Tracheostomies of Patients With COVID-19: A Survey of Infection Reported by Health Care Professionals.

BACKGROUND: Health care professionals (HCPs) performing tracheostomies in patients with COVID-19 may be at increased risk of infection. OBJECTIVE: To evaluate factors underlying HCPs' COVID-19 infection and determine whether tracheostomy providers report increased rates of infection. METHODS: An anonymous international survey examining factors associated with COVID-19 infection was made available November 2020 through July 2021 to HCPs at a convenience sample of hospitals, universities, and professional organizations. Infections reported were compared between HCPs involved in tracheostomy on patients with COVID-19 and HCPs who were not involved. RESULTS: Of the 361 respondents (from 33 countries), 50% (n = 179) had performed tracheostomies on patients with COVID-19. Performing tracheostomies on patients with COVID-19 was not associated with increased infection in either univariable (P = .06) or multivariable analysis (odds ratio, 1.48; 95% CI, 0.90-2.46; P = .13). Working in a low- or middle-income country (LMIC) was associated with increased infection in both univariable (P < .001) and multivariable analysis (odds ratio, 2.88; CI, 1.50-5.53; P = .001). CONCLUSIONS: Performing tracheostomy was not associated with COVID-19 infection, suggesting that tracheostomies can be safely performed in infected patients with appropriate precautions. However, HCPs in LMICs may face increased infection risk.

Outcomes of Early Versus Late Tracheostomy in Patients With COVID-19: A Multinational Cohort Study.

Timing of tracheostomy in patients with COVID-19 has attracted substantial attention. Initial guidelines recommended delaying or avoiding tracheostomy due to the potential for particle aerosolization and theoretical risk to providers. However, early tracheostomy could improve patient outcomes and alleviate resource shortages. This study compares outcomes in a diverse population of hospitalized COVID-19 patients who underwent tracheostomy either "early" (within 14 d of intubation) or "late" (more than 14 d after intubation). DESIGN: International multi-institute retrospective cohort study. SETTING: Thirteen hospitals in Bolivia, Brazil, Spain, and the United States. PATIENTS: Hospitalized patients with COVID-19 undergoing early or late tracheostomy between March 1, 2020, and March 31, 2021. INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: A total of 549 patients from 13 hospitals in four countries were included in the final analysis. Multivariable regression analysis showed that early tracheostomy was associated with a 12-day decrease in time on mechanical ventilation (95% CI, -16 to -8; p < 0.001). Further, ICU and hospital lengths of stay in patients undergoing early tracheostomy were 15 days (95% CI, -23 to -9 d; p < 0.001) and 22 days (95% CI, -31 to -12 d) shorter, respectively. In contrast, early tracheostomy patients experienced lower risk-adjusted survival at 30-day post-admission (hazard ratio, 3.0; 95% CI, 1.8-5.2). Differences in 90-day post-admission survival were not identified. CONCLUSIONS: COVID-19 patients undergoing tracheostomy within 14 days of intubation have reduced ventilator dependence as well as reduced lengths of stay. However, early tracheostomy patients experienced lower 30-day survival. Future efforts should identify patients most likely to benefit from early tracheostomy while accounting for location-specific capacity.

Antibodies to human leukocyte antigens and their association with blood product exposures in pediatric patients undergoing cardiac transplantation.

BACKGROUND AND AIMS: Previous blood product exposures may result in the development of antibodies to human leukocyte antigens (HLA). Pediatric heart transplant recipients who have these antibodies experience increased morbidity and mortality after transplantation. In this study, our aims were to confirm the association of previous allogeneic blood product exposures with the formation of anti-HLA antibodies, determine which blood components pose the greatest risk of developing antibodies, and assess differences in outcomes after transplantation between patients who had anti-HLA antibodies and those who did not. METHODS: This retrospective investigation included all children who underwent cardiac transplantation at Children's Healthcare of Atlanta from January 1, 2015 through December 31, 2018. Chart reviews were performed to collect pertinent data. Anti-HLA antibodies were detected by single antigen bead testing. Antibody burden was tabulated using the calculated panel reactive antibody (cPRA) score immediately prior to transplantation. Statistical analyses were conducted to examine differences based on HLA antibody status and identify associations with outcomes of interest. RESULTS: Our results show a significant association between pretransplant blood product exposures and HLA antibody status. Children with a pretransplant blood product exposure had 7.98 times the odds of developing an anti-HLA antibody compared to those without a pretransplant blood product exposure (p = .01). We also found a significant association between a previous red blood cell (RBC) exposure and HLA antibody status (p = .01) which was not found for other blood component exposures. Patients who were HLA antibody positive were more likely to develop a donor-specific antibody (DSA) after transplantation (p = .04). CONCLUSIONS: Exposure to previous allogeneic blood products affects the development of anti-HLA antibodies in children presenting for heart transplantation. Previous RBC exposures resulted in HLA antibody positivity more than other blood component exposures. Importantly, the presence of HLA antibodies was associated with the development of DSAs post-transplantation. Developing transfusion strategies to reduce allogeneic blood product exposures in children who may need future cardiac transplantation should be a high priority.

One-Stop Serum Assay Identifies COVID-19 Disease Severity and Vaccination Responses.

SARS-CoV-2 has caused over 100,000,000 cases and almost 2,500,000 deaths globally. Comprehensive assessment of the multifaceted antiviral Ab response is critical for diagnosis, differentiation of severity, and characterization of long-term immunity, especially as COVID-19 vaccines become available. Severe disease is associated with early, massive plasmablast responses. We developed a multiplex immunoassay from serum/plasma of acutely infected and convalescent COVID-19 patients and prepandemic and postpandemic healthy adults. We measured IgA, IgG, and/or IgM against SARS-CoV-2 nucleocapsid (N), spike domain 1 (S1), S1-receptor binding domain (RBD) and S1-N-terminal domain. For diagnosis, the combined [IgA + IgG + IgM] or IgG levels measured for N, S1, and S1-RBD yielded area under the curve values ≥0.90. Virus-specific Ig levels were higher in patients with severe/critical compared with mild/moderate infections. A strong prozone effect was observed in sera from severe/critical patients-a possible source of underestimated Ab concentrations in previous studies. Mild/moderate patients displayed a slower rise and lower peak in anti-N and anti-S1 IgG levels compared with severe/critical patients, but anti-RBD IgG and neutralization responses reached similar levels at 2-4 mo after symptom onset. Measurement of the Ab responses in sera from 18 COVID-19-vaccinated patients revealed specific responses for the S1-RBD Ag and none against the N protein. This highly sensitive, SARS-CoV-2-specific, multiplex immunoassay measures the magnitude, complexity, and kinetics of the Ab response and can distinguish serum Ab responses from natural SARS-CoV-2 infections (mild or severe) and mRNA COVID-19 vaccines.

A rarefaction-based extension of the LDM for testing presence-absence associations in the microbiome.

MOTIVATION: Many methods for testing association between the microbiome and covariates of interest (e.g. clinical outcomes, environmental factors) assume that these associations are driven by changes in the relative abundance of taxa. However, these associations may also result from changes in which taxa are present and which are absent. Analyses of such presence-absence associations face a unique challenge: confounding by library size (total sample read count), which occurs when library size is associated with covariates in the analysis. It is known that rarefaction (subsampling to a common library size) controls this bias, but at the potential cost of information loss as well as the introduction of a stochastic component into the analysis. Currently, there is a need for robust and efficient methods for testing presence-absence associations in the presence of such confounding, both at the community level and at the individual-taxon level, that avoid the drawbacks of rarefaction. RESULTS: We have previously developed the linear decomposition model (LDM) that unifies the community-level and taxon-level tests into one framework. Here, we present an extension of the LDM for testing presence-absence associations. The extended LDM is a non-stochastic approach that repeatedly applies the LDM to all rarefied taxa count tables, averages the residual sum-of-squares (RSS) terms over the rarefaction replicates, and then forms an F-statistic based on these average RSS terms. We show that this approach compares favorably to averaging the F-statistic from R rarefaction replicates, which can only be calculated stochastically. The flexible nature of the LDM allows discrete or continuous traits or interactions to be tested while allowing confounding covariates to be adjusted for. Our simulations indicate that our proposed method is robust to any systematic differences in library size and has better power than alternative approaches. We illustrate our method using an analysis of data on inflammatory bowel disease (IBD) in which cases have systematically smaller library sizes than controls. AVAILABILITYAND IMPLEMENTATION: The R package LDM is available on GitHub at https://github.com/yijuanhu/LDM in formats appropriate for Macintosh or Windows. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Elevated SARS-CoV-2 Antibodies Distinguish Severe Disease in Early COVID-19 Infection.

BACKGROUND: SARS-CoV-2 has caused over 36,000,000 cases and 1,000,000 deaths globally. Comprehensive assessment of the multifaceted anti-viral antibody response is critical for diagnosis, differentiation of severe disease, and characterization of long-term immunity. Initial observations suggest that severe disease is associated with higher antibody levels and greater B cell/plasmablast responses. A multi-antigen immunoassay to define the complex serological landscape and clinical associations is essential. METHODS: We developed a multiplex immunoassay and evaluated serum/plasma from adults with RT-PCR-confirmed SARS-CoV-2 infections during acute illness (N=52) and convalescence (N=69); and pre-pandemic (N=106) and post-pandemic (N=137) healthy adults. We measured IgA, IgG, and/or IgM against SARS-CoV-2 Nucleocapsid (N), Spike domain 1 (S1), receptor binding domain (S1-RBD) and S1-N-terminal domain (S1-NTD). RESULTS: To diagnose infection, the combined [IgA+IgG+IgM] or IgG for N, S1, and S1-RBD yielded AUC values -0.90 by ROC curves. From days 6-30 post-symptom onset, the levels of antigen-specific IgG, IgA or [IgA+IgG+IgM] were higher in patients with severe/critical compared to mild/moderate infections. Consistent with excessive concentrations of antibodies, a strong prozone effect was observed in sera from severe/critical patients. Notably, mild/moderate patients displayed a slower rise and lower peak in anti-N and anti-S1 IgG levels compared to severe/critical patients, but anti-RBD IgG and neutralization responses reached similar levels at 2-4 months. CONCLUSION: This SARS-CoV-2 multiplex immunoassay measures the magnitude, complexity and kinetics of the antibody response against multiple viral antigens. The IgG and combined-isotype SARS-CoV-2 multiplex assay is highly diagnostic of acute and convalescent disease and may prognosticate severity early in illness. ONE SENTENCE SUMMARY: In contrast to patients with moderate infections, those with severe COVID-19 develop prominent, early antibody responses to S1 and N proteins.

Vortex Dynamics in Trabeculated Embryonic Ventricles.

Proper heart morphogenesis requires a delicate balance between hemodynamic forces, myocardial activity, morphogen gradients, and epigenetic signaling, all of which are coupled with genetic regulatory networks. Recently both in vivo and in silico studies have tried to better understand hemodynamics at varying stages of veretebrate cardiogenesis. In particular, the intracardial hemodynamics during the onset of trabeculation is notably complex-the inertial and viscous fluid forces are approximately equal at this stage and small perturbations in morphology, scale, and steadiness of the flow can lead to significant changes in bulk flow structures, shear stress distributions, and chemical morphogen gradients. The immersed boundary method was used to numerically simulate fluid flow through simplified two-dimensional and stationary trabeculated ventricles of 72, 80, and 120 h post fertilization wild type zebrafish embryos and ErbB2-inhibited embryos at seven days post fertilization. A 2D idealized trabeculated ventricular model was also used to map the bifurcations in flow structure that occur as a result of the unsteadiness of flow, trabeculae height, and fluid scale ( R e ). Vortex formation occurred in intertrabecular regions for biologically relevant parameter spaces, wherein flow velocities increased. This indicates that trabecular morphology may alter intracardial flow patterns and hence ventricular shear stresses and morphogen gradients. A potential implication of this work is that the onset of vortical (disturbed) flows can upregulate Notch1 expression in endothelial cells in vivo and hence impacts chamber morphogenesis, valvulogenesis, and the formation of the trabeculae themselves. Our results also highlight the sensitivity of cardiac flow patterns to changes in morphology and blood rheology, motivating efforts to obtain spatially and temporally resolved chamber geometries and kinematics as well as the careful measurement of the embryonic blood rheology. The results also suggest that there may be significant changes in shear signalling due to morphological and mechanical variation across individuals and species.

Fluid dynamics in heart development: effects of hematocrit and trabeculation.

Recent in vivo experiments have illustrated the importance of understanding the haemodynamics of heart morphogenesis. In particular, ventricular trabeculation is governed by a delicate interaction between haemodynamic forces, myocardial activity, and morphogen gradients, all of which are coupled to genetic regulatory networks. The underlying haemodynamics at the stage of development in which the trabeculae form is particularly complex, given the balance between inertial and viscous forces. Small perturbations in the geometry, scale, and steadiness of the flow can lead to changes in the overall flow structures and chemical morphogen gradients, including the local direction of flow, the transport of morphogens, and the formation of vortices. The immersed boundary method was used to solve the two-dimensional fluid-structure interaction problem of fluid flow moving through a two chambered heart of a zebrafish (Danio rerio), with a trabeculated ventricle, at 96 hours post fertilization (hpf). Trabeculae heights and hematocrit were varied, and simulations were conducted for two orders of magnitude of Womersley number, extending beyond the biologically relevant range (0.2-12.0). Both intracardial and intertrabecular vortices formed in the ventricle for biologically relevant parameter values. The bifurcation from smooth streaming flow to vortical flow depends upon the trabeculae geometry, hematocrit, and Womersley number, $Wo$. This work shows the importance of hematocrit and geometry in determining the bulk flow patterns in the heart at this stage of development.

Medical imaging and consent: when is an X-ray assault?

New Zealand patients have rights in relation to their healthcare including the right to consent to medical treatment. Medical imaging is the third largest category of hospital procedure in New Zealand and it constitutes a circumstance where examination without consent could be assault. New Zealand assault law is unique, and medical radiation technologists (MRTs) must be educated about their responsibilities. A literature review was conducted focusing on the medicolegal aspects of consent as it relates to medical imaging. This was compared to the practical realities of practicing radiography as experienced by the author. Finally, the guidance given by the professional bodies for MRTs in New Zealand was examined to determine whether it adequately informs MRTs of the responsibilities and provides them with a framework to guide their practice. Medical imaging is a diverse area presenting a range of challenging circumstances for consent. Currently, the consent framework and guidance provided by professional bodies is insufficient and in need of updating.