTIVES: To assess current pathology resident training in genomic and molecular pathology. METHODS: The Training Residents in Genomics (TRIG) Working Group has developed survey questions for the pathology Resident In-Service Examination (RISE) since 2012. Responses to these questions, as well as knowledge questions, were analyzed. RESULTS: A total of 2,529 residents took the 2019 RISE. Since 2013, there has been an increase in postgraduate year 4 (PGY4) respondents indicating training in genomic medicine (58% to approximately 80%) but still less than almost 100% each year for molecular pathology. In 2019, PGY4 residents indicated less perceived knowledge and ability related to both genomic and traditional molecular pathology topics compared with control areas. Knowledge question results supported this subjective self-appraisal. CONCLUSIONS: The RISE is a powerful tool for assessing the current state and also trends related to resident training in genomic pathology. The results show progress but also the need for improvement in not only genomic pathology but traditional molecular pathology training as well.