Citations

AbstractBackgroundCurrent Association for the Advancement of Blood & Biotherapies (AABB) standards require transfusion services to have a policy on Rh immune globulin (RhIG) immunoprophylaxis for when RhD‐negative patients are exposed to RhD‐positive red cells. This is a survey of AABB‐accredited transfusion services in the United States (US) regarding institutional policies and practices on RhIG immunoprophylaxis after RhD‐negative patients receive RhD‐positive (i.e., RhD‐incompatible) packed red blood cell (pRBC) and platelet transfusions.ResultsApproximately half of the respondents (50.4%, 116/230) have policies on RhIG administration after RhD‐incompatible pRBC and platelet transfusions, while others had policies for only pRBC (13.5%, 31/230) or only platelet (17.8%, 41/230) transfusions, but not both. In contrast, 18.3% (42/230) report that their institution has no written policies on RhIG immunoprophylaxis after RhD‐incompatible transfusions. Most institutions (70.2%, 99/141) do not have policies addressing safety parameters to mitigate the risk of hemolysis associated with the high dose of RhIG required to prevent RhD alloimmunization after RhD‐incompatible pRBC transfusions.DiscussionWith approximately half of US AABB‐accredited institutions report having policies on RhIG immunoprophylaxis after both RhD‐incompatible pRBC and platelet transfusions, some institutions may not be in compliance with AABB standards. Further, most with policies on RhIG immunoprophylaxis after RhD‐incompatible pRBC transfusion do not have written safeguards to mitigate the risk of hemolysis associated with the high dose of RhIG required.ConclusionThis survey underscores the diverse and inadequate institutional policies on RhIG immunoprophylaxis after RhD exposure in Rh‐negative patients via transfusion. This observation identifies an opportunity to improve transfusion safety.

AbstractBackgroundImmunoglobulin (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 MethodsAn 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.ResultsSurvey 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.DiscussionAs 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.

The patterns of idiopathic pulmonary fibrosis (IPF) lung disease that directly correspond to elevated hyperpolarised gas diffusion-weighted (DW) MRI metrics are currently unknown. This study aims to develop a spatial co-registration framework for a voxel-wise comparison of hyperpolarised gas DW-MRI and CALIPER quantitative CT patterns. Sixteen IPF patients underwent 3He DW-MRI and CT at baseline, and eleven patients had a 1-year follow-up DW-MRI. Six healthy volunteers underwent 129Xe DW-MRI at baseline only. Moreover, 3He DW-MRI was indirectly co-registered to CT via spatially aligned 3He ventilation and structural 1H MRI. A voxel-wise comparison of the overlapping 3He apparent diffusion coefficient (ADC) and mean acinar dimension (LmD) maps with CALIPER CT patterns was performed at baseline and after 1 year. The abnormal lung percentage classified with the LmD value, based on a healthy volunteer 129Xe LmD, and CALIPER was compared with a Bland–Altman analysis. The largest DW-MRI metrics were found in the regions classified as honeycombing, and longitudinal DW-MRI changes were observed in the baseline-classified reticular changes and ground-glass opacities regions. A mean bias of −15.3% (95% interval −56.8% to 26.2%) towards CALIPER was observed for the abnormal lung percentage. This suggests DW-MRI may detect microstructural changes in areas of the lung that are determined visibly and quantitatively normal by CT.

Context Gene editing–based therapies are currently in development in the areas of oncology, inherited disease, and infectious disease. These potentially life-altering therapies are derived from decades of research in both academic and industry settings that developed technologies rooted in principles and products of nature. However, with such technologic developments come many important considerations, including adverse risks, high cost, and ethical questions. Objective To educate pathologists about gene editing technologies, inform them of potential indications and risks, outline regulatory and practical issues that could affect hospital-based practice and laboratory testing, and advocate that pathologists need to be present at discussions among industry and regulators pertaining to gene editing–based therapies. Design A Gene Editing Workgroup, facilitated by the College of American Pathologists Personalized Health Care Committee and consisting of pathologists of various backgrounds, was convened to develop an educational paper to serve as a stimulus to increase pathologist involvement and inquiry in gene editing therapeutic and diagnostic implementation. Results Through multiple discussions and literature review, the workgroup identified potential gaps in pathologists' knowledge of gene editing. Additional topics that could impact pathology and laboratory medicine were also identified and summarized in order to facilitate pathologists as stakeholders in gene editing therapy administration and monitoring and potential use in diagnostics. Conclusions Gene editing therapy is a complex but potentially transformative area of medicine. This article serves as an introduction to pathologists to assist them in future discussions with colleagues and potentially identify and alter pathology practices that relate to gene editing.

10520 Background: PATHFINDER (NCT04241796) was a prospective, interventional return of results study that enrolled 6,662 participants (pts) from 7 US institutions to assess clinical implementation of a blood-based multi-cancer early detection (MCED) test. Test results for those with a cancer signal detected also included a cancer signal origin prediction designed to help guide diagnostic evaluations. We analyzed whether the diagnostic evaluations in PATHFINDER were appropriately directed by cancer signal origin predictions, assessed the residual risk of cancer after negative initial evaluation, and examined the role of whole-body imaging (WBI, defined as PET/CT or CT chest/abdomen/pelvis) in diagnostic evaluation. Methods: Analysis included pts with a cancer signal detected result from the two different versions of an MCED test evaluated in PATHFINDER. Prespecified criteria blinded to study results were used to define expected diagnostic evaluations by cancer signal origin prediction. These criteria were then used to judge concordance between cancer signal origin predictions and the diagnostic evaluation actually performed. Definitive cancer or no cancer diagnosis (cancer status at end of study [EOS]) was assessed at 12 months after enrollment (EOS). Results: 39 pts had cancer signal detected results by both test versions. Diagnostic evaluations were consistent with cancer signal origin in 30/39 (77%) cases. Diagnostic resolution was achieved in 32/39 (82%) pts after initial evaluation, while 7/39 (18%) required additional workup. 25 of the 32 (78%) pts who achieved diagnostic resolution after initial evaluation had a cancer signal origin-guided workup. Additional evaluation of the 7 pts not achieving initial diagnostic resolution was based on persistent clinical suspicion of cancer due to prior cancer history (n = 1) or abnormal/equivocal findings on initial evaluation (n = 6). Additional workup led to diagnostic resolution in all 7 cases (3 with cancer and 4 with no cancer confirmed at EOS). WBI was ordered in 27 cases, of whom 9 had a prior cancer history, 10 had non-localizing cancer signal origin (hematologic or indeterminate), and 1 had both. WBI was equivocal or had no impact on diagnostic resolution in 8/27 (30%) cases. Conclusions: Most cases resulted in diagnostic resolution after cancer signal origin-directed diagnostic workup. In pts with a cancer history and negative initial evaluations, and those with equivocal initial evaluations, there was still a risk of cancer, suggesting the need for additional evaluation. WBI was used mostly in those with a cancer history or non-localizing cancer signal origins, and had no impact on diagnosis in almost one-third of pts. Clinical trial information: NCT04241796 .

AbstractObjectiveTo evaluate recurrence patterns and survival after recurrence among patients with sinonasal mucosal melanoma (SNMM).MethodsThis was a multi‐institutional retrospective review from seven U.S. institutions of patients with SNMM from 1991 to 2022. Recurrence was categorized as local, regional, distant, or multifocal. Kaplan‐Meier tests were used to evaluate disease‐free survival (DFS), overall survival (OS), and post‐recurrence survival (PRS) reported with standard errors (SE) and log‐rank testing used for comparison. Cox‐regression was further used, with hazard ratios (HR) and 95% confidence intervals (CI) reported.ResultsAmong 196 patients with SNMM, there were 146 patients with recurrence (74.5%). Among all patients, 60‐month DFS (SE) was 15.5% (2.9%), 60‐month OS (SE) was 44.7% (3.7%), mean age ± standard deviation at diagnosis was 69.7 ± 12.5 years, and 54.6% were female. In 26 patients who underwent primary treatment of the neck, 60‐month DFS did not differ from no treatment (p > 0.05). Isolated distant recurrence was most common (42.8%), followed by local (28.3%), multifocal (20.7%), and regional recurrence (8.3%). Among patients with regional recurrence in the neck, there was no 60‐month PRS benefit for patients undergoing salvage neck dissection or radiation (p > 0.05). Among patients with distant recurrence, only immunotherapy was associated with improved 12‐month PRS (HR = 0.32, 95% CI = 0.11–0.92, p = 0.034), and no treatment group was associated with improved 24‐ or 60‐month PRS (p > 0.05).ConclusionSNMM is associated with a high recurrence rate and poor survival. Primary treatment of the neck was not associated with reduced recurrence, and immunotherapy for treatment of distant recurrence was associated with increased 12‐month PRS.

Context.— Ankylosing spondylitis (AS) is an autoimmune disorder with a strong genetic risk, especially with HLA-B27. Clinical testing for HLA-B27 has been used to help diagnose patients with signs and symptoms of AS. Testing methods used by clinical laboratories for HLA-B27 fall into the broad categories of serologic/antibody- or molecular-based methods and have evolved over time. The College of American Pathologists (CAP) offers a proficiency testing survey for HLA-B27. Objective.— To analyze HLA-B27 testing trends and their performance in the past decade, using the proficiency testing survey data submitted to CAP. Design.— We analyzed the HLA-B27 CAP proficiency testing data from 2010 to 2020 for the method used, participant concordance, and error rates. Results from case scenarios to understand evolving scientific data around HLA-B27 risk alleles were also analyzed. Results.— Antibody-based flow cytometry is the most common method, though it has decreased from 60% in 2010 to 52% in 2020, with a corresponding increase in molecular methods. Among the molecular methods, real-time polymerase chain reaction has increased from 2% to 15%. Flow cytometry had the highest error rate (5.33%), and sequence-specific oligonucleotide (0%) is the most accurate (0%). Results of case scenarios demonstrated that most participants understood that allele-level HLA-B27 typing results inform clinical interpretation, for example HLA-B*27:06 is not associated with AS. Conclusions.— These data demonstrated the changing trends for HLA-B27 testing during the past decade. HLA-B27 allelic typing provides a better understanding of AS association. This is possible by testing for the second field with methods like next-generation sequencing.