Prevalence of Thyroid Nodules in Residents of Ukraine Exposed as Children or Adolescents to Iodine-131 from the Chornobyl Accident.

Background: Although childhood exposure to radioactive iodine-131 (I-131) is an established risk factor for thyroid cancer, evidence for an association with thyroid nodules is less clear. The objective of this study is to evaluate the association between childhood I-131 exposure and prevalence of ultrasound-detected thyroid nodules overall and by nodule histology/cytology (neoplastic/suspicious/non-neoplastic), size (<10 mm/≥10 mm), and number (single/multiple). Methods: This is a cross-sectional study of radiation dose (mean = 0.53 gray, range: 0.0003-31 gray) and screen-detected thyroid nodules conducted in 1998-2000 (median population age 21.5 years) in a cohort of 13,243 residents of Ukraine who were under 18 years at the time of the Chornobyl accident on April 26, 1986. Excess odds ratios per gray (excess odds ratio [EOR]/Gy) and confidence intervals (CIs) were estimated using logistic regression. Results: Among 13,078 eligible individuals, we identified 358 (2.7%) with at least one thyroid nodule. Significantly increased dose-response associations were found for all nodules and nodule groups with doses <5 Gy except individuals with non-neoplastic nodules. Among individuals with doses <5 Gy, the EOR/Gy for neoplastic nodules (5.35; CI: 2.19-15.5) was significantly higher than for non-neoplastic nodules (0.24; CI: 0.07-0.74), but the EOR/Gy did not vary by nodule size or number. Conclusions: Childhood exposure to I-131 is associated with an increased risk of thyroid nodules detected 12-14 years following exposure, and the risk for neoplastic nodules is higher than for non-neoplastic nodules. Analyses of incident thyroid nodules may help clarify dose-response patterns by nodule characteristics and provide insights into thyroid nodule etiology.

Radiation Dose Does Not Affect the Predictive Value of Thyroid Biopsy for Diagnosing Papillary Thyroid Cancer in a Belarusian Cohort Exposed to Chernobyl Fallout.

INTRODUCTION: The Chernobyl nuclear accident exposed residents of contaminated territories to substantial quantities of radioiodines and was followed by an increase in thyroid cancer, primarily papillary thyroid cancer (PTC), among exposed children and adolescents. Although thyroid biopsy is an essential component of screening programs following accidental exposure to radioiodines, it is unknown whether the predictive value of biopsy is affected by different levels of environmental exposure. METHODS: A cohort of 11,732 Belarusians aged ≤18 years at the time of the Chernobyl accident with individual thyroid radiation dose estimates was screened at least once 11-22 years later. Paired cytologic conclusions and histopathologic diagnoses were possible for 258 thyroid nodules from 238 cohort members. Cytologic conclusions were divided into five reporting categories, with all follicular lesion aspirates combined into a single indeterminate category. Standard performance indicators, risk of malignancy (ROM), and odds ratios for a correct cytologic conclusion were calculated, both overall and according to quintile of thyroid radiation dose. RESULTS: The arithmetic mean thyroid dose estimate for the study group was 1.73 Gy (range: 0.00-23.64 Gy). The final histopathologic diagnosis was cancer for 136 of 258 biopsies (52.7%; 135 papillary and 1 follicular). The overall ROM was 96.7% for cytologies definite for PTC, 83.7% for suspicious for PTC, 33.0% for indeterminate, 8.1% for benign, and 31.0% for non-diagnostic. The ROM showed little change according to level of radiation exposure. Overall, there was no association between thyroid radiation dose and the odds ratio for a correct cytologic conclusion (p = 0.24). When analyzed according to dose quintile, the odds ratio for a correct conclusion increased two-fold at 0.10-0.29 Gy compared to a dose of 0.00-0.09 Gy and decreased at doses of 0.3-24 Gy (p value for linear trend = 0.99). CONCLUSIONS: At radiation doses received by a cohort of young Belarusians exposed to radioiodines by the Chernobyl accident, the predictive value of thyroid biopsy for diagnosing PTC was not significantly affected by level of radiation exposure.

Maternal preconception stress produces sex-specific effects at the maternal:fetal interface to impact offspring development and phenotypic outcomes†.

Entering pregnancy with a history of adversity, including adverse childhood experiences and racial discrimination stress, is a predictor of negative maternal and fetal health outcomes. Little is known about the biological mechanisms by which preconception adverse experiences are stored and impact future offspring health outcomes. In our maternal preconception stress (MPS) model, female mice underwent chronic stress from postnatal days 28-70 and were mated 2 weeks post-stress. Maternal preconception stress dams blunted the pregnancy-induced shift in the circulating extracellular vesicle proteome and reduced glucose tolerance at mid-gestation, suggesting a shift in pregnancy adaptation. To investigate MPS effects at the maternal:fetal interface, we probed the mid-gestation placental, uterine, and fetal brain tissue transcriptome. Male and female placentas differentially regulated expression of genes involved in growth and metabolic signaling in response to gestation in an MPS dam. We also report novel offspring sex- and MPS-specific responses in the uterine tissue apposing these placentas. In the fetal compartment, MPS female offspring reduced expression of neurodevelopmental genes. Using a ribosome-tagging transgenic approach we detected a dramatic increase in genes involved in chromatin regulation in a PVN-enriched neuronal population in females at PN21. While MPS had an additive effect on high-fat-diet (HFD)-induced weight gain in male offspring, both MPS and HFD were necessary to induce significant weight gain in female offspring. These data highlight the preconception period as a determinant of maternal health in pregnancy and provides novel insights into mechanisms by which maternal stress history impacts offspring developmental programming.

The impact of feedback training on prediction of cancer clinical trial results.

INTRODUCTION: Funders must make difficult decisions about which squared treatments to prioritize for randomized trials. Earlier research suggests that experts have no ability to predict which treatments will vindicate their promise. We tested whether a brief training module could improve experts' trial predictions. METHODS: We randomized a sample of breast cancer and hematology-oncology experts to the presence or absence of a feedback training module where experts predicted outcomes for five recently completed randomized controlled trials and received feedback on accuracy. Experts then predicted primary outcome attainment for a sample of ongoing randomized controlled trials. Prediction skill was assessed by Brier scores, which measure the average deviation between their predictions and actual outcomes. Secondary outcomes were discrimination (ability to distinguish between positive and non-positive trials) and calibration (higher predictions reflecting higher probability of trials being positive). RESULTS: A total of 148 experts (46 for breast cancer, 54 for leukemia, and 48 for lymphoma) were randomized between May and December 2017 and included in the analysis (1217 forecasts for 25 trials). Feedback did not improve prediction skill (mean Brier score for control: 0.22, 95% confidence interval = 0.20-0.24 vs feedback arm: 0.21, 95% confidence interval = 0.20-0.23; p = 0.51). Control and feedback arms showed similar discrimination (area under the curve = 0.70 vs 0.73, p = 0.24) and calibration (calibration index = 0.01 vs 0.01, p = 0.81). However, experts in both arms offered predictions that were significantly more accurate than uninformative forecasts of 50% (Brier score = 0.25). DISCUSSION: A short training module did not improve predictions for cancer trial results. However, expert communities showed unexpected ability to anticipate positive trials.Pre-registration record: https://aspredicted.org/4ka6r.pdf.

Three-Dimensional Analysis of Metacarpal Head Articular Defects Created by Headless Screws.

Objectives: Headless screw fixation used to treat metacarpal neck and metacarpal shaft fractures is gaining popularity. The aim of the study is to determine the proportion of the metacarpal head articular surface that is compromised during retrograde insertion of headless screws. Methods: Metacarpal screw fixation through a metacarpal head starting point was performed using fluoroscopic guidance on 14 metacarpals. Headless compression screws, with a tail diameter of 3.6mm, were used. The specimens were subsequently skeletonized and digitized using a 3-dimensional surface scanner. The articular surface defects created by the screws were then determined using computer software. Screw position in the dorsal aspect of the metacarpal head was expressed as a percentage of the total volar-to-dorsal distance. Results: The 14 metacarpals studied consisted of 2 index, 4 long, 4 ring and 4 small metacarpals, taken from 4 hands. The average total metacarpal head surface area was 284.6 mm2 (range, 151.0-462.2 mm2); the average screw footprint in the metacarpal head was 13.3 mm2 (range, 10.3-17.4 mm2), which compromised a mean of 5.0% (3.0-7.8%) of the total cartilaginous metacarpal head surface area. In the sagittal plane, screw placement was found to lie in the dorsal 37.4% of the metacarpal head (range, 20.7-58.6%). Conclusion: The proportion of the articular surface area injured with retrograde insertion of headless compression screws into the metacarpal head is 5.0%. Screw placement is generally in the dorsal 37% of the metacarpal head.

Contrast-enhanced US Evaluation of Hepatocellular Carcinoma Response to Chemoembolization: A Prospective Multicenter Trial.

Background Contrast-enhanced (CE) US has been studied for use in the detection of residual viable hepatocellular carcinoma (HCC) after locoregional therapy, but multicenter data are lacking. Purpose To compare two-dimensional (2D) and three-dimensional (3D) CE US diagnostic performance with that of CE MRI or CT, the current clinical standard, in the detection of residual viable HCC after transarterial chemoembolization (TACE) in a prospective multicenter trial. Materials and Methods Participants aged at least 21 years with US-visible HCC scheduled for TACE were consecutively enrolled at one of three participating academic medical centers from May 2016 to March 2022. Each underwent baseline 2D and 3D CE US before TACE, 2D and 3D CE US 1-2 weeks and/or 4-6 weeks after TACE, and CE MRI or CT 4-6 weeks after TACE. CE US and CE MRI or CT were evaluated by three fellowship-trained radiologists for the presence or absence of viable tumors and were compared with reference standards of pathology (18%), angiography on re-treatment after identification of residual disease at 1-2-month follow-up imaging (31%), 4-8-month CE MRI or CT (42%), or short-term (approximately 1-2 months) CE MRI or CT if clinically decompensated and estimated viability was greater than 50% at imaging (9%). Diagnostic performance criteria, including sensitivity and specificity, were obtained for each modality and time point with generalized estimating equation analysis. Results A total of 132 participants were included (mean age, 64 years ± 7 [SD], 87 male). Sensitivity of 2D CE US 4-6 weeks after TACE was 91% (95% CI: 84, 95), which was higher than that of CE MRI or CT (68%; 95% CI: 58, 76; P < .001). Sensitivity of 3D CE US 4-6 weeks after TACE was 89% (95% CI: 81, 94), which was higher than that of CE MRI or CT (P < .001), with no evidence of a difference from 2D CE US (P = .22). CE MRI or CT had 85% (95% CI: 76, 91) specificity, higher than that of 4-6-week 2D and 3D CE US (70% [95% CI: 56, 80] and 67% [95% CI: 53, 78], respectively; P = .046 and P = .023, respectively). No evidence of differences in any diagnostic criteria were observed between 1-2-week and 4-6-week 2D CE US (P > .21). Conclusion The 2D and 3D CE US examinations 4-6 weeks after TACE revealed higher sensitivity in the detection of residual HCC than CE MRI or CT, albeit with lower specificity. Importantly, CE US performance was independent of follow-up time. Clinical trial registration no. NCT02764801 © RSNA, 2023 Supplemental material is available for this article.

Improved Tumor Control Following Radiosensitization with Ultrasound-Sensitive Oxygen Microbubbles and Tumor Mitochondrial Respiration Inhibitors in a Preclinical Model of Head and Neck Cancer.

Tumor hypoxia (oxygen deficiency) is a major contributor to radiotherapy resistance. Ultrasound-sensitive microbubbles containing oxygen have been explored as a mechanism for overcoming tumor hypoxia locally prior to radiotherapy. Previously, our group demonstrated the ability to encapsulate and deliver a pharmacological inhibitor of tumor mitochondrial respiration (lonidamine (LND)), which resulted in ultrasound-sensitive microbubbles loaded with O2 and LND providing prolonged oxygenation relative to oxygenated microbubbles alone. This follow-up study aimed to evaluate the therapeutic response to radiation following the administration of oxygen microbubbles combined with tumor mitochondrial respiration inhibitors in a head and neck squamous cell carcinoma (HNSCC) tumor model. The influences of different radiation dose rates and treatment combinations were also explored. The results demonstrated that the co-delivery of O2 and LND successfully sensitized HNSCC tumors to radiation, and this was also enhanced with oral metformin, significantly slowing tumor growth relative to unsensitized controls (p < 0.01). Microbubble sensitization was also shown to improve overall animal survival. Importantly, effects were found to be radiation dose-rate-dependent, reflecting the transient nature of tumor oxygenation.

Flexor Tendon Attritional Ruptures Following Distal Radius Volar Plate Fixation.

PURPOSE: To investigate patient and radiographic factors that may correlate with the time to flexor tendon rupture following volar plate fixation of distal radius fractures. METHODS: A total of 31 patients who underwent volar plate removal because of flexor tendon rupture were analyzed. Patient demographics and the interval from operative fixation until rupture were determined retrospectively. Volar tilt and lateral carpal alignment were measured radiographically. The Soong classification was used to grade volar plate prominence. The correlation between the duration to tendon rupture and volar tilt, carpal alignment, and age was evaluated. RESULTS: There were 7 men and 24 women. Mean age at the time of hardware removal and flexor tendon management was 66 years (n = 31). Radiographs were classified as Soong 1 (n = 24) and Soong 2 (n = 3). The mean measured volar tilt was -4° (range, -20°-+7°). The mean interval from operative fixation until complete tendon rupture was 4.9 years, (range, 0.3-13.1 years; n = 30). There was no correlation between the time interval to rupture and the magnitude of tilt, carpal alignment, or age at the time of operative fixation. CONCLUSIONS: Although volar plate prominence was present in all patients with flexor tendon ruptures, radiographic parameters including the degree of dorsal tilt, lateral carpal alignment, and patient age did not correlate with the time interval from fixation to tendon rupture. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic IV.

Varieties of Community Uncertainty and Clinical Equipoise.

The judgments of conscientious and informed experts play a central role in two elements of clinical equipoise. The first, and most widely discussed, element involves ensuring that no participant in a randomized trial is allocated to a level of treatment that everyone agrees is substandard. The second, and less often discussed, element involves ensuring that trials are likely to generate social value by producing the information necessary to resolve a clinically meaningful uncertainty or disagreement about the relative merits of a set of interventions. The distribution of judgments in expert communities can take many forms, each with important implications for whether a trial satisfies one or both elements of clinical equipoise. In this article we use a graphical approach to represent three ways in which expert community uncertainty can vary: by spread, modality, and skew. Understanding these different distributions of expert judgment has three important implications: it helps to make operational the requirement of social value, it shows that some conditions for initiating studies to promote social value diverge from common assumptions about clinical equipoise, and it has important implications for how trials should be designed and monitored, and what patients should be told during informed consent.

Tumoral oxygenation and biodistribution of Lonidamine oxygen microbubbles following localized ultrasound-triggered delivery.

Prior work has shown that microbubble-assisted delivery of oxygen improves tumor oxygenation and radiosensitivity, albeit over a limited duration. Lonidamine (LND) has been investigated because of its ability to stimulate glycolysis, lactate production, inhibit mitochondrial respiration, and inhibit oxygen consumption rates in tumors but suffers from poor bioavailability. The goal of this work was to characterize LND-loaded oxygen microbubbles and assess their ability to oxygenate a human head and neck squamous cell carcinoma (HNSCC) tumor model, while also assessing LND biodistribution. In tumors treated with surfactant-shelled microbubbles with oxygen core (SE61O2) and ultrasound, pO2 levels increased to a peak 19.5 ± 9.7 mmHg, 50 s after injection and returning to baseline after 120 s. In comparison, in tumors treated with SE61O2/LND and ultrasound, pO2 levels showed a peak increase of 29.0 ± 8.3 mmHg, which was achieved 70 s after injection returning to baseline after 300 s (p < 0.001). The co-delivery of O2andLNDvia SE61 also showed an improvement of LND biodistribution in both plasma and tumor tissues (p < 0.001). In summary, ultrasound-sensitive microbubbles loaded with O2 and LND provided prolonged oxygenation relative to oxygenated microbubbles alone, as well as provided an ability to locally deliver LND, making them more appropriate for clinical translation.

Label-free duplex SAMDI-MS screen reveals novel SARS-CoV-2 3CLpro inhibitors.

The 3-chymotrypsin-like cysteine protease (3CLpro) of severe acute respiratory syndrome conoravirus 2 (SARS-CoV-2) remains a promising therapeutic target to combat COVID-19. Our group recently described a novel duplexed biochemical assay that combines self-assembled monolayers of alkanethiolates on gold with matrix assisted laser desorption ionization (MALDI) time of flight (TOF) mass spectrometry (MS) to simultaneously measure 3CLpro and human rhinovirus 3C protease activities. This study describes applying the assay for the completion of a high-throughput duplexed screen of 300,000 diverse, drug-like small molecules in 3 days. The hits were confirmed and evaluated in dose response analyses against recombinant 3CLpro, HRV3C, and the human Cathepsin L proteases. The 3CLpro specific inhibitors were further assessed for activity in cellular cytotoxicity and anti-viral assays. Structure activity relationship studies informed on structural features required for activity and selectivity to 3CLpro over HRV3C. These results will guide the optimization of 3CLpro selective inhibitors to combat COVID-19 along with antiviral compounds against coronaviruses and rhinoviruses.

Relationship between lay and expert perceptions of COVID-19 vaccine development timelines in Canada and USA.

OBJECTIVES: Compare lay expectations of medical development to those of experts in the context of SARS-CoV-2 vaccine development. METHODS: A short online survey of experts and lay people measuring when participants believe important vaccine milestones would occur and how likely potential setbacks were. Samples of US and Canadian lay people recruited through Qualtrics. The expert sample was created through a contact network in vaccine development and supplemented with corresponding authors of recent scholarly review articles on vaccine development. RESULTS: In aggregate, lay people gave responses that were within 3 months of experts, tending to be later than experts for early milestones and earlier for later milestones. Median lay best estimates for when a vaccine would be available to the public were 08/2021 and 09/2021 for the US and Canadian samples, compared with 09-10/2021 for the experts. However, many individual lay responses showed more substantial disagreement with expert opinions, with 54% of lay best estimates of when a vaccine would be available to the public being before the median expert soonest estimate or after the median expert latest estimate. Lay people were much more pessimistic about vaccine development encountering setbacks than experts (median probability 59% of boxed warning compared with only 30% for experts). Misalignment between layperson and expert expectations was not explained by any demographic variables collected in our survey. CONCLUSION: Median lay expectations were generally similar to experts. At the individual level, however, lay people showed substantial variation with many believing milestones would occur much sooner than experts. Lay people were in general much more pessimistic about the prospect of setbacks than were experts.

Association between exposure to radioactive iodine after the Chernobyl accident and thyroid volume in Belarus 10-15 years later.

BACKGROUND: While there is a robust literature on environmental exposure to iodine-131 (131I) in childhood and adolescence and the risk of thyroid cancer and benign nodules, little is known about its effects on thyroid volume. METHODS: To assess the effect of 131I dose to the thyroid on the volume of the thyroid gland, we examined the data from the baseline screening of the Belarusian-American Cohort Study of residents of Belarus who were exposed to the Chernobyl fallout at ages ≤18 years. Thyroid dose estimates were based on individual thyroid activity measurements made shortly after the accident and dosimetric data from questionnaires obtained 10-15 years later at baseline screening. During baseline screening, thyroid gland volume was assessed from thyroid ultrasound measurements. The association between radiation dose and thyroid volume was modeled using linear regression where radiation dose was expressed with power terms to address non-linearity. The model was adjusted for attained age, sex, and place of residence, and their modifying effects were examined. RESULTS: The analysis was based on 10,703 subjects. We found a statistically significant positive association between radiation dose and thyroid volume (P < 0.001). Heterogeneity of association was observed by attained age (P < 0.001) with statistically significant association remaining only in the subgroup of ≥18 years at screening (P < 0.001). For this group, increase in dose from 0.0005 to 0.15 Gy was associated with a 1.27 ml (95% CI: 0.46, 2.07) increase in thyroid volume. The estimated effect did not change with increasing doses above 0.15 Gy. CONCLUSIONS: This is the first study to examine the association between 131I dose to the thyroid gland and thyroid volume in a population of individuals exposed during childhood and systematically screened 10-15 years later. It provides evidence for a moderate statistically significant increase in thyroid volume among those who were ≥ 18 years at screening. Given that this effect was observed at very low doses and was restricted to a narrow dose range, further studies are necessary to better understand the effect.

Contrast-Enhanced Ultrasound in Small Intestinal Ischemia: Proof of Concept.

BACKGROUND: Small intestinal ischemia is a challenging diagnosis to make, even with the combination of imaging, laboratory analysis, and physical exam. This pilot study investigated the role of CEUS in evaluating small bowel wall vascularity in participants with suspected ischemia. METHODS: In this IRB-approved pilot study, CEUS using perflutren lipid microspheres (DEFINITY®; Lantheus Medical Imaging Inc., N. Billerica, MA) was performed on participants determined by the clinical surgical team to have concerns for small intestinal ischemia. CEUS interpretations were performed at both the bedside and later by a blinded radiologist and compared to clinical imaging, surgical findings, or long-term clinical outcomes. RESULTS: Fifteen CEUS examinations were performed on 14 participants. Five of the participants underwent exploratory laparotomy. Of these, one had small intestinal ischemia (without necrosis). Point of care CEUS demonstrated no evidence of bowel necrosis in any case, and delayed enhancement (indicative of intestinal ischemia) in three cases, resulting in a sensitivity of 100% (95% CI 2.5-100%) and specificity of 85.7% (95% CI 57.2-98.2%). CEUS correctly ruled out ischemia in 91.7% of cases with CT suspicion of small bowel obstruction and 60% of cases that underwent surgical intervention. Additionally, the rate of agreement between bedside interpretation and later radiologist read was high (93%). CONCLUSIONS: CEUS is uniquely positioned for evaluating the small intestine, because of its high temporal resolution and immediacy of results. Combined with multi-sectional imaging for focal areas of ischemia and/or clinical suspicion for pan ischemia, CEUS may be a useful rule out test for small intestinal ischemia.

Is preclinical research in cancer biology reproducible enough?

The Reproducibility Project: Cancer Biology (RPCB) was established to provide evidence about reproducibility in basic and preclinical cancer research, and to identify the factors that influence reproducibility more generally. In this commentary we address some of the scientific, ethical and policy implications of the project. We liken the basic and preclinical cancer research enterprise to a vast 'diagnostic machine' that is used to determine which clinical hypotheses should be advanced for further development, including clinical trials. The results of the RPCB suggest that this diagnostic machine currently recommends advancing many findings that are not reproducible. While concerning, we believe that more work needs to be done to evaluate the performance of the diagnostic machine. Specifically, we believe three questions remain unanswered: how often does the diagnostic machine correctly recommend against advancing real effects to clinical testing?; what are the relative costs to society of false positive and false negatives?; and how well do scientists and others interpret the outputs of the machine?

The composition of human vaginal microbiota transferred at birth affects offspring health in a mouse model.

Newborns are colonized by maternal microbiota that is essential for offspring health and development. The composition of these pioneer communities exhibits individual differences, but the importance of this early-life heterogeneity to health outcomes is not understood. Here we validate a human microbiota-associated model in which fetal mice are cesarean delivered and gavaged with defined human vaginal microbial communities. This model replicates the inoculation that occurs during vaginal birth and reveals lasting effects on offspring metabolism, immunity, and the brain in a community-specific manner. This microbial effect is amplified by prior gestation in a maternal obesogenic or vaginal dysbiotic environment where placental and fetal ileum development are altered, and an augmented immune response increases rates of offspring mortality. Collectively, we describe a translationally relevant model to examine the defined role of specific human microbial communities on offspring health outcomes, and demonstrate that the prenatal environment dramatically shapes the postnatal response to inoculation.

Individualized therapy trials: navigating patient care, research goals and ethics.

'Individualized therapy' trials (sometimes called n-of-1 trials) use patients as their own controls to evaluate treatments. Here we divide such trials into three categories: multi-crossover trials aimed at individual patient management, multi-crossover trial series and pre-post trials. These trials all customize interventions for patients; however, the latter two categories also aim to inform medical practice and thus embody tensions between the goals of care and research that are typical of other types of clinical trials. In this Perspective, we discuss four domains where such tensions play out-clinical equipoise, informed consent, reporting and funding, and we provide recommendations for addressing each.

Predicting Long-Term Hepatocellular Carcinoma Response to Transarterial Radioembolization Using Contrast-Enhanced Ultrasound: Initial Experiences.

Conventional cross-sectional imaging done shortly after radioembolization of hepatocellular carcinoma (HCC) does not reliably predict long-term response to treatment. This study evaluated whether quantitative contrast-enhanced ultrasound (CEUS) can predict the long-term response of HCC to yttrium-90 (Y-90) treatment. Fifteen patients underwent CEUS at three time points: immediately following treatment and 1 and 2 wk post-treatment. Response 3-6 mo after treatment was categorized on contrast-enhanced magnetic resonance imaging by two experienced radiologists using the Modified Response Evaluation Criteria in Solid Tumors. CEUS data were analyzed by quantifying tumor perfusion and residual fractional vascularity using time-intensity curves. Patients with stable disease on magnetic resonance imaging had significantly greater fractional vascularity 2 wk post-treatment (65.15%) than those with partial or complete response (13.8 ± 9.9%, p = 0.007, and 14.9 ± 15.4%, p = 0.009, respectively). Complete responders had lower tumor vascularity at 2 wk than at post-operative examination (-38.3 ± 15.4%, p = 0.045). Thus, this pilot study suggests CEUS may provide an earlier indication of Y-90 treatment response than cross-sectional imaging.

Stress Radiographs for Ligamentous Knee Injuries.

Stress radiographs can provide an objective, quantifiable assessment of ligamentous knee injury. Commonly utilized techniques include varus, valgus, and posterior stress radiographs and can be used to augment findings on physical examination and magnetic resonance imaging. Both in vitro and in vivo studies have demonstrated reliability and validity of stress radiographs for diagnosing isolated and multiple ligament knee injuries. Varus stress radiographs are clinician applied at 20° flexion to detect injuries to the fibular collateral ligament and posterolateral corner. Valgus stress radiographs are clinician applied at 20° flexion to detect injuries to the medial collateral ligament or posteromedial corner. To evaluate the posterior cruciate ligament, posterior kneeling stress radiographs are obtained with the patient kneeling at 90° flexion on a firm platform. Bilateral radiographs are obtained and the side-to-side difference is compared to established criteria for injury severity. Stress radiographs support accurate diagnosis of complex knee injuries and also provide an objective measure of knee stability following ligament reconstruction. These imaging techniques can be performed in an ambulatory clinic setting with minimal additional equipment, and are thereby cost-effective, efficient, and support clinical decision-making in the treatment of complex knee injuries.

US-triggered Microbubble Destruction for Augmenting Hepatocellular Carcinoma Response to Transarterial Radioembolization: A Randomized Pilot Clinical Trial.

Background US contrast agents are gas-filled microbubbles (MBs) that can be locally destroyed by using external US. Among other bioeffects, US-triggered MB destruction, also known as UTMD, has been shown to sensitize solid tumors to radiation in preclinical models through localized insult to the vascular endothelial cells. Purpose To evaluate the safety and preliminary efficacy of combining US-triggered MB destruction and transarterial radioembolization (TARE) in participants with hepatocellular carcinoma (HCC). Materials and Methods In this pilot clinical trial, participants with HCC scheduled for sublobar TARE were randomized to undergo either TARE or TARE with US-triggered MB destruction 1-4 hours and approximately 1 and 2 weeks after TARE. Enrollment took place between July 2017 and February 2020. Safety of US-triggered MB destruction was evaluated by physiologic monitoring, changes in liver function tests, adverse events, and radiopharmaceutical distribution. Treatment efficacy was evaluated by using modified Response Evaluation Criteria in Solid Tumors (mRECIST) on cross-sectional images, time to required next treatment, transplant rates, and overall survival. Differences across mRECIST reads were compared by using a Mann-Whitney U test, and the difference in prevalence of tumor response was evaluated by Fisher exact test, whereas differences in time to required next treatment and overall survival curves were compared by using a log-rank (Mantel-Cox) test. Results Safety results from 28 participants (mean age, 70 years ± 10 [standard deviation]; 17 men) demonstrated no significant changes in temperature (P = .31), heart rate (P = .92), diastolic pressure (P = .31), or systolic pressure (P = .06) before and after US-triggered MB destruction. No changes in liver function tests between treatment arms were observed 1 month after TARE (P > .15). Preliminary efficacy results showed a greater prevalence of tumor response (14 of 15 [93%; 95% CI: 68, 100] vs five of 10 [50%; 95% CI: 19, 81]; P = .02) in participants who underwent both US-triggered MB destruction and TARE (P = .02). Conclusion The combination of US-triggered microbubble destruction and transarterial radioembolization is feasible with an excellent safety profile in this patient population and appears to result in improved hepatocellular carcinoma treatment response. © RSNA, 2020.