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BACKGROUND: When people with stroke recover gait speed, they report improved function and reduced disability. However, the minimal amount of change in gait speed that is clinically meaningful and associated with an important difference in function for people poststroke has not been determined. OBJECTIVE: The purpose of this study was to determine the minimal clinically important difference (MCID) for comfortable gait speed (CGS) associated with an improvement in the modified Rankin Scale (mRS) score for people between 20 to 60 days poststroke. DESIGN: This was a prospective, longitudinal, cohort study. METHODS: The participants in this study were 283 people with first-time stroke prospectively enrolled in the ongoing Locomotor Experience Applied Post Stroke (LEAPS) multi-site randomized clinical trial. Comfortable gait speed was measured and mRS scores were obtained at 20 and 60 days poststroke. Improvement of >or=1 on the mRS was used to detect meaningful change in disability level. RESULTS: Mean (SD) CGS was 0.18 (0.16) m/s at 20 days and 0.39 (0.22) m/s at 60 days poststroke. Among all participants, 47.3% experienced an improvement in disability level >or=1. The MCID was estimated as an improvement in CGS of 0.16 m/s anchored to the mRS. LIMITATIONS: Because the mRS is not a gait-specific measure of disability, the estimated MCID for CGS was only 73.9% sensitive and 57.0% specific for detecting improvement in mRS scores. CONCLUSIONS: We estimate that the MCID for gait speed among patients with subacute stroke and severe gait speed impairments is 0.16 m/s. Patients with subacute stroke who increase gait speed >or=0.16 m/s are more likely to experience a meaningful improvement in disability level than those who do not. Clinicians can use this reference value to develop goals and interpret progress in patients with subacute stroke. [ABSTRACT FROM AUTHOR]

Purpose: To determine the feasibility of simultaneous multi-slice (SMS) real-time MRI (RT-MRI) at 0.55T for the evaluation of cardiac function., Methods: Cardiac CINE MRI is routinely used to evaluate left-ventricular (LV) function. The standard is sequential multi-slice balanced SSFP (bSSFP) over a stack of short-axis slices using electrocardiogram (ECG) gating and breath-holds. SMS has been used in CINE imaging to reduce the number of breath-holds by a factor of 2-4 at 1.5T, 3T, and recently at 0.55T. This work aims to determine if SMS is similarly effective in the RT-MRI evaluation of cardiac function. We used an SMS bSSFP pulse sequence with golden-angle spirals at 0.55T with an SMS factor of three. We cover the LV with three acquisitions for SMS, and nine for single-band (SB). Imaging was performed on 9 healthy volunteers and 1 patient with myocardial fibrosis and sternal wires. A spatio-temporal constrained reconstruction is used, with regularization parameters selected by a board-certified cardiologist. Images were quantitatively analyzed with a normalized contrast and an Edge Sharpness (ES) score., Results: There was a statistically significant 2-fold difference in contrast between SMS and SB and no significant difference in ES score. The contrast for SMS and SB were 13.38/29.05 at mid-diastole and 10.79/22.26 at end-systole; the ES scores for SMS and SB were 1.77/1.83 at mid-diastole and 1.50/1.72 at end-systole., Conclusions: SMS cardiac RT-MRI at 0.55T is feasible and provides sufficient blood-myocardium contrast to evaluate LV function in three slices simultaneously without any gating or periodic motion assumptions., (© 2024 The Author(s). Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Ferroptosis is a specific form of cell death characterized by excessive accumulation of cellular lipid peroxides. Ferroptosis is closely associated with various diseases, inhibition of which may help alleviate multi-organ injury caused by ischemia-reperfusion and enhance the anti-tumor effect by promoting the immunity of T cells. However, clinical approved drugs targeting ferroptosis process remain rare. In this study, we unexpectedly found that (R)-crizotinib, the first-generation ALK inhibitor, has potent inhibitory activity against ferroptosis across various cell lines. Moreover, its chiral molecule (S)-crizotinib, which was considered to share no common targets with (R)-crizotinib, also suppresses ferroptosis with an efficacy similar to that of (R)-crizotinib. We further demonstrated that both crizotinib enantiomers inhibit ferroptosis independently of their known targets, but through a common mechanism involving the targeting of AGPAT3-mediated synthesis of ether-linked polyunsaturated fatty acids (PE-O-PUFA), which are known to promote lipid-ROS generation and ferroptosis. In line with their activity in cell lines, (R)-crizotinib and (S)-crizotinib effectively mitigate renal ischemia-reperfusion injury in mice. Furthermore, the two compounds also inhibit lipid-ROS accumulation in CD8 + T cells in draining lymph nodes of B16-F10 subcutaneous xenograft mice, thereby promoting anti-tumor effects. Collectively, our study firstly reports a common activity shared by (R)-crizotinib and (S)-crizotinib in ferroptosis regulation. As a clinically approved drug, (R)-crizotinib has well-established pharmacokinetics and safety, which makes it a promising candidate for repurposing. Given the current lack of FDA-approved ferroptosis inhibitors, our findings suggest therapeutically repurposing (R)-crizotinib as well as its enantiomer (S)-crizotinib for treating ferroptosis-related diseases., (© 2024. The Author(s).)

Purpose: Directly imaging the function of cerebral perforating arteries could provide valuable insight into the pathology of cerebral small vessel diseases (cSVD). Arterial pulsatility has been identified as a useful biomarker for assessing vascular dysfunction. In this study, we investigate the feasibility and reliability of using dual velocity encoding (VENC) phase-contrast MRI (PC-MRI) to measure the pulsatility of cerebral perforating arteries at 7 T., Methods: Twenty participants, including 12 young volunteers and 8 elder adults, underwent high-resolution 2D PC-MRI scans with VENCs of 20 cm/s and 40 cm/s at 7T. The sensitivity of perforator detection and the reliability of pulsatility measurement of cerebral perforating arteries using dual-VENC PC-MRI were evaluated by comparison with the single-VENC data. The effects of temporal resolution in the PC-MRI acquisition and aging on the pulsatility measurements were investigated., Results: Compared to the single VENCs, dual-VENC PC-MRI provided improved sensitivity of perforator detection and more reliable pulsatility measurements. Temporal resolution impacted the pulsatility measurements, as decreasing temporal resolution led to an underestimation of pulsatility. Elderly adults had elevated pulsatility in cerebral perforating arteries compared to young adults, but there was no difference in the number of detected perforators between the two age groups., Conclusion: Dual-VENC PC-MRI is a reliable imaging method for the assessment of pulsatility of cerebral perforating arteries, which could be useful as a potential imaging biomarker of aging and cSVD., (© 2024 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Early evidence-based medical interventions to improve patient outcomes after traumatic brain injury (TBI) are lacking. In patients admitted to the ICU after TBI, optimization of nutrition is an emerging field of interest. Specialized enteral nutrition (EN) formulas that include immunonutrition containing omega-3 polyunsaturated fatty acids (n-3 PUFAs) have been developed and are used for their proposed anti-inflammatory and proimmune properties; however, their use has not been rigorously studied in human TBI populations. A single-center, retrospective, descriptive observational study was conducted at the LAC + USC Medical Center. Patients with severe TBI (sTBI, Glasgow Coma Scale score ≤ 8) who remained in the ICU for ≥2 weeks and received EN were identified between 2017 and 2022 using the institutional trauma registry. Those who received immunonutrition formulas containing n-3 PUFAs were compared with those who received standard, polymeric EN with regard to baseline characteristics, clinical markers of inflammation and immune function, and short-term clinical outcomes. A total of 151 patients with sTBI were analyzed. Those who received immunonutrition with n-3 PUFA supplementation were more likely to be male, younger, Hispanic/Latinx, and have polytrauma needing non-central nervous system surgery. No differences in clinical markers of inflammation or infection rate were found. In multivariate regression analysis, immunonutrition was associated with reduced hospital length of stay (LOS). ICU LOS was also reduced in the subgroup of patients with polytrauma and TBI. This study identifies important differences in patient characteristics and outcomes associated with the EN formula prescribed. Study results can directly inform a prospective pragmatic study of immunonutrition with n-3 PUFA supplementation aimed to confirm the biomechanistic and clinical benefits of the intervention., (©Roy A. Poblete et al., 2024; Published by Mary Ann Liebert, Inc.)

Objective: This study identifies key characteristics to help build a physical liver computed tomography (CT) phantom for radiomics harmonization; particularly, the higher-order texture metrics., Materials and Methods: CT scans of a radiomics phantom comprising of 18 novel 3D printed inserts with varying size, shape, and material combinations were acquired on a 64-slice CT scanner (Brilliance 64, Philips Healthcare). The images were acquired at 120 kV, 250 mAs, CTDIvol of 16.36 mGy, 2 mm slice thickness, and iterative noise-reduction reconstruction (iDose, Philips Healthcare, Andover, MA). Radiomics analysis was performed using the Cancer Imaging Phenomics Toolkit (CaPTk), following automated segmentation of 3D regions of interest (ROI) of the 18 inserts. The findings were compared to three additional ROI obtained of an anthropomorphic liver phantom, a patient liver CT scan, and a water phantom, at comparable imaging settings. Percentage difference in radiomic metrics values between phantom and tissue was used to assess the biological equivalency and <10% was used to claim equivalent., Results: The HU for all 18 ROI from the phantom ranged from -30 to 120 which is within clinically observed HU range of the liver, showing that our phantom material (T3-6B) is representative of biological CT tissue densities (liver) with >50% radiomic features having <10% difference from liver tissue. Based on the assessment of the Neighborhood Gray Tone Difference Matrix (NGTDM) metrics it is evident that the water phantom ROI show extreme values compared to the ROIs from the phantom. This result may further reinforce the difference between a structureless quantity such as water HU values and tissue HU values found in liver., Conclusion: The 3-D printed patterns of the constructed radiomics phantom cover a wide span of liver tissue textures seen in CT images. Using our results, texture metrics can be selectively harmonized to establish clinically relevant and reliable radiomics panels., (© 2024 The Authors. Journal of Applied Clinical Medical Physics is published by Wiley Periodicals, Inc. on behalf of The American Association of Physicists in Medicine.)

Objective: This study assesses the robustness of first-order radiomic texture features namely interquartile range (IQR), coefficient of variation (CV) and standard deviation (SD) derived from computed tomography (CT) images by varying dose, reconstruction algorithms and slice thickness using scans of a uniform water phantom, a commercial anthropomorphic liver phantom, and a human liver in-vivo., Materials and Methods: Scans were acquired on a 16 cm detector GE Revolution Apex Edition CT scanner with variations across three different nominal slice thicknesses: 0.625, 1.25, and 2.5 mm, three different dose levels: CTDIvol of 13.86 mGy for the standard dose, 40% reduced dose and 60% reduced dose and two different reconstruction algorithms: a deep learning image reconstruction (DLIR-high) algorithm and a hybrid iterative reconstruction (IR) algorithm ASiR-V50% (AV50) were explored, varying one at a time. To assess the effect of non-linear modifications of images by AV50 and DLIR-high, images of the water phantom were also reconstructed using filtered back projection (FBP). Quantitative measures of IQR, CV and SD were extracted from twelve pre-selected, circular (1 cm diameter) regions of interest (ROIs) capturing different texture patterns across all scans., Results: Across all scans, imaging, and reconstruction settings, CV, IQR and SD were observed to increase with reduction in dose and slice thickness. An exception to this observation was found when using FBP reconstruction. Lower values of CV, IQR and SD were observed in DLIR-high reconstructions compared to AV50 and FBP. The Poisson statistics were more stringently noted in FBP than DLIR-high and AV50, due to the non-linear nature of the latter two algorithms., Conclusion: Variation in image noise due to dose reduction algorithms, tube current, and slice thickness show a consistent trend across phantom and patient scans. Prospective evaluation across multiple centers, scanners and imaging protocols is needed for establishing quality assurance standards of radiomics., (© 2023 The Authors. Journal of Applied Clinical Medical Physics is published by Wiley Periodicals, Inc. on behalf of The American Association of Physicists in Medicine.)

Background and Aims: Pseudocirrhosis is a poorly understood acquired morphologic change of the liver that occurs in the setting of metastatic malignancy and radiographically resembles cirrhosis. Pseudocirrhosis has been primarily described in metastatic breast carcinoma, with few case reports arising from other primary malignancies. We present 29 cases of pseudocirrhosis, including several cases from primary malignancies not previously described., Methods: Radiologic, clinical, demographic, and biomedical data were collected retrospectively and analyzed. We compared clinical and radiologic characteristics and outcomes between patients with pseudocirrhosis arising in metastatic breast cancer and non-breast primary malignancies., Results: Among the 29 patients, 14 had breast cancer and 15 had non-breast primaries including previously never reported primaries associated with pseudocirrhosis, melanoma, renal cell carcinoma, appendiceal carcinoid, and cholangiocarcinoma. Median time from cancer diagnosis to development of pseudocirrhosis was 80.8 months for patients with primary breast cancer and 29.8 months for non-breast primary (p = 0.02). Among all patients, 15 (52%) had radiographic features of portal hypertension. Radiographic evidence of portal hypertension was identified in 28.6% of breast cancer patients, compared to 73.3% of those with non-breast malignancies (p = 0.03)., Conclusion: Pseudocirrhosis has most commonly been described in the setting of metastatic breast cancer but occurs in any metastatic disease to the liver. Our study suggests that portal hypertensive complications are more common in the setting of non-breast primary cancers than in metastatic breast cancer. Prior exposure to multiple chemotherapeutic agents, and agents known to cause sinusoidal injury, is a common feature but not essential for the development of pseudocirrhosis., (© 2024. The Author(s).)

Introduction: Renal cell carcinoma (RCC) is the ninth most common cancer worldwide, with clear cell RCC (ccRCC) being the most frequent histological subtype. The tumor immune microenvironment (TIME) of ccRCC is an important factor to guide treatment, but current assessments are tissue-based, which can be time-consuming and resource-intensive. In this study, we used radiomics extracted from clinically performed computed tomography (CT) as a noninvasive surrogate for CD68 tumor-associated macrophages (TAMs), a significant component of ccRCC TIME., Methods: TAM population was measured by CD68+/PanCK+ ratio and tumor-TAM clustering was measured by normalized K function calculated from multiplex immunofluorescence (mIF). A total of 1,076 regions on mIF slides from 78 patients were included. Radiomic features were extracted from multiphase CT of the ccRCC tumor. Statistical machine learning models, including random forest, Adaptive Boosting, and ElasticNet, were used to predict TAM population and tumor-TAM clustering., Results: The best models achieved an area under the ROC curve of 0.81 (95% CI: [0.69, 0.92]) for TAM population and 0.77 (95% CI: [0.66, 0.88]) for tumor-TAM clustering, respectively., Conclusion: Our study demonstrates the potential of using CT radiomics-derived imaging markers as a surrogate for assessment of TAM in ccRCC for real-time treatment response monitoring and patient selection for targeted therapies and immunotherapies., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Objective: To assess the effect of body muscle and fat metrics on the development of radiologic incisional hernia (IH) following robotic nephrectomy., Materials and Methods: We retrospectively reviewed the records of patients who underwent robotic nephrectomy for kidney tumors between 2011 and 2017. All pre- and postoperative CTs were re-reviewed by experienced radiologists for detection of radiologic IH and calculation of the following metrics using Synapse 3D software: cross-sectional psoas muscle mass at the level of L3 and L4 as well as subcutaneous and visceral fat areas. Sarcopenia was defined as psoas muscle index below the lowest quartile. Cox proportional hazard model was constructed to examine the association between muscle and fat metrics and the risk of developing radiologic IH., Results: A total of 236 patients with a median (IQR) age of 64 (54-70) years were included in this study. In a median (IQR) follow-up of 23 (14-38) months, 62 (26%) patients developed radiologic IH. On Cox proportional hazard model, we were unable to detect an association between sarcopenia and risk of IH development. In terms of subcutaneous fat change from pre-op, both lower and higher values were associated with IH development (HR (95% CI) 2.1 (1.2-3.4), p = 0.01 and 2.4 (1.4-4.1), p < 0.01 for < Q1 and ≥ Q3, respectively). Similar trend was found for visceral fat area changes from pre-op with a HR of 2.8 for < Q1 and 1.8 for ≥ Q3., Conclusion: Both excessive body fat gain and loss are associated with development of radiologic IH in patients undergoing robotic nephrectomy., (© 2023. The Author(s).)

Background: Neoadjuvant chemotherapy (NAC) is the standard of care in muscle-invasive bladder cancer (MIBC). However, treatment is intense, and the overall benefit is small, necessitating effective biomarkers to identify patients who will benefit most., Objective: To characterize cell-free DNA (cfDNA) methylation in patients receiving NAC in SWOG S1314, a prospective cooperative group trial, and to correlate the methylation signatures with pathologic response at radical cystectomy., Design, Setting, and Participants: SWOG S1314 is a prospective cooperative group trial for patients with MIBC (cT2-T4aN0M0, ≥5 mm of viable tumor), with a primary objective of evaluating the coexpression extrapolation (COXEN) gene expression signature as a predictor of NAC response, defined as achieving pT0N0 or ≤pT1N0 at radical cystectomy. For the current exploratory analysis, blood samples were collected prospectively from 72 patients in S1314 before and during NAC, and plasma cfDNA methylation was measured using the Infinium MethylationEPIC BeadChip array., Intervention: No additional interventions besides plasma collection., Outcome Measurements and Statistical Analysis: Differential methylation between pathologic responders (≤pT1N0) and nonresponders was analyzed, and a classifier predictive of treatment response was generated using the Random Forest machine learning algorithm., Results and Limitations: Using prechemotherapy plasma cfDNA, we developed a methylation-based response score (mR-score) predictive of pathologic response. Plasma samples collected after the first cycle of NAC yielded mR-scores with similar predictive ability. Furthermore, we used cfDNA methylation data to calculate the circulating bladder DNA fraction, which had a modest but independent predictive ability for treatment response. In a model combining mR-score and circulating bladder DNA fraction, we correctly predicted pathologic response in 79% of patients based on their plasma collected at baseline and after one cycle of chemotherapy. Limitations of this study included a limited sample size and relatively low circulating bladder DNA levels., Conclusions: Our study provides the proof of concept that cfDNA methylation can be used to generate classifiers of NAC response in bladder cancer patients., Patient Summary: In this exploratory analysis of S1314, we demonstrated that cell-free DNA methylation can be profiled to generate biomarker signatures associated with neoadjuvant chemotherapy response. With validation in additional cohorts, this minimally invasive approach may be used to predict chemotherapy response in locally advanced bladder cancer and perhaps also in metastatic disease., (Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Introduction: 1.5 Tesla (1.5T) remain a significant field strength for brain imaging worldwide. Recent computer simulations and clinical studies at 3T MRI have suggested that dynamic susceptibility contrast (DSC) MRI using a 30° flip angle ("low-FA") with model-based leakage correction and no gadolinium-based contrast agent (GBCA) preload provides equivalent relative cerebral blood volume (rCBV) measurements to the reference-standard acquisition using a single-dose GBCA preload with a 60° flip angle ("intermediate-FA") and model-based leakage correction. However, it remains unclear whether this holds true at 1.5T. The purpose of this study was to test this at 1.5T in human high-grade glioma (HGG) patients., Methods: This was a single-institution cross-sectional study of patients who had undergone 1.5T MRI for HGG. DSC-MRI consisted of gradient-echo echo-planar imaging (GRE-EPI) with a low-FA without preload (30°/P-); this then subsequently served as a preload for the standard intermediate-FA acquisition (60°/P+). Both normalized (nrCBV) and standardized relative cerebral blood volumes (srCBV) were calculated using model-based leakage correction (C+) with IBNeuro™ software. Whole-enhancing lesion mean and median nrCBV and srCBV from the low- and intermediate-FA methods were compared using the Pearson's, Spearman's and intraclass correlation coefficients (ICC)., Results: Twenty-three HGG patients composing a total of 31 scans were analyzed. The Pearson and Spearman correlations and ICCs between the 30°/P-/C+ and 60°/P+/C+ acquisitions demonstrated high correlations for both mean and median nrCBV and srCBV., Conclusion: Our study provides preliminary evidence that for HGG patients at 1.5T MRI, a low FA, no preload DSC-MRI acquisition can be an appealing alternative to the reference standard higher FA acquisition that utilizes a preload., Competing Interests: Author KS was employed IQ-AI Ltd and Imaging Biometrics LLC. 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 © 2023 Shiroishi, Weinert, Cen, Varghese, Dondlinger, Prah, Mendoza, Nazemi, Ameli, Amini, Shohas, Chen, Bigjahan, Zada, Chen, Neman-Ebrahim, Chang, Chow, Fan, Yang, Attenello, Ye, Kim, Patel, Lerner, Acharya, Hu, Quarles, Boxerman, Wu and Schmainda.)

To date, studies investigating radiomics-based predictive models have tended to err on the side of data-driven or exploratory analysis of many thousands of extracted features. In particular, spatial assessments of texture have proven to be especially adept at assessing for features of intratumoral heterogeneity in oncologic imaging, which likewise may correspond with tumor biology and behavior. These spatial assessments can be generally classified as spatial filters, which detect areas of rapid change within the grayscale in order to enhance edges and/or textures within an image, or neighborhood-based methods, which quantify gray-level differences of neighboring pixels/voxels within a set distance. Given the high dimensionality of radiomics datasets, data dimensionality reduction methods have been proposed in an attempt to optimize model performance in machine learning studies; however, it should be noted that these approaches should only be applied to training data in order to avoid information leakage and model overfitting. While area under the curve of the receiver operating characteristic is perhaps the most commonly reported assessment of model performance, it is prone to overestimation when output classifications are unbalanced. In such cases, confusion matrices may be additionally reported, whereby diagnostic cut points for model predicted probability may hold more clinical significance to clinical colleagues with respect to related forms of diagnostic testing., Competing Interests: GRM is a consultant for Canon Medical Systems, USA. VAD is a consultant for Radmetrix and Westat and serves on the advisory board for DeepTek. The 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. The author(s) BKKF, BAV and GRM declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2023 Varghese, Fields, Hwang, Duddalwar, Matcuk and Cen.)

Objectives: To evaluate the performance of machine learning-augmented MRI-based radiomics models for predicting response to neoadjuvant chemotherapy (NAC) in soft tissue sarcomas., Methods: Forty-four subjects were identified retrospectively from patients who received NAC at our institution for pathologically proven soft tissue sarcomas. Only subjects who had both a baseline MRI prior to initiating chemotherapy and a post-treatment scan at least 2 months after initiating chemotherapy and prior to surgical resection were included. 3D ROIs were used to delineate whole-tumor volumes on pre- and post-treatment scans, from which 1708 radiomics features were extracted. Delta-radiomics features were calculated by subtraction of baseline from post-treatment values and used to distinguish treatment response through univariate analyses as well as machine learning-augmented radiomics analyses., Results: Though only 4.74% of variables overall reached significance at p ≤ 0.05 in univariate analyses, Laws Texture Energy (LTE)-derived metrics represented 46.04% of all such features reaching statistical significance. ROC analyses similarly failed to predict NAC response, with AUCs of 0.40 (95% CI 0.22-0.58) and 0.44 (95% CI 0.26-0.62) for RF and AdaBoost, respectively., Conclusion: Overall, while our result was not able to separate NAC responders from non-responders, our analyses did identify a subset of LTE-derived metrics that show promise for further investigations. Future studies will likely benefit from larger sample size constructions so as to avoid the need for data filtering and feature selection techniques, which have the potential to significantly bias the machine learning procedures., (© 2023. The Author(s).)

Obstructive sleep apnea (OSA) may lead to white mater (WM) disruptions and cognitive deficits. However, no studies have investigated the full extent of the brain WM, and its associations with cognitive deficits in OSA remain unclear. We thus applied diffusion tensor imaging (DTI) tractography with multi-fiber models and used atlas-based bundle-specific approach to investigate the WM abnormalities for various tracts of the cerebral cortex, thalamus, brainstem, and cerebellum in patients with untreated OSA. We enrolled 100 OSA patients and 63 healthy controls. Fractional anisotropy (FA) and mean diffusivity (MD) values mapped on 33 regions of interest including WM tracts of cortex, thalamus, brainstem, and cerebellum were obtained from tractography-based reconstructions. We compared FA/MD values between groups and correlated FA/MD with clinical data in the OSA group after controlling for age and body mass index. OSA patients showed significantly lower FA values in multiple WM fibers including corpus callosum, inferior fronto-occipital fasciculus, middle/superior longitudinal fasciculi, thalamic radiations, and uncinate (FDR <0.05). Higher FA values were found in medial lemniscus of patients compared to controls (FDR <0.05). Lower FA values of rostrum of corpus callosum correlated with lower visual memory performance in OSA group (p < .005). Our quantitative DTI analysis demonstrated that untreated OSA could negatively impact the integrity of pathways more broadly, including brainstem structures such as medial lemniscus, in comparison to previous findings. Fiber tract abnormalities of the rostral corpus callosum were associated with impaired visual memory in untreated OSA may provide insights into the related pathomechanism., (© 2023 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Importance: Live feedback in the operating room is essential in surgical training. Despite the role this feedback plays in developing surgical skills, an accepted methodology to characterize the salient features of feedback has not been defined., Objective: To quantify the intraoperative feedback provided to trainees during live surgical cases and propose a standardized deconstruction for feedback., Design, Setting, and Participants: In this qualitative study using a mixed methods analysis, surgeons at a single academic tertiary care hospital were audio and video recorded in the operating room from April to October 2022. Urological residents, fellows, and faculty attending surgeons involved in robotic teaching cases during which trainees had active control of the robotic console for at least some portion of a surgery were eligible to voluntarily participate. Feedback was time stamped and transcribed verbatim. An iterative coding process was performed using recordings and transcript data until recurring themes emerged., Exposure: Feedback in audiovisual recorded surgery., Main Outcomes and Measures: The primary outcomes were the reliability and generalizability of a feedback classification system in characterizing surgical feedback. Secondary outcomes included assessing the utility of our system., Results: In 29 surgical procedures that were recorded and analyzed, 4 attending surgeons, 6 minimally invasive surgery fellows, and 5 residents (postgraduate years, 3-5) were involved. For the reliability of the system, 3 trained raters achieved moderate to substantial interrater reliability in coding cases using 5 types of triggers, 6 types of feedback, and 9 types of responses (prevalence-adjusted and bias-adjusted κ range: a 0.56 [95% CI, 0.45-0.68] minimum for triggers to a 0.99 [95% CI, 0.97-1.00] maximum for feedback and responses). For the generalizability of the system, 6 types of surgical procedures and 3711 instances of feedback were analyzed and coded with types of triggers, feedback, and responses. Significant differences in triggers, feedback, and responses reflected surgeon experience level and surgical task being performed. For example, as a response, attending surgeons took over for safety concerns more often for fellows than residents (prevalence rate ratio [RR], 3.97 [95% CI, 3.12-4.82]; P = .002), and suturing involved more errors that triggered feedback than dissection (RR, 1.65 [95% CI, 1.03-3.33]; P = .007). For the utility of the system, different combinations of trainer feedback had associations with rates of different trainee responses. For example, technical feedback with a visual component was associated with an increased rate of trainee behavioral change or verbal acknowledgment responses (RR, 1.11 [95% CI, 1.03-1.20]; P = .02)., Conclusions and Relevance: These findings suggest that identifying different types of triggers, feedback, and responses may be a feasible and reliable method for classifying surgical feedback across several robotic procedures. Outcomes suggest that a system that can be generalized across surgical specialties and for trainees of different experience levels may help galvanize novel surgical education strategies.

Background Most low- and middle-income countries lack access to organized breast cancer screening, and women with lumps may wait months for diagnostic assessment. Purpose To demonstrate that artificial intelligence (AI) software applied to breast US images obtained with low-cost portable equipment and by minimally trained observers could accurately classify palpable breast masses for triage in a low-resource setting. Materials and Methods This prospective multicenter study evaluated participants with at least one palpable mass who were enrolled in a hospital in Jalisco, Mexico, from December 2017 through May 2021. Orthogonal US images were obtained first with portable US with and without calipers of any findings at the site of lump and adjacent tissue. Then women were imaged with standard-of-care (SOC) US with Breast Imaging Reporting and Data System assessments by a radiologist. After exclusions, 758 masses in 300 women were analyzable by AI, with outputs of benign, probably benign, suspicious, and malignant. Sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were determined. Results The mean patient age ± SD was 50.0 years ± 12.5 (range, 18-92 years) and mean largest lesion diameter was 13 mm ± 8 (range, 2-54 mm). Of 758 masses, 360 (47.5%) were palpable and 56 (7.4%) malignant, including six ductal carcinoma in situ. AI correctly identified 47 or 48 of 49 women (96%-98%) with cancer with either portable US or SOC US images, with AUCs of 0.91 and 0.95, respectively. One circumscribed invasive ductal carcinoma was classified as probably benign with SOC US, ipsilateral to a spiculated invasive ductal carcinoma. Of 251 women with benign masses, 168 (67%) imaged with SOC US were classified as benign or probably benign by AI, as were 96 of 251 masses (38%, P < .001) with portable US. AI performance with images obtained by a radiologist was significantly better than with images obtained by a minimally trained observer. Conclusion AI applied to portable US images of breast masses can accurately identify malignancies. Moderate specificity, which could triage 38%-67% of women with benign masses without tertiary referral, should further improve with AI and observer training with portable US. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Slanetz in this issue.

Rationale and Objectives: Work-life experience of physicians is a driver of work engagement vs. burnout. We aimed to determine individual and institutional factors affecting work-life experience of the clinical faculty at a large tertiary care academic medical center., Materials and Methods: The Department of Radiology clinical faculty (n = 62) were surveyed electronically in October 2022. Twenty-three questions, consisting of multiple choice, Yes/No, and Likert scale ratings were administered to obtain demographic information and data for life outside of work, life at work, and work-life integration for the prior 12 months. Work engagements in terms of clinical, research, administrative, and education; work practices including engagement in extra work and remote work; life responsibilities; and utilization of work-life balance strategies were analyzed for percentages and differences in seniority levels and genders. Ratings of faculty work engagement and life integration strategies were assessed utilizing a 1-5 Likert scale. Descriptive statistics were utilized to report mean, standard deviation, median, Q1 and Q3 for continuous measurements, while count and percentage for categories measurements. Comparisons between seniority and gender categories were conducted using independent t-test or Wilcoxon rank sum test depending on data normality assessed through histogram analysis. Chi-square test was used to make comparisons for categorical data. When encountered with small cell (category with <5 count), Fisher's exact test was used for 2 × 2 table analysis and Freeman-Halton test was used for comparisons with more than two categories. SAS 9.4 was used for the data analysis., Results: Twenty-eight faculty (M:F = 17:11) responded to the survey (survey response rate 45%). The vast majority of faculty reported working extra hours, with 40% working at least 10 hours extra per week. Total of 42.9% reported performing clinical work in the extra hours worked. Total 70.4% of faculty had caregiver responsibilities and 64.3% reported other individual stresses (e.g., financial, family/social, health-related), which required consistent demand of time and effort. A total of 35.7% of faculty reported not being able to balance competing life and work demands. A total of 21.4% respondents reported not utilizing any individual healthy lifestyle choices on a consistent basis over the prior 12 months. Protected time off work and remote work were perceived as effective strategies to provide adequate work-life balance; however, remote work engagement was relatively minor and 35.7% bought back vacation. Total 53.6% respondents reported a level 4 (out of 5) rating for work being meaningful and being positively engaged in their work., Conclusion: Institutions should invest in providing the infrastructure for physician work-life balance and in facilitating healthy lifestyle choices for physicians., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Background: Neurofibrillary tangle pathology detected with tau-PET correlates closely with neuronal injury and cognitive symptoms in Alzheimer's disease (AD). Complexity of rs-fMRI has been demonstrated to decrease with cognitive decline in AD., Objective: We hypothesize that the rs-fMRI complexity provides an index for tau-related neuronal injury and cognitive decline in the AD process., Methods: Data was obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI3) and the Estudio de la Enfermedad de Alzheimer en Jalisciences (EEAJ) study. Associations between tau-PET and rs-fMRI complexity were calculated. Potential pathways relating complexity to cognitive function mediated through tau-PET were assessed by path analysis., Results: We found significant negative correlations between rs-fMRI complexity and tau-PET in medial temporal lobe of both cohorts, and associations of rs-fMRI complexity with cognitive scores were mediated through tau-PET., Conclusion: The association of rs-fMRI complexity with tau-PET and cognition, suggests that a reduction in complexity is indicative of tau-related neuropathology and cognitive decline in AD processes.

Introduction: This study investigates how quantitative texture analysis can be used to non-invasively identify novel radiogenomic correlations with clear cell renal cell carcinoma (ccRCC) biomarkers., Methods: The Cancer Genome Atlas-Kidney Renal Clear Cell Carcinoma open-source database was used to identify 190 sets of patient genomic data that had corresponding multiphase contrast-enhanced CT images in The Cancer Imaging Archive. 2,824 radiomic features spanning fifteen texture families were extracted from CT images using a custom-built MATLAB software package. Robust radiomic features with strong inter-scanner reproducibility were selected. Random forest, AdaBoost, and elastic net machine learning (ML) algorithms evaluated the ability of the selected radiomic features to predict the presence of 12 clinically relevant molecular biomarkers identified from the literature. ML analysis was repeated with cases stratified by stage (I/II vs. III/IV) and grade (1/2 vs. 3/4). 10-fold cross validation was used to evaluate model performance., Results: Before stratification by tumor grade and stage, radiomics predicted the presence of several biomarkers with weak discrimination (AUC 0.60-0.68). Once stratified, radiomics predicted KDM5C, SETD2, PBRM1, and mTOR mutation status with acceptable to excellent predictive discrimination (AUC ranges from 0.70 to 0.86)., Conclusions: Radiomic texture analysis can potentially identify a variety of clinically relevant biomarkers in patients with ccRCC and may have a prognostic implication., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Ferroptosis is a nonapoptotic form of cell death characterized by iron-dependent lipid peroxidation and has been implicated in multiple pathological conditions. Glutathione peroxidase 4 (GPX4) plays an essential role in inhibiting ferroptosis by eliminating lipid peroxide using glutathione (GSH) as a reductant. In this study, we found Ellman's reagent DTNB and a series of disulfide compounds, including disulfiram (DSF), an FDA-approved drug, which protect cells from erastin-induced ferroptosis. Mechanistically, DTNB or DSF is conjugated to multiple cysteine residues in GPX4 and disrupts GPX4 interaction with HSC70, an adaptor protein for chaperone mediated autophagy, thus preventing GPX4 degradation induced by erastin. In addition, DSF ameliorates concanavalin A induced acute liver injury by suppressing ferroptosis in a mouse model. Our work reveals a novel regulatory mechanism for GPX4 protein stability control. We also discover disulfide compounds as a new class of ferroptosis inhibitors and suggest therapeutic repurposing of DSF in treating ferroptosis-related diseases.

Objectives: To investigate the accuracy, sensitivity, and specificity of contrast-enhanced ultrasound (CEUS) for detection of parathyroid adenomas and compare it to those of 4-dimensional computed tomography (4DCT), which has been established as a reliable, effective tool for preoperative localization of parathyroid adenomas., Methods: About 27 patients with suspected parathyroid pathology underwent imaging evaluations with 4DCT and CEUS and 22 patients subsequently underwent surgical resection of parathyroid lesions. 4DCT and CEUS were performed and interpreted by consensus of two expert radiologists with extensive experience in each modality. Assessment for the side, z-axis (craniocaudal axis), and quadrant of the pathologically proven lesion was performed based on the surgical report., Results: For single-gland disease, the accuracy for CEUS localization to the correct quadrant and side were 81.0 and 90.1% respectively. For single-gland disease, the accuracy for 4DCT localization to the correct quadrant and side were 81.0 and 90.5% respectively. 4DCT localization sensitivity and specificity were comparable to those for CEUS. 4DCT allowed for accurate diagnosis in multigland disease in contradistinction to CEUS., Conclusions: CEUS is a noninvasive, real-time imaging technique that has relatively high diagnostic confidence and accuracy of localization which are comparable to the accuracy of 4DCT for preoperative parathyroid adenoma detection, characterization, and localization. This technique should be considered for primary preoperative diagnosis, especially in younger patients., (© 2021 American Institute of Ultrasound in Medicine.)

Objective: To perform a systematic assessment and analyze the quality of radiomics methodology in current literature in the evaluation of renal masses using the Radiomics Quality Score (RQS) approach., Methods: We systematically reviewed recent radiomics literature in renal masses published in PubMed, EMBASE, Elsevier, and Web of Science. Two reviewers blinded by each other's scores evaluated the quality of radiomics methodology in studies published from 2015 to August 2021 using the RQS approach. Owing to the diversity in the imaging modalities and radiomics applications, a meta-analysis could not be performed., Results: Based on our inclusion/exclusion criteria, a total of 87 published studies were included in our study. The highest RQS was noted in three categories: reporting of clinical utility, gold standard, and feature reduction. The average RQS of the two reviewers ranged from 5 ≤ RQS≤19, with the maximum attainable RQS being 36. Very few (7/87 i.e., 8%) studies received an average RQS that ranged from 17 < RQS≤19, which represents studies with the highest RQS in our study. Many (39/87 i.e., 45%) studies received an average RQS that ranged from 13 < RQS≤15. No significant interreviewer scoring differences were observed., Conclusions: We report that the overall scientific quality and reporting of radiomics studies in renal masses is suboptimal, and subsequent studies should bolster current deficiencies to improve reporting of radiomics methodologies., Advances in Knowledge: The RQS approach is a meaningful quantitative scoring system to assess radiomics methodology quality and supports a comprehensive evaluation of the radiomics approach before its incorporation into clinical practice.

Background: A substantial proportion of patients undergo treatment for renal masses where active surveillance or observation may be more appropriate., Objective: To determine whether radiomic-based machine learning platforms can distinguish benign from malignant renal masses., Design, Setting, and Participants: A prospectively maintained single-institutional renal mass registry was queried to identify patients with a computed tomography-proven clinically localized renal mass who underwent partial or radical nephrectomy., Intervention: Radiomic analysis of preoperative scans was performed. Clinical and radiomic variables of importance were identified through decision tree analysis, which were incorporated into Random Forest and REAL Adaboost predictive models., Outcome Measurements and Statistical Analysis: The primary outcome was the degree of congruity between the virtual diagnosis and final pathology. Subanalyses were performed for small renal masses and patients who had percutaneous renal mass biopsies as part of their workup. Receiver operating characteristic curves were used to evaluate each model's discriminatory function., Results and Limitations: A total of 684 patients met the selection criteria. Of them, 76% had renal cell carcinoma; 57% had small renal masses, of which 73% were malignant. Predictive modeling differentiated benign pathology from malignant with an area under the curve (AUC) of 0.84 (95% confidence interval [CI] 0.79-0.9). In small renal masses, radiomic analysis yielded a discriminatory AUC of 0.77 (95% CI 0.69-0.85). When negative and nondiagnostic biopsies were supplemented with radiomic analysis, accuracy increased from 83.3% to 93.4%., Conclusions: Radiomic-based predictive modeling may distinguish benign from malignant renal masses. Clinical factors did not substantially improve the diagnostic accuracy of predictive models. Enhanced diagnostic predictability may improve patient selection before surgery and increase the utilization of active surveillance protocols., Patient Summary: Not all kidney tumors are cancerous, and some can be watched. We evaluated a new method that uses radiographic features invisible to the naked eye to distinguish benign masses from true cancers and found that it can do so with acceptable accuracy., (Copyright © 2021 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background Studies suggest the presence of sex differences in hypertension prevalence and its associated outcomes in atherosclerosis and stroke. We hypothesized a higher intracranial atherosclerosis burden among men with hypertension and acute ischemic stroke compared with women. Methods and Results A multicenter retrospective study was performed from a prospective database identifying patients with hypertension presenting with intracranial atherosclerosis-related acute ischemic stroke and imaged with intracranial vessel wall magnetic resonance imaging. Proximal and distal plaques on vessel wall magnetic resonance imaging were scored. Negative binomial models assessed the associations between plaque-count and sex and the interaction between sex and treatment. Covariates were selected by a least absolute shrinkage and selection operator procedure. Sixty-one patients (n=42 men) were included. There were no significant differences in demographic or cardiovascular risk factors except for smoking history ( P =0.002). Adjusted total and proximal plaque counts for men were 1.6 (95% CI, 1.2-2.1; P <0.01) and 1.4 (95% CI, 1.0-1.9; P =0.03) times as high as women, respectively. Female sex was more protective for proximal plaque if treated for hypertension. The risk ratio of men versus women was 1.5 (95% CI, 1.0-2.1) for treated patients. The risk ratio of men versus women was 0.7 (95% CI, 0.4-1.3) for untreated patients. The relative difference between these 2 risk ratios was 2.0 (95% CI, 1.1-3.9), which was statistically significant from the interaction test, P =0.04. Conclusions Men with hypertension with acute ischemic stroke have significantly higher total and proximal plaque burdens than women. Women with hypertension on anti-hypertensive medication showed a greater reduction in proximal plaque burden than men. Further confirmation with a longitudinal cohort study is needed and may help evaluate whether different treatment guidelines for managing hypertension by sex can help reduce intracranial atherosclerosis burden and ultimately acute ischemic stroke risk.

Purpose: We attempt to understand the relationship between surgeon technical skills, cognitive workload, and errors during a simulated robotic dissection task. Materials and Methods: Participant surgeons performed a robotic surgery dissection exercise. Participants were grouped based on surgical experience. Technical skills were evaluated utilizing the validated Global Evaluative Assessment of Robotic Skills (GEARS) assessment tool. The dissection task was evaluated for errors during active dissection or passive retraction maneuvers. We quantified cognitive workload of surgeon participants as an index of cognitive activity (ICA), derived from task-evoked pupillary response metrics; ICA ranged 0 to 1, with 1 representing maximum ICA. Generalized estimating equation (GEE) was used for all modelings to establish relationships between surgeon technical skills, cognitive workload, and errors. Results: We found a strong association between technical skills as measured by multiple GEARS domains (depth perception, force sensitivity, and robotic control) and passive errors, with higher GEARS scores associated with a lower relative risk of errors (all p  < 0.01). For novice surgeons, as average GEARS scores increased, the average estimated ICA decreased. In contrast, as average GEARS increased for expert surgeons, the average estimated ICA increased. When exhibiting optimal technical skill (maximal GEARS scores), novices and experts reached a similar range of ICA scores (ICA: 0.47 and 0.42, respectively). Conclusions: This study found that there is an optimal cognitive workload level for surgeons of all experience levels during our robotic surgical exercise. Select technical skill domains were strong predictors of errors. Future research will explore whether an ideal cognitive workload range truly optimizes surgical training and reduces surgical errors.

Objectives: To evaluate the utility of CT-based radiomics signatures in discriminating low-grade (grades 1-2) clear cell renal cell carcinomas (ccRCC) from high-grade (grades 3-4) and low TNM stage (stages I-II) ccRCC from high TNM stage (stages III-IV)., Methods: A total of 587 subjects (mean age 60.2 years ± 12.2; range 22-88.7 years) with ccRCC were included. A total of 255 tumors were high grade and 153 were high stage. For each subject, one dominant tumor was delineated as the region of interest (ROI). Our institutional radiomics pipeline was then used to extract 2824 radiomics features across 12 texture families from the manually segmented volumes of interest. Separate iterations of the machine learning models using all extracted features (full model) as well as only a subset of previously identified robust metrics (robust model) were developed. Variable of importance (VOI) analysis was performed using the out-of-bag Gini index to identify the top 10 radiomics metrics driving each classifier. Model performance was reported using area under the receiver operating curve (AUC)., Results: The highest AUC to distinguish between low- and high-grade ccRCC was 0.70 (95% CI 0.62-0.78) and the highest AUC to distinguish between low- and high-stage ccRCC was 0.80 (95% CI 0.74-0.86). Comparable AUCs of 0.73 (95% CI 0.65-0.8) and 0.77 (95% CI 0.7-0.84) were reported using the robust model for grade and stage classification, respectively. VOI analysis revealed the importance of neighborhood operation-based methods, including GLCM, GLDM, and GLRLM, in driving the performance of the robust models for both grade and stage classification., Conclusion: Post-validation, CT-based radiomics signatures may prove to be useful tools to assess ccRCC grade and stage and could potentially add to current prognostic models. Multiphase CT-based radiomics signatures have potential to serve as a non-invasive stratification schema for distinguishing between low- and high-grade as well as low- and high-stage ccRCC., Key Points: • Radiomics signatures derived from clinical multiphase CT images were able to stratify low- from high-grade ccRCC, with an AUC of 0.70 (95% CI 0.62-0.78). • Radiomics signatures derived from multiphase CT images yielded discriminative power to stratify low from high TNM stage in ccRCC, with an AUC of 0.80 (95% CI 0.74-0.86). • Models created using only robust radiomics features achieved comparable AUCs of 0.73 (95% CI 0.65-0.80) and 0.77 (95% CI 0.70-0.84) to the model with all radiomics features in classifying ccRCC grade and stage, respectively., (© 2021. European Society of Radiology.)

Integrating liquid biopsies of circulating tumor cells (CTCs) and cell-free DNA (cfDNA) with other minimally invasive measures may yield more comprehensive disease profiles. We evaluated the feasibility of concurrent cellular and molecular analysis of CTCs and cfDNA combined with radiomic analysis of CT scans from patients with metastatic castration-resistant PC (mCRPC). CTCs from 22 patients were enumerated, stained for PC-relevant markers, and clustered based on morphometric and immunofluorescent features using machine learning. DNA from single CTCs, matched cfDNA, and buffy coats was sequenced using a targeted amplicon cancer hotspot panel. Radiomic analysis was performed on bone metastases identified on CT scans from the same patients. CTCs were detected in 77% of patients and clustered reproducibly. cfDNA sequencing had high sensitivity (98.8%) for germline variants compared to WBC. Shared and unique somatic variants in PC-related genes were detected in cfDNA in 45% of patients (MAF > 0.1%) and in CTCs in 92% of patients (MAF > 10%). Radiomic analysis identified a signature that strongly correlated with CTC count and plasma cfDNA level. Integration of cellular, molecular, and radiomic data in a multi-parametric approach is feasible, yielding complementary profiles that may enable more comprehensive non-invasive disease modeling and prediction.

Introduction: Glycemic gap (GG), as determined by the difference between glucose and the hemoglobin A1c (HbA1c)-derived estimated average glucose (eAG), is associated with poor outcomes in various clinical settings. There is a paucity of data describing GG and outcomes after aneurysmal subarachnoid hemorrhage (aSAH). Our main objectives were to evaluate the association of admission glycemic gap (aGG) with in-hospital mortality and with poor composite outcome and to compare aGG's predictive value to admission serum glucose. Secondary outcomes were the associations between aGG and neurologic complications including vasospasm and delayed cerebral ischemia following aSAH. Methods: We retrospectively reviewed 119 adult patients with aSAH admitted to a single tertiary care neuroscience ICU. Spearman method was used for correlation for non-normality of data. Area under the curve (AUC) for Receiver Operating Characteristic (ROC) curve was used to estimate prediction accuracy of aGG and admission glucose on outcome measures. Multivariable analyses were conducted to assess the value of aGG in predicting in-hospital poor composite outcome and death. Results: Elevated aGG at or above 30 mg/dL was identified in 79 (66.4%) of patients. Vasospasm was not associated with the elevated aGG. Admission GG correlated with admission serum glucose ( r = 0.94, p < 0.01), lactate ( r = 0.41, p < 0.01), procalcitonin ( r = 0.38, p < 0.01), and Hunt and Hess score ( r = 0.51, p < 0.01), but not with HbA1c ( r = 0.02, p = 0.82). Compared to admission glucose, aGG had a statistically significantly improved accuracy in predicting inpatient mortality (AUC mean ± SEM: 0.77 ± 0.05 vs. 0.72 ± 0.06, p = 0.03) and trended toward statistically improved accuracy in predicting poor composite outcome (AUC: 0.69 ± 0.05 vs. 0.66 ± 0.05, p = 0.07). When controlling for aSAH severity, aGG was not independently associated with delayed cerebral ischemia, poor composite outcome, and in-hospital mortality. Conclusion: Admission GG was not independently associated with in-hospital mortality or poor outcome in a population of aSAH. An aGG ≥30 mg/dL was common in our population, and further study is needed to fully understand the clinical importance of this biomarker., Competing Interests: The 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 © 2021 Sun, Poblete, Nguyen, Bulic, Kim-Tenser, Marehbian, Cen and Emanuel.)

Objectives: Our purpose was to differentiate between malignant from benign soft tissue neoplasms using a combination of MRI-based radiomics metrics and machine learning., Methods: Our retrospective study identified 128 histologically diagnosed benign (n = 36) and malignant (n = 92) soft tissue lesions. 3D ROIs were manually drawn on 1 sequence of interest and co-registered to other sequences obtained during the same study. One thousand seven hundred eight radiomics features were extracted from each ROI. Univariate analyses with supportive ROC analyses were conducted to evaluate the discriminative power of predictive models constructed using Real Adaptive Boosting (Adaboost) and Random Forest (RF) machine learning approaches., Results: Univariate analyses demonstrated that 36.89% of individual radiomics varied significantly between benign and malignant lesions at the p ≤ 0.05 level. Adaboost and RF performed similarly well, with AUCs of 0.77 (95% CI 0.68-0.85) and 0.72 (95% CI 0.63-0.81), respectively, after 10-fold cross-validation. Restricting the machine learning models to only sequences extracted from T2FS and STIR sequences maintained comparable performance, with AUCs of 0.73 (95% CI 0.64-0.82) and 0.75 (95% CI 0.65-0.84), respectively., Conclusion: Machine learning decision classifiers constructed from MRI-based radiomics features show promising ability to preoperatively discriminate between benign and malignant soft tissue masses. Our approach maintains applicability even when the dataset is restricted to T2FS and STIR fluid-sensitive sequences, which may bolster practicality in clinical application scenarios by eliminating the need for complex co-registrations for multisequence analysis., Key Points: • Predictive models constructed from MRI-based radiomics data and machine learning-augmented approaches yielded good discriminative power to correctly classify benign and malignant lesions on preoperative scans, with AUCs of 0.77 (95% CI 0.68-0.85) and 0.72 (95% CI 0.63-0.81) for Real Adaptive Boosting (Adaboost) and Random Forest (RF), respectively. • Restricting the models to only use metrics extracted from T2 fat-saturated (T2FS) and Short-Tau Inversion Recovery (STIR) sequences yielded similar performance, with AUCs of 0.73 (95% CI 0.64-0.82) and 0.75 (95% CI 0.65-0.84) for Adaboost and RF, respectively. • Radiomics-based machine learning decision classifiers constructed from multicentric data more closely mimic the real-world practice environment and warrant additional validation ahead of prospective implementation into clinical workflows., (© 2021. European Society of Radiology.)

Developing a highly sensitive immunoassay for tumor biomarkers is particularly important in bioanalysis and early disease diagnosis. In this work, a simple one-pot solvothermal method was developed for controllable synthesis of well-dispersed PtCo alloyed nanodendrites (PtCo NDs) by using l-carnosine as the co-structure-directing agent. The PtCo NDs had a large specific surface area and provided abundant active sites available for electrocatalytic oxygen reduction reaction (ORR). Based on the highly enhanced currents of the ORR, a novel label-free electrochemical immunosensor was fabricated for highly sensitive assay of carbohydrate antigen 15-3 (CA15-3). The sensor showed a wide linear range of 0.1-200 U mL -1 and a low limit of detection (LOD) down to 0.0114 U mL -1 (S/N = 3), in turn exploring its application to diluted human serum samples with satisfactory results. This study provides a feasible platform for monitoring other tumor markers in clinical diagnosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Purpose: Racial and ethnic disparities have exacerbated during the COVID-19 pandemic as the healthcare system is overwhelmed. While Hispanics are disproportionately affected by COVID-19, little is known about ethnic disparities in the hospital settings. This study investigates imaging utilization and clinical outcomes between Hispanic and non-Hispanic COVID-19 patients in the Emergency Department (ED) and during hospitalization., Methods: Through retrospective chart review, we included 331 symptomatic COVID-19 patients (mean age 53.2 years) at a metropolitan healthcare system from March to June 2020. Poisson regression was used to compare diagnostic imaging utilization and clinical outcomes between Hispanic and non-Hispanic patients., Results: After adjusting for confounders, no statistically significant difference was found between Hispanic and non-Hispanic patients for the number of weekly chest X-rays. Results were categorized into four clinical outcomes: ED management (0.16 ± 0.05 vs. 0.14 ± 0.8, p:0.79); requiring inpatient management (1.31 ± 0.11 vs. 1.46 ± 0.16, p:0.43); ICU admission without invasive ventilation (1.4 ± 0.17 vs. 1.35 ± 0.26, p:0.86); and ICU admission and ventilator support (3.29 ± 0.22 vs. 3.59 ± 0.37, p:0.38). There were no statistically significant relative differences in adjusted prevalence rate between ethnic groups for all clinical outcomes (p > 0.05). There was a statistically significant longer adjusted length of stay (days) in non-Hispanics for two subcohorts: inpatient management (8.16 ± 0.31 vs. 9.72 ± 0.5, p < 0.01) and ICU admission without invasive ventilation (10.39 ± 0.57 vs. 13.45 ± 1.13, p < 0.01)., Conclusions: For Hispanic and non-Hispanic COVID-19 patients in the ED or hospitalized, there were no statistically significant differences in imaging utilization and clinical outcomes., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: Increased arterial stiffness has been shown to be one of the earliest markers of cerebrovascular dysfunction. As a surrogate marker of arterial stiffness, pulse wave velocity (PWV) quantifications are generally carried out on central and peripheral arteries. The purpose of this study was to develop and evaluate an MRI approach to assess carotid stiffness by measuring carotid PWV (cPWV) using a fast oblique-sagittal phase-contrast MRI sequence., Methods: In 29 volunteers, a single-slice oblique-sagittal phase-contrast MRI sequence with retrospective cardiac gating was used to quantify blood velocity waveforms along a vessel segment covering the common carotid artery (CCA) and the internal carotid artery (ICA). The CCA-ICA segment length was measured from a region of interest selected on the magnitude image. Phase-contrast MRI-measured velocities were also used to quantify the ICA pulsatility index along with cPWV quantification., Results: The mean value of cPWV calculated using the middle upslope area algorithm was 2.86 ± 0.71 and 3.97 ± 1.14 m/s in young and elderly subjects, respectively. Oblique-sagittal phase-contrast MRI-derived cPWV measurements showed excellent intrascan and interscan repeatability. cPWV and ICA pulsatility index were significantly greater in older subjects compared to those in the young subjects (P < .01 and P = .01, respectively). Also, increased cPWV values were associated with elevated systolic blood pressure (β = 0.05, P = .03)., Conclusion: This study demonstrated that oblique-sagittal phase-contrast MRI is a feasible technique for the quantification of both cPWV and ICA pulsatility index and showed their potential utility in evaluating cerebroarterial aging and age-related neurovascular disorders., (© 2021 International Society for Magnetic Resonance in Medicine.)

Objective: To compare transoral robotic surgery (TORS) versus non-TORS tongue resection procedures performed for obstructive sleep apnea from January 2010 to September 2015 using a national database, focusing on patient characteristics, performance of concurrent procedures, operative time, length of hospital stay, and postoperative complications., Methods: A cohort of adults undergoing TORS and non-TORS tongue resection procedures was identified in the Nationwide Inpatient Sample, a publicly-available national administrative database incorporating a stratified sample of hospital discharge records. Outcomes were annual case volumes, prolonged (≥3 days) hospital stay, and complications. Statistical analyses examined potential associations between TORS and prolonged hospital stay and complications., Results: From 2010 to 2015, 5709 hospital discharges included tongue resection surgery to treat obstructive sleep apnea. There was a gradual decline and stabilization in overall volumes, with the proportion of TORS use showing an initial increase, followed by a decrease and rebound increase. TORS patients were less likely to undergo concurrent nasal surgery (15% vs. 44%, P < .01), but there was no association between the use of TORS and concurrent palatal surgery. TORS use was not associated with concurrent hypopharyngeal surgery overall, but it was associated with specific types of hypopharyngeal surgery. TORS use was associated with patient age, payor, and certain hospital characteristics. TORS use was associated with an increased risk of prolonged hospital stay (33% vs. 25%, P = .045) but was not associated with complications., Conclusion: This study provides insight into TORS use in tongue resection surgery for obstructive sleep apnea during this period of early TORS adoption., Level of Evidence: Level 3 (cohort study). Laryngoscope, 131:E1735-E1740, 2021., (© 2020 American Laryngological, Rhinological and Otological Society Inc, "The Triological Society" and American Laryngological Association (ALA).)

Objectives: Using a radiomics framework to quantitatively analyze tumor shape and texture features in three dimensions, we tested its ability to objectively and robustly distinguish between benign and malignant renal masses. We assessed the relative contributions of shape and texture metrics separately and together in the prediction model., Materials and Methods: Computed tomography (CT) images of 735 patients with 539 malignant and 196 benign masses were segmented in this retrospective study. Thirty-three shape and 760 texture metrics were calculated per tumor. Tumor classification models using shape, texture, and both metrics were built using random forest and AdaBoost with tenfold cross-validation. Sensitivity analyses on five sub-cohorts with respect to the acquisition phase were conducted. Additional sensitivity analyses after multiple imputation were also conducted. Model performance was assessed using AUC., Results: Random forest classifier showed shape metrics featuring within the top 10% performing metrics regardless of phase, attaining the highest variable importance in the corticomedullary phase. Convex hull perimeter ratio is a consistently high-performing shape feature. Shape metrics alone achieved an AUC ranging 0.64-0.68 across multiple classifiers, compared with 0.67-0.75 and 0.68-0.75 achieved by texture-only and combined models, respectively., Conclusion: Shape metrics alone attain high prediction performance and high variable importance in the combined model, while being independent of the acquisition phase (unlike texture). Shape analysis therefore should not be overlooked in its potential to distinguish benign from malignant tumors, and future radiomics platforms powered by machine learning should harness both shape and texture metrics., Key Points: • Current radiomics research is heavily weighted towards texture analysis, but quantitative shape metrics should not be ignored in their potential to distinguish benign from malignant renal tumors. • Shape metrics alone can attain high prediction performance and demonstrate high variable importance in the combined shape and texture radiomics model. • Any future radiomics platform powered by machine learning should harness both shape and texture metrics, especially since tumor shape (unlike texture) is independent of the acquisition phase and more robust from the imaging variations.

Objective: The objective of this study was to evaluate the robustness and reproducibility of computed tomography-based texture analysis (CTTA) metrics extracted from CT images of a customized texture phantom built for assessing the association of texture metrics to three-dimensional (3D) printed progressively increasing textural heterogeneity., Materials and Methods: A custom-built 3D-printed texture phantom comprising of six texture patterns was used to evaluate the robustness and reproducibility of a radiomics panel under a variety of routine abdominal imaging protocols. The phantom was scanned on four CT scanners (Philips, Canon, GE, and Siemens) to assess reproducibility. The robustness assessment was conducted by imaging the texture phantom across different CT imaging parameters such as slice thickness, field of view (FOV), tube voltage, and tube current for each scanner. The texture panel comprised of 387 features belonging to 15 subgroups of texture extraction methods (e.g., Gray-level Co-occurrence Matrix: GLCM). Twelve unique image settings were tested on all the four scanners (e.g., FOV125). Interclass correlation two-way mixed with absolute agreement (ICC3) was used to assess the robustness and reproducibility of radiomic features. Linear regression was used to test the association between change in radiomic features and increased texture heterogeneity. Results were summarized in heat maps., Results: A total of 5612 (23.2%) of 24 090 features showed excellent robustness and reproducibility (ICC ≥ 0.9). Intensity, GLCM 3D, and gray-level run length matrix (GLRLM) 3D features showed best performance. Among imaging variables, changes in slice thickness affected all metrics more intensely compared to other imaging variables in reducing the ICC3. From the analysis of linear trend effect of the CTTA metrics, the top three metrics with high linear correlations across all scanners and scanning settings were from the GLRLM 2D/3D and discrete cosine transform (DCT) texture family., Conclusion: The choice of scanner and imaging protocols affect texture metrics. Furthermore, not all CTTA metrics have a linear association with linearly varying texture patterns., (© 2021 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

Cerebral small vessel disease (cSVD) affects arterioles, capillaries, and venules and can lead to cognitive impairments and clinical symptomatology of vascular cognitive impairment and dementia (VCID). VCID symptoms are similar to Alzheimer's disease (AD) but the neurophysiologic alterations are less well studied, resulting in no established biomarkers. The purpose of this study was to evaluate cerebral blood flow (CBF) measured by 3D pseudo-continuous arterial spin labeling (pCASL) as a potential biomarker of VCID in a cohort of elderly Latinx subjects at risk of cSVD. Forty-five elderly Latinx subjects (12 males, 69 ± 7 years) underwent repeated MRI scans ∼6 weeks apart. CBF was measured using 3D pCASL in the whole brain, white matter and 4 main vascular territories (leptomeningeal anterior, middle, and posterior cerebral artery (leptoACA, leptoMCA, leptoPCA), as well as MCA perforator). The test-retest repeatability of CBF was assessed by intra-class correlation coefficient (ICC) and within-subject coefficient of variation (wsCV). Absolute and relative CBF was correlated with gross cognitive measures and domain specific assessment of executive and memory function, vascular risks, and Fazekas scores and volumes of white matter hyperintensity (WMH). Neurocognitive evaluations were performed using Montreal Cognitive Assessment (MoCA) and neuropsychological test battery in the Uniform Data Set v3 (UDS3). Good to excellent test-retest repeatability was achieved (ICC = 0.77-0.85, wsCV 3-9%) for CBF measurements in the whole brain, white matter, and 4 vascular territories. Relative CBF normalized by global mean CBF in the leptoMCA territory was positively correlated with the executive function composite score, while relative CBF in the leptoMCA and MCA perforator territory was positively correlated with MoCA scores, controlling for age, gender, years of education, and testing language. Relative CBF in WM was negatively correlated with WMH volume and MoCA scores, while relative leptoMCA CBF was positively correlated with WMH volume. Reliable 3D pCASL CBF measurements were achieved in the cohort of elderly Latinx subjects. Relative CBF in the leptomeningeal and perforator MCA territories were the most likely candidate biomarker of VCID. These findings need to be replicated in larger cohorts with greater variability of stages of cSVD., Competing Interests: The 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 © 2021 Jann, Shao, Ma, Cen, D’Orazio, Barisano, Yan, Casey, Lamas, Staffaroni, Kramer, Ringman and Wang.)

Background: Efforts to reduce nosocomial spread of COVID-19 have resulted in unprecedented disruptions in clinical workflows and numerous unexpected stressors for imaging departments across the country. Our purpose was to more precisely evaluate these impacts on radiologists through a nationwide survey., Methods: A 43-item anonymous questionnaire was adapted from the AO Spine Foundation's survey and distributed to 1521 unique email addresses using REDCap™ (Research Electronic Data Capture). Additional invitations were sent out to American Society of Emergency Radiology (ASER) and Association of University Radiologists (AUR) members. Responses were collected over a period of 8 days. Descriptive analyses and multivariate modeling were performed using SAS v9.4 software., Results: A total of 689 responses from radiologists across 44 different states met the criteria for inclusion in the analysis. As many as 61% of respondents rated their level of anxiety with regard to COVID-19 to be a 7 out of 10 or greater, and higher scores were positively correlated the standardized number of COVID-19 cases in a respondent's state (RR = 1.11, 95% CI: 1.02-1.21, p = 0.01). Citing the stressor of "personal health" was a strong predictor of higher anxiety scores (RR 1.23; 95% CI: 1.13-1.34, p < 0.01). By contrast, participants who reported needing no coping methods were more likely to self-report lower anxiety scores (RR 0.4; 95% CI: 0.3-0.53, p < 0.01)., Conclusion: COVID-19 has had a significant impact on radiologists across the nation. As these unique stressors continue to evolve, further attention must be paid to the ways in which we may continue to support radiologists working in drastically altered practice environments and in remote settings., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Direct ethylene glycol fuel cells (DEGFCs) and water splitting devices have received intensive interest during the past few decades. However, the commonly used Pt catalysts are seriously restricted by the high cost and very low resistance to CO-like intermediates during the catalysis. Herein, a general and simple solvothermal method was developed to synthesize three-dimensional (3D) bimetallic alloyed PtRh nanodendrites (NDs) for ethylene glycol oxidation reaction (EGOR) and hydrogen evolution reaction (HER). Citric acid (CA) and cetyltrimethylammonium chloride (CTAC) played important roles in formation of such dendritic structures. The optimized Pt 56 Rh 44 NDs displayed the greatest mass activity (MA) for EGOR in 0.5 M KOH, which was 2.6-fold higher than commercial Pt black, coupled with the remarkable increase in the HER activity with a decayed overpotential of 20.0 mV to drive a current density of 10 mA cm -2 relative to the homemade Pt 41 Rh 59 NDs (26.2 mV), Pt 81 Rh 19 NDs (26.2 mV), Pt black (44.3 mV), Pt/C (44.4 mV) and Rh NFs (37.3 mV). This work offers some constructive guidelines for synthesis of advanced Pt-based catalysts in such energy devices., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To characterize long-term repopulation of peripheral immune cells following alemtuzumab-induced lymphopenia in relapsing-remitting MS (RRMS), with a focus on regulatory cell types, and to explore associations with clinical outcome measures., Methods: The project was designed as a multicenter add-on longitudinal mechanistic study for RRMS patients enrolled in CARE-MS II, CARE-MS II extension at the University of Southern California and Stanford University, and an investigator-initiated study conducted at the Universities of British Columbia and Chicago. Methods involved collection of blood at baseline, prior to alemtuzumab administration, and at months 5, 11, 17, 23, 36, and 48 post-treatment. T cell, B cell, and natural killer (NK) cell subsets, chemokine receptor expression in T cells, in vitro cytokine secretion patterns, and regulatory T cell (Treg) function were assessed. Clinical outcomes, including expanded disability status score (EDSS), relapses, conventional magnetic resonance imaging (MRI) measures, and incidents of secondary autoimmunity were tracked., Results: Variable shifts in lymphocyte populations occurred over time in favor of CD4+ T cells, B cells, and NK cells with surface phenotypes characteristic of regulatory subsets, accompanied by reduced ratios of effector to regulatory cell types. Evidence of increased Treg competence was observed after each treatment course. CD4+ and CD8+ T cells that express CXCR3 and CCR5 and CD8+ T cells that express CDR3 and CCR4 were also enriched after treatment, indicating heightened trafficking potential in activated T cells. Patterns of repopulation were not associated with measures of clinical efficacy or secondary autoimmunity, but exploratory analyses using a random generalized estimating equation (GEE) Poisson model provide preliminary evidence of associations between pro-inflammatory cell types and increased risk for gadolinium (Gd+) enhancing lesions, while regulatory subsets were associated with reduced risk. In addition, the risk for T2 lesions correlated with increases in CD3+CD8+CXCR3+ cells., Conclusions: Lymphocyte repopulation after alemtuzumab treatment favors regulatory subsets in the T cell, B cell, and NK cell compartments. Clinical efficacy may reflect the sum of interactions among them, leading to control of potentially pathogenic effector cell types. Several immune measures were identified as possible biomarkers of lesion activity. Future studies are necessary to more precisely define regulatory and effector subsets and their contributions to clinical efficacy and risk for secondary autoimmunity in alemtuzumab-treated patients, and to reveal new insights into mechanisms of immunopathogenesis in MS., Trial Registration: Parent trials for this study are registered with ClinicalTrials.gov: CARE-MS II: NCT00548405, CARE-MS II extension: NCT00930553 and ISS: NCT01307332.

Background: Human immunoglobulin G (hIgG) includes four different subtypes (IgG1, IgG2, IgG3, and IgG4). Due to genetic variations, each IgG subtype contains different isoallotypes. It was previously shown that a Food and Drug Administration-approved monoclonal anti-IgG failed to recognize 2 of 15 recombinant, human IgG3 anti-Kell (K1) isoallotypes (rIgG3-03 and rIgG3-13) by indirect antiglobulin test (IAT)., Study Design and Methods: We expressed and purified 15 recombinant human rIgG3 anti-K1 isoallotypes and investigated their antigen binding and ability to induce phagocytosis using homozygous (KK) and heterozygous (Kk) K1-positive red blood cells (RBCs) by gel IAT, flow cytometry, and a monocyte monolayer assay (MMA) with peripheral blood monocytes and cultured inflammatory (M1) and anti-inflammatory (M2) macrophages., Results: MMA results showed that differences in the Fc region of rIgG3 anti-K1 led to distinctive phagocytic activity with both monocytes and M1 macrophages. rIgG3-18 and rIgG3-19 showed an enhanced ability to induce phagocytosis. Differences in Fc regions also led to variations in the number of antibodies bound to KK RBCs. Despite the differences in phagocytic activity, all 15 rIgG3 clones are predicted to induce clinically significant hemolysis if K1-positive blood was transfused into patients., Conclusion: These results argue that antiglobulin reagents that fail to detect isoallotype rIgG3-03 or rIgG3-13 could present a transfusion risk or lack of detection of a potentially clinically significant anti-K1 in hemolytic disease of the fetus and newborn., (© 2020 AABB.)

Background: Lymph node metastasis (LNM) of lung cancer is an important factor associated with prognosis. Dysregulated microRNAs (miRNAs) are becoming a new powerful tool to characterize tumorigenesis and metastasis. We have developed and validated a miRNA disease signature to predict LNM in lung adenocarcinoma (LUAD). Method: LUAD miRNAs and clinical data from The Cancer Genome Atlas (TCGA) were obtained and divided randomly into training (n = 259) and validation (n = 83) cohorts. A miRNA signature was built using least absolute shrinkage and selection operator (LASSO) (λ =-1.268) and logistic regression model. The performance of the miRNA signature was evaluated using the area under curve (AUC) of receiver operating characteristic curve (ROC). We performed decision curve analysis (DCA) to assess the clinical usefulness of the signature. We also conducted a miRNA-regulatory network analysis to look for potential genes engaged in LNM in LUAD. Result: Thirteen miRNAs were selected to build our miRNA disease signature. The model showed good calibration in the training cohort, with an AUC of 0.782 (95% CI: 0.725-0.839). In the validation cohort, AUC was 0.691 (95% CI: 0.575-0.806). DCA demonstrated that the miRNA signature was clinically useful. Conclusion: The miRNA disease signature can be used as a noninvasive method to predict LNM in patients with lung adenocarcinoma objectively and the signature achieved high accuracy for prediction.

Background: Immunoglobulin therapy including intravenous immunoglobulin (IVIg) has been used as an effective treatment for autoimmune/inflammatory conditions with few side effects. However, high-dose IVIg (1-2 g/kg) has been recognized as a cause of hemolytic anemia in non-blood group O patients. Hemolysis when observed has been due to anti-A/anti-B isoagglutinins contained in the IVIg. Recently, an isoagglutinin-reduced IVIg, whereby the anti-A and anti-B titers have been reduced by immunoaffinity chromatography, has been introduced; however, whether this new product is as efficacious as nonreduced immunoglobulin (Ig) or will result in less IVIg-associated hemolysis has not been resolved., Study Design and Methods: We used in vitro phagocytosis by monocytes and proinflammatory/anti-inflammatory macrophages, with isoagglutinin-reduced and -nonreduced Ig opsonized group A 1 , B, and A 1 B red blood cells, to estimate clinical significance of the IgG isoagglutinins. We also used immune thrombocytopenia (ITP) and rheumatoid arthritis (RA) mouse models to examine the in vivo efficacy of isoagglutinin-reduced versus -nonreduced Ig on the amelioration of the diseases., Results: In contrast to nonreduced Ig, phagocytosis was largely absent when isoagglutinin-reduced Ig was used at a concentration equivalent to a patient receiving 2 g/kg. The in vivo efficacy of isoagglutinin-reduced versus nonreduced Ig on the amelioration of experimental ITP and RA was similar, indicating no loss of efficacy due to the chromatographic removal of isoagglutinins., Conclusion: Isoagglutinin-reduced Ig should have efficacy similar to nonreduced Ig and result in less IVIg-associated hemolysis., (© 2019 AABB.)

OBJECTIVE. Liver transplant patients are monitored for rejection and hepatic fibrosis and often undergo liver biopsies. The purpose of the present study is to determine whether noninvasive shear wave elastography (SWE) can quantify fibrosis in liver transplant recipients, with the aim of decreasing and possibly eliminating unnecessary biopsies for patients with suspected or progressive hepatic fibrosis. MATERIALS AND METHODS. Between May 1, 2015, and December 31, 2017, our prospective study evaluated 111 adult liver transplant patients (age range, 23-79 years) who underwent 147 ultrasound (US) SWE examinations of the right hepatic lobe followed by biopsies. SWE values were compared with the histologic fibrosis (Metavir) scores of the biopsy samples. SWE threshold values were determined using classification and regression tree analysis by anchoring to the degree of fibrosis. The sensitivity, specificity, positive predictive value, and negative predictive value (with 95% CIs) were calculated on the basis of the threshold value. Overall prediction accuracy was estimated using the AUC value from the ROC curve. RESULTS. From the 147 US SWE examinations and liver biopsies, consistent threshold values were identified for patients with no or minimal fibrosis (Metavir scores of F0 and F1, respectively) compared with significant fibrosis (Metavir scores of F2, F3, or F4). A median SWE value of 1.76 m/s or less denoted no or minimal fibrosis, whereas a value greater than 1.76 m/s denoted significant fibrosis. The sensitivity of US SWE examinations in classifying fibrosis was 0.77 (95% CI, 0.5-0.93). The specificity, positive predictive value, and negative predictive value were 0.79 (95% CI, 0.71-0.86), 0.33 (95% CI, 0.19-0.49), and 0.96 (95% CI, 0.91-0.99), respectively. CONCLUSION. Liver transplant patients may avoid liver biopsy if US SWE examination shows a median shear wave velocity of 1.76 or less, which corresponds to a Metavir score of F0 or F1, denoting no or minimal fibrosis.

Objective: To identify the top brain regions affected by MS-specific atrophy (i.e., atrophy in excess of normal aging) and to test whether normal aging and MS-specific atrophy increase or decrease in these regions with age., Methods: Six hundred fifty subjects (2,790 MRI time points) were analyzed: 520 subjects with relapse-onset MS from a 5-year prospective cohort with annual standardized 1-mm 3D T1-weighted images (3DT1s; 2,483 MRIs) and 130 healthy controls with longitudinal 3DT1s (307 MRIs). Rates of change in all FreeSurfer regions (v5.3) and Structural Image Evaluation Using Normalization of Atrophy (SIENA) were estimated with mixed-effects models. All FreeSurfer regions were ranked by the MS-specific atrophy slope/standard error ratio (β MS × time /SE βMS × time ). In the top regions, age was added as an effect modifier to test whether MS-specific atrophy varied by age., Results: The top-ranked regions were all gray matter structures. For SIENA, normal aging increased from 0.01%/y at age 30 years to -0.31%/y at age 60 years (-0.11% ± 0.032%/decade, p < 0.01), whereas MS-specific atrophy decreased from -0.38%/y at age 30 years to -0.12%/y at age 60 years (0.09% ± 0.035%/decade, p = 0.01). Similarly, in the thalamus, normal aging increased from -0.15%/y at age 30 years to -0.62%/y at age 60 years (-0.16% ± 0.079%/decade, p < 0.05), and MS-specific atrophy decreased from -0.59%/y at age 30 years to -0.05%/y at age 60 years (0.18% ± 0.08%/decade, p < 0.05). In the putamen and caudate, normal aging and MS-specific atrophy did not vary by age., Conclusions: For SIENA and thalamic atrophy, the contribution of normal aging increases with age, but does not change in the putamen and caudate. This may have substantial implications to understand the biology of brain atrophy in MS., (Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)