Citations

ABSTRACT Prior surveys of chronic automated red blood cell exchange (RCE) for patients with sickle cell disease (SCD) have identified considerable procedural variability, especially with the use of isovolemic hemodilution red blood cell exchange (IHD‐RCE). We conducted a survey of chronic RCE practices among American Society for Apheresis (ASFA) members to identify opportunities for practice harmonization and future studies. The ASFA SCD Research Subcommittee developed a 72‐item survey of chronic RCE practices, with a focus on IHD‐RCE. The survey was validated internally and distributed by email to all ASFA members from September 2024 to February 2025. One survey response from each institution was retained for data analysis. Descriptive statistics were performed. Sixty‐two survey responses, including three from international institutions, were retained for analysis. Sixty‐one percent of respondents (38/62) reported using at least one fixed RCE target, with end hematocrit being the most common fixed parameter (40%, 25/62), followed by fraction of cells remaining (31%, 19/62) and hemoglobin S% (27%, 17/62). Most respondents (60%, 37/61) performed IHD‐RCE at their institution, though other details such as the minimum hematocrit, exclusion criteria, and response to adverse effects were variable. Consistent pre‐ and post‐RCE laboratory monitoring practices were reported. Consistent with earlier surveys, procedural variability in chronic RCE practices for patients with SCD is observed. This highlights opportunities to compare outcomes where practice variability exists. Consensus guidelines based on institutional practices with optimal outcomes should be developed.

ABSTRACT The concentration of cells is a key component of modern blood tests. Given the biomarker potential of extracellular vesicles (EVs) in blood, we aimed to establish reference ranges for blood cell‐derived EVs using flow cytometry. To address the orders‐of‐magnitude variability in reported EV concentrations between different flow cytometers (FCMs), we first validated a calibration methodology to enable reproducible EV concentration measurements. The methodology was evaluated in an interlaboratory comparison study and shows that calibration reduces the median absolute deviation of EV concentrations measured on 25 different FCMs from 67 % to 25 %–31 %. The calibration methodology was then used to determine reference ranges of erythrocyte‐, leukocyte‐, and platelet‐derived EVs in human blood plasma in a cohort of healthy individuals ( n = 224). This study demonstrates that calibration enables comparable concentration measurements of blood cell‐derived EVs, thereby bringing EVs one step closer to clinical applications.

Abstract Blood is the most commonly used body fluid for extracellular vesicle (EV) research. The composition of a blood sample and its derivatives (i.e., plasma and serum) are not only donor‐dependent but also influenced by collection and preparation protocols. Since there are hundreds of pre‐analytical protocols and over forty variables, the development of standard operating procedures for EV research is very challenging. To improve the reproducibility of blood EV research, the International Society for Extracellular Vesicles (ISEV) Blood EV Task Force proposes standardized reporting of (i) the applied blood collection and preparation protocol and (ii) the quality of the prepared plasma and serum samples. Gathering detailed information will provide insight into the performance of the protocols and more effectively identify potential confounders in the prepared plasma and serum samples. To collect this information, the ISEV Blood EV Task Force created the Minimal Information for Blood EV research (MIBlood‐EV), a tool to record and report information about pre‐analytical protocols used for plasma and serum preparation as well as assays used to assess the quality of these preparations. This tool does not require modifications of established local pre‐analytical protocols and can be easily implemented to enhance existing databases thereby enabling evidence‐based optimization of pre‐analytical protocols through meta‐analysis. Taken together, insight into the quality of prepared plasma and serum samples will (i) improve the quality of biobanks for EV research, (ii) guide the exchange of plasma and serum samples between biobanks and laboratories, (iii) facilitate inter‐laboratory comparative EV studies, and (iv) improve the peer review process.

Abstract Glioblastoma is the most common primary malignant brain tumor. Despite maximal safe resection, followed by chemoradiation, median survival is 15 months, and 5-year survival is 6.8%. Efficacy of immunotherapy is limited by glioblastoma-mediated immunosuppression. Extracellular vesicles (EVs) are a heterogeneous group of small membrane-bound particles that are released from all cell types. Glioblastoma-derived EVs regulate the tumor microenvironment and tumor progression in a paracrine manner. They also regulate glioblastoma-mediated systemic immunosuppression in an IL6- and PDL1-dependent manner by inducing myeloid-derived suppressor cells (MDSCs) ultimately resulting in T cell depletion. Primary cilia are ubiquitous microtubule-based organelles that project from the mother centriole and are present on glioblastoma cells. Inhibition of ciliogenesis–through knockdown of KIF3A, IFT88, or ARL13B (structural ciliary proteins required for ciliogenesis)–abolishes IL6 induction in response to chemoradiation and significantly reduces the induction of MDSCs in normal human donor monocytes exposed to glioblastoma-derived EVs. Inhibition of ciliogenesis does not affect the biophysical properties of EVs but our data instead suggest significant alterations in EV packaging and content in response to ciliary loss. These data suggest a novel role for primary cilia in packaging of EV contents and connects these organelles with tumor EV-mediated immunosuppression in glioblastomas. These findings have potential implications for improving the efficacy of immunotherapy in glioblastoma–a universally fatal disease.

INTRODUCTION: Treatment options for patients with moderate-severe ulcerative colitis (UC) are increasing. The appropriateness of their use in mild-moderate UC is less clear, as is the role of surgical intervention. Our aim was to define the appropriateness of therapeutic options in a range of clinical scenarios in mild-moderate UC METHODS: We applied the RAND/UCLA Appropriateness Method to rate appropriateness of treatment choices in patients with mild-moderate UC; severe disease (likely to need hospitalization or surgery within 2 weeks) was excluded. A literature review was presented to the BRIDGe group, a panel of 13 IBD specialists, as well as 1 external IBD expert and 2 IBD surgical experts. 12 chapters were constructed including failed 5-ASA, steroid or thiopurine therapy, and primary/secondary non-response to biologics or tofacitinib. Scenarios were also divided by disease extent (proctitis vs more extensive) and activity (mild vs moderate) creating 260 scenarios in all. Panellists used a modified Delphi method to anonymously rate the appropriateness of a therapy on a 1-9 scale (1-3 not appropriate, 4-6 uncertain, 7-9 appropriate). Disagreement was assessed using a validated index (DI) and was defined as a DI > 1. The panellists then convened in person to discuss areas of disagreement, followed by a second round of rating. Scenarios rated a median of 7 or higher were deemed appropriate and those rated 3 or lower were deemed inappropriate. Scenarios rated 4-6 were considered uncertain, as were any with a DI > 1 RESULTS: Appropriateness was agreed in 131 and inappropriateness in 47 scenarios. Greatest disagreement was around the use of thiopurines, but no scenario had a DI > 1. There were 82 scenarios were rated uncertain. Biologics and tofacitinib were more likely to be rated appropriate for treatment resistance and greater disease activity; disease extent less likely to influence decision making. Surgery was felt to be appropriate in 8 scenarios, generally in more extensive and active disease that had failed to respond to medical therapy. Surgery was felt to be inappropriate in 16 scenarios and was uncertain in 24 CONCLUSION: Although there was little disagreement amongst an expert panel of IBD physicians and surgeons, there remained uncertainty about the use of medical and surgical therapy in nearly one third of situations in patients with mild-moderate UC. These results could be used to guide the design of clinical trials for these patient groups in order to guide best practice.

Abstract Background & Aims Crohn’s disease (CD) is a lifelong illness with substantial morbidity, although new therapies and treatment paradigms have been developed. We provide guidance for treatment of ambulatory patients with mild to severe active luminal CD. Methods We performed a systematic review to identify published studies of the management of CD. The quality of evidence and strength of recommendations were rated according to the Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach. Statements were developed through an iterative online platform and then finalized and voted on by a group of specialists. Results The consensus includes 41 statements focused on 6 main drug classes: antibiotics, 5-aminosalicylate, corticosteroids, immunosuppressants, biologic therapies, and other therapies. The group suggested against the use of antibiotics or 5-aminosalicylate as induction or maintenance therapies. Corticosteroid therapies (including budesonide) can be used as induction, but not maintenance therapies. Among immunosuppressants, thiopurines should not be used for induction, but can be used for maintenance therapy for selected low-risk patients. Parenteral methotrexate was proposed for induction and maintenance therapy in patients with corticosteroid-dependent CD. Biologic agents, including tumor necrosis factor antagonists, vedolizumab, and ustekinumab, were recommended for patients failed by conventional induction therapies and as maintenance therapy. The consensus group was unable to clearly define the role of concomitant immunosuppressant therapies in initiation of treatment with a biologic agent. Conclusions Optimal management of CD requires careful patient assessment, acknowledgement of patient preferences, evidence-based use of existing therapies, and thorough assessment to define treatment success.