Quantitative perfusion and water transport time model from multi b-value diffusion magnetic resonance imaging validated against neutron capture microspheres.

Purpose: Quantification of perfusion in ml/100 g/min, rather than comparing relative values side-to-side, is critical at the clinical and research levels for large longitudinal and multi-center trials. Intravoxel incoherent motion (IVIM) is a non-contrast magnetic resonance imaging diffusion-based scan that uses a multitude of b-values to measure various speeds of molecular perfusion and diffusion, sidestepping inaccuracy of arterial input functions or bolus kinetics. Questions remain as to the original of the signal and whether IVIM returns quantitative and accurate perfusion in a pathology setting. This study tests a novel method of IVIM perfusion quantification compared with neutron capture microspheres. Approach: We derive an expression for the quantification of capillary blood flow in ml/100 g/min by solving the three-dimensional Gaussian probability distribution and defining water transport time (WTT) as when 50% of the original water remains in the tissue of interest. Calculations were verified in a six-subject pre-clinical canine model of normocapnia, CO2 induced hypercapnia, and middle cerebral artery occlusion (ischemic stroke) and compared with quantitative microsphere perfusion. Results: Linear regression analysis of IVIM and microsphere perfusion showed agreement (slope = 0.55, intercept = 52.5, R2=0.64) with a Bland-Altman mean difference of -11.8 [-78,54] ml/100 g/min. Linear regression between dynamic susceptibility contrast mean transit time and IVIM WTT asymmetry in infarcted tissue was excellent (slope=0.59, intercept = 0.3, R2=0.93). Strong linear agreement was found between IVIM and reference standard infarct volume (slope = 1.01, R2=0.79). The simulation of cerebrospinal fluid (CSF) suppression via inversion recovery returned a blood signal reduced by 82% from combined T1 and T2 effects. Conclusions: The accuracy and sensitivity of IVIM provides evidence that observed signal changes reflect cytotoxic edema and tissue perfusion and can be quantified with WTT. Partial volume contamination of CSF may be better removed during post-processing rather than with inversion recovery.

Corrigendum: Absolute oxygen-guided radiation therapy improves tumor control in three preclinical tumor models.

[This corrects the article DOI: 10.3389/fmed.2023.1269689.].

Preconception care utilization: Self-report versus claims-based measures among women with Medicaid.

The objective of this study is to compare self-reported preconception care utilization (PCU) among Medicaid-covered births to Medicaid claims. We identified all Medicaid-covered births to women ages 15-45 in 26 states in the year 2012 among the Pregnancy Risk Assessment and Monitoring System (PRAMS) survey and Medicaid Analytic eXtract (MAX) claims data, and identified preconception services in the latter using diagnosis codes published by Health and Human Services' Office of Population Affairs. We fit mixed-effects logistic regression models for the probability of PCU on sociodemographic factors (age, race, and ethnicity) and clinical diagnoses (depression, diabetes, or hypertension), separately for each dataset. Among 652,929 women delivering in MAX, 28.1% received at least one claims-based preconception service while an estimated 23.6% (95% CI 22.1-25.3) of PRAMS respondents reported receiving preconception care. Adjusting for age, chronic diseases, and state, PCU rates in both MAX and PRAMS were higher for non-Hispanic Black versus non-Hispanic White women (OR 1.51, 95% CI 1.49-1.54 and OR 2.05, 95% CI 1.60-2.62, respectively). Adjusting for differences in age, race and ethnicity, and state, PCU rates were higher for patients with diabetes (OR 1.34, 95% CI 1.29-1.40 and OR 1.82, 95% CI 1.16-2.85) or hypertension (OR 1.22, 95% CI 1.18-1.27 and OR 1.85, 95% CI 1.41-2.44). While Hispanic and Asian women were also more likely to report PCU than their non-Hispanic White counterparts (OR 2.07, 95% CI 1.53-2.80 and OR 3.37, 95% CI 2.28-4.98), they were less likely to have received it (OR 0.74, 95% CI 0.73-0.75 and OR 0.65, 95% CI 0.63-0.67). In conclusion, comparing self-report to claims measures of PCU, we found similar trends in the differences between non-Hispanic Black and White women, and between those with vs. without diabetes and hypertension. However, the two data sources differed in trends in other racial/ethnic groups (differences between Hispanic vs. non-Hispanic White women, and between Asian vs. non-Hispanic White women), and in those with vs. without depression. This suggests that while Medicaid claims can be a useful tool for studying preconception care, they may miss certain types of care among some sub-groups of the population or be subject to reporting differences that are hard to surmise. Both data sets have potential benefits and drawbacks as research tools.

Vulnerable and Stabilized States After Cerebral Ischemic Events: Implications of Kinetic Modeling in the SOCRATES, POINT, and THALES Trials.

BACKGROUND AND OBJECTIVES: Trials of acute secondary prevention after minor stroke or transient ischemic attack (TIA), such as SOCRATES, POINT, and THALES, demonstrate a high initial rate of recurrence after ischemic events that drop quickly to a lower rate, suggesting a transient vulnerable clinical state, which may call for different treatments than the subsequent stabilized state. A kinetic model incorporating vulnerable and stabilized states provides estimates of the distinct kinetic rates reflecting the temporal features of underlying stroke mechanisms. We aimed to compare these kinetic rates between treatments and across trials, asking whether these features point to common pathophysiologic processes underlying stroke recurrence, and inform the targeting and timing of enhanced antiplatelet therapy in recurrent stroke prevention. METHODS: Kaplan-Meier recurrence-free survival curves in the SOCRATES, POINT, and THALES trials were estimated for each treatment group and fitted by nonlinear regression to the 2-state kinetic model, producing estimates of kinetic parameters, with standard errors estimated using the nonparametric bootstrap with repetitive resampling. RESULTS: For each trial, the 2-state kinetic model fit the survival curves better than did the null (single-state) kinetic model or the Weibull model (p < 0.05). Recurrence rates in the vulnerable state (k 1 ) were 100-fold higher than in the stabilized state (k 2 ). Transition rates from the vulnerable to stabilized state (k 0 ) were still more rapid. Kinetic parameters were consistent across the trials, without significant differences between the trials. Enhanced antiplatelet regimens produced significant reductions in k 1 (aspirin alone: 0.030 ± 0.004 d-1; active treatment: 0.016 ± 0.003 d-1; p < 0.01) but did not affect k 0 or k 2 , suggesting that active treatment only affected risk in the vulnerable state. Modeling based on these kinetic parameters suggests that most of the benefit of active treatment occurred within 3 days. DISCUSSION: Across multiple trials of acute secondary prevention after minor stroke or TIA, recurrence of stroke is well-described by a 2-state kinetic model postulating vulnerable and stabilized states, with similar kinetic parameters across trials. Enhanced antiplatelet regimens only affected the recurrence rates in the vulnerable state, over a brief period. This analysis suggests that 2 distinct states follow acute cerebral ischemic events, subject to differential impact of immediate or delayed therapies.

Absolute oxygen-guided radiation therapy improves tumor control in three preclinical tumor models.

Background: Clinical attempts to find benefit from specifically targeting and boosting resistant hypoxic tumor subvolumes have been promising but inconclusive. While a first preclinical murine tumor type showed significant improved control with hypoxic tumor boosts, a more thorough investigation of efficacy from boosting hypoxic subvolumes defined by electron paramagnetic resonance oxygen imaging (EPROI) is necessary. The present study confirms improved hypoxic tumor control results in three different tumor types using a clonogenic assay and explores potential confounding experimental conditions. Materials and methods: Three murine tumor models were used for multi-modal imaging and radiotherapy: MCa-4 mammary adenocarcinomas, SCC7 squamous cell carcinomas, and FSa fibrosarcomas. Registered T2-weighted MRI tumor boundaries, hypoxia defined by EPROI as pO2 ≤ 10 mmHg, and X-RAD 225Cx CT boost boundaries were obtained for all animals. 13 Gy boosts were directed to hypoxic or equal-integral-volume oxygenated tumor regions and monitored for regrowth. Kaplan-Meier survival analysis was used to assess local tumor control probability (LTCP). The Cox proportional hazards model was used to assess the hazard ratio of tumor progression of Hypoxic Boost vs. Oxygenated Boost for each tumor type controlling for experimental confounding variables such as EPROI radiofrequency, tumor volume, hypoxic fraction, and delay between imaging and radiation treatment. Results: An overall significant increase in LTCP from Hypoxia Boost vs. Oxygenated Boost treatments was observed in the full group of three tumor types (p < 0.0001). The effects of tumor volume and hypoxic fraction on LTCP were dependent on tumor type. The delay between imaging and boost treatments did not have a significant effect on LTCP for all tumor types. Conclusion: This study confirms that EPROI locates resistant tumor hypoxic regions for radiation boost, increasing clonogenic LTCP, with potential enhanced therapeutic index in three tumor types. Preclinical absolute EPROI may provide correction for clinical hypoxia images using additional clinical physiologic MRI.

Variation in HIV Transmission Behaviors Among People Who Use Drugs in Rural US Communities.

Importance: People who use drugs (PWUD) continue to be at risk of HIV infection, but the frequency and distribution of transmission-associated behaviors within various rural communities is poorly understood. Objective: To examine the association of characteristics of rural PWUD with HIV transmission behaviors. Design, Setting, and Participants: In this cross-sectional study, surveys of PWUD in rural communities in 10 states (Illinois, Kentucky, New Hampshire, Massachusetts, North Carolina, Ohio, Oregon, Vermont, West Virginia, and Wisconsin) were collected January 2018 through March 2020 and analyzed August through December 2022. A chain-referral sampling strategy identified convenience sample seeds who referred others who used drugs. Rural PWUD who reported any past 30-day injection drug use or noninjection opioid use "to get high" were included. Exposures: Individual characteristics, including age, race, gender identity, sexual orientation, partnership status, drug of choice, and location, were collected. Main Outcomes and Measures: Past 30-day frequency of behaviors associated with HIV transmission, including drug injection, syringe sharing, opposite- and same-gender partners, transactional sex, and condomless sex, was assessed. Results: Of 3048 rural PWUD (mean [SD] age, 36.1 [10.3] years; 225 American Indian [7.4%], 96 Black [3.2%], and 2576 White [84.5%] among 3045 with responses; and 1737 men [57.0%] among 3046 with responses), most participants were heterosexual (1771 individuals [86.8%] among 2040 with responses) and single (1974 individuals [68.6%] among 2879 with responses). Opioids and stimulants were reported as drug of choice by 1636 individuals (53.9%) and 1258 individuals (41.5%), respectively, among 3033 individuals with responses. Most participants reported recent injection (2587 of 3046 individuals [84.9%] with responses) and condomless sex (1406 of 1757 individuals [80.0%] with responses), among whom 904 of 1391 individuals (65.0%) with responses indicated that it occurred with people who inject drugs. Syringe sharing (1016 of 2433 individuals [41.8%] with responses) and transactional sex (230 of 1799 individuals [12.8%] with responses) were reported less frequently. All characteristics and behaviors, except the number of men partners reported by women, varied significantly across locations (eg, mean [SD] age ranged from 34.5 [10.0] years in Wisconsin to 39.7 [11.0] years in Illinois; P < .001). In multivariable modeling, younger age (adjusted odds ratio [aOR] for ages 15-33 vs ≥34 years, 1.36; 95% CI, 1.08-1.72) and being single (aOR, 1.37; 95% CI, 1.08-1.74) were associated with recent injection; younger age (aOR, 1.49; 95% CI, 1.20-1.85) and bisexual orientation (aOR vs heterosexual orientation, 2.27; 95% CI, 1.60-3.23) with syringe sharing; gender identity as a woman (aOR vs gender identity as a man, 1.46; 95% CI, 1.01-2.12), bisexual orientation (aOR vs heterosexual orientation, 2.59; 95% CI, 1.67-4.03), and being single (aOR, 1.71; 95% CI, 1.15-2.55) with transactional sex; and bisexual orientation (aOR vs heterosexual orientation, 1.60; 95% CI, 1.04-2.46) and stimulants as the drug of choice (aOR vs opioids, 1.45; 95 CI, 1.09-1.93) with condomless sex with someone who injects drugs. Conclusions and Relevance: This study found that behaviors associated with HIV transmission were common and varied across communities. These findings suggest that interventions to reduce HIV risk among rural PWUD may need to be tailored to locally relevant factors.

Door-in-Door-out Times for Interhospital Transfer of Patients With Stroke.

Importance: Treatments for time-sensitive acute stroke are not available at every hospital, often requiring interhospital transfer. Current guidelines recommend hospitals achieve a door-in-door-out time of no more than 120 minutes at the transferring emergency department (ED). Objective: To evaluate door-in-door-out times for acute stroke transfers in the American Heart Association Get With The Guidelines-Stroke registry and to identify patient and hospital factors associated with door-in-door-out times. Design, Setting, and Participants: US registry-based, retrospective study of patients with ischemic or hemorrhagic stroke from January 2019 through December 2021 who were transferred from the ED at registry-affiliated hospitals to other acute care hospitals. Exposure: Patient- and hospital-level characteristics. Main Outcomes and Measures: The primary outcome was the door-in-door-out time (time of transfer out minus time of arrival to the transferring ED) as a continuous variable and a categorical variable (≤120 minutes, >120 minutes). Generalized estimating equation (GEE) regression models were used to identify patient and hospital-level characteristics associated with door-in-door-out time overall and in subgroups of patients with hemorrhagic stroke, acute ischemic stroke eligible for endovascular therapy, and acute ischemic stroke transferred for reasons other than endovascular therapy. Results: Among 108 913 patients (mean [SD] age, 66.7 [15.2] years; 71.7% non-Hispanic White; 50.6% male) transferred from 1925 hospitals, 67 235 had acute ischemic stroke and 41 678 had hemorrhagic stroke. Overall, the median door-in-door-out time was 174 minutes (IQR, 116-276 minutes): 29 741 patients (27.3%) had a door-in-door-out time of 120 minutes or less. The factors significantly associated with longer median times were age 80 years or older (vs 18-59 years; 14.9 minutes, 95% CI, 12.3 to 17.5 minutes), female sex (5.2 minutes; 95% CI, 3.6 to 6.9 minutes), non-Hispanic Black vs non-Hispanic White (8.2 minutes, 95% CI, 5.7 to 10.8 minutes), and Hispanic ethnicity vs non-Hispanic White (5.4 minutes, 95% CI, 1.8 to 9.0 minutes). The following were significantly associated with shorter median door-in-door-out time: emergency medical services prenotification (-20.1 minutes; 95% CI, -22.1 to -18.1 minutes), National Institutes of Health Stroke Scale (NIHSS) score exceeding 12 vs a score of 0 to 1 (-66.7 minutes; 95% CI, -68.7 to -64.7 minutes), and patients with acute ischemic stroke eligible for endovascular therapy vs the hemorrhagic stroke subgroup (-16.8 minutes; 95% CI, -21.0 to -12.7 minutes). Among patients with acute ischemic stroke eligible for endovascular therapy, female sex, Black race, and Hispanic ethnicity were associated with a significantly higher door-in-door-out time, whereas emergency medical services prenotification, intravenous thrombolysis, and a higher NIHSS score were associated with significantly lower door-in-door-out times. Conclusions and Relevance: In this US registry-based study of interhospital transfer for acute stroke, the median door-in-door-out time was 174 minutes, which is longer than current recommendations for acute stroke transfer. Disparities and modifiable health system factors associated with longer door-in-door-out times are suitable targets for quality improvement initiatives.

Improving reader accuracy and specificity with the addition of hybrid multidimensional-MRI to multiparametric-MRI in diagnosing clinically significant prostate cancers.

PURPOSE: Compare reader performance when adding the Hybrid Multidimensional-MRI (HM-MRI) map to multiparametric MRI (mpMRI+HM-MRI) versus mpMRI alone and inter-reader agreement in diagnosing clinically significant prostate cancers (CSPCa). METHODS: All 61 patients who underwent mpMRI (T2-, diffusion-weighted (DWI), and contrast-enhanced scans) and HM-MRI (with multiple TE/b-value combinations) before prostatectomy or MRI-fused-transrectal ultrasound-guided biopsy between August, 2012 and February, 2020, were retrospectively analyzed. Two experienced readers (R1, R2) and two less-experienced readers (less than 6-year MRI prostate experience) (R3, R4) interpreted mpMRI without/with HM-MRI in the same sitting. Readers recorded the PI-RADS 3-5 score, lesion location, and change in score after adding HM-MRI. Each radiologist's mpMRI+HM-MRI and mpMRI performance measures (AUC, sensitivity, specificity, PPV, NPV, and accuracy) based on pathology, and Fleiss' kappa inter-reader agreement was calculated and compared. RESULTS: Per-sextant R3 and R4 mpMRI+HM-MRI accuracy (82% 81% vs. 77%, 71%; p=.006, <.001) and specificity (89%, 88% vs. 84%, 75%; p=.009, <.001) were higher than with mpMRI. Per-patient R4 mpMRI+HM-MRI specificity improved (48% from 7%; p<.001). R1 and R2 mpMRI+HM-MRI specificity per-sextant (80%, 93% vs. 81%, 93%; p=.51,>.99) and per-patient (37%, 41% vs. 48%, 37%; p=.16, .57) remained similar to mpMRI. R1 and R2 per-patient AUC with mpMRI+HM-MRI (0.63, 0.64 vs. 0.67, 0.61; p=.33, .36) remained similar to mpMRI, but R3 and R4 mpMRI+HM-MRI AUC (0.73, 0.62) approached R1 and R2 AUC. Per-patient inter-reader agreement, mpMRI+HM-MRI Fleiss Kappa, was higher than mpMRI (0.36 [95% CI 0.26, 0.46] vs. 0.17 [95% CI 0.07, 0.27]); p=.009). CONCLUSION: Adding HM-MRI to mpMRI (mpMRI+HM-MRI) improved specificity and accuracy for less-experienced readers, improving overall inter-reader agreement.

Subsampling based variable selection for generalized linear models.

A novel variable selection method for low-dimensional generalized linear models is introduced. The new approach called AIC OPTimization via STABility Selection (OPT-STABS) repeatedly subsamples the data, minimizes Akaike's Information Criterion (AIC) over a sequence of nested models for each subsample, and includes in the final model those predictors selected in the minimum AIC model in a large fraction of the subsamples. New methods are also introduced to establish an optimal variable selection cutoff over repeated subsamples. An extensive simulation study examining a variety of proposec variable selection methods shows that, although no single method uniformly outperforms the others in all the scenarios considered, OPT-STABS is consistently among the best-performing methods in most settings while it performs competitively for the rest. This is in contrast to other candidate methods which either have poor performance across the board or exhibit good performance in some settings, but very poor in others. In addition, the asymptotic properties of the OPT-STABS estimator are derived, and its root-n consistency and asymptotic normality are proved. The methods are applied to two datasets involving logistic and Poisson regressions.

A population-based evaluation of tunica vaginalis mesothelioma: An analysis of the National Cancer Database.

PURPOSE: Primary mesothelioma of the tunica vaginalis (TVM) is a rare and poorly understood malignancy with insufficient population-level data to guide management decisions. MATERIALS AND METHODS: A retrospective analysis of TVM cases recorded in the National Cancer Database from 2004 to 2015 was performed. Cases were identified using International Classification of Diseases for Oncology histology codes. Associations between demographic, clinical and therapeutic factors were analyzed using Kaplan-Meier survival estimates for overall survival (OS) and Cox proportional hazard modeling. Propensity score matching for receipt of systemic chemotherapy was performed to assess the impact on OS. RESULTS: One hundred fifty-one men with a median age of 65 years (interquartile range [IQR] 51-78) were included. Median OS from diagnosis was 72.5 months (IQR 20.2-Not Reached [NR]) after a median follow up of 34.9 months. Multivariate analysis demonstrated an increased risk of death for patients in the fourth quartile of age (hazard ratio [HR] 5.57, 95% confidence interval [CI] 1.70-18.17, P = 0.004), those with biphasic or fibrous histology (HR 2.59, 95% CI 1.15-6.42, P = 0.04) and positive surgical margins (HR 3.27, 95% CI 1.61-6.63, P = 0.001). There was no significant difference in OS associated with receiving chemotherapy (P = 0.5) even after propensity score matching (P = 0.07). CONCLUSIONS: Margin-negative surgical resection is paramount to improving OS. There are insufficient data to recommend for or against adjuvant systemic chemotherapy or RT, although the limited available data does not suggest apparent benefit in terms of OS.

Immunomodulatory fecal metabolites are associated with mortality in COVID-19 patients with respiratory failure.

Respiratory failure and mortality from COVID-19 result from virus- and inflammation-induced lung tissue damage. The intestinal microbiome and associated metabolites are implicated in immune responses to respiratory viral infections, however their impact on progression of severe COVID-19 remains unclear. We prospectively enrolled 71 patients with COVID-19 associated critical illness, collected fecal specimens within 3 days of medical intensive care unit admission, defined microbiome compositions by shotgun metagenomic sequencing, and quantified microbiota-derived metabolites (NCT #04552834). Of the 71 patients, 39 survived and 32 died. Mortality was associated with increased representation of Proteobacteria in the fecal microbiota and decreased concentrations of fecal secondary bile acids and desaminotyrosine (DAT). A microbiome metabolic profile (MMP) that accounts for fecal secondary bile acids and desaminotyrosine concentrations was independently associated with progression of respiratory failure leading to mechanical ventilation. Our findings demonstrate that fecal microbiota composition and microbiota-derived metabolite concentrations can predict the trajectory of respiratory function and death in patients with severe SARS-Cov-2 infection and suggest that the gut-lung axis plays an important role in the recovery from COVID-19.

Racial and ethnic disparities in the observed COVID-19 case fatality rate among the U.S. population.

PURPOSE: During the initial 12 months of the pandemic, racial and ethnic disparities in COVID-19 death rates received considerable attention but it has been unclear whether disparities in death rates were due to disparities in case fatality rates (CFRs), incidence rates or both. We examined differences in observed COVID-19 CFRs between U.S. White, Black/African American, and Latinx individuals during this period. METHODS: Using data from the COVID Tracking Project and the Centers for Disease Control and Prevention COVID-19 Case Surveillance Public Use dataset, we calculated CFR ratios comparing Black and Latinx to White individuals, both overall and separately by age group. We also used a model of monthly COVID-19 deaths to estimate CFR ratios, adjusting for age, gender, and differences across states and time. RESULTS: Overall Black and Latinx individuals had lower CFRs than their White counterparts. However, when adjusting for age, Black and Latinx had higher CFRs than White individuals among those younger than 65. CFRs varied substantially across states and time. CONCLUSIONS: Disparities in COVID-19 case fatality among U.S. Black and Latinx individuals under age 65 were evident during the first year of the pandemic. Understanding racial and ethnic differences in COVID-19 CFRs is challenging due to limitations in available data.

The optimal 18F-fluoromisonidazole PET threshold to define tumor hypoxia in preclinical squamous cell carcinomas using pO2 electron paramagnetic resonance imaging as reference truth.

PURPOSE: To identify the optimal threshold in 18F-fluoromisonidazole (FMISO) PET images to accurately locate tumor hypoxia by using electron paramagnetic resonance imaging (pO2 EPRI) as ground truth for hypoxia, defined by pO2 [Formula: see text] 10 mmHg. METHODS: Tumor hypoxia images in mouse models of SCCVII squamous cell carcinoma (n = 16) were acquired in a hybrid PET/EPRI imaging system 2 h post-injection of FMISO. T2-weighted MRI was used to delineate tumor and muscle tissue. Dynamic contrast enhanced (DCE) MRI parametric images of Ktrans and ve were generated to model tumor vascular properties. Images from PET/EPR/MRI were co-registered and resampled to isotropic 0.5 mm voxel resolution for analysis. PET images were converted to standardized uptake value (SUV) and tumor-to-muscle ratio (TMR) units. FMISO uptake thresholds were evaluated using receiver operating characteristic (ROC) curve analysis to find the optimal FMISO threshold and unit with maximum overall hypoxia similarity (OHS) with pO2 EPRI, where OHS = 1 shows perfect overlap and OHS = 0 shows no overlap. The means of dice similarity coefficient, normalized Hausdorff distance, and accuracy were used to define the OHS. Monotonic relationships between EPRI/PET/DCE-MRI were evaluated with the Spearman correlation coefficient ([Formula: see text]) to quantify association of vasculature on hypoxia imaged with both FMISO PET and pO2 EPRI. RESULTS: FMISO PET thresholds to define hypoxia with maximum OHS (both OHS = 0.728 [Formula: see text] 0.2) were SUV [Formula: see text] 1.4 [Formula: see text] SUVmean and SUV [Formula: see text] 0.6 [Formula: see text] SUVmax. Weak-to-moderate correlations (|[Formula: see text]|< 0.70) were observed between PET/EPRI hypoxia images with vascular permeability (Ktrans) or fractional extracellular-extravascular space (ve) from DCE-MRI. CONCLUSION: This is the first in vivo comparison of FMISO uptake with pO2 EPRI to identify the optimal FMISO threshold to define tumor hypoxia, which may successfully direct hypoxic tumor boosts in patients, thereby enhancing tumor control.

Directional and inter-acquisition variability in diffusion-weighted imaging and editing for restricted diffusion.

PURPOSE: To evaluate and quantify inter-directional and inter-acquisition variation in diffusion-weighted imaging (DWI) and emphasize signals that report restricted diffusion to enhance cancer conspicuity, while reducing the effects of local microscopic motion and magnetic field fluctuations. METHODS: Ten patients with biopsy-proven prostate cancer were studied under an Institutional Review Board-approved protocol. Individual acquisitions of DWI signal intensities were reconstructed to calculate inter-acquisition distributions and their statistics, which were compared for healthy versus cancer tissue. A method was proposed to detect and filter the acquisitions affected by motion-induced signal loss. First, signals that reflect restricted diffusion were separated from the acquisitions that suffer from signal loss, likely due to microscopic motion, by imposing a cutoff value. Furthermore, corrected apparent diffusion coefficient maps were calculated by employing a weighted sum of the multiple acquisitions, instead of conventional averaging. These weights were calculated by applying a soft-max function to the set of acquisitions per-voxel, making the analysis immune to acquisitions with significant signal loss, even if the number of such acquisitions is high. RESULTS: Inter-acquisition variation is much larger than the Rician noise variance, local spatial variations, and the estimates of diffusion anisotropy based on the current data, as well as the published values of anisotropy. The proposed method increases the contrast for cancers and yields a sensitivity of 98 . 8 % $$ 98.8\% $$ with a false positive rate of 3 . 9 % $$ 3.9\% $$ . CONCLUSION: Motion-induced signal loss makes conventional signal-averaging suboptimal and can obscure signals from areas with restricted diffusion. Filtering or weighting individual acquisitions prior to image analysis can overcome this problem.

Comparing Radiologist Performance in Diagnosing Clinically Significant Prostate Cancer with Multiparametric versus Hybrid Multidimensional MRI.

Background Variability of acquisition and interpretation of prostate multiparametric MRI (mpMRI) persists despite implementation of the Prostate Imaging Reporting and Data System (PI-RADS) version 2.1 due to the range of reader experience and subjectivity of lesion characterization. A quantitative method, hybrid multidimensional MRI (HM-MRI), may introduce objectivity. Purpose To compare performance, interobserver agreement, and interpretation time of radiologists using mpMRI versus HM-MRI to diagnose clinically significant prostate cancer. Materials and Methods In this retrospective analysis, men with prostatectomy or MRI-fused transrectal US biopsy-confirmed prostate cancer underwent mpMRI (triplanar T2-weighted, diffusion-weighted, and dynamic contrast-enhanced imaging) and HM-MRI (with multiple echo times and b value combinations) from August 2012 to February 2020. Four readers with 1-20 years of experience interpreted mpMRI and HM-MRI examinations independently, with a 4-week washout period between interpretations. PI-RADS score, lesion location, and interpretation time were recorded. mpMRI and HM-MRI interpretation time, interobserver agreement (Cronbach alpha), and performance of area under the receiver operating characteristic curve (AUC) analysis were compared for each radiologist with use of bootstrap analysis. Results Sixty-one men (mean age, 61 years ± 8 [SD]) were evaluated. Per-patient AUC was higher for HM-MRI for reader 4 compared with mpMRI (AUCs for readers 1-4: 0.61, 0.71, 0.59, and 0.64 vs 0.66, 0.60, 0.50, and 0.46; P = .57, .20, .32, and .04, respectively). Per-patient specificity was higher for HM-MRI for readers 2-4 compared with mpMRI (specificity for readers 1-4: 48%, 78%, 48%, and 46% vs 37%, 26%, 0%, and 7%; P = .34, P < .001, P < .001, and P < .001, respectively). Diagnostic performance improved for the reader least experienced with HM-MRI, reader 4 (AUC, 0.64 vs 0.46; P = .04). HM-MRI interobserver agreement (Cronbach alpha = 0.88 [95% CI: 0.82, 0.92]) was higher than that of mpMRI (Cronbach alpha = 0.26 [95% CI: 0.10, 0.52]; α > .60 indicates reliability; P = .03). HM-MRI mean interpretation time (73 seconds ± 43 [SD]) was shorter than that of mpMRI (254 seconds ± 133; P = .03). Conclusion Radiologists had similar or improved diagnostic performance, higher interobserver agreement, and lower interpretation time for clinically significant prostate cancer with hybrid multidimensional MRI than multiparametric MRI. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Turkbey in this issue.

Prostate MRI: Is Endorectal Coil Necessary?-A Review.

To assess the necessity of endorectal coil use in 3 Tesla (T) prostate magnetic resonance imaging (MRI), a literature review comparing the image quality and diagnostic performance with an endorectal coil (ERC) and a without endorectal coil (NERC), with a phased array coil or a wearable perineal coil (WPC), was performed. A PubMed search of 3T prostate MRI using an endorectal coil for studies published until 31 July 2021 was performed. A total of 14 studies comparing 3T prostate MRI with and without endorectal coil use were identified. The quality scores and diagnostic performances were recorded for each study. In total, five studies compared image quality; five studies compared quality and performance; and four studies compared performance of detection, size of detected lesions, accuracy of cancer localization, and aggressiveness/staging. The use of an endorectal coil improved image quality with a higher overall signal to noise ratio, posterior and peripheral zone signal to noise ratio, high b-value attenuation diffusion coefficient (ADC) signal to noise ratio, and contrast to noise ratio. Endorectal coil use improved subjective image quality for anatomic detail on T2 weighted images (T2WI) and diffusion weighted images (DWI). Endorectal coil use had less motion artifact on DWI than non-endorectal coil use, but produced a higher occurrence of other artifacts on DWI. Endorectal coils had higher sensitivity, specificity, and positive predictive value (PPV) in the detection of overall and index lesions, as well as smaller and less aggressive lesions, missing fewer and smaller lesions than non-endorectal coils. Endorectal coils had higher sensitivity than non-endorectal coils in localizing and staging lesions. Endorectal coils improved quantitative and qualitative image quality and diagnostic performance in the detection of smaller and less aggressive cancers in 3T prostate MRI.

Nonparametric inference in the accelerated failure time model using restricted means.

We propose a nonparametric estimate of the scale-change parameter for characterizing the difference between two survival functions under the accelerated failure time model using an estimating equation based on restricted means. Advantages of our restricted means based approach compared to current nonparametric procedures is the strictly monotone nature of the estimating equation as a function of the scale-change parameter, leading to a unique root, as well as the availability of a direct standard error estimate, avoiding the need for hazard function estimation or re-sampling to conduct inference. We derive the asymptotic properties of the proposed estimator for fixed and for random point of restriction. In a simulation study, we compare the performance of the proposed estimator with parametric and nonparametric competitors in terms of bias, efficiency, and accuracy of coverage probabilities. The restricted means based approach provides unbiased estimates and accurate confidence interval coverage rates with efficiency ranging from 81% to 95% relative to fitting the correct parametric model. An example from a randomized clinical trial in head and neck cancer is provided to illustrate an application of the methodology in practice.

Measuring Healthcare Worker Satisfaction in the Operating Room.

MINI-ABSTRACT: This report highlights the efficacy of using a 5-point Likert scale to measure healthcare worker satisfaction in the operating room. This assessment is significant because it is a critical step in assessing a novel scheduling apparatus that hopes to improve team satisfaction, operative efficiency, and operating room waste.

Pediatric Invasive Fungal Risk Score in Cancer and Hematopoietic Stem Cell Transplantation Patients With Febrile Neutropenia.

BACKGROUND: Invasive fungal diseases (IFDs) are opportunistic infections that result in significant morbidity and mortality in pediatric oncology patients. Predictive risk tools for IFD in pediatric cancer are not available. METHODS: We conducted a 7-year retrospective study of pediatric oncology patients with a diagnosis of febrile neutropenia at UCM Comer Children's Hospitals. Fourteen clinical, laboratory, and treatment-related risk factors for IFD were analyzed. Stepwise variable selection for multiple logistic regression was used to develop a risk prediction model for IFD. Two comparative analyses have been conducted: (i) all suspected IFD cases and (ii) all proven and probable IFD cases. RESULTS: A total of 667 febrile neutropenia episodes were identified in 265 patients. IFD was diagnosed in 62 episodes: 13 proven, 27 probable, and 22 possible. In the final multiple logistic regression models, 5 variables were independently significant for both analyses: fever days, neutropenia days, hypotension, and absolute lymphocyte count <250 at the time of diagnosis. The odds ratio and a relative weight for each factor were then calculated and summed to calculate a predictive score. A risk score of ≤4 and ≤5 (10/11 maximum) for each model signifies low risk, respectively (<1.2% incidence). Model discrimination was evaluated by the area under the receiver operator characteristics curve with an area under the curve of 0.95/0.94 for each model. CONCLUSION: Our prediction IFD risk models perform well, are easy-to-use, and are based on readily available clinical data. Profound lymphopenia absolute lymphocyte count <250 mm3 could serve as a new important prognostic marker for the development of IFD in pediatric cancer and hematopoietic stem cell transplant patients.

Extended Absorption of Liothyronine from Poly-Zinc-Liothyronine: Results from a Phase 1, Double-Blind, Randomized, and Controlled Study in Humans.

Background: L-triiodothyronine (LT3) has been increasingly used in combination with levothyroxine in the treatment of hypothyroidism. A metal coordinated form of LT3, known as poly-zinc-liothyronine (PZL), avoided in rats the typical triiodothyronine (T3) peak seen after oral administration of LT3. Objectives: To evaluate in healthy volunteers (i) the pharmacokinetics (PK) of PZL-derived T3 after a single dose, (ii) the pharmacodynamics of PZL-derived T3, (iii) incidence of adverse events, and (iv) exploratory analysis of the sleep patterns after LT3, PZL, or placebo (PB) administration. Methods: Twelve healthy volunteers 18-50 years of age were recruited for a Phase 1, double-blind, randomized, single-dose PB-controlled, crossover study to compare PZL against LT3 or PB. Subjects were admitted three separate times to receive a randomly assigned capsule containing PB, 50 µg LT3, or 50 µg PZL, and were observed for 48 hours. A 2-week washout period separated each admission. Results: LT3-derived serum T3 levels exhibited the expected profile, with a Tmax at 2 hours and return to basal levels by 24-36 hours. PZL-derived serum T3 levels exhibited ∼30% lower Cmax that was 1 hour delayed and extended into a plateau that lasted up to 6 hours. This was followed by a lower but much longer plateau; by 24 hours serum T3 levels still exceeded ½ of Cmax. Thyrotropin levels were similarly reduced in both groups. Conclusion: PZL possesses the necessary properties to achieve a much improved T3 PK. PZL is on track to provide hypothyroid patients with stable levels of serum T3.