Variants in tubule epithelial regulatory elements mediate most heritable differences in human kidney function.

Kidney disease is highly heritable; however, the causal genetic variants, the cell types in which these variants function, and the molecular mechanisms underlying kidney disease remain largely unknown. To identify genetic loci affecting kidney function, we performed a GWAS using multiple kidney function biomarkers and identified 462 loci. To begin to investigate how these loci affect kidney function, we generated single-cell chromatin accessibility (scATAC-seq) maps of the human kidney and identified candidate cis -regulatory elements (cCREs) for kidney podocytes, tubule epithelial cells, and kidney endothelial, stromal, and immune cells. Kidney tubule epithelial cCREs explained 58% of kidney function SNP-heritability and kidney podocyte cCREs explained an additional 6.5% of SNP-heritability. In contrast, little kidney function heritability was explained by kidney endothelial, stromal, or immune cell-specific cCREs. Through functionally informed fine-mapping, we identified putative causal kidney function variants and their corresponding cCREs. Using kidney scATAC-seq data, we created a deep learning model (which we named ChromKid) to predict kidney cell type-specific chromatin accessibility from sequence. ChromKid and allele specific kidney scATAC-seq revealed that many fine-mapped kidney function variants locally change chromatin accessibility in tubule epithelial cells. Enhancer assays confirmed that fine-mapped kidney function variants alter tubule epithelial regulatory element function. To map the genes which these regulatory elements control, we used CRISPR interference (CRISPRi) to target these regulatory elements in tubule epithelial cells and assessed changes in gene expression. CRISPRi of enhancers harboring kidney function variants regulated NDRG1 and RBPMS expression. Thus, inherited differences in tubule epithelial NDRG1 and RBPMS expression may predispose to kidney disease in humans. We conclude that genetic variants affecting tubule epithelial regulatory element function account for most SNP-heritability of human kidney function. This work provides an experimental approach to identify the variants, regulatory elements, and genes involved in polygenic disease.

Beta-band power modulation in the human amygdala differentiates between go/no-go responses in an arm-reaching task.

Objective. Traditionally known for its involvement in emotional processing, the amygdala's involvement in motor control remains relatively unexplored, with sparse investigations into the neural mechanisms governing amygdaloid motor movement and inhibition. This study aimed to characterize the amygdaloid beta-band (13-30 Hz) power between 'Go' and 'No-go' trials of an arm-reaching task.Approach. Ten participants with drug-resistant epilepsy implanted with stereoelectroencephalographic (SEEG) electrodes in the amygdala were enrolled in this study. SEEG data was recorded throughout discrete phases of a direct reach Go/No-go task, during which participants reached a touchscreen monitor or withheld movement based on a colored cue. Multitaper power analysis along with Wilcoxon signed-rank and Yates-correctedZtests were used to assess significant modulations of beta power between the Response and fixation (baseline) phases in the 'Go' and 'No-go' conditions.Main results. In the 'Go' condition, nine out of the ten participants showed a significant decrease in relative beta-band power during the Response phase (p⩽ 0.0499). In the 'No-go' condition, eight out of the ten participants presented a statistically significant increase in relative beta-band power during the response phase (p⩽ 0.0494). Four out of the eight participants with electrodes in the contralateral hemisphere and seven out of the eight participants with electrodes in the ipsilateral hemisphere presented significant modulation in beta-band power in both the 'Go' and 'No-go' conditions. At the group level, no significant differences were found between the contralateral and ipsilateral sides or between genders.Significance.This study reports beta-band power modulation in the human amygdala during voluntary movement in the setting of motor execution and inhibition. This finding supplements prior research in various brain regions associating beta-band power with motor control. The distinct beta-power modulation observed between these response conditions suggests involvement of amygdaloid oscillations in differentiating between motor inhibition and execution.

Beta-band power classification of go/no-go arm-reaching responses in the human hippocampus.

Objective.Can we classify movement execution and inhibition from hippocampal oscillations during arm-reaching tasks? Traditionally associated with memory encoding, spatial navigation, and motor sequence consolidation, the hippocampus has come under scrutiny for its potential role in movement processing. Stereotactic electroencephalography (SEEG) has provided a unique opportunity to study the neurophysiology of the human hippocampus during motor tasks. In this study, we assess the accuracy of discriminant functions, in combination with principal component analysis (PCA), in classifying between 'Go' and 'No-go' trials in a Go/No-go arm-reaching task.Approach.Our approach centers on capturing the modulation of beta-band (13-30 Hz) power from multiple SEEG contacts in the hippocampus and minimizing the dimensional complexity of channels and frequency bins. This study utilizes SEEG data from the human hippocampus of 10 participants diagnosed with epilepsy. Spectral power was computed during a 'center-out' Go/No-go arm-reaching task, where participants reached or withheld their hand based on a colored cue. PCA was used to reduce data dimension and isolate the highest-variance components within the beta band. The Silhouette score was employed to measure the quality of clustering between 'Go' and 'No-go' trials. The accuracy of five different discriminant functions was evaluated using cross-validation.Main results.The Diagonal-Quadratic model performed best of the 5 classification models, exhibiting the lowest error rate in all participants (median: 9.91%, average: 14.67%). PCA showed that the first two principal components collectively accounted for 54.83% of the total variance explained on average across all participants, ranging from 36.92% to 81.25% among participants.Significance.This study shows that PCA paired with a Diagonal-Quadratic model can be an effective method for classifying between Go/No-go trials from beta-band power in the hippocampus during arm-reaching responses. This emphasizes the significance of hippocampal beta-power modulation in motor control, unveiling its potential implications for brain-computer interface applications.

Critical assessment of missense variant effect predictors on disease-relevant variant data.

Regular, systematic, and independent assessment of computational tools used to predict the pathogenicity of missense variants is necessary to evaluate their clinical and research utility and suggest directions for future improvement. Here, as part of the sixth edition of the Critical Assessment of Genome Interpretation (CAGI) challenge, we assess missense variant effect predictors (or variant impact predictors) on an evaluation dataset of rare missense variants from disease-relevant databases. Our assessment evaluates predictors submitted to the CAGI6 Annotate-All-Missense challenge, predictors commonly used by the clinical genetics community, and recently developed deep learning methods for variant effect prediction. To explore a variety of settings that are relevant for different clinical and research applications, we assess performance within different subsets of the evaluation data and within high-specificity and high-sensitivity regimes. We find strong performance of many predictors across multiple settings. Meta-predictors tend to outperform their constituent individual predictors; however, several individual predictors have performance similar to that of commonly used meta-predictors. The relative performance of predictors differs in high-specificity and high-sensitivity regimes, suggesting that different methods may be best suited to different use cases. We also characterize two potential sources of bias. Predictors that incorporate allele frequency as a predictive feature tend to have reduced performance when distinguishing pathogenic variants from very rare benign variants, and predictors supervised on pathogenicity labels from curated variant databases often learn label imbalances within genes. Overall, we find notable advances over the oldest and most cited missense variant effect predictors and continued improvements among the most recently developed tools, and the CAGI Annotate-All-Missense challenge (also termed the Missense Marathon) will continue to assess state-of-the-art methods as the field progresses. Together, our results help illuminate the current clinical and research utility of missense variant effect predictors and identify potential areas for future development.

Endoscopic Endonasal Transsphenoidal Resection of Pituitary Adenomas in Patients Presenting With Monocular Blindness.

BACKGROUND AND OBJECTIVES: Suprasellar tumors, particularly pituitary adenomas (PAs), commonly present with visual decline, and the endoscopic endonasal transsphenoidal approach (EETA) is the primary management for optic apparatus decompression. Patients presenting with complete preoperative monocular blindness comprise a high-risk subgroup, given concern for complete blindness. This retrospective cohort study evaluates outcomes after EETA for patients with PA presenting with monocular blindness. METHODS: Retrospective analysis of all EETA cases at our institution from June 2012 to August 2023 was performed. Inclusion criteria included adults with confirmed PA and complete monocular blindness, defined as no light perception, and a relative afferent pupillary defect secondary to tumor mass effect. RESULTS: Our cohort includes 15 patients (9 males, 6 females), comprising 2.4% of the overall PA cohort screened. The mean tumor diameter was 3.8 cm, with 6 being giant PAs (>4 cm). The mean duration of preoperative monocular blindness was 568 days. Additional symptoms included contralateral visual field defects (n = 11) and headaches (n = 10). Two patients presented with subacute PA apoplexy. Gross total resection was achieved in 46% of patients, reflecting tumor size and invasiveness. Postoperatively, 2 patients experienced improvement in their effectively blind eye and 2 had improved visual fields of the contralateral eye. Those with improvements were operated within 10 days of presentation, and no patients experienced worsened vision. CONCLUSION: This is the first series of EETA outcomes in patients with higher-risk PA with monocular blindness on presentation. In these extensive lesions, vision remained stable for most without further decline and improvement from monocular blindness was observed in a small subset of patients with no light perception and relative afferent pupillary defect. Timing from vision loss to surgical intervention seemed to be associated with improvement. From a surgical perspective, caution is warranted to protect remaining vision and we conclude that EETA is safe in the management of these patients.

Clinical Intricacies and Advances in Neuroendocrine Tumors: An Organ-Based Multidisciplinary Approach.

ABSTRACT: Neuroendocrine neoplasms (NENs) are rare neoplasms originating from neuroendocrine cells, with increasing incidence due to enhanced detection methods. These tumors display considerable heterogeneity, necessitating diverse management strategies based on factors like organ of origin and tumor size. This article provides a comprehensive overview of therapeutic approaches for NENs, emphasizing the role of imaging in treatment decisions. It categorizes tumors based on their locations: gastric, duodenal, pancreatic, small bowel, colonic, rectal, appendiceal, gallbladder, prostate, lung, gynecological, and others. The piece also elucidates the challenges in managing metastatic disease and controversies surrounding MEN1-neuroendocrine tumor management. The article underscores the significance of individualized treatment plans, underscoring the need for a multidisciplinary approach to ensure optimal patient outcomes.

Understanding the human conflict processing network: A review of the literature on direct neural recordings during performance of a modified stroop task.

The Stroop Task is a well-known neuropsychological task developed to investigate conflict processing in the human brain. Our group has utilized direct intracranial neural recordings in various brain regions during performance of a modified color-word Stroop Task to gain a mechanistic understanding of non-emotional human conflict processing. The purpose of this review article is to: 1) synthesize our own studies into a model of human conflict processing, 2) review the current literature on the Stroop Task and other conflict tasks to put our research in context, and 3) describe how these studies define a network in conflict processing. The figures presented are reprinted from our prior publications and key publications referenced in the manuscript. We summarize all studies to date that employ invasive intracranial recordings in humans during performance of conflict-inducing tasks. For our own studies, we analyzed local field potentials (LFPs) from patients with implanted stereotactic electroencephalography (SEEG) electrodes, and we observed intracortical oscillation patterns as well as intercortical temporal relationships in the hippocampus, amygdala, and orbitofrontal cortex (OFC) during the cue-processing phase of a modified Stroop Task. Our findings suggest that non-emotional human conflict processing involves modulation across multiple frequency bands within and between brain structures.

Society of Radiologists in Ultrasound Consensus Conference Recommendations for Incidental Gallbladder Polyp Management: Interreader Agreement Among 10 Radiologists.

BACKGROUND. The 2022 Society of Radiologists in Ultrasound (SRU) consensus conference recommendations for small gallbladder polyps support management that is less aggressive than earlier approaches and may help standardize evaluation of polyps by radiologists. OBJECTIVE. The purpose of the present study was to assess the interreader agreement of radiologists in applying SRU recommendations for management of incidental gallbladder polyps on ultrasound. METHODS. This retrospective study included 105 patients (75 women and 30 men; median age, 51 years) with a gallbladder polyp on ultrasound (without features highly suspicious for invasive or malignant tumor) who underwent cholecystectomy between January 1, 2003, and January 1, 2021. Ten abdominal radiologists independently reviewed ultrasound examinations and, using the SRU recommendations, assessed one polyp per patient to assign risk category (extremely low risk, low risk, or indeterminate risk) and make a possible recommendation for surgical consultation. Five radiologists were considered less experienced (< 5 years of experience), and five were considered more experienced (≥ 5 years of experience). Interreader agreement was evaluated. Polyps were classified pathologically as nonneoplastic or neoplastic. RESULTS. For risk category assignments, interreader agreement was substantial among all readers (k = 0.710), less-experienced readers (k = 0.705), and more-experienced readers (k = 0.692). For surgical consultation recommendations, inter-reader agreement was substantial among all readers (k = 0.795) and more-experienced readers (k = 0.740) and was almost perfect among less-experienced readers (k = 0.811). Of 10 readers, a median of 5.0 (IQR, 2.0-8.0), 4.0 (IQR, 2.0-7.0), and 0.0 (IQR, 0.0-0.0) readers classified polyps as extremely low risk, low risk, and indeterminate risk, respectively. Across readers, the percentage of polyps classified as extremely low risk ranged from 32% to 72%; as low risk, from 24% to 65%; and as indeterminate risk, from 0% to 8%. Of 10 readers, a median of zero change to 0 (IQR, 0.0-1.0) readers recommended surgical consultation; the percentage of polyps receiving a recommendation for surgical consultation ranged from 4% to 22%. Of a total of 105 polyps, 102 were nonneo-plastic and three were neoplastic (all benign). Based on readers' most common assessments for nonneoplastic polyps, the risk category was extremely low risk for 53 polyps, low risk for 48 polyps, and indeterminate risk for one polyp; surgical consultation was recommended for 16 polyps. CONCLUSION. Ten abdominal radiologists showed substantial agreement for polyp risk categorizations and surgical consultation recommendations, although areas of reader variability were identified. CLINICAL IMPACT. The findings support the overall reproducibility of the SRU recommendations, while indicating opportunity for improvement.

Stereotactic Frame-Based Electrode Insertion: The Accuracy of Increasingly Oblique Insertion Angles.

AIM: To investigate the relationship between planned drill approach angle and angular deviation of the stereotactically placed intracranial electrode tips. MATERIAL AND METHODS: Stereotactic electrode implantation was performed in 13 patients with drug resistant epilepsy. A total of 136 electrodes were included in our analysis. Stereotactic targets were planned on pre-operative magnetic resonance imaging (MRI) scans and implantation was carried out using a Cosman-Roberts-Wells stereotactic frame with the Ad-Tech drill guide and electrodes. Post implant electrode angles in the axial, coronal, and sagittal planes were determined from post-operative computerized tomography (CT) scans and compared with planned angles using Bland-Altman plots and linear regression. RESULTS: Qualitative assessment of correlation plots between planned and actual angles demonstrated a linear relationship for axial, coronal, and sagittal planes, with no overt angular deflection for any magnitude of the planned angle. CONCLUSION: The accuracy of CRW frame-based electrode placement using the Ad-Tech drill guide and electrodes is not significantly affected by the magnitude of the planning angle. Based on our results, oblique electrode insertion is a safe and accurate procedure.

Implementation of an Institution-Wide Rules-Based Automated CT Protocoling System.

BACKGROUND. Examination protocoling is a noninterpretive task that increases radiologists' workload and can cause workflow inefficiencies. OBJECTIVE. The purpose of this study was to evaluate effects of an automated CT protocoling system on examination process times and protocol error rates. METHODS. This retrospective study included 317,597 CT examinations (mean age, 61.8 ± 18.1 [SD] years; male, 161,125; female, 156,447; unspecified sex, 25) from July 2020 to June 2022. A rules-based automated protocoling system was implemented institution-wide; the system evaluated all CT orders in the EHR and assigned a protocol or directed the order for manual radiologist protocoling. The study period comprised pilot (July 2020 to December 2020), implementation (January 2021 to December 2021), and postimplementation (January 2022 to June 2022) phases. Proportions of automatically protocoled examinations were summarized. Process times were recorded. Protocol error rates were assessed by counts of quality improvement (QI) reports and examination recalls and comparison with retrospectively assigned protocols in 450 randomly selected examinations. RESULTS. Frequency of automatic protocoling was 19,366/70,780 (27.4%), 68,875/163,068 (42.2%), and 54,045/83,749 (64.5%) in pilot, implementation, and postimplementation phases, respectively (p < .001). Mean (± SD) times from order entry to protocol assignment for automatically and manually protocoled examinations for emergency department examinations were 0.2 ± 18.2 and 2.1 ± 69.7 hours, respectively; mean inpatient examination times were 0.5 ± 50.0 and 3.5 ± 105.5 hours; and mean outpatient examination times were 361.7 ± 1165.5 and 1289.9 ± 2050.9 hours (all p < .001). Mean (± SD) times from order entry to examination completion for automatically and manually protocoled examinations for emergency department examinations were 2.6 ± 38.6 and 4.2 ± 73.0 hours, respectively (p < .001); for inpatient examinations were 6.3 ± 74.6 and 8.7 ± 109.3 hours (p = .001); and for outpatient examinations were 1367.2 ± 1795.8 and 1471.8 ± 2118.3 hours (p < .001). In the three phases, there were three, 19, and 25 QI reports and zero, one, and three recalls, respectively, for automatically protocoled examinations, versus nine, 19, and five QI reports and one, seven, and zero recalls for manually protocoled examinations. Retrospectively assigned protocols were concordant with 212/214 (99.1%) of automatically protocoled versus 233/236 (98.7%) of manually protocoled examinations. CONCLUSION. The automated protocoling system substantially reduced radiologists' protocoling workload and decreased times from order entry to protocol assignment and examination completion; protocol errors and recalls were infrequent. CLINICAL IMPACT. The system represents a solution for reducing radiologists' time spent performing noninterpretive tasks and improving care efficiency.

Personal transcriptome variation is poorly explained by current genomic deep learning models.

Genomic deep learning models can predict genome-wide epigenetic features and gene expression levels directly from DNA sequence. While current models perform well at predicting gene expression levels across genes in different cell types from the reference genome, their ability to explain expression variation between individuals due to cis-regulatory genetic variants remains largely unexplored. Here, we evaluate four state-of-the-art models on paired personal genome and transcriptome data and find limited performance when explaining variation in expression across individuals. In addition, models often fail to predict the correct direction of effect of cis-regulatory genetic variation on expression.

Dual-Energy Computed Tomography: Technological Considerations.

Compared to conventional single-energy CT (SECT), dual-energy CT (DECT) provides additional information to better characterize imaged tissues. Approaches to DECT acquisition vary by vendor and include source-based and detector-based systems, each with its own advantages and disadvantages. Despite the different approaches to DECT acquisition, the most utilized DECT images include routine SECT equivalent, virtual monoenergetic, material density (eg, iodine map), and virtual non-contrast images. These images are generated either through reconstructions in the projection or image domains. Designing and implementing an optimal DECT workflow into routine clinical practice depends on radiologist and technologist input with special considerations including appropriate patient and protocol selection and workflow automation. In addition to better tissue characterization, DECT provides numerous advantages over SECT such as the characterization of incidental findings and dose reduction in radiation and iodinated contrast.

Prioritising cardiovascular disease risk assessment to high risk individuals based on primary care records.

OBJECTIVE: To provide quantitative evidence for systematically prioritising individuals for full formal cardiovascular disease (CVD) risk assessment using primary care records with a novel tool (eHEART) with age- and sex- specific risk thresholds. METHODS AND ANALYSIS: eHEART was derived using landmark Cox models for incident CVD with repeated measures of conventional CVD risk predictors in 1,642,498 individuals from the Clinical Practice Research Datalink. Using 119,137 individuals from UK Biobank, we modelled the implications of initiating guideline-recommended statin therapy using eHEART with age- and sex-specific prioritisation thresholds corresponding to 5% false negative rates to prioritise adults aged 40-69 years in a population in England for invitation to a formal CVD risk assessment. RESULTS: Formal CVD risk assessment on all adults would identify 76% and 49% of future CVD events amongst men and women respectively, and 93 (95% CI: 90, 95) men and 279 (95% CI: 259, 297) women would need to be screened (NNS) to prevent one CVD event. In contrast, if eHEART was first used to prioritise individuals for formal CVD risk assessment, we would identify 73% and 47% of future events amongst men and women respectively, and a NNS of 75 (95% CI: 72, 77) men and 162 (95% CI: 150, 172) women. Replacing the age- and sex-specific prioritisation thresholds with a 10% threshold identify around 10% less events. CONCLUSIONS: The use of prioritisation tools with age- and sex-specific thresholds could lead to more efficient CVD assessment programmes with only small reductions in effectiveness at preventing new CVD events.

Evaluation of interventions to prevent vasovagal reactions among whole blood donors: rationale and design of a large cluster randomised trial.

BACKGROUND: Vasovagal reactions (VVRs) are the most common acute complications of blood donation. Responsible for substantial morbidity, they also reduce the likelihood of repeated donations and are disruptive and costly for blood services. Although blood establishments worldwide have adopted different strategies to prevent VVRs (including water loading and applied muscle tension [AMT]), robust evidence is limited. The Strategies to Improve Donor Experiences (STRIDES) trial aims to reliably assess the impact of four different interventions to prevent VVRs among blood donors. METHODS: STRIDES is a cluster-randomised cross-over/stepped-wedge factorial trial of four interventions to reduce VVRs involving about 1.4 million whole blood donors enrolled from all 73 blood donation sites (mobile teams and donor centres) of National Health Service Blood and Transplant (NHSBT) in England. Each site ("cluster") has been randomly allocated to receive one or more interventions during a 36-month period, using principles of cross-over, stepped-wedge and factorial trial design to assign the sequence of interventions. Each of the four interventions is compared to NHSBT's current practices: (i) 500-ml isotonic drink before donation (vs current 500-ml plain water); (ii) 3-min rest on donation chair after donation (vs current 2 min); (iii) new modified AMT (vs current practice of AMT); and (iv) psychosocial intervention using preparatory materials (vs current practice of nothing). The primary outcome is the number of in-session VVRs with loss of consciousness (i.e. episodes involving loss of consciousness of any duration, with or without additional complications). Secondary outcomes include all in-session VVRs (i.e. with and without loss of consciousness), all delayed VVRs (i.e. those occurring after leaving the venue) and any in-session non-VVR adverse events or reactions. DISCUSSION: The STRIDES trial should yield novel information about interventions, singly and in combination, for the prevention of VVRs, with the aim of generating policy-shaping evidence to help inform blood services to improve donor health, donor experience, and service efficiency. TRIAL REGISTRATION: ISRCTN: 10412338. Registration date: October 24, 2019.

Using Polygenic Risk Scores for Prioritizing Individuals at Greatest Need of a Cardiovascular Disease Risk Assessment.

Background The aim of this study was to provide quantitative evidence of the use of polygenic risk scores for systematically identifying individuals for invitation for full formal cardiovascular disease (CVD) risk assessment. Methods and Results A total of 108 685 participants aged 40 to 69 years, with measured biomarkers, linked primary care records, and genetic data in UK Biobank were used for model derivation and population health modeling. Prioritization tools using age, polygenic risk scores for coronary artery disease and stroke, and conventional risk factors for CVD available within longitudinal primary care records were derived using sex-specific Cox models. We modeled the implications of initiating guideline-recommended statin therapy after prioritizing individuals for invitation to a formal CVD risk assessment. If primary care records were used to prioritize individuals for formal risk assessment using age- and sex-specific thresholds corresponding to 5% false-negative rates, then the numbers of men and women needed to be screened to prevent 1 CVD event are 149 and 280, respectively. In contrast, adding polygenic risk scores to both prioritization and formal assessments, and selecting thresholds to capture the same number of events, resulted in a number needed to screen of 116 for men and 180 for women. Conclusions Using both polygenic risk scores and primary care records to prioritize individuals at highest risk of a CVD event for a formal CVD risk assessment can efficiently prioritize those who need interventions the most than using primary care records alone. This could lead to better allocation of resources by reducing the number of risk assessments in primary care while still preventing the same number of CVD events.

Adrenal Neoplasms: Lessons from Adrenal Multidisciplinary Tumor Boards.

The radiologic diagnosis of adrenal disease can be challenging in settings of atypical presentations, mimics of benign and malignant adrenal masses, and rare adrenal anomalies. Misdiagnosis may lead to suboptimal management and adverse outcomes. Adrenal adenoma is the most common benign adrenal tumor that arises from the cortex, whereas adrenocortical carcinoma (ACC) is a rare malignant tumor of the cortex. Adrenal cyst and myelolipoma are other benign adrenal lesions and are characterized by their fluid and fat content, respectively. Pheochromocytoma is a rare neuroendocrine tumor of the adrenal medulla. Metastases to the adrenal glands are the most common malignant adrenal tumors. While many of these masses have classic imaging appearances, considerable overlap exists between benign and malignant lesions and can pose a diagnostic challenge. Atypical adrenal adenomas include those that are lipid poor; contain macroscopic fat, hemorrhage, and/or iron; are heterogeneous and/or large; and demonstrate growth. Heterogeneous adrenal adenomas may mimic ACC, metastasis, or pheochromocytoma, particularly when they are 4 cm or larger, whereas smaller versions of ACC, metastasis, and pheochromocytoma and those with washout greater than 60% may mimic adenoma. Because of its nonenhanced CT attenuation of less than or equal to 10 HU, a lipid-rich adrenal adenoma may be mimicked by a benign adrenal cyst, or it may be mimicked by a tumor with central cystic and/or necrotic change such as ACC, pheochromocytoma, or metastasis. Rare adrenal tumors such as hemangioma, ganglioneuroma, and oncocytoma also may mimic adrenal adenoma, ACC, metastasis, and pheochromocytoma. The authors describe cases of adrenal neoplasms that they have encountered in clinical practice and presented to adrenal multidisciplinary tumor boards. Key lessons to aid in diagnosis and further guide appropriate management are provided. © RSNA, 2023 Online supplemental material is available for this article. Quiz questions for this article are available through the Online Learning Center.

Diagnostic Accuracy of Unenhanced Computed Tomography for Evaluation of Acute Abdominal Pain in the Emergency Department.

Importance: Intravenous (IV) contrast medium is sometimes withheld due to risk of complication or lack of availability in patients undergoing computed tomography (CT) for abdominal pain. The risk from withholding contrast medium is understudied. Objective: To determine the diagnostic accuracy of unenhanced abdominopelvic CT using contemporaneous contrast-enhanced CT as the reference standard in emergency department (ED) patients with acute abdominal pain. Design, Setting, and Participants: This was an institutional review board-approved, multicenter retrospective diagnostic accuracy study of 201 consecutive adult ED patients who underwent dual-energy contrast-enhanced CT for the evaluation of acute abdominal pain from April 1, 2017, through April 22, 2017. Three blinded radiologists interpreted these scans to establish the reference standard by majority rule. IV and oral contrast media were then digitally subtracted using dual-energy techniques. Six different blinded radiologists from 3 institutions (3 specialist faculty and 3 residents) interpreted the resulting unenhanced CT examinations. Participants included a consecutive sample of ED patients with abdominal pain who underwent dual-energy CT. Exposure: Contrast-enhanced and virtual unenhanced CT derived from dual-energy CT. Main outcome: Diagnostic accuracy of unenhanced CT for primary (ie, principal cause[s] of pain) and actionable secondary (ie, incidental findings requiring management) diagnoses. The Gwet interrater agreement coefficient was calculated. Results: There were 201 included patients (female, 108; male, 93) with a mean age of 50.1 (SD, 20.9) years and mean BMI of 25.5 (SD, 5.4). Overall accuracy of unenhanced CT was 70% (faculty, 68% to 74%; residents, 69% to 70%). Faculty had higher accuracy than residents for primary diagnoses (82% vs 76%; adjusted odds ratio [OR], 1.83; 95% CI, 1.26-2.67; P = .002) but lower accuracy for actionable secondary diagnoses (87% vs 90%; OR, 0.57; 95% CI, 0.35-0.93; P < .001). This was because faculty made fewer false-negative primary diagnoses (38% vs 62%; OR, 0.23; 95% CI, 0.13-0.41; P < .001) but more false-positive actionable secondary diagnoses (63% vs 37%; OR, 2.11, 95% CI, 1.26-3.54; P = .01). False-negative (19%) and false-positive (14%) results were common. Interrater agreement for overall accuracy was moderate (Gwet agreement coefficient, 0.58). Conclusion: Unenhanced CT was approximately 30% less accurate than contrast-enhanced CT for evaluating abdominal pain in the ED. This should be balanced with the risk of administering contrast material to patients with risk factors for kidney injury or hypersensitivity reaction.

A review of neurophysiological effects and efficiency of waveform parameters in deep brain stimulation.

Neurostimulation has diverse clinical applications and potential as a treatment for medically refractory movement disorders, epilepsy, and other neurological disorders. However, the parameters used to program electrodes-polarity, pulse width, amplitude, and frequency-and how they are adjusted have remained largely untouched since the 1970 s. This review summarizes the state-of-the-art in Deep Brain Stimulation (DBS) and highlights the need for further research to uncover the physiological mechanisms of neurostimulation. We focus on studies that reveal the potential for clinicians to use waveform parameters to selectively stimulate neural tissue for therapeutic benefit, while avoiding activating tissue associated with adverse effects. DBS uses cathodic monophasic rectangular pulses with passive recharging in clinical practice to treat neurological conditions such as Parkinson's Disease. However, research has shown that stimulation efficiency can be improved, and side effects reduced, through modulating parameters and adding novel waveform properties. These developments can prolong implantable pulse generator lifespan, reducing costs and surgery-associated risks. Waveform parameters can stimulate neurons based on axon orientation and intrinsic structural properties, providing clinicians with more precise targeting of neural pathways. These findings could expand the spectrum of diseases treatable with neuromodulation and improve patient outcomes.

Improving Prostate Cancer Detection With MRI: A Multi-Reader, Multi-Case Study Using Computer-Aided Detection (CAD).

RATIONALE AND OBJECTIVES: To evaluate whether addition of a computer-aided diagnostic (CAD) generated MRI series improves detection of clinically significant prostate cancer. MATERIALS AND METHODS: Nine radiologists retrospectively interpreted 150 prostate MRI examinations without and then with an additional random forest-based CAD model-generated MRI series. Characteristics of biopsy negative versus positive (Gleason ≥ 7 adenocarcinoma) groups were compared using the Wilcoxon test for continuous and Pearson's chi-squared test for categorical variables. The diagnostic performance of readers was compared without versus with CAD using MRMC methods to estimate the area under the receiver operator characteristic curve (AUC). Inter-reader agreement was assessed using weighted inter-rater agreement statistics. Analyses were repeated in peripheral and transition zone subgroups. RESULTS: Among 150 men with median age 67 ± 7.4 years, those with clinically significant prostate cancer were older (68 ± 7.6 years vs. 66 ± 7.0 years; p < .02), had smaller prostate volume (43.9 mL vs. 60.6 mL; p < .001), and no difference in prostate specific antigen (PSA) levels (7.8 ng/mL vs. 6.9 ng/mL; p = .08), but higher PSA density (0.17 ng/mL/cc vs. 0.10 ng/mL/cc; p < .001). Inter-rater agreement (IRA) for PI-RADS scores was moderate without CAD and significantly improved to substantial with CAD (IRA = 0.47 vs. 0.65; p < .001). CAD also significantly improved average reader AUC (AUC = 0.72, vs. AUC = 0.67; p = .02). CONCLUSION: Addition of a random forest method-based, CAD-generated MRI image series improved inter-reader agreement and diagnostic performance for detection of clinically significant prostate cancer, particularly in the transition zone.