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Hyperpolarized 129Xe MRI has emerged as a novel means to evaluate pulmonary function via 3D mapping of ventilation, interstitial barrier uptake, and RBC transfer. However, the physiological interpretation of these measurements has yet to be firmly established. Here, we propose a model that uses the three components of 129Xe gas-exchange MRI to estimate accessible alveolar volume (VA), membrane conductance, and capillary blood volume contributions to DLCO. 129Xe ventilated volume (VV) was related to VA by a scaling factor kV = 1.47 with 95% confidence interval [1.42, 1.52], relative 129Xe barrier uptake (normalized by the healthy reference value) was used to estimate the membrane-specific conductance coefficient kB = 10.6 [8.6, 13.6] mL/min/mmHg/L, whereas normalized RBC transfer was used to calculate the capillary blood volume-specific conductance coefficient kR = 13.6 [11.4, 16.7] mL/min/mmHg/L. In this way, the barrier and RBC transfer per unit volume determined the transfer coefficient KCO, which was then multiplied by image-estimated VA to obtain DLCO. The model was built on a cohort of 41 healthy subjects and 101 patients with pulmonary disorders. The resulting 129Xe-derived DLCO correlated strongly (R² = 0.75, P < 0.001) with the measured values, a finding that was preserved within each individual disease cohort. The ability to use 129Xe MRI measures of ventilation, barrier uptake, and RBC transfer to estimate each of the underlying constituents of DLCO clarifies the interpretation of these images while enabling their use to monitor these aspects of gas exchange independently and regionally. [ABSTRACT FROM AUTHOR]

Background: Limited data are available on the association between clinically measured disease severity markers and quality of life (QOL) in idiopathic pulmonary fibrosis (IPF). The study examined the associations between objective disease severity metrics and QOL in a contemporary IPF population.Methods: This study evaluated baseline data from patients enrolled in the multicenter, US-based Idiopathic Pulmonary Fibrosis Prospective Outcomes Registry between June 2014 and July 2018. Disease severity metrics included FVC % predicted, diffusing capacity for carbon monoxide (Dlco) % predicted, supplemental oxygen use with activity, supplemental oxygen use at rest, and two summary scores (the Gender-Age-Lung Physiology index, based on gender, age, and % predicted values for Dlco and FVC; and the Composite Physiologic Index, based on % predicted values for Dlco, FVC, and FEV1). Multivariable adjusted regression models were used to examine cross-sectional associations between each severity measure and St. George's Respiratory Questionnaire (SGRQ) total score.Results: Among 829 patients with complete SGRQ data, the median (interquartile range) SGRQ score at enrollment was 40 (26-53), with higher scores indicating worse QOL. Modest SGRQ impairments were observed with increasing Gender-Age-Lung Physiology score (2.9 [1.8-4.0] per 1-point increase] and with increasing Composite Physiologic Index scores (3.0 [2.4-3.6] per 5-point increase). Substantial SGRQ impairments were observed for oxygen use with activity (15.6 [12.9-18.2]), oxygen use at rest (16.2 [13.0-19.4]), and decreasing Dlco (5.0 [4.0-6.1] per 10% decrease in % predicted).Conclusions: Objective measures of disease severity, including severity scores, physiologic parameters, and supplemental oxygen use, are associated with worse QOL in patients with IPF.Trial Registry: ClinicalTrials.gov; No.: NCT01915511; URL: www.clinicaltrials.gov. [ABSTRACT FROM AUTHOR]

Peripheral artery disease affects over eight million Americans and is associated with an increased risk of mortality, cardiovascular disease, functional limitation, and limb loss. In its most severe form, critical limb ischemia, patients are often treated with lower extremity (LE) amputation (LEA), although the overall incidence of LEA is declining. In the US, there is significant geographic variation in the performing of major LEA. The rate of death after major LEA in the US is approximately 48% at 1 year and 71% at 3 years. Despite this significant morbidity and mortality, the use of diagnostic testing (both noninvasive and invasive testing) in the year prior to LEA is low and varies based on patient, provider, and regional factors. In this review we discuss the significance of LEA and methods to reduce its occurrence. These methods include improved recognition of the risk factors for LEA by clinicians and patients, strong advocacy for noninvasive and/or invasive imaging prior to LEA, improved endovascular revascularization techniques, and novel therapies. [ABSTRACT FROM AUTHOR]

Mine-risk education programmes will fall short of their intended impact for as long as they fail to take into account local responses--knowledge, logic and everyday practices--to mine threats. Community information, systematically collected through household and institutional surveys, can help to define and understand endogenous 'mine smartness'. The same evidence provides insight into the impact of mine-risk education, including its unintended consequences. Using six criteria of mine smartness, CIET carried out evaluations of mine-risk education in Afghanistan (1997) and Angola (1999). The first clear lesson to be drawn from these evaluations is that people in mine-affected areas do generate their own broadly effective means of facing the daily threat of mines. The second lesson is that people take risks for reasons that make sense to them: 'education' that landmines are dangerous probably adds little value for them. The third lesson is that mine-risk education that does not take into account these first two lessons can cause harm. The evaluations produced evidence of unintended risk-taking by people exposed to mine-risk education programmes. [ABSTRACT FROM AUTHOR]

This study elucidated the clinical, humoral immune response and genomic analysis of vaccine breakthrough (VBT) infections after ChAdOx1 nCoV-19/Covishield vaccine in healthcare workers (HCWs). Amongst 1858 HCWs, 1639 had received either two doses (1346) or a single dose (293) of ChAdOx1 nCoV-19 vaccine. SARS-CoV-2 IgG antibodies and neutralizing antibodies were measured in the vaccinated group and the development of SARS-CoV-2 infection was monitored.Forty-six RT-PCR positive samples from the 203 positive samples were subjected to whole genome sequencing (WGS). Of the 203 (10.92%) infected HCWs, 21.46% (47/219) were non-vaccinated, which was significantly more than 9.52% (156/1639) who were vaccinated and infection was higher in doctors and nurses. Unvaccinated HCWs had 1.57 times higher risk compared to partially vaccinated HCWs and 2.49 times higher risk than those who were fully vaccinated.The partially vaccinated were at higher risk than the fully vaccinated (RR 1.58). Antibody non-response was seen in 3.44% (4/116), low antibody levels in 15.51% (18/116) and medium levels were found in 81.03% (94/116). Fully vaccinated HCWs had a higher antibody response at day 42 than those who were partially vaccinated (8.96 + 4.00 vs. 7.17 + 3.82). Whole genome sequencing of 46 samples revealed that the Delta variant (B.1.617.2) was predominant (69.5%). HCWs who had received two doses of vaccine showed better protection from mild, moderate, or severe infection, with a higher humoral immune response than those who had received a single dose. The genomic analysis revealed the predominance of the Delta variant (B.1.617.2) in the VBT infections. [ABSTRACT FROM AUTHOR]

Rationale: Outpatients with interstitial lung disease often experience serious symptoms, yet infrequently receive palliative care. Objective: To determine the feasibility and clinical impact of a mobile application (PCplanner) in an outpatient setting. Methods: We conducted a pilot randomized controlled trial among adults with interstitial lung disease in a single-center academic clinic. Clinical outcomes included change in Needs at the End-of-Life Screening Tool (NEST) scale between baseline and 3 months as well as frequency of advance care planning discussions and referrals to palliative care services. Results: Observed feasibility outcomes were similar to targeted benchmarks including randomization rates (82.1% vs 80%) and retention (84.8% vs 80%). Mean NEST scores between the intervention and control group were 38.9 (SD, 18.9) vs 41.5 (SD, 20.5) at baseline, 34.6 (SD, 18.9) vs 33.6 (SD, 19.4) at 1 month after clinic visit, 40.5 (SD, 21.6) vs 35.3 (SD, 25.0) at 3 months after clinic visit. Changes in NEST scores between baseline and 3 months showed no difference in the primary outcome ( P = 0.481, 95% CI [-8.45, 17.62]). Conclusion: Among patients with interstitial lung disease, a mobile app designed to focus patients and clinicians on palliative care principles demonstrated evidence of feasibility. Although changes in self-reported needs were similar between intervention and control groups, more patients in the intervention group updated their advance directives and code status compared to the control group. Clinical Trial Registration: Palliative Care Planner (PCplanner) NCT05095363. https://www.clinicaltrials.gov/study/NCT05095363., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Hyperpolarized 129 Xe MRI and spectroscopy is a rapidly growing technique for assessing lung function, with applications in a wide range of obstructive, restrictive, and pulmonary vascular disease. However, normal variations in 129 Xe measures of gas exchange across healthy subjects are not well characterized, presenting an obstacle to differentiating disease processes from the consequences of expected physiological heterogeneity. Here, we use multivariate models to evaluate the role of age, sex, and BMI in a range of commonly used 129 Xe measures of gas exchange., Materials and Methods: Healthy subjects ( N = 40, 16F, age 44.3 ± 17.8 yrs., min-max 22-87 years) with no history of cardiopulmonary disease underwent 129 Xe gas exchange MRI and spectroscopy. We used multivariate linear models to assess the associations of age, sex, and body mass index (BMI) with the RBC:Membrane (RBC:M), membrane to gas (Mem:Gas), and red blood cell to gas (RBC:Gas) ratios, as well as measurements of RBC oscillation amplitude and RBC chemical shift., Results: Age, sex, and BMI were all significant covariates in the RBC:M model. Each additional 10 years of age was associated with a 0.05 decrease in RBC:M ( p  < 0.001), each additional 10 points of BMI was associated with a decrease of 0.07 ( p  = 0.02), and males were associated with a 0.17 higher RBC:M than females ( p  < 0.001). For Mem:Gas, male sex was associated with a decrease and BMI was associated with an increase. For RBC:Gas, age was associated with a decrease and male sex was associated with an increase. RBC oscillation amplitude increased with age and RBC chemical shift was not associated with any of the three covariates., Discussion: 129 Xe MRI and spectroscopy measurements in healthy subjects, particularly the widely used RBC:M measurement, exhibit heterogeneity associated in part with variations in subject age, sex, and BMI. Elucidating the contributions of these and other factors to 129 Xe gas exchange measurements is a critical component for differentiating disease processes from expected variation in healthy subjects. Notably, the Mem:Gas and RBC chemical shift appear to be stable with aging, suggesting that unexplained deviations in these metrics may be signs of underlying abnormalities., Competing Interests: BD is founder and chief technology officer for Polarean Imaging. DM is a consultant for Polarean Imaging. Polarean Imaging manufactures the hyperpolarization equipment used in this study but had no involvement whatsoever in the development of this study or writing of the manuscript. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Mummy, Zhang, Bechtel, Lu, Mammarappallil, Leewiwatwong, Costelle, Swaminathan and Driehuys.)

Hyperpolarized 129 Xe MRI has emerged as a novel means to evaluate pulmonary function via 3D mapping of ventilation, interstitial barrier uptake, and RBC transfer. However, the physiological interpretation of these measurements has yet to be firmly established. Here, we propose a model that uses the three components of 129 Xe gas-exchange MRI to estimate accessible alveolar volume ( V A ), membrane conductance, and capillary blood volume contributions to DL CO . 129 Xe ventilated volume (VV) was related to V A by a scaling factor k V = 1.47 with 95% confidence interval [1.42, 1.52], relative 129 Xe barrier uptake (normalized by the healthy reference value) was used to estimate the membrane-specific conductance coefficient k B = 10.6 [8.6, 13.6] mL/min/mmHg/L, whereas normalized RBC transfer was used to calculate the capillary blood volume-specific conductance coefficient k R = 13.6 [11.4, 16.7] mL/min/mmHg/L. In this way, the barrier and RBC transfer per unit volume determined the transfer coefficient K CO , which was then multiplied by image-estimated V A to obtain DL CO . The model was built on a cohort of 41 healthy subjects and 101 patients with pulmonary disorders. The resulting 129 Xe-derived DL CO correlated strongly ( R 2 = 0.75, P < 0.001) with the measured values, a finding that was preserved within each individual disease cohort. The ability to use 129 Xe MRI measures of ventilation, barrier uptake, and RBC transfer to estimate each of the underlying constituents of DL CO clarifies the interpretation of these images while enabling their use to monitor these aspects of gas exchange independently and regionally. NEW & NOTEWORTHY The diffusing capacity for carbon monoxide (DL CO ) is perhaps one of the most comprehensive physiological measures used in pulmonary medicine. Here, we spatially resolve and estimate its key components-accessible alveolar volume, membrane, and capillary blood volume conductances-using hyperpolarized 129 Xe MRI of ventilation, interstitial barrier uptake, and red blood cell transfer. This image-derived DL CO correlates strongly with measured values in 142 subjects with a broad range of pulmonary disorders.