BACKGROUND AND OBJECTIVES:Requests for "unvaccinated" blood have been discouraged by professional and regulatory bodies because they lack scientific support and may negatively impact patient care. We describe a single-center series in which patients or surrogates refused standard blood components unless sourced from directed donors perceived to be "unvaccinated." MATERIALS AND METHODS:We performed a retrospective review of directed donations received at Vanderbilt University Medical Center between January 1, 2024 and December 31, 2025. Data included demographics, clinical scenario, component details, and documented operational or clinical consequences. RESULTS:Directed donor units were received for 15 patients; 13 of these patients were transfused at least one unit (n = 31 directed components: 22 red blood cell [RBC] units, 5 platelet units, 2 plasma units, 2 cryoprecipitate units). Median age was 17 years (range 0.33-73); nine patients were pediatric (<18 years). An ethics consultation was documented for one case, and a transfusion medicine consultation was documented for one case. Seven patients (47%) had at least one directed unit that was not transfused to them. Two patients clinically deteriorated in the setting of refusal of standard components, one of which also received a transfusion that deviated from institutional transfusion guidelines to avoid outdating, and two additional patients had surgical delay/cancellation with rescheduling associated with directed component availability. CONCLUSION:In this series, all directed units were from "unvaccinated" donors. These requests were associated with care delays, escalation, and inefficiencies. Health systems should implement standardized counseling, documentation, and escalation pathways consistent with existing guidance.
Background Timely clinical microbiology laboratory testing is crucial for effective infectious disease management, impacting antibiotic selection, patient outcomes, and health care costs. This study aimed to evaluate changes in geographic access to comprehensive (Tier 1) clinical microbiology laboratories in Tennessee between 2019 and 2024.Methods With the help of the Tennessee Department of Health, Tier 1 microbiology laboratories in Tennessee were identified for both 2019 and 2024. Catchment areas were calculated using a 25-mile drive-time radius around each laboratory. Changes in the number and location of Tier 1 laboratories were quantified, and demographic data were compared between laboratories that stayed open and those that closed.Results The number of Tier 1 microbiology laboratories in Tennessee decreased by 38% over the 5-year period, and this resulted in a 35% decrease in square-mile coverage across the state. Covariates associated with laboratory closure included rurality, lower income, higher poverty, race, higher disability, and less education.Conclusions A substantial decline in the number of Tier 1 clinical microbiology laboratories in Tennessee between 2019 and 2024 has decreased local access to comprehensive testing in areas with at-risk patient populations. This may have implications for timely diagnosis, appropriate antimicrobial therapy, and, ultimately, patient outcomes. Further research is needed to evaluate the clinical and economic consequences of these changes in laboratory access.
BACKGROUND:Prekallikrein (PK) deficiency is a rare contact factor deficiency that can markedly prolong the activated partial thromboplastin time (aPTT) without a bleeding phenotype. Because viscoelastic hemostatic assays also rely on contact activation, their behavior in severe PK deficiency is relevant to perioperative evaluation of isolated aPTT prolongation. We describe thromboelastography (TEG) 6s findings in a patient with severe PK deficiency. STUDY DESIGN AND METHODS:A 59-year-old woman without a bleeding history was evaluated for an isolated prolonged aPTT identified during preoperative testing. Studies included prothrombin time (PT), thrombin time, an anti-factor Xa assay, aPTT mixing studies including with PK-deficient plasma, and factor VIII, IX, XI, and XII activities. PK antigen was assessed by western immunoblotting. Whole blood viscoelastic testing was performed on a TEG 6s analyzer. RESULTS:The patient had a markedly prolonged aPTT (87.4 s, reference range [RR]: 24.5-34.0 s) with normal PT, thrombin time, and a negative anti-factor Xa assay. The aPTT corrected on mixing with normal pooled plasma but not with PK-deficient plasma. Factor VIII, IX, XI, and XII activities were normal or modestly elevated. Western immunoblotting showed absent PK antigen, establishing cross-reactive material-negative PK deficiency. Despite the prolonged aPTT, TEG 6s parameters were normal, including the citrated kaolin R time (4.6 min, RR: 4.6-9.1 min). The patient underwent surgery without hemostatic complications or transfusion. DISCUSSION:Severe PK deficiency may markedly prolong the plasma-based aPTT without parallel abnormalities on TEG 6s, highlighting assay-specific differences in sensitivity to PK deficiency.
This Viewpoint discusses transfusion safety among infants and children who rely on blood products following the Advisory Committee on Immunization Practices rescinding its recommendation of newborn hepatitis B virus vaccination.
Background: Transfusion-related alpha-gal syndrome (TRAGS) has recently been proposed as a cause of allergic transfusion reactions (ATRs) in which alpha-gal-specific IgE in sensitized group O (or potentially group A) recipients reacts with epitopes on group B or AB plasma-containing components. Fewer than 10 cases have been reported, all from the Northeast and mid-Atlantic United States, and alpha-gal-specific ATR evaluation practices are unstudied. Study Design and Methods: Two patients with ATRs consistent with TRAGS at a large academic medical center in Nashville, Tennessee are reported alongside a 5-year retrospective cohort analysis of group O and A recipients experiencing ATRs following transfusion of group B or AB plasma-containing products. Alpha-gal IgE testing, AGS diagnosis documentation, and documented consideration of IgA deficiency were assessed for each qualifying reaction. Results: Both index patients had pre-existing AGS diagnoses unrecognized at component selection; one was a 42-year-old female and the second an 83-year-old male. Among 50 qualifying ATRs in 44 patients, including 13 severe or anaphylactic reactions, alpha-gal IgE testing was not performed for any event, and no patient had a documented AGS diagnosis. IgA deficiency was considered in eight patients (18%), yielding no diagnoses. Conclusion: TRAGS occurs in the tick-endemic southeastern United States across a broader demographic range than previously recognized. IgA deficiency, present in <0.3% of the population, was considered in 18% of qualifying patients while alpha-gal sensitization, affecting 20%-30% in this region, was investigated in none. Integration of AGS history into pre-transfusion risk assessment and ATR evaluation protocols is warranted.
Alpha-gal syndrome (AGS) is an immunoglobulin E (IgE)-mediated hypersensitivity to the oligosaccharide galactose-α-1,3-galactose, acquired through tick bites and increasingly recognized as a cause of allergic reactions to mammalian-derived medical products. Every major transplant modality creates distinct conditions under which sensitized patients may encounter alpha-gal, yet AGS knowledge has developed almost entirely outside the transplant literature. In conventional solid organ transplantation, risk arises primarily from perioperative exposures to porcine-derived heparin, gelatin-based hemostatic agents, and other mammalian-derived materials. In xenotransplantation, the well-characterized role of alpha-gal as the principal xenoantigen has driven the development of glycoprotein alpha-galactosyltransferase 1-knockout swine, but the distinct IgE-mediated pathway that defines AGS has received little attention. Hematopoietic stem cell transplantation introduces questions about conditioning-related immune remodeling of preexisting IgE sensitization, rabbit antithymocyte globulin as an underrecognized alpha-gal exposure, and transfusion-related alpha-gal syndrome when group B or AB plasma-containing blood products are transfused to susceptible patients. Cellular therapy manufacturing workflows that use animal-derived ancillary materials represent a further theoretical exposure pathway. Importantly, detectable anti-alpha-gal IgE does not invariably predict clinical reactivity, and the most appropriate clinical approach is risk stratification rather than reflexive exclusion. Generating the evidence base to support such stratification will require collaboration across allergy, transplant, and transfusion medicine.
Real-time federal surveillance of diseases and health care delivery informs clinical guidance and public health policy. However, in 2025, some U.S. Centers for Disease Control and Prevention (CDC) databases seemed to have "unexplained pauses" and ceased or delayed updates. The CDC public data catalog was audited to identify paused databases that had previously been updated at least monthly and evaluated their characteristics. Of 1359 catalog records examined on 28 October 2025, eighty-two were previously updated at least monthly. On the basis of each database's stated periodicity, allowing for an additional 30-day grace period, their status was classified as either current or paused as of 28 October 2025. Forty-four databases (54%) were current, and 38 (46%) were paused. Thirty-four of the 38 databases (89%) had no data entries dated within 6 months of the date of analysis, whereas 4 (11%) paused more recently. Of the 38 paused databases, 33 (87%) were vaccination-related topics compared with none of the 44 current databases. Of the 5 paused databases on other topics, 4 addressed respiratory diseases, including disease burden and nonvaccine prevention measures, whereas 1 addressed public health (drug overdose deaths). The persistence of pauses as of 2 December 2025 was examined. Only 1 of the 38 paused databases had been updated. Such long pauses may have compromised evidence for decision making and policies by clinicians, administrators, professional organizations, and policymakers. Federal databases should adopt minimum transparency standards, including displaying the current update status, with a rationale if paused, and next expected update with criteria for resumption. Without such standards, unexplained pauses in surveillance risk undermining evidence-based medicine and public trust.
Factor XIII (FXIII) deficiency is a rare bleeding disorder characterized by unstable hemostatic clots due to defective fibrin cross‑linking. Congenital FXIII deficiency arises from variants in the F13A1 (FXIII-A subunit) or F13B (FXIII-B subunit) genes, and classically presents with delayed umbilical stump hemorrhage, soft‑tissue and intracranial bleeding, impaired wound healing, and recurrent pregnancy loss. Acquired deficiency stems from inhibitory autoantibodies or from reduced synthesis or consumption in critical illness and surgery. Routine coagulation screening tests are normal and diagnosis relies on quantitative FXIII activity assays with or without antigenic phenotyping and, when indicated, inhibitor testing and molecular confirmation. Plasma‑derived FXIII concentrate reduces spontaneous and intracranial bleeding; recombinant FXIII‑A2 is appropriate for F13A1 defects but not patients with F13B variants. Perioperative and obstetric care target activity thresholds suited to procedural risk and individual pharmacokinetics. This review synthesizes the molecular biology, epidemiology, clinical features, diagnostic methods, and evidence‑based management of FXIII deficiency, with practical guidance for assay selection, validation, and result interpretation.
The American Society for Apheresis (ASFA) guidelines serve as a global standard for therapeutic apheresis practice. However, our analysis of the 2023 guidelines reveals discordance between the strength of recommendation and the quality of evidence. Among 166 indications, one-third carry strong recommendations, yet only 8% are supported by high-quality evidence. Over half (55%) are informed by low- or very-low quality evidence. This mismatch is most pronounced for Category I indications, where apheresis is considered first-line therapy: nearly one-third are based on low-quality data, yet 89% receive strong recommendations. Weak evidence is nine times more likely to prompt a strong recommendation for Category I versus Category III indications. This misalignment risks overutilization of apheresis, introduces ethical hurdles for clinical trials by diminishing equipoise, and may mislead patient expectations during informed consent. We advocate for greater transparency by stating the rationale underlying strong recommendations despite low-quality evidence, acknowledgment of uncertainty where applicable, and suggested research to strengthen the evidence.
IMPORTANCE:Recognition awards from medical societies are a key marker of professional achievement and play a crucial role in physician career advancement. At many academic institutions, national honors-such as society-based recognition awards-are integral to the criteria for promotion to the rank of full professor. OBJECTIVE:To systematically review and conduct a meta-analysis of studies assessing the gender distribution of recognition awards conferred by United States (U.S.)-based medical societies. MATERIALS AND METHODS:A systematic search of Ovid MEDLINE, Embase, Web of Science, Cochrane CENTRAL, and ClinicalTrials.gov was conducted in November 2023. Studies evaluating the gender composition of recipients of recognition awards from U.S. physician-focused medical societies were included. Studies without explicit methodology for selecting recognition awards were excluded. Data were independently extracted by two reviewers following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Study quality was assessed using the Newcastle-Ottawa Scale. A random-effects meta-analysis was performed to estimate the pooled proportion of women award recipients. The primary outcome was the proportion of women among recognition award recipients from U.S. medical societies. RESULTS:A total of 35 studies comprising 16,994 award recipients were included. Across 25 medical specialties, the pooled proportion of women award recipients was 19% (95% CI: 15-23%). A similar pattern was observed among women physician recipients at 17% (95% CI: 13-23%). Substantial heterogeneity was observed (I2 = 95.5%), reflecting variations across specialties and award categories. Funnel plot analysis suggested minimal publication bias. Notably, representation of women overall varied widely across disciplines, with pediatric emergency medicine and pathology showing the highest proportion of women recipients, whereas neurosurgery and orthopedics were among the lowest. CONCLUSIONS AND RELEVANCE:Overall, women are underrepresented among recipients of recognition awards from U.S. medical societies. Addressing this gap will require intentional, systemic efforts by both medical societies and academic institutions to promote equitable recognition and advancement for all physicians.
Achieving health equity requires data systems that recognize and reflect provider diversity. The National Provider Identifier (NPI) system underpins United States health care administration, yet its gender data standards remain outdated, conflating sex and gender and lacking inclusive options. These deficiencies undermine research, equity initiatives, and the visibility of transgender and nonbinary providers. In an era of growing political hostility to diversity, administrative neutrality is insufficient. The National Plan and Provider Enumeration System must establish itself as a model of gender-inclusive policy by separating sex and gender variables, expanding identity categories, and implementing transparent, regularly updated standards grounded in science.
Disparities persist throughout medicine, including among conference speakership invitations. The National Institutes of Health have highlighted the importance of diversity at academic conferences. We assessed the gender composition of speakers at the American Society for Apheresis (ASFA) annual meeting. We assessed all session chairs and speakers at the annual ASFA meeting from 2019 to 2024. Two authors independently assessed individuals' genders. The primary outcome was the gender composition of all session chairs and speakers by position. Subset analyzes were performed to assess the gender composition of unique individuals (i.e., examining the total number of unique men and women, independent of the number of sessions at which they spoke) and by professional degree. 820 positions (665 speaker positions and 155 chair positions) were identified; women comprised significantly more positions than men [64.3%, 528/820 (95% CI 61.1%-67.6%) vs. 35.6% 292/820 (32.4%-38.9%); p < 0.0001]. 52.7% (432/820) of all session positions were held by physicians, with no significant difference in the gender composition [women 47.5%, 205/432 (42.8%-52.2%) vs. men 52.6%, 227/432 (47.8%-57.2%); p = 0.31]. When limited to unique physician individuals, women were significantly outnumbered by men [40.1%, 71/177 (33.2%-47.5%) vs. 59.9%, 106/177 (52.5%-66.8%); p = 0.01]. This analysis demonstrated mixed findings, with more women across all positions overall but significantly more men when limited to unique physicians. Diversity in conference positions begets a broader array of perspectives, knowledge, and expertise, and can aid in realizing greater diversity in related areas. Thus, academic conference diversity should be prioritized and thoughtfully pursued.
BACKGROUND:In 2021, the United States implemented a federal price transparency mandate to help combat price variability across the country. Initial studies conducted within several months of the mandate showed persistent price variability. METHODS:To assess continued price variability for laboratory tests and factors associated with prices across all licensed hospitals in Tennessee approximately 2.5 years since the mandate, hospital websites were queried for gross, cash, and Blue Cross Blue Shield (BCBS) prices for common laboratory tests (n = 8). Hospital ownership and county demographic data including income, region, and population density were also collected. RESULTS:All tests showed considerable price variability. Gross price was set higher than cash and BCBS prices. For the majority (n = 6) of tests, cash was higher than BCBS price. Maximum to minimum price ratios for each test ranged from 29 to 114 for gross, 57 to 243 for cash, and 25 to 115 for BCBS prices. Gross and cash prices were associated with median household income of the hospital's county while BCBS prices were not. Overall, prices were associated with hospital county income, for-profit status, and region. CONCLUSIONS:Our study shows continued price variability in Tennessee 2.5 years after the federal price transparency mandate.
Postpartum hemorrhage (PPH) remains the leading cause of preventable maternal mortality despite standard interventions. Recent fibrinogen trials failed to improve outcomes, prompting interest in coagulation factor XIII (FXIII). FXIII functions as "molecular cement," cross-linking fibrin and stabilizing clots. During pregnancy, FXIII activity decreases 20%-30%, with further depletion during PPH. Observational studies show low antepartum FXIII predicts bleeding risk, while ex vivo supplementation restores clot firmness. The SWIFT trial (NCT06481995) represents the first randomized controlled trial evaluating early FXIII supplementation in PPH. Although implementation challenges are significant (diagnostic accessibility, thrombotic monitoring, supply constraints), even modest hemostatic improvements could substantially reduce maternal mortality.