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Trauma is the leading cause of death in individuals up to 45 years of age. Alterations in platelet function are a critical component of trauma-induced coagulopathy (TIC), yet these changes and the potential resulting dysfunction is incompletely understood. The lack of clinical assays available to explore platelet function in this patient population has hindered detailed understanding of the role of platelets in TIC. The objective of this study was to assess trauma patient ex vivo flow-dependent platelet hemostatic capacity in a microfluidic model. We hypothesized that trauma patients would have flow-regime dependent alterations in platelet function. Blood was collected from trauma patients with level I activations (N = 34) within 60 min of hospital arrival, as well as healthy volunteer controls (N = 10). Samples were perfused through a microfluidic model of injury at venous and arterial shear rates, and a subset of experiments were performed after incubation with fluorescent anti-CD41 to quantify platelets. Complete blood counts were performed as well as plasma-based assays to quantify coagulation times, fibrinogen, and von Willebrand factor (VWF). Exploratory correlation analyses were employed to identify relationships with microfluidic hemostatic parameters. Trauma patients had increased microfluidic bleeding times compared to healthy controls. While trauma patient samples were able to deposit a substantial amount of clot in the model injury site, the platelet contribution to microfluidic hemostasis was attenuated. Trauma patients had largely normal hematology and plasma-based coagulation times, yet had elevated D-Dimer and VWF. Venous microfluidic bleeding time negatively correlated with VWF, D-Dimer, and mean platelet volume (MPV), while arterial microfluidic bleeding time positively correlated with oxygenation. Arterial clot growth rate negatively correlated with red cell count, and positively with mean corpuscular volume (MCV). We observed changes in clot composition in trauma patient samples reflected by significantly diminished platelet contribution, which resulted in reduced hemostatic function in a microfluidic model of vessel injury. We observed a reduction in platelet clot contribution under both venous and arterial flow ex vivo in trauma patient samples. While our population was heterogenous and had relatively mild injury severity, microfluidic hemostatic parameters correlated with different patient-specific data depending on the flow setting, indicating potentially differential mechanistic pathways contributing to platelet hemostatic capacity in the context of TIC. These data were generated with the goal of identifying key features of platelet dysfunction in bleeding trauma patients under conditions of flow and to determine if these features correlate with clinically available metrics, thus providing preliminary surrogate markers of physiological platelet dysfunction to be further studied across larger cohorts. Future studies will continue to explore those relationships and further define mechanisms of TIC and their relationship with patient outcomes., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: PCS: Consultant for Hemanext, Cerus, CSL Behring, Octapharma. Advisory Board, Haima. Co-founder and Chief Medical Officer, Kalocyte. MDN: Chief Medical Officer, Haima Therapeutics, Research funding: Haemonetics, Instrumentation Laboratories, Alexion; Advisory Board and honoraria: Takeda and Haemonetics. RMGR, KAT, RK, DMD, KCR, RF, MC, JA, HA, KB, GVB, and SMS declare that no competing interests exist. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Thomas et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Evidence suggests that variation in light exposure strongly influences the dynamic of inflammation, coagulation, and the immune system. Multiple injuries induce systemic inflammation that can lead to end-organ injury. Here, we hypothesize that alterations in light exposure influence posttrauma inflammation, coagulopathy, and end-organ injury., Methods: C57BL/6 mice underwent a validated multiple-injury and hemorrhage model performed following 72 hours of exposure to red (617 nm, 1,700 lux), blue (321 nm, 1,700 lux), and fluorescent white light (300 lux) (n = 6-8/group). The animals were sacrificed at 6 hours posttrauma. Plasma samples were evaluated and compared for proinflammatory cytokine expression levels, coagulation parameters, markers of liver and renal injury, and histological changes (Carstairs staining). One-way analysis of variance statistical tests were applied to compare study groups., Results: Preexposure to long-wavelength red light significantly reduced the inflammatory response at 6 hours after multiple injuries compared with blue and ambient light, as evidenced by decreased levels of interleukin 6, monocyte chemoattractant protein-1 (both p < 0.001), liver injury markers (alanine transaminase, p < 0.05), and kidney injury markers (cystatin C, p < 0.01). In addition, Carstairs staining of organ tissues revealed milder histological changes in the red light-exposed group, indicating reduced end-organ damage. Furthermore, prothrombin time was significantly lower ( p < 0.001), and fibrinogen levels were better maintained ( p < 0.01) in the red light-exposed mice compared with those exposed to blue and ambient light., Conclusion: Prophylactic light exposure can be optimized to reduce systemic inflammation and coagulopathy and minimize acute organ injury following multiple injuries. Understanding the mechanisms by which light exposure attenuates inflammation may provide a novel strategy to reducing trauma-related morbidity., (Copyright © 2023 American Association for the Surgery of Trauma.)

Here, we present a series of illustrated capsules from the State of the Art (SOA) speakers at the 2024 International Society on Thrombosis and Haemostasis Congress in Bangkok, Thailand. This year's Congress marks the first time that the International Society on Thrombosis and Haemostasis has held its flagship scientific meeting in Southeast Asia and is the first to be organized by an international Planning Committee. The Bangkok program will feature innovative science and clinical updates from around the world, reflecting the diversity and multidisciplinary growth of our field. In these illustrated SOA capsules, you will find an exploration of novel models of thrombosis and bleeding and biomaterial discoveries that can trigger or block coagulation. Thromboinflammation is now understood to drive many disease states, and the SOA speakers cover cellular and coagulation responses to COVID-19 and other infections. The theme of crosstalk between coagulation and inflammation expands with capsules on protein S signaling, complement, and fibrinolytic inhibitors. Novel agents for hemophilia and thrombosis prevention are introduced. Challenging clinical conditions are also covered, such as inherited platelet disorders and antiphospholipid antibody syndrome. The scientific program in Bangkok will also showcase the work of clinicians and scientists from all parts of the world and chronicle real-world challenges. For example, 2 SOA capsules address the diagnosis and management of von Willebrand disease in low-income settings. Take some time to browse through these short illustrated reviews; we're sure that you'll be entertained, educated, and inspired to further explore the world of thrombosis and hemostasis., (© 2024 The Authors.)

Background: Thrombosis within extracorporeal membrane oxygenation (ECMO) circuits is a common complication that dominates clinical management of patients receiving mechanical circulatory support. Prior studies have identified that over 80% of circuit thrombosis can be attributed to tubing-connector junctions., Methods: A novel connector was designed that reduces local regions of flow stagnation at the tubing-connector junction to eliminate a primary source of ECMO circuit thrombi. To compare clotting between the novel connectors and the traditional connectors, both in vitro loops and an in vivo caprine model of long-term (48 h) ECMO were used to generate tubing-connector junction clots., Results: In vitro, the traditional connectors uniformly (9/9) formed large thrombi, while novel connectors formed a small thrombus in only one of nine ( p  < 0.0001). In the long-term goat ECMO circuits, the traditional connectors exhibited more thrombi ( p  < 0.04), and these thrombi were more likely to protrude into the lumen of the tubing ( p  < 0.001)., Conclusion: Both in vitro and in vivo validation experiments successfully recreated circuit thrombosis and demonstrate that the adoption of novel connectors can reduce the burden of circuit thrombosis., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: We express our gratitude to the ECMO clinical staff at Children’s Healthcare of Atlanta. S.M.S., S.R.D., K.O.M., and D.N.K. have a submitted a provisional application for a patent on the described connector technology.

Objective: We report an updated analysis of the outcomes and toxicities of MRI-based brachytherapy for locally advanced cervical cancer from a U.S. academic center., Methods: A retrospective review was performed on patients treated with MRI-based brachytherapy for cervical cancer. EBRT was standardly 45 Gy in 25 fractions with weekly cisplatin. MRI was performed with the brachytherapy applicator in situ. Dose specification was most commonly 7 Gy for 4 fractions with optimization aim of D90 HR-CTV EQD2 of 85-95 Gy α/β=10 Gy in 2 implants each delivering 2 fractions., Results: Ninety-eight patients were included with median follow up of 24.5 months (IQR 11.9-39.8). Stage IIIA-IVB accounted for 31.6% of cases. Dosimetry results include median GTV D98 of 101.0 Gy (IQR 93.3-118.8) and HR-CTV D90 of 89 Gy (IQR 86.1-90.6). Median D2cc bladder, rectum, sigmoid, and bowel doses were 82.1 Gy (IQR 75.9-88.0), 65.9 Gy (IQR 59.6-71.2), 65.1 Gy (IQR 57.7-69.6), and 55 Gy (IQR 48.9-60.9). Chronic grade 3+ toxicities were seen in the bladder (8.2%), rectosigmoid (4.1%), and vagina (1.0%). Three-year LC, PFS, and OS were estimated to be 84%, 61.7%, and 76.1%, respectively., Conclusion: MRI-based brachytherapy demonstrates excellent local control and acceptable rates of high-grade morbidity. These results are possible in our population with relatively large volume primary tumors and extensive local disease., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to report., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Platelet (PLT) product transfusion is a life-saving therapy for actively bleeding patients. There is an urgent need to maintain PLT function and extend shelf life to improve outcomes in these patients. Cold-stored PLT (CS-PLT) maintain hemostatic potential better than room temperature-stored PLT (RT-PLT). However, whether function in long-term CS-PLT is maintained under physiological flow regimes and/or determined by cold-induced metabolic changes is unknown., Objectives: This study aimed to (i) compare the function of RT-PLT and CS-PLT under physiological flow conditions, (ii) determine whether CS-PLT maintain function after 3 weeks of storage, and (iii) identify metabolic pathways associated with the CS-PLT lesion., Methods: We performed phenotypic and functional assessments of RT- and CS-PLT (22 °C and 4 °C storage, respectively; N = 10 unique donors) at storage days 0, 5, and/or 21 via metabolomics, flow cytometry, aggregation, thrombin generation, viscoelastic testing, and a microfluidic assay to measure primary hemostatic function., Results: Day 21 4 °C PLT formed an occlusive thrombus under arterial shear at a similar rate to day 5 22 °C PLT. Day 21 4 °C PLTs had enhanced thrombin generation capacity compared with day 0 PLT and maintained functionality comparable to day RT-PLT across all assays performed. Key metrics from microfluidic assessment, flow cytometry, thrombin generation, and aggregation were associated with 4 °C storage, and metabolites involved in taurine and purine metabolism significantly correlated with these metrics. Taurine supplementation of PLT during storage improved hemostatic function under flow., Conclusion: CS-PLT stored for 3 weeks maintain hemostatic activity, and storage-induced phenotype and function are associated with taurine and purine metabolism., Competing Interests: Declaration of competing interests P.C.S. is a consultant for Cerus Corporation and Haima Therapeutics. All other authors have no competing interests to disclose., (Copyright © 2023 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)

Background: Low-titer group O whole blood (LTOWB) or component therapy (CT) may be used to resuscitate hemorrhaging trauma patients. LTOWB may have clinical and logistical benefits and may improve survival., Objectives: We hypothesized LTOWB would improve 24-hour survival in hemorrhaging patients and would be safe and equally efficacious in non-group O compared with group O patients., Methods: Adult trauma patients with massive transfusion protocol activations were enrolled in this observational study. The primary outcome was 24-hour mortality. Secondary outcomes included 72-hour total blood product use. A Cox regression determined the independent associations with 24-hour mortality., Results: In total, 348 patients were included (CT, n = 180; LTOWB, n = 168). Demographics were similar between cohorts. Unadjusted 24-hour mortality was reduced in LTOWB vs CT: 8% vs 19% (P = .003), but 6-hour and 28-day mortality were similar. In an adjusted analysis with multivariable Cox regression, LTOWB was independently associated with reduced 24-hour mortality (hazard ratio, 0.21; 95% CI, 0.07-0.67; P = .004). LTOWB patients received significantly less 72-hour total blood products (80.9 [41.6-139.3] mL/kg vs 48.9 [25.9-106.9] mL/kg; P < .001). In stratified 24-hour survival analyses, LTOWB was associated with improved survival for patients in shock or with coagulopathy. LTOWB use in non-group O patients was not associated with increased mortality, organ injury, or adverse events., Conclusion: In this hypothesis-generating study, LTOWB use was independently associated with improved 24-hour survival, predominantly in patients with shock or coagulopathy. LTOWB also resulted in a 40% reduction in blood product use which equates to a median 2.4 L reduction in transfused products., Competing Interests: Declaration of competing interests P.C.S. is a consultant for Hemanext, Cerus, Haima, and Co-Founder and Chief Medical Officer for Kalocyte. The authors have no other conflicts of interest to disclose., (Copyright © 2023 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study is to evaluate the impact of radiologist and urologist variability on detection of prostate cancer (PCa) and clinically significant prostate cancer (csPCa) with magnetic resonance imaging (MRI)-transrectal ultrasound (TRUS) fusion prostate biopsies., Patients and Methods: The Prospective Loyola University MRI (PLUM) Prostate Biopsy Cohort (January 2015 to December 2020) was used to identify men receiving their first MRI and MRI/TRUS fusion biopsy for suspected PCa. Clinical, MRI and biopsy data were stratified by radiologist and urologist to evaluate variation in Prostate Imaging-Reporting and Data System (PI-RADS) grading, lesion number and cancer detection. Multivariable logistic regression (MVR) models and area under the curve (AUC) comparisons assessed the relative impact of individual radiologists and urologists., Results: A total of 865 patients (469 biopsy-naïve) were included across 5 urologists and 10 radiologists. Radiologists varied with grading 15.4% to 44.8% of patients with MRI lesions as PI-RADS 3. PCa detection varied significantly by radiologist, from 34.5% to 66.7% ( p  = 0.003) for PCa and 17.2% to 50% ( p  = 0.001) for csPCa. Urologists' PCa diagnosis rates varied between 29.2% and 55.8% ( p  = 0.013) and between 24.6% and 39.8% ( p  = 0.36) for csPCa. After adjustment for case-mix on MVR, a fourfold to fivefold difference in PCa detection was observed between the highest-performing and lowest-performing radiologist (OR 0.22, 95%CI 0.10-0.47, p  < 0.001). MVR demonstrated improved AUC for any PCa and csPCa detection when controlling for radiologist variation ( p  = 0.017 and p  = 0.038), but controlling for urologist was not significant ( p  = 0.22 and p  = 0.086). Any PCa detection (OR 1.64, 95%CI 1.06-2.55, p  = 0.03) and csPCa detection (OR 1.57, 95%CI 1.00-2.48, p  = 0.05) improved over time (2018-2020 vs. 2015-2017)., Conclusions: Variability among radiologists in PI-RADS grading is a key area for quality improvement significantly impacting the detection of PCa and csPCa. Variability for performance of MRI-TRUS fusion prostate biopsies exists by urologist but with less impact on overall detection of csPCa., Competing Interests: None., (© 2023 The Authors. BJUI Compass published by John Wiley & Sons Ltd on behalf of BJU International Company.)

Background: The use of low-titer group O whole blood is increasing. To reduce wastage, unused units can be converted to packed red blood cells. Supernatant is currently discarded post-conversion; however, it could be a valuable transfusable product. The aim of this study was to evaluate supernatant prepared from late-storage low-titer group O whole blood being converted to red blood cells, hypothesizing it will have higher hemostatic activity compared to fresh never-frozen liquid plasma., Methods: Low-titer group O whole blood supernatant (n = 12) prepared on storage day 15 was tested on days 15, 21, and 26 and liquid plasma (n = 12) on 3, 15, 21, and 26. Same-day assays included cell counts, rotational thromboelastometry, and thrombin generation. Centrifuged plasma from units was banked for microparticle characterization, conventional coagulation, clot structure, hemoglobin, and additional thrombin generation assays., Results: Low-titer group O whole blood supernatant contained more residual platelets and microparticles compared to liquid plasma. At day 15, low-titer group O whole blood supernatant elicited a faster intrinsic clotting time compared to liquid plasma (257 ± 41 vs. 299 ± 36 s, P = 0.044), and increased clot firmness (49 ± 9 vs. 28 ± 5 mm, P < 0.0001). Low-titer group O whole blood supernatant showed more significant thrombin generation compared to liquid plasma (day 15 endogenous thrombin potential 1,071 ± 315 vs. 285 ± 221 nM·min, P < 0.0001). Flow cytometry demonstrated low-titer group O whole blood supernatant contained significantly more phosphatidylserine and CD41+ microparticles. However, thrombin generation in isolated plasma suggested residual platelets in low-titer group O whole blood supernatant were a greater contributor than microparticles. Additionally, low-titer group O whole blood supernatant and liquid plasma showed no difference in clot structure, despite higher CD61+ microparticle presence., Conclusions: Plasma supernatant produced from late-storage low-titer group O whole blood shows comparable, if not enhanced, in vitro hemostatic efficacy to liquid plasma., (Copyright © 2023 American Society of Anesthesiologists. All Rights Reserved.)

Background: Platelet concentrates (PLT) can be manufactured using a combination of apheresis collection devices and suspension media (plasma or platelet additive solution (PAS)). It is unclear how platelet quality and hemostatic function differ across the current in-use manufacturing methods in the United States. The objective of this study was therefore to compare baseline function of PLT collected using different apheresis collection platforms and storage media., Study Design and Methods: PLT were collected at two sites with identical protocols (N = 5 per site, N = 10 total per group) on the MCS® + 9000 (Haemonetics; "MCS"), the Trima Accel® 7 (Terumo; "Trima"), and the Amicus Cell Separator (Fresenius Kabi, "Amicus"). MCS PLT were collected into plasma while Trima and Amicus PLT were collected into plasma or PAS (Trima into Isoplate and Amicus into InterSol; yielding groups "TP", "TI" and "AP", "AI", respectively). PLT units were sampled 1 h after collection and assayed to compare cellular counts, biochemistry, and hemostatic function., Results: Differences in biochemistry were most evident between plasma and PAS groups, as anticipated. MCS and TP had the highest clot strength as assessed by viscoelastometry. AI had the lowest thrombin generation capacity. Both TP and TI had the highest responses on platelet aggregometry. AI had the greatest number of microparticles., Discussion: Platelet quality and function differ among collection platforms at baseline. MCS and Trima platelets overall appear to trend toward higher hemostatic function. Future investigations will assess how these differences change throughout storage, and if these in vitro measures are clinically relevant., (© 2023 AABB.)

Background: The rapid provision of blood products is life-saving for patients with massive hemorrhage. Ideally, RhD-negative blood products would be supplied to a woman of childbearing potential whose Rh type is unknown due to the risk of D-alloimmunization and the potential for hemolytic disease of the fetus and newborn to occur if RhD-positive blood products are transfused. Therefore, there is a need for a test that rapidly determines her RhD type. This study compared the RhD type determined using a rapid ABO and RhD test to the RhD type determined by an immunohematology reference laboratory., Methods: After receiving ethics review board approval, 200 random, unique, deidentified patient samples that had undergone routine pretransfusion testing in an immunohematology reference laboratory using column agglutination technology were collected and tested using a rapid ABO and RhD test (Eldoncard Home kit 2511). The RhD typing results from these two methods were compared to determine the accuracy of the rapid ABO and RhD test., Results: The rapid ABO and RhD test produced results that were concordant with the transfusion service's results in 199/200 (99.5%) of cases, with a negative predictive value of 98.2% and 99.3% sensitivity. The single outlier was likely an RhD variant due to its serological characteristics., Discussion: These data indicate that this rapid ABO and RhD test could be used for the rapid determination of a patient's RhD type, perhaps even in the emergency department, which could guide the selection of blood products provided during their resuscitation., (© 2023 AABB.)

Purpose: Magnetic resonance imaging (MRI) prior to biopsy has improved detection of clinically significant prostate cancer (CaP), but its impact on surgical outcomes is less well established. We compared MRI vs. non-MRI diagnostic pathways among patients receiving radical prostatectomy (RP) for impact on surgical outcomes., Materials and Methods: Men diagnosed with CaP and receiving RP at Loyola University Medical Center (2014-2021) were categorized into MRI or non-MRI diagnostic pathways based on receipt of MRI before prostate biopsy. Primary outcomes of interest included positive surgical margin (PSM) rates, the performance of bilateral nerve-sparing, and biochemical recurrence (BCR). Multivariable logistic regression models, Kaplan-Meier curves, and Cox proportional hazards regression were employed., Results: Of 609 patients, 281 (46.1%) were in the MRI and 328 (53.9%) in the non-MRI groups. MRI patients had similar PSA, biopsy grade group (GG) distribution, RP GG, pT stage, and RP CaP volume compared to non-MRI patients. PSM rates were not statistically different for the MRI vs. non-MRI groups (22.8% vs. 26.8%, P = 0.25). Bilateral nerve-sparing rates were higher for the MRI vs. non-MRI groups (OR 1.95 (95%CI 1.32-2.88), P = 0.001). The MRI group demonstrated improved BCR (HR 0.64 (95%CI 0.41-0.99), P = 0.04) after adjustment for age, PSA, RP GG, pT, pN, and PSM status. On meta-analysis, a 5.2% PSM reduction was observed but high heterogeneity for use of nerve-sparing., Conclusions: An MRI-based diagnostic approach selected patients for RP with a small reduction in PSM rates, greater utilization of bilateral nerve-sparing, and improved cancer control by BCR compared to a non-MRI approach even after adjustment for known prognostic factors., Competing Interests: Conflict of Interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: To develop and validate a prostate cancer (PCa) risk calculator (RC) incorporating multiparametric magnetic resonance imaging (mpMRI) and to compare its performance with that of the Prostate Biopsy Collaborative Group (PBCG) RC., Patients and Methods: Men without a PCa diagnosis receiving mpMRI before biopsy in the Prospective Loyola University mpMRI (PLUM) Prostate Biopsy Cohort (2015-2020) were included. Data from a separate institution were used for external validation. The primary outcome was diagnosis of no cancer, grade group (GG)1 PCa, and clinically significant (cs)PCa (≥GG2). Binary logistic regression was used to explore standard clinical and mpMRI variables (prostate volume, Prostate Imaging-Reporting Data System [PI-RADS] version 2.0 lesions) with the final PLUM RC, based on a multinomial logistic regression model. Receiver-operating characteristic curve, calibration curves, and decision-curve analysis were evaluated in the training and validation cohorts., Results: A total of 1010 patients were included for development (N = 674 training [47.8% PCa, 30.9% csPCa], N = 336 internal validation) and 371 for external validation. The PLUM RC outperformed the PBCG RC in the training (area under the curve [AUC] 85.9% vs 66.0%; P < 0.001), internal validation (AUC 88.2% vs 67.8%; P < 0.001) and external validation (AUC 83.9% vs 69.4%; P < 0.001) cohorts for csPCa detection. The PBCG RC was prone to overprediction while the PLUM RC was well calibrated. At a threshold probability of 15%, the PLUM RC vs the PBCG RC could avoid 13.8 vs 2.7 biopsies per 100 patients without missing any csPCa. At a cost level of missing 7.5% of csPCa, the PLUM RC could have avoided 41.0% (566/1381) of biopsies compared to 19.1% (264/1381) for the PBCG RC. The PLUM RC compared favourably with the Stanford Prostate Cancer Calculator (SPCC; AUC 84.1% vs 81.1%; P = 0.002) and the MRI-European Randomized Study of Screening for Prostate Cancer (ERSPC) RC (AUC 84.5% vs 82.6%; P = 0.05)., Conclusions: The mpMRI-based PLUM RC significantly outperformed the PBCG RC and compared favourably with other mpMRI-based RCs. A large proportion of biopsies could be avoided using the PLUM RC in shared decision making while maintaining optimal detection of csPCa., (© 2022 The Authors. BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Objectives: To compare multiparametric magnetic resonance imaging (mpMRI) and transrectal ultrasound (TRUS) to estimate prostate volume and prostate specific antigen density (PSAD) as well as subsequent impact on prostate cancer (PCa) detection., Methods: Patients referred for mpMRI prior to mpMRI-TRUS fusion-guided prostate biopsy between 2015 and 2020 were identified. Volume and calculated PSAD by mpMRI and TRUS were compared. Associations with presence of any PCa and clinically significant PCa (csPCa; Gleason ≥3 + 4) were evaluated using linear regression (interaction by volume quartile), logistic regression, and receiver operating characteristics., Results: Among 640 men, TRUS underestimated prostate volume relative to mpMRI (median 49.2cc vs. 54.1cc) with 8% lower volume per cc up to 77.5cc (First-third quartile) and 39% lower volume per additional cc above 77.5cc (fourth quartile). For men undergoing radical prostatectomy, mpMRI had a higher correlation coefficient relative to TRUS (0.913 vs 0.878) when compared to surgical pathology. mpMRI PSAD had slightly higher odds vs TRUS PSAD for detecting any PCa (OR 2.94 and OR 2.78, both P <.001) or csPCa (OR 4.20 and OR 4.02, both P <.001). AUC improvements were of borderline significance for mpMRI vs. TRUS PSAD for any PCa (0.689 vs 0.675, P = .05) and not significant for csPCa (0.732 vs 0.722, P = .20). PSAD was not associated with PCa detection for prostates ≥77.5cc., Conclusion: TRUS underestimates prostate volume relative to mpMRI. PSAD based on mpMRI may be better associated with detection of PCa compared to TRUS, but utility of PSAD may be limited for larger prostates., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: To evaluate the effect of a deep learning-based computer-aided diagnosis (DL-CAD) system on experienced and less-experienced radiologists in reading prostate mpMRI., Methods: In this retrospective, multi-reader multi-case study, a consecutive set of 184 patients examined between 01/2018 and 08/2019 were enrolled. Ground truth was combined targeted and 12-core systematic transrectal ultrasound-guided biopsy. Four radiologists, two experienced and two less-experienced, evaluated each case twice, once without (DL-CAD-) and once assisted by DL-CAD (DL-CAD+). ROC analysis, sensitivities, specificities, PPV and NPV were calculated to compare the diagnostic accuracy for the diagnosis of prostate cancer (PCa) between the two groups (DL-CAD- vs. DL-CAD+). Spearman's correlation coefficients were evaluated to assess the relationship between PI-RADS category and Gleason score (GS). Also, the median reading times were compared for the two reading groups., Results: In total, 172 patients were included in the final analysis. With DL-CAD assistance, the overall AUC of the less-experienced radiologists increased significantly from 0.66 to 0.80 (p = 0.001; cutoff ISUP GG ≥ 1) and from 0.68 to 0.80 (p = 0.002; cutoff ISUP GG ≥ 2). Experienced radiologists showed an AUC increase from 0.81 to 0.86 (p = 0.146; cutoff ISUP GG ≥ 1) and from 0.81 to 0.84 (p = 0.433; cutoff ISUP GG ≥ 2). Furthermore, the correlation between PI-RADS category and GS improved significantly in the DL-CAD + group (0.45 vs. 0.57; p = 0.03), while the median reading time was reduced from 157 to 150 s (p = 0.023)., Conclusions: DL-CAD assistance increased the mean detection performance, with the most significant benefit for the less-experienced radiologist; with the help of DL-CAD less-experienced radiologists reached performances comparable to that of experienced radiologists., Key Points: • DL-CAD used as a concurrent reading aid helps radiologists to distinguish between benign and cancerous lesions in prostate MRI. • With the help of DL-CAD, less-experienced radiologists may achieve detection performances comparable to that of experienced radiologists. • DL-CAD assistance increases the correlation between PI-RADS category and cancer grade., (© 2022. The Author(s), under exclusive licence to European Society of Radiology.)

Von Willebrand Factor (VWF) plays a critical role in thrombus formation, stabilization, and propagation. Previous studies have demonstrated that targeted inhibition of VWF induces thrombolysis when administered in vivo in animal models of ischemic stroke. The study objective was to quantify dose-dependent inhibition of VWF-platelet function and its relationship with thrombolysis using BB-031, an aptamer that binds VWF and inhibits its function. VWF:Ac, VWF:RCo, T-TAS, and ristocetin-induced impedance aggregometry were used to assess BB-031-mediated inhibition of VWF. Reductions in original thrombus surface area and new deposition during administration of treatment were measured in a microfluidic model of arterial thrombolysis. Rotational thromboelastometry was used to assess changes in hemostasis. BB-031 induced maximal inhibition at the highest dose (3384 nM) in VWF:Ac, and demonstrated dose-dependent responses in all other assays. BB-031, but not vehicle, induced recanalization in the microfluidic model. Maximal lytic efficacy in the microfluidic model was seen at 1692 nM and not 3384 nM BB-031 when assessed by surface area. Minor changes in ROTEM parameters were seen at 3384 nM BB-031. Targeted VWF inhibition by BB-031 results in clinically measurable impairment of VWF function, and specifically VWF-GPIb function as measured by VWF:Ac. BB-031 also induced thrombolysis as measured in a microfluidic model of occlusion and reperfusion. Moderate correlation between inhibition and lysis was observed. Additional studies are required to further examine off-target effects of BB-031 at high doses, however, these are expected to be above the range of clinical targeted dosing.

Background: Accurate assessment of hemostatic function is essential to guide care in critically ill children with acute and acquired coagulopathies. Thrombin generation (TG) provides a global assessment of procoagulant and anticoagulant factors and is commonly used in hemostasis research laboratories. Our objective was to determine the correlation of clinically available hemostasis assays with TG in critically ill children., Methods: Children (<18 years old, >3 kg in weight) in the intensive care unit were enrolled from March 2016 to December 2019 in a prospective 2-center study. Coagulation tests were prothrombin time, activated thromboplastin time, anti-Xa assay, viscoelastic assays (thromboelastography [TEG], rotational thromboelastometry [ROTEM]), and TG (induced by 20 pM tissue factor in platelet poor plasma and reported as endogenous thrombin potential [ETP; nM*min]). Data are reported as median (interquartile range) or Spearman coefficient (ρ)., Results: Patients (n = 106, age 10.2 years [3.8-15.3]) were divided into 3 groups: (a) no anticoagulation (n = 46), (b) anticoagulation (unfractionated heparin) without extracorporeal life support (n = 34), or (c) with extracorporeal life support (n = 26). ETP was decreased in anticoagulated compared to non-anticoagulated patients (group 1: 902.4 [560.8-1234], group 2: 315.6 [0.0-962.2], group 3: 258.5 [0.0-716.6]; P < 0.0001). Across all patients, ETP correlated best with TEG kinetic time (TEG-K), in min (ρ = -0.639), followed by TEG reaction time, in min (ρ = -0.596). By group, ETP correlated best with international normalized ratio for group 1 (ρ = -0.469), TEG-K time for group 2 (ρ = -0.640), and anti-Xa for group 3 (ρ = -0.793)., Conclusions: Standard and viscoelastic assays have varying correlation with TG in critically ill children. TEG-K time had the most consistent moderate correlation with ETP across all groups., Competing Interests: Authors’ Disclosures or Potential Conflicts of Interest: Upon manuscript submission, all authors completed the author disclosure form. Disclosures and/or potential conflicts of interest: Employment or Leadership: None declared. Consultant or Advisory Role: None declared. Stock Ownership: None declared. Honoraria: None declared. Research Funding: ROTEM devices were supplied by Instrumentation Laboratory, a Werfen Company. Expert Testimony: None declared. Patents: None declared., (© American Association for Clinical Chemistry 2022. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Cold storage of platelets (CS-PLT), results in better maintained hemostatic function compared to room-temperature stored platelets (RT-PLT), leading to increased interest and use of CS-PLT for actively bleeding patients. However, questions remain on best storage practices for CS-PLT, as agitation of CS-PLT is optional per the United States Food and Drug Administration. CS-PLT storage and handling protocols needed to be determined prior to upcoming clinical trials, and blood banking standard operating procedures need to be updated accordingly for the release of units due to potentially modified aggregate morphology without agitation., Study Design and Methods: We visually assessed aggregate formation, then measured surface receptor expression (GPVI, CD42b (GPIbα), CD49 (GPIa/ITGA2), CD41/61 (ITGA2B/ITGB3; GPIIB/GPIIIA; PACI), CD62P, CD63, HLAI), thrombin generation, aggregation (collagen, adenosine diphosphate [ADP], and epinephrine activation), and viscoelastic function (ExTEM, FibTEM) in CS-PLT (Trima collection, 100% plasma) stored for 21 days either with or without agitation (Phase 1, n = 10 donor-paired units) and then without agitation with or without daily manual mixing to minimize aggregate formation and reduce potential effects of sedimentation (Phase 2, n = 10 donor-paired units)., Results: Agitation resulted in macroaggregate formation, whereas no agitation caused film-like sediment. We found no substantial differences in CS-PLT function between storage conditions, as surface receptor expression, thrombin generation, aggregation, and clot formation were relatively similar between intra-Phase storage conditions., Discussion: Storage duration and not condition impacted phenotype and function. CS-PLT can be stored with or without agitation, and with or without daily mixing and standard metrics of hemostatic function will not be significantly altered., (© 2022 AABB.)

Background: Screening for the risk of thromboembolism (TE) due to tranexamic acid (TXA) in patients with severe traumatic injury has not been performed in randomized clinical trials. Our objective was to determine if TXA dose was independently-associated with thromboembolism., Study Design and Methods: This is a secondary analysis of a single-center, double-blinded, randomized controlled trial comparing placebo to a 2-g or 4-g intravenous TXA bolus dose in trauma patients with severe injury. We used multivariable discrete-time Cox regression models to identify associations with risk for thromboembolic events within 30 days post-enrollment. Event curves were created using discrete-time Cox regression., Results: There were 50 patients in the placebo group, 49 in the 2-g, and 50 in the 4-g TXA group. In adjusted analyses for thromboembolism, a 2-g dose of TXA had an hazard ratio (HR, 95% confidence interval [CI]) of 3.20 (1.12-9.11) (p = .029), and a 4-g dose of TXA had an HR (95% CI) of 5.33 (1.94-14.63) (p = .001). Event curves demonstrated a higher probability of thromboembolism for both doses of TXA compared to placebo. Other parameters independently associated with thromboembolism include time from injury to TXA administration, body mass index, and total blood products transfused., Discussion: In patients with severe traumatic injury, there was a dose-dependent increase in the risk of at least one thromboembolic event with TXA. TXA should not be withheld, but thromboembolism screening should be considered for patients receiving a dose of at least 2-g TXA intravenously for traumatic hemorrhage., (© 2022 AABB.)

Background: While it is well recognized that different biomaterials induce thrombosis at low shear rates, the effect of high shear rates may be quite different. We hypothesize that the amount of thrombus formation on a given material can be greatly influenced by the local shear rate., Methods: We tested this hypothesis with two different whole blood perfusion loop assays to quantify biomaterial thrombogenicity as a function of shear stress. One assay uses obstructive posts (pins) of material positioned centrally in a tube perfused at high shear rate of >5000/s for 24 h. A second assay uses a parallel plate chamber to perfuse low (<150/s), medium (~500/s), and high shear rates over 96 h. We evaluated the thrombogenicity of seven different biomaterials including stainless steel, acrylic, ceramic, Dacron, polytetrafluoroethylene (PTFE), silicone, and polyvinyl chloride (PVC)., Results: For the pin assay, thrombus mass was significantly greater for stainless steel than either zirconia ceramic or acrylic (p < 0.001). Similarly, the parallel plate chamber at high shear showed that steel and PTFE (p < 0.02) occluded the chamber faster than acrylic. In contrast, a low shear parallel plate chamber revealed that stainless steel and PTFE were least thrombogenic, while silicone, Dacron, and other plastics such as acrylic were most thrombogenic. Histology revealed that high shear thrombi had a large proportion of platelets not seen in the low shear fibrin-rich thrombi., Conclusion: This differential thrombogenicity based on shear rate conditions may be important in the selection of biomaterials for blood-contacting devices., (© 2021 International Center for Artificial Organs and Transplantation and Wiley Periodicals LLC.)

Purpose: Multiparametric magnetic resonance imaging (mpMRI)-ultrasound (US) fusion-guided biopsy may improve prostate cancer (PCa) detection and reduce grade misclassification. We compared PCa detection rates on systematic, magnetic resonance imaging-targeted, and combined biopsy with evaluation of important subgroups., Materials and Methods: Men with clinical suspicion of harboring PCa from 2 institutions with visible Prostate Imaging-Reporting and Data System (PI-RADS TM v2) lesions receiving mpMRI-US fusion-guided prostate biopsy were included (2015-2020). Detection of PCa was categorized by grade group (GG). Clinically-significant PCa (csPCa) was defined as ≥GG2. Patients were stratified by biopsy setting and PI-RADS., Results: Of 1,236 patients (647 biopsy-naïve) included, 626 (50.6%) harbored PCa and 412 (33.3%) had csPCa on combined biopsy. Detection of csPCa was 27.9% vs 23.3% (+4.6%) and GG1 PCa was 11.3% vs 17.8% (-6.5%) for targeted vs systematic cores. Benefit in csPCa detection was higher in the prior negative than biopsy-naïve setting (+7.8% [p <0.0001] vs +1.7% [p=0.3]) while reduction in GG1 PCa detection remained similar (-5.6% [p=0.0002] vs -7.3% [p=0.0001]). Targeted biopsy showed increased csPCa detection for PI-RADS 5, decrease in GG1 for PI-RADS 3, and both for PI-RADS 4 relative to systematic biopsy. Combined biopsy detected more csPCa (+10.0%) and slightly fewer GG1 PCa (-0.5%) compared to systematic alone. Upgrading to ≥GG2 by targeted biopsy occurred in 9.8% with no cancer and 23.6% with GG1 on systematic biopsy., Conclusions: Combined biopsy doubled the benefit of targeted biopsy alone in detection of csPCa without increasing GG1 PCa diagnoses relative to systematic biopsy. Utility of targeted biopsy was higher in the prior negative biopsy cohort, but advantages of combined biopsy were maintained regardless of biopsy history.

Background: Men with prior negative prostate biopsies have a lower risk of being diagnosed with prostate cancer in comparison with biopsy-naive men. However, the relative clinical utility of identified lesions on multiparametric magnetic resonance imaging (mpMRI) is uncertain between the 2 settings., Methods: Patients from the Prospective Loyola University mpMRI (PLUM) Prostate Biopsy Cohort (January 2015 to June 2020) were examined. The detection of any prostate cancer and clinically significant prostate cancer (Gleason score ≥ 3 + 4) was stratified by Prostate Imaging-Reporting and Data System (PI-RADS) scores in the prior negative and biopsy-naive settings. Multivariable logistic regression models (PLUM models) assessed predictors, and decision curve analyses were used to estimate the clinical utility of PI-RADS cutoffs relative to the models., Results: Nine hundred men (420 prior negative patients and 480 biopsy-naive patients) were included. Prior negative patients had lower risks of any prostate cancer (27.9% vs 54.4%) and clinically significant prostate cancer (20.0% vs 38.3%) in comparison with biopsy-naive patients, and this persisted when they were stratified by PI-RADS (eg, PI-RADS 3: 13.6% vs 27.4% [any prostate cancer] and 5.2% vs 15.4% [clinically significant prostate cancer]). The rate of detection of clinically significant prostate cancer was 5.3% among men with prior negative biopsy and PI-RADS ≤ 3. Family history and Asian ancestry were significant predictors among biopsy-naive patients. PLUM models demonstrated a greater net benefit and reduction in biopsies (45.8%) without missing clinically significant cancer in comparison with PI-RADS cutoffs (PI-RADS 4: 34.0%)., Conclusions: Patients with prior negative biopsies had lower prostate cancer detection by PI-RADS score category in comparison with biopsy-naive men. Decision curve analyses suggested that many biopsies could be avoided by the use of the PLUM models or a PI-RADS 4 cutoff without any clinically significant cancer being missed., Lay Summary: Men with a prior negative prostate biopsy had a lower risk of harboring prostate cancer in comparison with those who never had a biopsy. This was true even when patients in each group had similar multiparametric magnetic resonance imaging (mpMRI) findings in terms of Prostate Imaging-Reporting and Data System (PI-RADS)-graded lesions. Decision curve analyses showed that many biopsies could be avoided by the use of the Prospective Loyola University mpMRI prediction models or a PI-RADS 4 cutoff for patients with prior negative biopsies., (© 2021 American Cancer Society.)

Given the extensive and routine use of cardiovascular devices, a major limiting factor to their success is the thrombotic rate that occurs. This both poses direct risk to the patient and requires counterbalancing with anticoagulation and other treatment strategies, contributing additional risks. Developing a better understanding of the mechanisms of device-induced thrombosis to aid in device design and medical management of patients is critical to advance the ubiquitous use and durability. Thus, mathematical and computational modelling of device-induced thrombosis has received significant attention recently, but challenges remain. Additional areas that need to be explored include microscopic/macroscopic approaches, reconciling physical and numerical timescales, immune/inflammatory responses, experimental validation, and incorporating pathologies and blood conditions. Addressing these areas will provide engineers and clinicians the tools to provide safe and effective cardiovascular devices., Competing Interests: Declaration of Interest None