Thromboembolism after treatment with 4-factor prothrombin complex concentrate or plasma for warfarin-related bleeding.

Limited data exist in large, representative populations about whether the risk of thromboembolic events varies after receiving four-factor human prothrombin complex concentrate (4F-PCC) versus treatment with human plasma for urgent reversal of oral vitamin K antagonist therapy. We conducted a multicenter observational study to compare the 45-day risk of thromboembolic events in adults with warfarin-associated major bleeding after treatment with 4F-PCC (Kcentra®) or plasma. Hospitalized patients in two large integrated healthcare delivery systems who received 4F-PCC or plasma for reversal of warfarin due to major bleeding from January 1, 2008 to March 31, 2020 were identified and were matched 1:1 on potential confounders and a high-dimensional propensity score. Arterial and venous thromboembolic events were identified up to 45 days after receiving 4F-PCC or plasma from electronic health records and adjudicated by physician review. Among 1119 patients receiving 4F-PCC and a matched historical cohort of 1119 patients receiving plasma without a recent history of thromboembolism, mean (SD) age was 76.7 (10.5) years, 45.6% were women, and 9.4% Black, 14.6% Asian/Pacific Islander, and 15.7% Hispanic. The 45-day risk of thromboembolic events was 3.4% in those receiving 4F-PCC and 4.1% in those receiving plasma (P = 0.26; adjusted hazard ratio 0.76; 95% confidence interval 0.49-1.16). The adjusted risk of all-cause death at 45 days post-treatment was lower in those receiving 4F-PCC compared with plasma. Among a large, ethnically diverse cohort of adults treated for reversal of warfarin-associated bleeding, receipt of 4F-PCC was not associated with an excess risk of thromboembolic events at 45 days compared with plasma therapy.

Hyperspectral imaging of nanoparticles in biological samples: Simultaneous visualization and elemental identification.

While engineered nanomaterials (ENMs) are increasingly incorporated into industrial processes and consumer products, the potential biological effects and health outcomes of exposure remain unknown. Novel advanced direct visualization techniques that require less time, cost, and resource investment than electron microscopy (EM) are needed for identifying and locating ENMs in biological samples. Hyperspectral imaging (HSI) combines spectrophotometry and imaging, using advanced optics and algorithms to capture a spectrum from 400 to 1000 nm at each pixel in an enhanced dark-field microscopic (EDFM) image. HSI-EDFM can be used to confirm the identity of the materials of interest in a sample and generate an image "mapping" their presence and location in a sample. Hyperspectral mapping is particularly important for biological samples, where ENM morphology is visually indistinct from surrounding tissue structures. While use of HSI (without mapping) is increasing, no studies to date have compared results from hyperspectral mapping with conventional methods. Thus, the objective of this study was to utilize EDFM-HSI to locate, identify, and map metal oxide ENMs in ex vivo histological porcine skin tissues, a toxicological model of cutaneous exposure, and compare findings with those of Raman spectroscopy (RS), energy-dispersive X-ray spectroscopy (EDS), and scanning electron microscopy (SEM). Results demonstrate that EDFM-HSI mapping is capable of locating and identifying ENMs in tissue, as confirmed by conventional methods. This study serves as initial confirmation of EDFM-HSI mapping as a novel and higher throughput technique for ENM identification in biological samples, and serves as the basis for further protocol development utilizing EDFM-HSI for semiquantitation of ENMs.

Optimizing the experimental design for ankle dorsiflexion fMRI.

Compared to motor studies of the upper limb, few experiments have sought a relationship between blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) sensorimotor signals and the resulting lower limb output. In Experiment 1, using an fMRI simulator system, we determined the optimized experimental protocol based on two design types and four behavioral movement types during ankle dorsiflexion. Experiment 2 involved testing the BOLD sensitivity at 1.5 T during ankle movements. Subjects performed large- and small-amplitude dorsiflexion movement types using an event-related design, with the intent of contrasting spatial and temporal features of the BOLD signal. In both experiments, the subject's behavior was guided by visual biofeedback of their ankle flexion angle, using an MR-compatible fiberoptic tape. From Experiment 1, we found electromyography (EMG) difference voltage ratio of approximately 2:1 for large (40 degrees ) and small (15 degrees ) dorsiflexion, 0.13 mV and 0.07 mV, respectively. In Experimental 2, we found the peak BOLD % signal changes of 1.04% and 0.89%, for large (40 degrees ) and small (15 degrees ) dorsiflexion, respectively. In addition, graded dorsiflexion produced graded BOLD signals in the primary sensorimotor and supplementary motor areas in 10 of 12 healthy young subjects, attesting to the feasibility of lower-limb fMRI at 1.5 T. This study provides insight into the cortical network involved in dorsiflexion using an experimental paradigm that is likely to translate effectively to hemiparetic stroke subjects.