Large-scale real-world data analysis of source plasma collections using a novel technology-enabled nomogram.

BACKGROUND: Source plasma collections are needed to satisfy the growing demand for plasma-derived medicinal products. The US plasma collection target volume has been guided by a standard weight-based FDA-issued nomogram (STAN) since 1992. In this research, large-scale US-based real-world data (RWD) were analyzed to confirm the safety and volume gains of a newly introduced personalized nomogram (PERS) that was previously studied in a premarket randomized controlled environment. STUDY DESIGN AND METHODS: A non-inferiority (NI) analysis was conducted to compare the novel nomogram's significant hypotensive adverse event (AE) incidence rate with large historical standard nomogram AE datasets. Additionally, the average target volumes and donor return rates were compared for collections following PERS and STAN. RESULTS: A total of 4,816,784 donations (PERS) by 414,957 donors resulted in a rate of 0.0998% (95% CI [0.0970, 0.1027]) significant hypotensive AEs. NI analysis suggested strong non-inferiority of the new technology (Δ = -0.0082%, 95% CI [-0.0113, -0.0050], prespecified NI margin = 0.1080). Average plasma collection target volumes increased by 66.39 mL (8.49%; p < .0001). Consecutive weekly donor return rates were consistent between the two nomograms (PERS: 73.6%, 95% CI [69.6%-76.7%]; STAN: 74.1%, 95% CI [66.1%-77.2%]). DISCUSSION: This analysis confirms in a large-scale real-world dataset the key safety parameter and collection benefit of a novel, technology-enabled nomogram. The nomogram may help meet the growing demand for plasma-derived therapies by providing approximately 8.5% more plasma per donation on average while maintaining donor safety and return rates.

DI-5-Cuffs: Lumbar Intervertebral Disc Proteoglycan and Water Content Changes in Humans after Five Days of Dry Immersion to Simulate Microgravity.

Most astronauts experience back pain after spaceflight, primarily located in the lumbar region. Intervertebral disc herniations have been observed after real and simulated microgravity. Spinal deconditioning after exposure to microgravity has been described, but the underlying mechanisms are not well understood. The dry immersion (DI) model of microgravity was used with eighteen male volunteers. Half of the participants wore thigh cuffs as a potential countermeasure. The spinal changes and intervertebral disc (IVD) content changes were investigated using magnetic resonance imaging (MRI) analyses with T1-T2 mapping sequences. IVD water content was estimated by the apparent diffusion coefficient (ADC), with proteoglycan content measured using MRI T1-mapping sequences centered in the nucleus pulposus. The use of thigh cuffs had no effect on any of the spinal variables measured. There was significant spinal lengthening for all of the subjects. The ADC and IVD proteoglycan content both increased significantly with DI (7.34 ± 2.23% and 10.09 ± 1.39%, respectively; mean ± standard deviation), p < 0.05). The ADC changes suggest dynamic and rapid water diffusion inside IVDs, linked to gravitational unloading. Further investigation is needed to determine whether similar changes occur in the cervical IVDs. A better understanding of the mechanisms involved in spinal deconditioning with spaceflight would assist in the development of alternative countermeasures to prevent IVD herniation.

TEG® 6s coagulation testing with a novel heparin neutralization cartridge: Technical validation and determination of normal reference ranges.

OBJECTIVES: We sought to establish normal reference ranges (NRRs) for a novel TEG 6s cartridge (TEG 6s Citrated: K, KH, RTH, FFH [Global Hemostasis]) (Haemonetics Corporation, Boston, MA, US). METHODS: Healthy volunteers (≥18 years of age) included in this single-arm study provided single samples of whole blood. Primary end points included TEG parameters in the citrated kaolin (CK), CK with heparinase (CKH), RapidTEG with heparinase (CRTH), and functional fibrinogen with heparinase (CFFH) assays. RESULTS: Evaluable data were contributed by 164 volunteers (48.8% female; 62% White/Caucasian). The following NRRs were established: CK maximum amplitude (MA), 51.0 to 67.6 mm; CKH-MA, 51.8 to 67.9 mm; CRTH-MA, 53.0 to 68.9 mm; CFFH-MA, 15.3 to 34.4 mm; CK reaction time, 5.0 to 9.1 minutes; CKH reaction time, 4.9 to 9.4 minutes; CKH lysis 30 minutes after MA, 0% to 3.2%. Duplicate measurements demonstrated high reproducibility. CFFH-MA correlated with Clauss fibrinogen concentration (Pearson correlation coefficient, 0.74). Laboratory-based studies demonstrated maintenance of the relationship between CFFH-MA and fibrinogen up to 1344 mg/dL (hyperfibrinogenemic samples) and acceptability of heparin neutralization up to concentrations of low molecular weight and unfractionated heparin of 1.3 IU/mL and 5 IU/mL, respectively. CONCLUSIONS: This study established NRRs for the Global Hemostasis cartridge and serves as a proof of concept for the validity of results obtained using this cartridge.

First combined in vivo X-ray tomography and high-resolution molecular electron paramagnetic resonance (EPR) imaging of the mouse knee joint taking into account the disappearance kinetics of the EPR probe.

Although laboratory data clearly suggest a role for oxidants (dioxygen and free radicals derived from dioxygen) in the pathogenesis of many age-related and degenerative diseases (such as arthrosis and arthritis), methods to image such species in vivo are still very limited. This methodological problem limits physiopathologic studies about the role of those species in vivo, the effects of their regulation using various drugs, and the evaluation of their levels for diagnosis of degenerative diseases. In vivo electron paramagnetic resonance (EPR) imaging and spectroscopy are unique, noninvasive methods used to specifically detect and quantify paramagnetic species. However, two problems limit their application: the anatomic location of the EPR image in the animal body and the relative instability of the EPR probes. Our aim is to use EPR imaging to obtain physiologic and pathologic information on the mouse knee joint. This article reports the first in vivo EPR image of a small tissue, the mouse knee joint, with good resolution (≈ 160 µm) after intra-articular injection of a triarylmethyl radical EPR probe. It was obtained by combining EPR and x-ray micro-computed tomography for the first time and by taking into account the disappearance kinetics of the EPR probe during image acquisition to reconstruct the image. This multidisciplinary approach opens the way to high-resolution EPR imaging and local metabolism studies of radical species in vivo in different physiologic and pathologic situations.

Intervertebral Disc Swelling Demonstrated by 3D and Water Content Magnetic Resonance Analyses after a 3-Day Dry Immersion Simulating Microgravity.

Background: Vertebral deconditioning is commonly experienced after space flight and simulation studies. Disc herniation is quadrupled after space flight. Purpose: The main hypothesis formulated by the authors is that microgravity results in intervertebral disc (IVD) swelling. Study Design: The aim of the study was to identify the morphological changes of the spine and their clinical consequences after simulated microgravity by 3-day dry immersion (DI). The experimental protocol was performed on 12 male volunteers using magnetic resonance imaging and spectroscopy before and after DI. Methods: All the experiment was financially supported by CNES (Centre national d'études spatiales i.e., French Space Agency). Results: We observed an increase in spine height of 1.5 ± 0.4 cm and a decrease in curvature, particularly for the lumbar region with a decrease of -4 ± 2.5°. We found a significant increase in IVD volume of +8 ± 9% at T12-L1 and +11 ± 9% at L5-S1. This phenomenon is likely associated with the increase in disc intervertebral water content (IWC), 17 ± 27%. During the 3 days in DI, 92% of the subjects developed back pain in the lumbar region below the diaphragmatic muscle. This clinical observation may be linked to the morphological changes of the spine. Conclusions: The morphological changes observed and, specifically, the disc swelling caused by increased IWC may contribute to understanding disc herniation after microgravity exposure. Our results confirmed the efficiency of the 3-day DI model to reproduce quickly the effects of microgravity on spine morphology. Our findings raise the question of the subject selection in spatial studies, especially studies about spine morphology and reconditioning programs after space flight. These results may contribute to a better understanding of the mechanisms underlying disc herniation and may serve as the basis to develop countermeasures for astronauts and to prevent IVD herniation and back pain on Earth.