Association of Metal Cations with the Anti-PF4/Heparin Antibody Response in Heparin-Induced Thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is an antibody-mediated immune response against complexes of heparin and platelet factor 4 (PF4). The electrostatic interaction between heparin and PF4 is critical for the anti-PF4/heparin antibody response seen in HIT. The binding of metal cations to heparin induces conformational changes and charge neutralization of the heparin molecule, and cation-heparin binding can modulate the specificity and affinity for heparin-binding partners. However, the effects of metal cation binding to heparin in the context of anti-PF4/heparin antibody response have not been determined. Here, we utilized inductively coupled plasma mass spectrometry (ICP-MS) to quantify 16 metal cations in patient plasma and tested for correlation with anti-PF4/heparin IgG levels and platelet count after clinical suspicion of HIT in a cohort of heparin-treated patients. The average age of the cohort (n = 32) was 60.53 (SD = 14.31) years old, had a mean anti-PF4/heparin antibody optical density [OD 405 ] of 0.93 (SD = 1.21) units and was primarily female (n = 23). Patients with positive anti-PF4/heparin antibody test results (OD 405 ≥ 0.5 units) were younger, had increased weight and BMI, and were more likely to have a positive serotonin release assay (SRA) result compared to antibody negative patients. We observed statistical differences between antibody positive and negative groups for sodium and aluminum and significant correlations of anti-PF4/heparin antibody levels with sodium and silver. While differences in sodium concentrations were associated with antibody positive status and correlated with antibody levels, no replication was performed. Additional studies are warranted to confirm our observed association, including in vitro binding studies and larger observational cohorts.

White Matter Hyperintensities and Microstructural Alterations in Contact Sport Athletes from Adolescence to Early Midlife.

Studies have demonstrated associations between cumulative concussion and repetitive head impact exposure (RHI) via contact sports with white matter (WM) alterations later in life. The course of WM changes associated with exposure earlier in the lifespan are unclear. This study investigated alterations in white matter (WM hyperintensity [WMH] volume and microstructural changes) associated with concussion and RHI exposure from adolescence to early midlife, as well as the interaction between exposure and age-cohort (i.e., adolescent/young adult compared to early midlife athlete cohorts) on WM outcomes. Participating football players included an adolescent/young adulthood cohort (n=82; Mage=18.41.7) and an early midlife cohort (37 former collegiate players approximately 15-years removed from sport; Mage=37.71.4). Years of football participation and number of prior concussions were exposures of interest. White matter outcomes included log-transformed manually segmented total WMH volume and neurite orientation dispersion and density imaging metrics of microstructure/organization (isotropic volume fraction[Viso], intra-cellular volume fraction[Vic], and orientation dispersion[OD]). Regression models were fit to test effects of concussion history, years of football participation, and age-cohort by years of football participation with WM outcomes. Spearman's correlations assessed associations between significant WM metrics and measures of cognitive and psychological function. A significant age-cohort by years of participation effect was observed for whole brain white matter OD, B=-0.002, SE=0.001, p=0.001. The interaction was driven by a negative association between years of participation and OD within the younger cohort, B=-0.001, SE=0.0004, p=0.008, whereas a positive association between participation and OD in the early midlife cohort, B=0.001, SE=0.0003, p=0.039, was observed. Follow-up ROI analyses showed significant interaction effects for OD in the body of the corpus callosum, genu of the corpus callosum, cingulum, inferior fronto-occipital fasciculus, superior longitudinal fasciculus, posterior thalamic radiation (ps<0.05). Greater concussion history was significantly associated with greater Viso in the early midlife cohort, B=0.001, SE= 0.0002, p=0.010. Years of participation and concussion history were not associated with WMH volume, ps>0.05. Performance on a measure of executive function was significantly associated with years of participation, =.34, p=.04, and a trend was observed for OD, =.28, p=.09 in the early midlife cohort only. The global characterization of white matter changes associated with years of football participation were broadly similar and stable from adolescence through early midlife (i.e., microstructural alterations, but not macroscopic lesions). An inverse association between years of participation and orientation dispersion across age-cohorts may represent a process of initial recovery/reorganization proximal to sport, followed by later reduction of white matter coherence.

Iterative eigensolver using fixed-point photonic primitive.

Photonic computing has potential advantages in speed and energy consumption yet is subject to inaccuracy due to the limited equivalent bitwidth of the analog signal. In this Letter, we demonstrate a configurable, fixed-point coherent photonic iterative solver for numerical eigenvalue problems using shifted inverse iteration. The photonic primitive can accommodate arbitrarily sized sparse matrix-vector multiplication and is deployed to solve eigenmodes in a photonic waveguide structure. The photonic iterative eigensolver does not accumulate errors from each iteration, providing a path toward implementing scientific computing applications on photonic primitives.

Contemporary Management and Outcomes of Patients With High-Risk Pulmonary Embolism.

BACKGROUND: Contemporary care patterns/outcomes in high-risk pulmonary embolism (PE) patients are unknown. OBJECTIVES: This study sought to characterize the management of high-risk PE patients and identify factors associated with poor outcomes. METHODS: A retrospective analysis of the PERT (Pulmonary Embolism Response Team) Consortium Registry was performed. Patients presenting with intermediate-risk PE, high-risk PE, and catastrophic PE (those with hemodynamic collapse) were identified. Patient characteristics were compared with chi-square testing for categorical covariates and Student's t-test for continuous covariates. Multivariable logistic regression was used to assess associations between clinical characteristics and outcomes in the high-risk population. RESULTS: Of 5,790 registry patients, 2,976 presented with intermediate-risk PE and 1,442 with high-risk PE. High-risk PE patients were more frequently treated with advanced therapies than intermediate-risk PE patients (41.9% vs 30.2%; P < 0.001). In-hospital mortality (20.6% vs 3.7%; P < 0.001) and major bleeding (10.5% vs. 3.5%; P < 0.001) were more common in high-risk PE. Multivariable regression analysis demonstrated vasopressor use (OR: 4.56; 95% CI: 3.27-6.38; P < 0.01), extracorporeal membrane oxygenation use (OR: 2.86; 95% CI: 1.12-7.30; P = 0.03), identified clot-in-transit (OR: 2.26; 95% CI: 1.13-4.52; P = 0.02), and malignancy (OR: = 1.70; 95% CI: 1.13-2.56; P = 0.01) as factors associated with in-hospital mortality. Catastrophic PE patients (n = 197 [13.7% of high-risk PE patients]) had higher in-hospital mortality (42.1% vs 17.2%; P < 0.001) than those presenting with noncatastrophic high-risk PE. Extracorporeal membrane oxygenation (13.3% vs. 4.8% P < 0.001) and systemic thrombolysis (25% vs 11.3%; P < 0.001) were used more commonly in catastrophic PE. CONCLUSIONS: In the largest analysis of high-risk PE patients to date, mortality rates were high with the worst outcomes among patients with hemodynamic collapse.

Accelerated fixed-point iterative reconstruction for fiber borescope imaging.

Computational imaging systems with embedded processing have potential advantages in power consumption, computing speed, and cost. However, common processors in embedded vision systems have limited computing capacity and low level of parallelism. The widely used iterative algorithms for image reconstruction rely on floating-point processors to ensure calculation precision, which require more computing resources than fixed-point processors. Here we present a regularized Landweber fixed-point iterative solver for image reconstruction, implemented on a field programmable gated array (FPGA). Compared with floating-point embedded uniprocessors, iterative solvers implemented on the fixed-point FPGA gain 1 to 2 orders of magnitude acceleration, while achieving the same reconstruction accuracy in comparable number of effective iterations. Specifically, we have demonstrated the proposed fixed-point iterative solver in fiber borescope image reconstruction, successfully correcting the artifacts introduced by the lenses and fiber bundle.

Focused transoesophageal TOE (fTOE): A new accreditation pathway.

The concept of a focused ultrasound study to identify sources of haemodynamic instability has revolutionized patient care. Point-of-care ultrasound (POCUS) using transthoracic scanning protocols, such as FUSIC Heart, has empowered non-cardiologists to rapidly identify and treat the major causes of haemodynamic instability. There are, however, circumstances when a transoesphageal, rather than transthoracic approach, may be preferrable. Due to the close anatomical proximity between the oesophagus, stomach and heart, a transoesphageal echocardiogram (TOE) can potentially overcome many of the limitations encountered in patients with poor transthoracic ultrasound windows. These are typically patients with severe obesity, chest wall injuries, inability to lie in the left lateral decubitus position and those receiving high levels of positive airway pressure. In 2022, to provide all acute care practitioners with the opportunity to acquire competency in focused TOE, the Intensive Care Society (ICS) and Association of Anaesthetists (AA) launched a new accreditation pathway, known as Focused Transoesophageal Echo (fTOE). The aim of fTOE is to provide the practitioner with the necessary information to identify the aetiology of haemodynamic instability. Focused TOE can be taught in a shorter period of time than comprehensive and teaching programmes are achievable with support from cardiothoracic anaesthetists, intensivists and cardiologists. Registration for fTOE accreditation requires registration via the ICS website. Learning material include theoretical modules, clinical cases and multiple-choice questions. Fifty fTOE examinations are required for the logbook, and these must cover a range of pathology, including ventricular dysfunction, pericardial effusion, tamponade, pleural effusion and low preload. The final practical assessment may be undertaken when the supervisors deem the candidate's knowledge and skills consistent with that required for independent practice. After the practitioner has been accredited in fTOE, they must maintain knowledge and competence through relevant continuing medical education. Accreditation in fTOE represents a joint venture between the ICS and AA and is endorsed by Association of Cardiothoracic Anaesthesia and Critical care (ACTACC). The process is led by TOE experts, and represents a valuable expansion in the armamentarium of acute care practitioners to assess haemodynamically unstable patients.

Diffusion-weighted MRI of the spinal cord in cervical spondylotic myelopathy after instrumented fusion.

Introduction: This study investigated tissue diffusion properties within the spinal cord of individuals treated for cervical spondylotic myelopathy (CSM) using post-decompression stabilization hardware. While previous research has indicated the potential of diffusion-weighted MRI (DW-MRI) markers of CSM, the metallic implants often used to stabilize the decompressed spine hamper conventional DW-MRI. Methods: Utilizing recent developments in DW-MRI metal-artifact suppression technologies, imaging data was acquired from 38 CSM study participants who had undergone instrumented fusion, as well as asymptomatic (non-instrumented) control participants. Apparent diffusion coefficients were determined in axial slice sections and split into four categories: a) instrumented levels, b) non-instrumented CSM levels, c) adjacent-segment (to instrumentation) CSM levels, and d) non-instrumented control levels. Multi-linear regression models accounting for age, sex, and body mass index were used to investigate ADC measures within each category. Furthermore, the cord diffusivity within CSM subjects was correlated with symptom scores and the duration since fusion procedures. Results: ADC measures of the spinal cord in CSM subjects were globally reduced relative to control subjects (p = 0.005). In addition, instrumented levels within the CSM subjects showed reduced diffusivity relative to controls (p = 0.003), while ADC within non-instrumented CSM levels did not statistically deviate from control levels (p = 0.107). Discussion: Multi-spectral DW-MRI technology can be effectively employed to evaluate cord diffusivity near fusion hardware in subjects who have undergone surgery for CSM. Leveraging this advanced technology, this study had identified significant reductions in cord diffusivity, relative to control subjects, in CSM patients treated with conventional metallic fusion instrumentation.

A Narrative Review of Clinical Decision Support Systems for Perioperative Bleeding Management in Cardiac Surgery.

Bleeding complications in patients undergoing cardiac surgery are common. The clinician must assimilate multiple sources of monitoring information, make rational decisions on the etiology of the bleeding, and then formulate a treatment strategy. Clinical decision support systems that acquire this information and present the data in an easily usable format may be useful tools to guide the physician in optimizing treatment strategies through adherence to evidence-based best practice guidelines. The authors present a narrative review of the literature and discuss how clinical decision support systems may be useful to the clinician.

Barriers and facilitators to interhospital transfer of acute pulmonary embolism: An inductive qualitative analysis.

Background: Interhospital transfer (IHT) of patients with acute life-threatening pulmonary embolism (PE) is necessary to facilitate specialized care and access to advanced therapies. Our goal was to understand what barriers and facilitators may exist during this transfer process from the perspective of both receiving and referring physicians. Methods: This qualitative descriptive study explored physician experience taking care of patients with life threatening PE. Subject matter expert physicians across several different specialties from academic and community United States hospitals participated in qualitative semi-structured interviews. Interview transcripts were subsequently analyzed using inductive qualitative description approach. Results: Four major themes were identified as barriers that impede IHT among patients with life threatening PE. Inefficient communication which mainly pertained to difficulty when multiple points of contact were required to complete a transfer. Subjectivity in the indication for transfer which highlighted the importance of physicians understanding how to use standardized risk stratification tools and to properly triage these patients. Delays in data acquisition were identified in regards to both obtaining clinical information and imaging in a timely fashion. Operation barriers which included difficulty finding available beds for transfer and poor weather conditions inhibiting transportation. In contrast, two main facilitators to transfer were identified: good communication and reliance on colleagues and dedicated team for transferring and treating PE patients. Conclusion: The most prominent themes identified as barriers to IHT for patients with acute life-threatening PE were: (1) inefficient communication, (2) subjectivity in the indication for transfer, (3) delays in data acquisition (imaging or clinical), and (4) operational barriers. Themes identified as facilitators that enable the transfer of patients were: (1) good communication and (2) a dedicated transfer team. The themes presented in our study are useful in identifying opportunities to optimize the IHT of patients with acute PE and improve patient care. These opportunities include instituting educational programs, streamlining the transfer process, and formulating a consensus statement to serve as a guideline regarding IHT of patients with acute PE.

Fixed-point iterative linear inverse solver with extended precision.

Solving linear systems, often accomplished by iterative algorithms, is a ubiquitous task in science and engineering. To accommodate the dynamic range and precision requirements, these iterative solvers are carried out on floating-point processing units, which are not efficient in handling large-scale matrix multiplications and inversions. Low-precision, fixed-point digital or analog processors consume only a fraction of the energy per operation than their floating-point counterparts, yet their current usages exclude iterative solvers due to the cumulative computational errors arising from fixed-point arithmetic. In this work, we show that for a simple iterative algorithm, such as Richardson iteration, using a fixed-point processor can provide the same convergence rate and achieve solutions beyond its native precision when combined with residual iteration. These results indicate that power-efficient computing platforms consisting of analog computing devices can be used to solve a broad range of problems without compromising the speed or precision.

Intravascular Lithotripsy for the Treatment of Severely Calcified Coronary Artery Disease: A DISRUPT CAD III Intravascular Ultrasound Substudy.

BACKGROUND: Coronary intravascular lithotripsy (IVL) has emerged as a novel technique for the treatment of severely calcified coronary lesions. We evaluated the mechanism and efficacy of IVL in facilitating optimal stent implantation in heavily calcified coronary lesions using intravascular ultrasound (IVUS). METHODS: Forty-six patients were initially enrolled as a part of the Disrupt CAD III study. Of these, 33 had pre-IVL, 24 had post-IVL, and 44 had post-stent IVUS evaluation. The final analysis was performed on 18 patients who had IVUS images interpretable at all three intervals. The primary endpoint was increase in minimum lumen area (MLA) from pre-IVL to post-IVL treatment to post-stenting. RESULTS: Pre-IVL, MLA was 2.75 ± 0.84 mm2, percent area stenosis was 67.22 % ± 20.95 % with maximum calcium angle of 266.90° ± 78.30°, confirming severely calcified lesions. After IVL, MLA increased to 4.06 ± 1.41 mm2 (p = 0.0003), percent area stenosis decreased to 54.80 % ± 25.71 % (p = 0.0009), and maximum calcium angle decreased to 239.40° ± 76.73° (p = 0.003). There was a further increase in MLA to 6.84 ± 2.18 mm2 (p < 0.0001) and decrease in percent area stenosis to 30.33 % ± 35.08 % (p < 0.0001) post-stenting with minimum stent area of 6.99 ± 2.14 mm2. The success rate of stent delivery, implantation, and post-stent dilation was 100 % post-IVL. CONCLUSION: In this first study evaluating the mechanism of IVL using IVUS, the primary endpoint of increase in MLA from pre-IVL to post-IVL treatment to post-stenting was successfully achieved. Our study showed that the use of IVL-assisted percutaneous coronary intervention is associated with improved vessel compliance, facilitating optimal stent implantation in de novo severely calcified lesions.

Evaluation of a Closed Suction System With Integrated Tube-Scraping Technology.

BACKGROUND: Endotracheal tube (ETT) scraping or sweeping refers to mucus removal from an ETT that can increase airway resistance. The study objective was to evaluate the effect of ETT scraping on the duration of mechanical ventilation, time to first successful spontaneous breathing trial (SBT), duration of hospital stay, and occurrence of ventilator-associated events (VAEs). METHODS: This was a single-center, randomized clinical trial of adult subjects intubated between October 2019-October 2021. Subjects were randomly assigned to either ETT suctioning via a standard in-line suction catheter (control group) or ETT suctioning and scraping via a suction catheter with balloon-sweeping technology (experimental group). Airway suctioning was performed as clinically indicated, and the ETT was scraped every time a respiratory therapist suctioned the subject. The study outcome was duration of mechanical ventilation, time to first successful SBT, hospital length of stay, and VAE rate. Intent-to-treat statistical analysis was performed. RESULTS: Of 272 randomized subjects, the median age was 63 (interquartile range [IQR] 52-73) y; 143 (53%) were males, and 154 (57%) had a primary diagnosis of acute respiratory failure. There were no significant differences between the groups in median duration (h) of mechanical ventilation (72 [37-187] vs 70.6 [37-148], P = .58). There was no significant difference between the study groups in median time (h) to the first successful SBT (46.7 [IQR 30-87] vs 45.7 [IQR 27-95], P = .81), length of hospital stay (P = .76), the incidences of ventilator-associated conditions (P = .13), or infection-related ventilator-associated complications (P = .47). CONCLUSIONS: ETT suctioning plus scraping, compared to ETT suctioning alone, did not significantly improve the duration of mechanical ventilation, time to first successful SBT, length of hospital stay, and VAEs. These study findings do not support the routine use of ETT scraping for mechanically ventilated patients.

The importance of vitamin B12 for individuals choosing plant-based diets.

Vitamin B12 is an essential nutrient that is not made by plants; consequently, unfortified plant-based foods are not a reliable supply. Recent estimates suggest high rates of vitamin B12 deficiency among the vegetarian and vegan populations, particularly in pregnant women or women of child-bearing age who, for ethical and health reasons, are shifting towards higher consumption of plant-based foods in ever-increasing numbers. Vitamin B12 plays crucial metabolic roles across the life-course and in particular during pregnancy and in early development (first 1000 days of life). Evidence now implicates vitamin B12 deficiency with increased risk to a range of neuro, vascular, immune, and inflammatory disorders. However, the current UK recommended nutrient intake for vitamin B12 does not adequately consider the vitamin B12 deficit for those choosing a plant-based diet, including vegetarianism and in particular veganism, representing a hidden hunger. We provide a cautionary note on the importance of preventing vitamin B12 deficits for those individuals choosing a plant-based diet and the health professionals advising them.

Impact of Shift Volume on Neuroradiology Diagnostic Errors at a Large Tertiary Academic Center.

BACKGROUND AND PURPOSE: Medical errors can result in significant morbidity and mortality. The goal of our study is to evaluate correlation between shift volume and errors made by attending neuroradiologists at an academic medical center, using a large data set. MATERIALS AND METHODS: CT and MRI reports from our Neuroradiology Quality Assurance database (years 2014 - 2020) were searched for attending physician errors. Data were collected on shift volume, category of missed findings, error type, interpretation setting, exam type, clinical significance. RESULTS: 654 reports contained diagnostic error. There was a significant difference between mean volume of interpreted studies on shifts when an error was made compared with shifts in which no error was documented (46.58 (SD=22.37) vs 34.09 (SD=18.60), p<0.00001); and between shifts when perceptual error was made compared with shifts when interpretive errors were made (49.50 (SD=21.9) vs 43.26 (SD=21.75), p=0.0094). 59.6% of errors occurred in the emergency/inpatient setting, 84% were perceptual and 91.1% clinically significant. Categorical distribution of errors was: vascular 25.8%, brain 23.4%, skull base 13.8%, spine 12.4%, head/neck 11.3%, fractures 10.2%, other 3.1%. Errors were detected most often on brain MRI (25.4%), head CT (18.7%), head/neck CTA (13.8%), spine MRI (13.7%). CONCLUSION: Errors were associated with higher volume shifts, were primarily perceptual and clinically significant. We need National guidelines establishing a range of what is a safe number of interpreted cross-sectional studies per day.

Detecting Primary Progressive Aphasia Atrophy Patterns: A Comparison of Visual Assessment and Quantitative Neuroimaging Techniques.

Background: There are now clinically available automated MRI analysis software programs that compare brain volumes of patients to a normative sample and provide z-score data for various brain regions. These programs have yet to be validated in primary progressive aphasia (PPA). Objective: To address this gap in the literature, we examined Neuroreader™ z-scores in PPA, relative to visual MRI assessment. We predicted that Neuroreader™ 1) would be more sensitive for detecting left > right atrophy in the cortical lobar regions in logopenic variant PPA clinical phenotype (lvPPA), and 2) would distinguish lvPPA (n = 11) from amnestic mild cognitive impairment (aMCI; n = 12). Methods: lvPPA or aMCI patients who underwent MRI with Neuroreader™ were included in this study. Two neuroradiologists rated 10 regions. Neuroreader™ lobar z-scores for those 10 regions, as well as a hippocampal asymmetry metric, were included in analyses. Results: Cohen's Kappa coefficients were significant in 10 of the 28 computations (k = 0.351 to 0.593, p≤0.029). Neuroradiologists agreed 0% of the time that left asymmetry was present across regions. No significant differences emerged between aMCI and lvPPA in Neuroreader™ z-scores across left or right frontal, temporal, or parietal regions (ps > 0.10). There were significantly lower z-scores in the left compared to right for the hippocampus, as well as parietal, occipital, and temporal cortices in lvPPA. Conclusion: Overall, our results indicated moderate to low interrater reliability, and raters never agreed that left asymmetry was present. While lower z-scores in the left hemisphere regions emerged in lvPPA, Neuroreader™ failed to differentiate lvPPA from aMCI.

Pharmacomechanical Catheter-Directed Thrombolysis With the Bashir Endovascular Catheter for Acute Pulmonary Embolism: The RESCUE Study.

BACKGROUND: Catheter-directed thrombolysis (CDT) has been associated with rapid recovery of right ventricular (RV) function. The Bashir catheter was developed for enhanced thrombolysis in large vessels such as the pulmonary arteries (PAs) with lower doses of tissue plasminogen activator (tPA). OBJECTIVES: The aim of this study was to evaluate the efficacy and safety of tPA infused using a pharmacomechanical (PM) CDT device called the Bashir endovascular catheter in patients with intermediate-risk acute pulmonary embolism (PE). METHODS: Patients with symptoms of acute PE with computed tomographic evidence of RV dilatation were enrolled. The Bashir catheter was used to deliver 7 mg tPA into each PA over 5 hours. The primary efficacy endpoint was the core laboratory-assessed change in computed tomographic angiography-derived RV/left ventricular (LV) diameter ratio at 48 hours, and the primary safety endpoint was serious adverse events (SAEs) including major bleeding at 72 hours. RESULTS: At 18 U.S. sites, 109 patients were enrolled. The median device placement time was 15 minutes. At 48 hours after PM-CDT, the RV/LV diameter ratio decreased by 0.56 (33.3%; P < 0.0001). PA obstruction as measured by the refined modified Miller index was reduced by 35.9% (P < 0.0001). One patient (0.92%) had 2 SAEs: a retroperitoneal bleed (procedure related) and iliac vein thrombosis (device related). Two other procedure-related SAEs were epistaxis and non-access site hematoma with anemia. CONCLUSIONS: PM-CDT with the Bashir endovascular catheter is associated with a significant reduction in RV/LV diameter ratio and a very low rate of adverse events or major bleeding in patients with intermediate-risk acute PE. The notable finding was a significant reduction in PA obstruction with low-dose tPA. (Recombinant tPA by Endovascular Administration for the Treatment of Submassive PE Using CDT for the Reduction of Thrombus Burden [RESCUE]; NCT04248868).