Consistency of Radiological Grading of Cervical Foraminal Stenosis.

BACKGROUND: The degree of cervical foraminal stenosis on MRI scans may be measured and categorised using the Kim or modified Kim methods. These grading scales have not previously been validated in a cohort of patients awaiting surgery. OBJECTIVES: To establish the normal foraminal and root diameters as well as the consistency of inter and intra-rater grading using the Kim and modified Kim grading systems in pre-operative surgical patients. METHODS: Asymptomatic cervical nerve roots and foramina demonstrated on the pre-operative MRI scans of adult surgical patients with cervical radiculopathy were measured and categorised by six raters using the Kim and modified Kim grading methods. Repeat "second pass" measurements were made by the same assessors on the same images a minimum of one month later. RESULTS: Foraminal diameters (mm) in asymptomatic foramina were C2/C3 (mean±SD): 4.18±1.44, C3/C4 2.96±1.23, C4/C5 3.02±1.19, C5/C6 3.15±1.33, C6/C7 3.53±1.36, C7/T1 3.93±1.34. Nerve root diameters were C3 3.11±0.87, C4 2.95±0.77, C5 2.56±0.73, C6 2.26±0.76, C7 2.56±0.82, C8 3.83±0.86. Inter-rater consistency was kappa [95% CI]: Kim 0.01 [0.00, 0.03], modified Kim 0.08 [0.05, 0.10]. Intra-rater consistency was kappa [95% CI]: Kim 0.81 [0.77, 0.86], modified Kim 0.69 [0.62, 0.76]. CONCLUSION: There was poor inter-rater consistency but good intra-rater consistency when assessing the severity of foraminal stenosis on axial T2 MRI scans. Foraminal diameter was narrowest at C3/C4 and C4/C5, whereas the smallest root diameter was C5/C6. Volumetric or oblique MR may improve consistency.

Medical Crowdfunding and Disparities in Health Care Access in the United States, 2016‒2020.

Objectives. To assess whether medical crowdfunding use and outcomes are aligned with health financing needs in the United States. Methods. We collected data on 437 596 US medical GoFundMe campaigns between 2016 and 2020. In addition to summarizing trends in campaign initiation and earnings, we used state- and county-level data to assess whether crowdfunding usage and earnings were higher in areas with greater medical debt, uninsured populations, and poverty. Results. Campaigns raised more than $2 billion from 21.7 million donations between 2016 and 2020. Returns were highly unequal, and success was low, especially in 2020: only 12% of campaigns met their goals, and 16% received no donations at all. Campaigns in 2020 raised substantially less money in areas with more medical debt, higher uninsurance rates, and lower incomes. Conclusions. Despite its popularity and portrayals as an ad-hoc safety net, medical crowdfunding is misaligned with key indicators of health financing needs in the United States. It is best positioned to help in populations that need it the least. (Am J Public Health. 2022;112(3):491-498. https://doi.org/10.2105/AJPH.2021.306617).

Crowdfunding as a response to COVID-19: Increasing inequities at a time of crisis.

During the first seven months of the COVID-19 pandemic, more than 175,000 crowdfunding campaigns were established in the US for coronavirus-related needs using the platform GoFundMe. Though charitable crowdfunding has been popular in recent years, the widespread creation of COVID-19 related campaigns points to potential shifts in how the platform is being used, and the volume of needs users have brought to the site during a profound economic, social, and epidemiological crisis. This study offers a systematic examination of the scope and impacts of COVID-19 related crowdfunding in the early months of the pandemic and assesses how existing social and health inequities shaped crowdfunding use and outcomes. Using data collected from all US-based GoFundMe campaigns mentioning COVID or coronavirus, we used descriptive analysis and a series of negative binomial and linear models to assess the contributions of demographic factors and COVID-19 impacts to campaign creation and outcome. We find significant evidence of growing inequalities in outcomes for campaigners. We find that crowdfunding provides substantially higher benefits in wealthier counties with higher levels of education. People from these areas are more likely to initiate campaigns in response to adverse health and economic impacts of COVID-19, and they also receive more funding compared to people living in areas with lower income and education. Modeling also indicates differential outcomes based on the racial and ethnic composition of county population, though without more detail about who is creating and funding campaigns we cannot explain causality. A targeted qualitative analysis of the top earning COVID-19 campaigns offers further evidence of how user privilege and corporate practices contribute to highly unequal outcomes. Taken together, these findings demonstrate how a market-oriented digital technology used to respond to large-scale crisis can exacerbate inequalities and further benefit already privileged groups.

Do Optic Canal Dimensions Measured on CT Influence the Degree of Papilloedema and Visual Dysfunction in Idiopathic Intracranial Hypertension?

A recent study found that increased optic canal area on magnetic resonance imaging was associated with worse papilloedema in idiopathic intracranial hypertension (IIH). We repeated this study using more accurate computerized tomography derived measurements. Optic canal dimensions were measured from 42 IIH patients and 24 controls.  These were compared with papilloedema grade.  There was no correlation between any of the optic canal measurements and papilloedema grade and no significant difference in optic canal measurements between patients and controls. Our results cast doubt on the existing literature regarding the association between optic canal size and the degree of papilloedema in IIH. CT delineates bony anatomy more accurately than MRI and our CT-derived optic canal measurements cast doubt on the existing literature regarding the association between optic canal size and the degree of Papilloedema in IIH.

Silent cerebral infarction and cognitive function following TAVI: an observational two-centre UK comparison of the first-generation CoreValve and second-generation Lotus valve.

OBJECTIVE: To compare the incidence of silent cerebral infarction and impact on cognitive function following transcatheter aortic valve implantation (TAVI) with the first-generation CoreValve (Medtronic, Minneapolis, Minnesota, USA) and second-generation Lotus valve (Boston Scientific, Natick Massachusetts, USA). DESIGN: A prospective observational study comprising a 1.5 T cerebral MRI scan, performed preoperatively and immediately following TAVI, and neurocognitive assessments performed at baseline, 30 days and 1 year follow-up. SETTING: University hospitals of Leeds and Leicester, UK. PATIENTS: 66 (80.6±8.0 years, 47% male) patients with high-risk severe symptomatic aortic stenosis recruited between April 2012 and May 2015. MAIN OUTCOME MEASURES: Incidence of new cerebral microinfarction and objective decline in neurocognitive performance. RESULTS: All underwent cerebral MRI at baseline and immediately following TAVI, and 49 (25 Lotus, 24 CoreValve) completed neurocognitive assessments at baseline, 30 days and 1 year. There was a significantly greater incidence of new cerebral microinfarction observed following the Lotus TAVI (23 (79%) vs 22 (59%), p=0.025) with a greater number of new infarcts per patient (median 3.5 (IQR 7.0) vs 2.0 (IQR 3.0), p=0.002). The mean volume of infarcted cerebral tissue per patient was equivalent following the two prostheses (p=0.166). More patients suffered new anterior (14 (48%) vs 2 (5%), p=0.001) and vertebrobasilar (15 (52%) vs 7 (19%), p=0.005) lesions following Lotus. Lotus was associated with a decline in verbal memory and psychomotor speed at 30 days. However, performance longitudinally at 1 year was preserved in all neurocognitive domains. CONCLUSIONS: There was a higher incidence of silent cerebral microinfarction and a greater number of lesions per patient following Lotus compared with CoreValve. However, there was no objective decline in neurocognitive function discernible at 1 year following TAVI with either prosthesis.

Pituitary tumour apoplexy within prolactinomas in children: a more aggressive condition?

OBJECTIVES: To evaluate clinical presentations, diagnosis and management of paediatric patients presenting with pituitary apoplexy. METHODS: A retrospective case series describing a cohort of paediatric patients presenting with this condition from 2010-2016 to a tertiary referral children's hospital in the United Kingdom. RESULTS: Pituitary apoplexy is a rare condition that seems to have a higher relative incidence in children than adults. Our series suggests that pituitary apoplexy in paediatric patients with adenomas appears more common than previously described. All our patients required surgery, either as an acute or delayed procedure, for visual compromise. Two patients had commenced growth hormone (GH) for GH deficiency two weeks prior to the onset of pituitary apoplexy. CONCLUSIONS: With only a limited number of published case reports surrounding this topic our case series contributes to help further understand and manage this condition.

Brain-injured Survivors of Monochorionic Twin Pregnancies Complicated by Single Intrauterine Death: MR Findings in a Multicenter Study.

Purpose To describe and classify the range of brain injuries present at prenatal, in-utero magnetic resonance (MR) imaging in co-twin survivors of monochorionic (MC) twin pregnancies complicated by single intrauterine death (SIUD). Materials and Methods This retrospective, observational study from six tertiary fetal medicine centers that perform tertiary-level prenatal in-utero MR studies reviewed cases in which prenatal in-utero MR imaging had shown a brain injury in a surviving co-twin of a twin pregnancy with a MC component complicated by SIUD. Results Forty-two surviving MC twins were described. The primary distinction of brain abnormalities was into nonfocal and focal lesions. The nonfocal lesions included periventricular leukomalacia (group 1; two fetuses), generalized encephalomalacia (group 2; nine fetuses), posterior encephalomalacia (group 3; seven fetuses), and bilateral parasagittal and perisylvian injury (group 4; three fetuses). The focal lesions included nonhemorrhagic lesions (group 5; 14 fetuses) and hemorrhagic lesions (group 6; seven fetuses). Focal brain lesions were more likely to be found in the surviving MC pregnancies complicated by twin-twin transfusion syndrome (TTTS) (odds ratio, 2.4; 95% confidence interval: 1.3, 18.5; P = .01) and in fetuses that underwent an obstetric intervention (odds ratio, 2.8; 95% confidence interval: 1.8, 23.6; P = .006). Conclusion Brain injury of the surviving co-twin after SIUD in MC pregnancies is usually of ischemic origin and spares the brainstem and cerebellum. Focal brain lesions are more frequent in pregnancies complicated by TTTS or in those where an intervention has been performed.

Multiple sclerosis update: use of MRI for early diagnosis, disease monitoring and assessment of treatment related complications.

MRI has long been established as the most sensitive in vivo technique for detecting multiple sclerosis (MS) lesions. The 2010 revisions of the McDonald Criteria have simplified imaging criteria, such that a diagnosis of MS can be made on a single contrast-enhanced MRI scan in the appropriate clinical context. New disease-modifying therapies have proven effective in reducing relapse rate and severity. Several of these therapies, most particularly natalizumab, but also dimethyl fumarate and fingolimod, have been associated with progressive multifocal leukoencephalopathy (PML). PML-immune reconstitution inflammatory syndrome (IRIS) has been recognized in patients following cessation of natalizumab owing to PML, and discontinuation for other reasons can lead to the phenomenon of rebound MS. These complications often provide a diagnostic dilemma and have implications for imaging surveillance of patients. We demonstrate how the updated McDonald Criteria aid the diagnosis of MS and describe the imaging characteristics of conditions such as PML and PML-IRIS in the context of MS. Potential imaging surveillance protocols are considered for the diagnosis and assessment of complications. We will explain how changes in MS treatment are leading to new imaging demands in order to monitor patients for disease progression and treatment-related complications.

Consequence of cerebral embolism after transcatheter aortic valve implantation compared with contemporary surgical aortic valve replacement: effect on health-related quality of life.

BACKGROUND: Incidence of cerebral microinfarcts is higher after transcatheter aortic valve implantation (TAVI) compared with surgical aortic valve replacement (SAVR). It is unknown whether these lesions persist and what direct impact they have on health-related quality of life. The objective was to identify predictors of cerebral microinfarction and measure their effect on health-related quality of life during 6 months after TAVI when compared with SAVR. METHODS AND RESULTS: Cerebral MRI was conducted at baseline, post procedure, and 6 months using diffusion-weighted imaging. Health-related quality of life was measured at baseline, 30 days, and 6 months with short form-12 health outcomes and EuroQol 5 dimensions questionnaires. One hundred eleven patients (TAVI, n=71; SAVR, n=40) were studied. The incidence (54 [77%] versus 17 [43%]; P=0.001) and number (3.4±4.9 versus 1.2±1.8; P=0.001) of new microinfarcts were greater after TAVI than after SAVR. The total volume per microinfarct was smaller in TAVI than in SAVR (0.23±0.24 versus 0.76±1.8 mL; P=0.04). The strongest associations for microinfarction were: TAVI (arch atheroma grade: r=0.46; P=0.0001) and SAVR (concomitant coronary artery bypass grafting: r=-0.33; P=0.03). Physical component score in TAVI increased after 30 days (32.1±6.6 versus 38.9±7.0; P<0.0001) and 6 months (40.4±9.3; P<0.0001); the improvement occurred later in SAVR (baseline: 34.9±10.6; 30 days: 35.9±10.2; 6 months: 42.8±11.2; P<0.001). After TAVI, there were no differences in the short form-12 health outcome scores according to the presence or size of new cerebral infarction. CONCLUSIONS: Cerebral microinfarctions are more common after TAVI compared with SAVR but seem to have no negative effect on early (30 days) or medium term (6 months) health-related quality of life. Aortic atheroma (TAVI) and concomitant coronary artery bypass grafting (SAVR) are independent risk factors for cerebral microinfarction.

Ancillary study management systems: a review of needs.

BACKGROUND: The valuable clinical data, specimens, and assay results collected during a primary clinical trial or observational study can enable researchers to answer additional, pressing questions with relatively small investments in new measurements. However, management of such follow-on, "ancillary" studies is complex. It requires coordinating across institutions, sites, repositories, and approval boards, as well as distributing, integrating, and analyzing diverse data types. General-purpose software systems that simplify the management of ancillary studies have not yet been explored in the research literature. METHODS: We have identified requirements for ancillary study management primarily as part of our ongoing work with a number of large research consortia. These organizations include the Center for HIV/AIDS Vaccine Immunology (CHAVI), the Immune Tolerance Network (ITN), the HIV Vaccine Trials Network (HVTN), the U.S. Military HIV Research Program (MHRP), and the Network for Pancreatic Organ Donors with Diabetes (nPOD). We also consulted with researchers at a range of other disease research organizations regarding their workflows and data management strategies. Lastly, to enhance breadth, we reviewed process documents for ancillary study management from other organizations. RESULTS: By exploring characteristics of ancillary studies, we identify differentiating requirements and scenarios for ancillary study management systems (ASMSs). Distinguishing characteristics of ancillary studies may include the collection of additional measurements (particularly new analyses of existing specimens); the initiation of studies by investigators unaffiliated with the original study; cross-protocol data pooling and analysis; pre-existing participant consent; and pre-existing data context and provenance. For an ASMS to address these characteristics, it would need to address both operational requirements (e.g., allocating existing specimens) and data management requirements (e.g., securely distributing and integrating primary and ancillary data). CONCLUSIONS: The scenarios and requirements we describe can help guide the development of systems that make conducting ancillary studies easier, less expensive, and less error-prone. Given the relatively consistent characteristics and challenges of ancillary study management, general-purpose ASMSs are likely to be useful to a wide range of organizations. Using the requirements identified in this paper, we are currently developing an open-source, general-purpose ASMS based on LabKey Server (http://www.labkey.org) in collaboration with CHAVI, the ITN and nPOD.

Installation and use of LabKey Server for proteomics.

LabKey Server (formerly CPAS, the Computational Proteomics Analysis System) provides a Web-based platform for mining data from liquid chromatography-tandem mass spectrometry (LC-MS/MS) proteomic experiments. This open source platform supports systematic proteomic analyses and secure data management, integration, and sharing. LabKey Server incorporates several tools currently used in proteomic analysis, including the X! Tandem search engine, the ProteoWizard toolkit, and the PeptideProphet and ProteinProphet data mining tools. These tools and others are integrated into LabKey Server, which provides an extensible architecture for developing high-throughput biological applications. The LabKey Server analysis pipeline acts on data in standardized file formats, so that researchers may use LabKey Server with other search engines, including Mascot or SEQUEST, that follow a standardized format for reporting search engine results. Supported builds of LabKey Server are freely available at http://www.labkey.com/. Documentation and source code are available under the Apache License 2.0 at http://www.labkey.org.

LabKey Server NAb: a tool for analyzing, visualizing and sharing results from neutralizing antibody assays.

BACKGROUND: Multiple types of assays allow sensitive detection of virus-specific neutralizing antibodies. For example, the extent of antibody neutralization of HIV-1, SIV and SHIV can be measured in the TZM-bl cell line through the degree of luciferase reporter gene expression after infection. In the past, neutralization curves and titers for this standard assay have been calculated using an Excel macro. Updating all instances of such a macro with new techniques can be unwieldy and introduce non-uniformity across multi-lab teams. Using Excel also poses challenges in centrally storing, sharing and associating raw data files and results. RESULTS: We present LabKey Server's NAb tool for organizing, analyzing and securely sharing data, files and results for neutralizing antibody (NAb) assays, including the luciferase-based TZM-bl NAb assay. The customizable tool supports high-throughput experiments and includes a graphical plate template designer, allowing researchers to quickly adapt calculations to new plate layouts. The tool calculates the percent neutralization for each serum dilution based on luminescence measurements, fits a range of neutralization curves to titration results and uses these curves to estimate the neutralizing antibody titers for benchmark dilutions. Results, curve visualizations and raw data files are stored in a database and shared through a secure, web-based interface. NAb results can be integrated with other data sources based on sample identifiers. It is simple to make results public after publication by updating folder security settings. CONCLUSIONS: Standardized tools for analyzing, archiving and sharing assay results can improve the reproducibility, comparability and reliability of results obtained across many labs. LabKey Server and its NAb tool are freely available as open source software at http://www.labkey.com under the Apache 2.0 license. Many members of the HIV research community can also access the LabKey Server NAb tool without installing the software by using the Atlas Science Portal (https://atlas.scharp.org). Atlas is an installation of LabKey Server.

LabKey Server: an open source platform for scientific data integration, analysis and collaboration.

BACKGROUND: Broad-based collaborations are becoming increasingly common among disease researchers. For example, the Global HIV Enterprise has united cross-disciplinary consortia to speed progress towards HIV vaccines through coordinated research across the boundaries of institutions, continents and specialties. New, end-to-end software tools for data and specimen management are necessary to achieve the ambitious goals of such alliances. These tools must enable researchers to organize and integrate heterogeneous data early in the discovery process, standardize processes, gain new insights into pooled data and collaborate securely. RESULTS: To meet these needs, we enhanced the LabKey Server platform, formerly known as CPAS. This freely available, open source software is maintained by professional engineers who use commercially proven practices for software development and maintenance. Recent enhancements support: (i) Submitting specimens requests across collaborating organizations (ii) Graphically defining new experimental data types, metadata and wizards for data collection (iii) Transitioning experimental results from a multiplicity of spreadsheets to custom tables in a shared database (iv) Securely organizing, integrating, analyzing, visualizing and sharing diverse data types, from clinical records to specimens to complex assays (v) Interacting dynamically with external data sources (vi) Tracking study participants and cohorts over time (vii) Developing custom interfaces using client libraries (viii) Authoring custom visualizations in a built-in R scripting environment. Diverse research organizations have adopted and adapted LabKey Server, including consortia within the Global HIV Enterprise. Atlas is an installation of LabKey Server that has been tailored to serve these consortia. It is in production use and demonstrates the core capabilities of LabKey Server. Atlas now has over 2,800 active user accounts originating from approximately 36 countries and 350 organizations. It tracks roughly 27,000 assay runs, 860,000 specimen vials and 1,300,000 vial transfers. CONCLUSIONS: Sharing data, analysis tools and infrastructure can speed the efforts of large research consortia by enhancing efficiency and enabling new insights. The Atlas installation of LabKey Server demonstrates the utility of the LabKey platform for collaborative research. Stable, supported builds of LabKey Server are freely available for download at http://www.labkey.org. Documentation and source code are available under the Apache License 2.0.

A mouse model repository for cancer biomarker discovery.

Early detection of cancer using biomarkers obtained from blood or other easily accessible tissues would have a significant impact on reducing cancer mortality. However, identifying new blood-based biomarkers has been hindered by the dynamic complexity of the human plasma proteome, confounded by genetic and environmental variability, and the scarcity of high quality controlled samples. In this report, we discuss a new paradigm for biomarker discovery through the use of mouse models. Inbred mouse models of cancer recapitulate many critical features of human cancer, while eliminating sources of environmental and genetic variability. The ability to collect samples from highly matched cases and controls under identical conditions further reduces variability which is critical for successful biomarker discovery. We describe the establishment of a repository containing tumor, plasma, urine, and other tissues from 10 different mouse models of human cancer, including two breast, two lung, two prostate, two gastrointestinal, one ovarian, and one skin tumor model. We present the overall design of this resource and its potential use by the research community for biomarker discovery.

The Functional Genomics Experiment model (FuGE): an extensible framework for standards in functional genomics.

The Functional Genomics Experiment data model (FuGE) has been developed to facilitate convergence of data standards for high-throughput, comprehensive analyses in biology. FuGE models the components of an experimental activity that are common across different technologies, including protocols, samples and data. FuGE provides a foundation for describing entire laboratory workflows and for the development of new data formats. The Microarray Gene Expression Data society and the Proteomics Standards Initiative have committed to using FuGE as the basis for defining their respective standards, and other standards groups, including the Metabolomics Standards Initiative, are evaluating FuGE in their development efforts. Adoption of FuGE by multiple standards bodies will enable uniform reporting of common parts of functional genomics workflows, simplify data-integration efforts and ease the burden on researchers seeking to fulfill multiple minimum reporting requirements. Such advances are important for transparent data management and mining in functional genomics and systems biology.

A suite of algorithms for the comprehensive analysis of complex protein mixtures using high-resolution LC-MS.

MOTIVATION: Comparing two or more complex protein mixtures using liquid chromatography mass spectrometry (LC-MS) requires multiple analysis steps to locate and quantitate natural peptides within a single experiment and to align and normalize findings across multiple experiments. RESULTS: We describe msInspect, an open-source application comprising algorithms and visualization tools for the analysis of multiple LC-MS experimental measurements. The platform integrates novel algorithms for detecting signatures of natural peptides within a single LC-MS measurement and combines multiple experimental measurements into a peptide array, which may then be mined using analysis tools traditionally applied to genomic array analysis. The platform supports quantitation by both label-free and isotopic labeling approaches. The software implementation has been designed so that many key components may be easily replaced, making it useful as a workbench for integrating other novel algorithms developed by a growing research community. AVAILABILITY: The msInspect software is distributed freely under an Apache 2.0 license. The software as well as a Zip file with all peptide feature files and scripts needed to generate the tables and figures in this article are available at http://proteomics.fhcrc.org/.

Computational Proteomics Analysis System (CPAS): an extensible, open-source analytic system for evaluating and publishing proteomic data and high throughput biological experiments.

The open-source Computational Proteomics Analysis System (CPAS) contains an entire data analysis and management pipeline for Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS) proteomics, including experiment annotation, protein database searching and sequence management, and mining LC-MS/MS peptide and protein identifications. CPAS architecture and features, such as a general experiment annotation component, installation software, and data security management, make it useful for collaborative projects across geographical locations and for proteomics laboratories without substantial computational support.