Functional imaging for assessing regional lung ventilation in preclinical and clinical research.

Dynamic heterogeneity in lung ventilation is an important measure of pulmonary function and may be characteristic of early pulmonary disease. While standard indices like spirometry, body plethysmography, and blood gases have been utilized to assess lung function, they do not provide adequate information on regional ventilatory distribution nor function assessments of ventilation during the respiratory cycle. Emerging technologies such as xenon CT, volumetric CT, functional MRI and X-ray velocimetry can assess regional ventilation using non-invasive radiographic methods that may complement current methods of assessing lung function. As a supplement to current modalities of pulmonary function assessment, functional lung imaging has the potential to identify respiratory disease phenotypes with distinct natural histories. Moreover, these novel technologies may offer an optimal strategy to evaluate the effectiveness of novel therapies and therapies targeting localized small airways disease in preclinical and clinical research. In this review, we aim to discuss the features of functional lung imaging, as well as its potential application and limitations to adoption in research.

Additive value of lung ultrasound to clinical parameters for prognosticating COVID-19.

The inclusion of LUS with simple, point-of-care clinical parameters have potential to improve COVID-19 prognostication above that from standard clinical care delivery. https://bit.ly/3InePYK.

Do worsening lung ultrasound scans identify severe COVID-19 trajectories?

Background: While point-of-care ultrasound (POCUS) has been used to track worsening COVID-19 disease it is unclear if there are dynamic differences between severity trajectories. Methods: We studied 12-lung zone protocol scans from 244 participants [with repeat scans obtained in 3 days (N = 114), 7 days (N = 53), and weekly (N = 9)] ≥ 18 years of age hospitalized for COVID-19 pneumonia. Differences in mean lung ultrasound (LUS) scores and percent of lung fields with A-lines over time were compared between peak severity levels (as defined by the WHO clinical progression scale) using linear mixed-effects models. Results: Mean LUS scores were elevated by 0.19 (p = 0.035) and A-lines were present in 14.7% fewer lung fields (p = 0.02) among those with ICU-level or fatal peak illness compared to less severe hospitalized illness, regardless of duration of illness. There were no differences between severity groups in the trajectories of mean LUS score 0.19 (p = 0.66) or percent A-lines (p = 0.40). Discussion: Our results do not support the use of serial LUS scans to monitor COVID-19 disease progression among hospitalized adults.

Society of General Internal Medicine Position Statement on Social Risk and Equity in Medicare's Mandatory Value-Based Payment Programs.

The Affordable Care Act (2010) and Medicare Access and CHIP Reauthorization Act (2015) ushered in a new era of Medicare value-based payment programs. Five major mandatory pay-for-performance programs have been implemented since 2012 with increasing positive and negative payment adjustments over time. A growing body of evidence indicates that these programs are inequitable and financially penalize safety-net systems and systems that care for a higher proportion of racial and ethnic minority patients. Payments from penalized systems are often redistributed to those with higher performance scores, which are predominantly better-financed, large, urban systems that serve less vulnerable patient populations - a "Reverse Robin Hood" effect. This inequity may be diminished by adjusting for social risk factors in payment policy. In this position statement, we review the literature evaluating equity across Medicare value-based payment programs, major policy reports evaluating the use of social risk data, and provide recommendations on behalf of the Society of General Internal Medicine regarding how to address social risk and unmet health-related social needs in these programs. Immediate recommendations include implementing peer grouping (stratification of healthcare systems by proportion of dual eligible Medicare/Medicaid patients served, and evaluation of performance and subsequent payment adjustments within strata) until optimal methods for accounting for social risk are defined. Short-term recommendations include using census-based, area-level indices to account for neighborhood-level social risk, and developing standardized approaches to collecting individual socioeconomic data in a robust but sensitive way. Long-term recommendations include implementing a research agenda to evaluate best practices for accounting for social risk, developing validated health equity specific measures of care, and creating policies to better integrate healthcare and social services.

Prevalence of Visible Subdural Spaces in Benign Enlargement of Subarachnoid Spaces in Infancy: A Retrospective Analysis Utilizing Magnetic Resonance Imaging.

OBJECTIVE: Benign Enlargement of the Subarachnoid Spaces in Infancy (BESSI) is a common finding during workup for progressive macrocephaly. BESSI has been associated with slightly higher prevalence of subdural (SD) spaces and a risk for developing subdural hematoma. This study utilizes fast brain magnetic resonance imaging (MRI) to investigate the prevalence of visible SD spaces in BESSI. METHODS: A retrospective review was performed for all pediatric patients who underwent brain MRI for macrocephaly. Patients with a diagnosis of BESSI were included in the study. A total of 109 patients met the inclusion criteria. Patient demographics were collected, and images were reviewed for size of subarachnoid, visible SD spaces, and ventricle size. Descriptive and inferential statistics were performed. RESULTS: The average age was 8 ± 4.6 months, 64 (59%) were male, and 55 patients had no previous medical history (50%). Sixty-seven percent of all patients were identified to have visible SD spaces. Eleven patients had confirmed SD hematomas; 1 patient was deemed to have abusive head trauma. Visible SD spaces were associated with younger age (6.9 months). Thirty-one patients with visible SD spaces had follow-up MRI, with complete resolution by 33 months. CONCLUSIONS: BESSI is a self-limiting pathology that has been associated with visible SD spaces and potential risk for SD hemorrhages. We report a high prevalence of visible SD spaces within BESSI through utilization of fast brain MRI. These spaces may contribute to the higher rate of incidental subdural hematoma in this population.

Glycoengineering tobacco plants to stably express recombinant human erythropoietin with different N-glycan profiles.

Plant-based expression system has many potential advantages to produce biopharmaceuticals, but plants cannot be directly used to express human glycoproteins because of their differences in glycosylation abilities from mammals. To exploit plant-based expression system for producing recombinant human erythropoietin (rhuEPO), we glycoengineered tobacco plants by stably introducing seven to eight mammalian genes including a target human EPO into tobacco in order to generate capacities for ß1,4-galactosylation, bisecting N-acetylglucosamine (GlcNAc) and sialylation. Wild type human ß1,4-galactosyltransferase gene (GalT) or a chimeric GalT gene (ST/GalT) was co-expressed to produce rhuEPO bearing ß1,4-galactose-extended N-glycan chains as well as compare their ß1,4-galactosylation efficiencies. Five mammalian genes encoding enzymes/transporter for sialic acid biosynthesis, transport and transfer were co-expressed to build sialylation capacity in plants. The human MGAT3 was co-expressed to produce N-glycan chains with bisecting GlcNAc. Our results demonstrated that the above transgenes were incorporated into tobacco genome and transcribed. ST/GalT was found to be more efficient than GalT for ß1,4-galactosylation. Furthermore, co-expressing MGAT3 generated N-glycans likely bearing bisected GlcNAc. However, our current efforts did not result in generating sialylation capacity. Created transgenic plants expressing EPO and ST/GalT could be used to produce rhuEPO with high proportion of ß1,4-galactose-extended N-glycan chains for tissue protective purposes.