A Randomized Comparison of Radial Artery Intimal Hyperplasia Following Distal Versus Proximal Transradial Access for Coronary Angiography: PRESERVE RADIAL.

BACKGROUND: Distal transradial access (dTRA) is an alternative to conventional forearm transradial access (fTRA) for coronary angiography (CAG). Differences in healing of the radial artery (RA) in the forearm have not been evaluated between these 2 access strategies. We sought to compare the mean difference in forearm RA intimal-medial thickening (IMT) in patients randomized to dTRA versus fTRA. METHODS AND RESULTS: In this single-center randomized clinical trial, 64 patients undergoing nonemergent CAG were randomized (1:1) to dTRA versus fTRA. Ultra-high-resolution (55-MHz) vascular ultrasound of the forearm and distal RA was performed pre-CAG and at 90 days. The primary end point was the mean change in forearm RA IMT. Secondary end points included procedural characteristics, vascular injury, RA occlusion, and ipsilateral hand pain and function. Baseline demographics and clinical characteristics, mean forearm RA IMT, and procedural specifics were similar between the dTRA and fTRA cohorts. There was no difference in mean change in forearm RA IMT between the 2 cohorts (0.07 versus 0.07 mm; P=0.37). No RA occlusions or signs of major vascular injury were observed at 90 days. Ipsilateral hand pain and function (Borg pain scale score: 12 versus 11; P=0.24; Disabilities of the Arm, Shoulders, and Hand scale score: 6 versus 8; P=0.46) were comparable. CONCLUSIONS: Following CAG, dTRA was associated with no differences in mean change of forearm RA IMT, hand pain, and function versus fTRA for CAG. Further investigation is warranted to elucidate mechanisms and predictors of RA healing and identify effective strategies to preserving RA integrity for repeated procedures. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04801901.

Time Thresholds for Using Pressure Reactivity Index in Neuroprognostication for Patients With Severe Traumatic Brain Injury.

BACKGROUND AND OBJECTIVES: Severe traumatic brain injury (sTBI) represents a diffuse, heterogeneous disease where therapeutic targets for optimizing clinical outcome remain unclear. Mean pressure reactivity index (PRx) values have demonstrated associations with clinical outcome in sTBI. However, the retrospective derivation of a mean value diminishes its bedside significance. We evaluated PRx temporal profiles for patients with sTBI and identified time thresholds suggesting optimal neuroprognostication. METHODS: Patients with sTBI and continuous bolt intracranial pressure monitoring were identified. Outcomes were dichotomized by disposition status ("good outcome" was denoted by home and acute rehabilitation). PRx values were obtained every minute by taking moving correlation coefficients of intracranial pressures and mean arterial pressures. Average PRx trajectories for good and poor outcome groups were calculated by extending the last daily averaged PRx value to day 18. Each patient also had smoothed PRx trajectories that were used to generate "candidate features." These "candidate features" included daily average PRx's, cumulative first-order changes in PRx and cumulative second-order changes in PRx. Changes in sensitivity over time for predicting poor outcome was then evaluated by generating penalized logistic regression models that were derived from the "candidate features" and maximized specificity. RESULTS: Among 33 patients with sTBI, 18 patients achieved good outcome and 15 patients had poor outcome. Average PRx trajectories for the good and poor outcome groups started on day 6 and consistently diverged at day 9. When targeting a specificity >83.3%, an 85% maximum sensitivity for determining poor outcome was achieved at hospital day 6. Subsequent days of PRx monitoring showed diminishing sensitivities. CONCLUSION: Our findings suggest that in a population of sTBI, PRx sensitivities for predicting poor outcome was maximized at hospital day 6. Additional study is warranted to validate this model in larger populations.

Recording animal-view videos of the natural world using a novel camera system and software package.

Plants, animals, and fungi display a rich tapestry of colors. Animals, in particular, use colors in dynamic displays performed in spatially complex environments. Although current approaches for studying colors are objective and repeatable, they miss the temporal variation of color signals entirely. Here, we introduce hardware and software that provide ecologists and filmmakers the ability to accurately record animal-perceived colors in motion. Specifically, our Python codes transform photos or videos into perceivable units (quantum catches) for animals of known photoreceptor sensitivity. The plans and codes necessary for end-users to capture animal-view videos are all open source and publicly available to encourage continual community development. The camera system and the associated software package will allow ecologists to investigate how animals use colors in dynamic behavioral displays, the ways natural illumination alters perceived colors, and other questions that remained unaddressed until now due to a lack of suitable tools. Finally, it provides scientists and filmmakers with a new, empirically grounded approach for depicting the perceptual worlds of nonhuman animals.

Whole blood coagulation in an ex vivo thrombus is sufficient to induce clot neutrophils to adopt a myeloid-derived suppressor cell signature and shed soluble Lox-1.

BACKGROUND: Blood clots are living tissues that release inflammatory mediators including IL-8/CXCL8 and MCP-1/CCL2. A deeper understanding of blood clots is needed to develop new therapies for prothrombotic disease states and regenerative medicine. OBJECTIVES: To identify a common transcriptional shift in cultured blood clot leukocytes. METHODS: Differential gene expression of whole blood and cultured clots (4 hours at 37 °C) was assessed by RNA sequencing (RNAseq), reverse transcriptase-polymerase chain reaction, proteomics, and histology (23 diverse healthy human donors). Cultured clot serum bioactivity was tested in endothelial barrier functional assays. RESULTS: All cultured clots developed a polymorphonuclear myeloid-derived suppressor cell (PMN-MDSC) signature, including up-regulation of OLR1 (mRNA encoding lectin-like oxidized low-density lipoprotein receptor 1 [Lox-1]), IL-8/CXCL8, CXCL2, CCL2, IL10, IL1A, SPP1, TREM1, and DUSP4/MKP. Lipopolysaccharide enhanced PMN-MDSC gene expression and specifically induced a type II interferon response with IL-6 production. Lox-1 was specifically expressed by cultured clot CD15+ neutrophils. Cultured clot neutrophils, but not activated platelets, shed copious amounts of soluble Lox-1 (sLox-1) with a donor-dependent amplitude. sLox-1 shedding was enhanced by phorbol ester and suppressed by heparin and by beta-glycerol phosphate, a phosphatase inhibitor. Cultured clot serum significantly enhanced endothelial cell monolayer barrier function, consistent with a proresolving bioactivity. CONCLUSION: This study suggests that PMN-MDSC activation is part of the innate immune response to coagulation which may have a protective role in inflammation. The cultured blood clot is an innovative thrombus model that can be used to study both sterile and nonsterile inflammatory states and could be used as a personalized medicine tool for drug screening.

A Randomized Comparison of Radial Artery Intimal Hyperplasia Following Distal vs. Proximal Transradial Access for Coronary Angiography: PRESERVE RADIAL Trial.

Background: Distal transradial access (dTRA) is an alternative to conventional forearm transradial access (fTRA) for coronary angiography (CAG). Differences in healing of the radial artery in the forearm (FRA) have not been evaluated between these 2 access strategies. We sought to compare FRA intimal-medial thickening (IMT) in patients randomized to dTRA vs. fTRA for CAG. Methods and Results: Sixty-four consecutive patients undergoing non-emergent CAG were randomized (1:1) to dTRA vs. fTRA. Ultrahigh resolution (55 MHz) vascular ultrasound) of the FRA and distal RA was performed pre-CAG and at 90 days. Primary endpoint was 90-day FRA IMT. Secondary endpoints included procedural characteristics, vascular injury, RA occlusion and ipsilateral hand pain and function. Baseline demographics and clinical characteristics, mean FRA IMT, time to RA access, procedure time, and radiation exposure were similar between the dTRA and fTRA cohorts. There were no between group differences in 90-day FRA IMT (0.37 mm vs 0.38 mm, respectively; p =0.73). No RA occlusions or signs of major vascular injury were observed at 90 days. Ipsilateral hand pain and function (Borg pain scale:12 vs 11, p =0.24; DASH scores: 6 vs 8, p =0.46) were comparable. Conclusions: In this single center randomized clinical trial, similar patterns of FRA vascular healing at 90 days, procedural results as well as hand pain and function were observed following dTRA vs. fTRA for CAG. Further investigation is warranted to better understand the mechanistics and predictors of RA healing and to identify strategies aimed at preserving RA integrity for future procedures. What is New?: DTRA has been proposed as an alternative to traditional fTRA in the wrist for CAG and PCI because of ergonomic and post-procedural recovery benefits to the patient, as well as potential reductions in occlusion of the FRA.There are gaps in knowledge, however, regarding potential differences in remodeling of the FRA in patients undergoing dTRA versus fTRA.In this randomized clinical trial, there were no differences in IMT and patterns of vascular injury and healing, using ultrahigh resolution (55 MHz) ultrasound, at 90 days in patients randomized to dTRA or FTRA for elective and non-emergent CAG and PCI. What Are the Clinical Implications: Our findings highlight the need for further inquiry through large multicenter randomized clinical trials to better the understand the mechanistics and predictors of IMT and to identify strategies to mitigate the adverse effects of vessel remodeling in patients undergoing TRA across the entire severity spectrum of cardiovascular disease.

Pressure reactivity index for early neuroprognostication in poor-grade subarachnoid hemorrhage.

BACKGROUND: Pressure reactivity index (PRx) utilizes moving correlation coefficients from intracranial pressure (ICP) and mean arterial pressures to evaluate cerebral autoregulation. We evaluated patients with poor-grade subarachnoid hemorrhage (SAH), identified their PRx trajectories over time, and identified threshold time points where PRx could be used for neuroprognostication. METHODS: Patients with poor-grade SAH were identified and received continuous bolt ICP measurements. Dichotomized outcomes were based on ninety-day modified Rankin scores and disposition. Smoothed PRx trajectories for each patient were created to generate "candidate features" that looked at daily average PRx, cumulative first-order changes in PRx, and cumulative second-order changes in PRx. "Candidate features" were then used to perform penalized logistic regression analysis using poor outcome as the dependent variable. Penalized logistic regression models that maximized specificity for poor outcome were generated over several time periods and evaluated how sensitivities changed over time. RESULTS: 16 patients with poor-grade SAH were evaluated. Average PRx trajectories for the good (PRx < 0.25) and poor outcome groups (PRx > 0.5) started diverging at post-ictus day 8. When targeting specificities ≥88% for poor outcome, sensitivities for poor outcome consistently increased to >70% starting at post-ictus days 12-14 with a maximum sensitivity of 75% occurring at day 18. CONCLUSIONS: Our results suggest that by using PRx trends, early neuroprognostication in patients with SAH and poor clinical exams may start becoming apparent at post-ictus day 8 and reach adequate sensitivities by post-ictus days 12-14. Further study is required to validate this in larger poor-grade SAH populations.

Robust Prediction and Protein Selection with Adaptive PENSE.

Adaptive PENSE is a method that can be used to build models for predicting clinical outcomes from a small subset of a potentially large number of candidate proteins. Adaptive PENSE is designed to give reliable results under two common challenges often encountered in these kinds of studies: (1) the number of samples with known clinical outcome and proteomic data is small, while the number of candidate proteins is large and/or (2) proteomic data and the clinical outcome measurements suffer from data quality issues in a small fraction of samples. Even in the presence of these challenges, adaptive PENSE reliably identifies proteins relevant for prediction and estimates accurate predictive models. Adaptive PENSE is designed to be resilient to data quality issues in up to 50% of samples. Almost half of the samples could have aberrant values in the measured protein levels and clinical outcome values without causing severe detrimental effects to the estimated predictive model. The method is implemented as an R package and supports the user in the model selection process by automating most steps and providing diagnostic visualizations to guide the user. Users can choose among several predictive models to select the model with high prediction accuracy and an appropriate number of selected proteins.

PGCA: An algorithm to link protein groups created from MS/MS data.

The quantitation of proteins using shotgun proteomics has gained popularity in the last decades, simplifying sample handling procedures, removing extensive protein separation steps and achieving a relatively high throughput readout. The process starts with the digestion of the protein mixture into peptides, which are then separated by liquid chromatography and sequenced by tandem mass spectrometry (MS/MS). At the end of the workflow, recovering the identity of the proteins originally present in the sample is often a difficult and ambiguous process, because more than one protein identifier may match a set of peptides identified from the MS/MS spectra. To address this identification problem, many MS/MS data processing software tools combine all plausible protein identifiers matching a common set of peptides into a protein group. However, this solution introduces new challenges in studies with multiple experimental runs, which can be characterized by three main factors: i) protein groups' identifiers are local, i.e., they vary run to run, ii) the composition of each group may change across runs, and iii) the supporting evidence of proteins within each group may also change across runs. Since in general there is no conclusive evidence about the absence of proteins in the groups, protein groups need to be linked across different runs in subsequent statistical analyses. We propose an algorithm, called Protein Group Code Algorithm (PGCA), to link groups from multiple experimental runs by forming global protein groups from connected local groups. The algorithm is computationally inexpensive and enables the connection and analysis of lists of protein groups across runs needed in biomarkers studies. We illustrate the identification problem and the stability of the PGCA mapping using 65 iTRAQ experimental runs. Further, we use two biomarker studies to show how PGCA enables the discovery of relevant candidate protein group markers with similar but non-identical compositions in different runs.