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Is the Clinical Application of CXCR4 Imaging in the Diagnosis and Management of Primary Aldosteronism Really Happening?




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Drug-Drug Interactions and Synergy: From Pharmacological Models to Clinical Application [Review Article]

This review explores the concept of synergy in pharmacology, emphasizing its importance in optimizing treatment outcomes through the combination of drugs with different mechanisms of action. Synergy, defined as an effect greater than the expected additive effect elicited by individual agents according to specific predictive models, offers a promising approach to enhance therapeutic efficacy while minimizing adverse events. The historical evolution of synergy research, from ancient civilizations to modern pharmacology, highlights the ongoing quest to understand and harness synergistic interactions. Key concepts, such as concentration-response curves, additive effects, and predictive models, are discussed in detail, emphasizing the need for accurate assessment methods throughout translational drug development. Although various mathematical models exist for synergy analysis, selecting the appropriate model and software tools remains a challenge, necessitating careful consideration of experimental design and data interpretation. Furthermore, this review addresses practical considerations in synergy assessment, including preclinical and clinical approaches, mechanism of action, and statistical analysis. Optimizing synergy requires attention to concentration/dose ratios, target site localization, and timing of drug administration, ensuring that the benefits of combination therapy detected bench-side are translatable into clinical practice. Overall, the review advocates for a systematic approach to synergy assessment, incorporating robust statistical analysis, effective and simplified predictive models, and collaborative efforts across pivotal sectors, such as academic institutions, pharmaceutical companies, and regulatory agencies. By overcoming critical challenges and maximizing therapeutic potential, effective synergy assessment in drug development holds promise for advancing patient care.

Significance Statement

Combining drugs with different mechanisms of action for synergistic interactions optimizes treatment efficacy and safety. Accurate interpretation of synergy requires the identification of the expected additive effect. Despite innovative models to predict the additive effect, consensus in drug-drug interactions research is lacking, hindering the bench-to-bedside development of combination therapies. Collaboration among science, industry, and regulation is crucial for advancing combination therapy development, ensuring rigorous application of predictive models in clinical settings.




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International Union of Basic and Clinical Pharmacology CXV: The Class F of G Protein-Coupled Receptors [75th Anniversary Celebration Collection Special Section]

The class F of G protein-coupled receptors (GPCRs) consists of 10 Frizzleds (FZD1–10) and Smoothened (SMO). FZDs bind and are activated by secreted lipoglycoproteins of the Wingless/Int-1 (WNT) family, and SMO is indirectly activated by the Hedgehog (Hh) family of morphogens acting on the transmembrane protein Patched. The advance of our understanding of FZDs and SMO as dynamic transmembrane receptors and molecular machines, which emerged during the past 14 years since the first-class F GPCR IUPHAR nomenclature report, justifies an update. This article focuses on the advances in molecular pharmacology and structural biology providing new mechanistic insight into ligand recognition, receptor activation mechanisms, signal initiation, and signal specification. Furthermore, class F GPCRs continue to develop as drug targets, and novel technologies and tools such as genetically encoded biosensors and CRISP/Cas9 edited cell systems have contributed to refined functional analysis of these receptors. Also, advances in crystal structure analysis and cryogenic electron microscopy contribute to the rapid development of our knowledge about structure-function relationships, providing a great starting point for drug development. Despite the progress, questions and challenges remain to fully understand the complexity of the WNT/FZD and Hh/SMO signaling systems.

Significance Statement

The recent years of research have brought about substantial functional and structural insight into mechanisms of activation of Frizzleds and Smoothened. While the advance furthers our mechanistic understanding of ligand recognition, receptor activation, signal specification, and initiation, broader opportunities emerge that allow targeting class F GPCRs for therapy and regenerative medicine employing both biologics and small molecule compounds.




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Low-Field (64 mT) Portable MRI for Rapid Point-of-Care Diagnosis of Dissemination in Space in Patients Presenting with Optic Neuritis [CLINICAL PRACTICE]

BACKGROUND AND PURPOSE:

Low-field 64 mT portable brain MRI has recently shown diagnostic promise for MS. This study aimed to evaluate the utility of portable MRI (pMRI) in assessing dissemination in space (DIS) in patients presenting with optic neuritis and determine whether deploying pMRI in the MS clinic can shorten the time from symptom onset to MRI.

MATERIALS AND METHODS:

Newly diagnosed patients with optic neuritis referred to a tertiary academic MS center from July 2022 to January 2024 underwent both point-of-care pMRI and subsequent 3T conventional MRI (cMRI). Images were evaluated for periventricular (PV), juxtacortical (JC), and infratentorial (IT) lesions. DIS was determined on brain MRI per 2017 McDonald criteria. Test characteristics were computed by using cMRI as the reference. Interrater and intermodality agreement between pMRI and cMRI were evaluated by using the Cohen . Time from symptom onset to pMRI and cMRI during the study period was compared with the preceding 1.5 years before pMRI implementation by using Kruskal-Wallis with post hoc Dunn tests.

RESULTS:

Twenty patients (median age: 32.5 years [interquartile range {IQR}, 28–40]; 80% women) were included, of whom 9 (45%) and 5 (25%) had DIS on cMRI and pMRI, respectively. Median time interval between pMRI and cMRI was 7 days (IQR, 3.5–12.5). Interrater agreement was very good for PV (95%, = 0.89), and good for JC and IT lesions (90%, = 0.69 for both). Intermodality agreement was good for PV (90%, = 0.80) and JC (85%, = 0.63), and moderate for IT lesions (75%, = 0.42) and DIS (80%, = 0.58). pMRI had a sensitivity of 56% and specificity of 100% for DIS. The median time from symptom onset to pMRI was significantly shorter (8.5 days [IQR 7–12]) compared with the interval to cMRI before pMRI deployment (21 days [IQR 8–49], n = 50) and after pMRI deployment (15 days [IQR 12–29], n = 30) (both P < .01). Time from symptom onset to cMRI in those periods was not significantly different (P = .29).

CONCLUSIONS:

In patients with optic neuritis, pMRI exhibited moderate concordance, moderate sensitivity, and high specificity for DIS compared with cMRI. Its integration into the MS clinic reduced the time from symptom onset to MRI. Further studies are warranted to evaluate the role of pMRI in expediting early MS diagnosis and as an imaging tool in resource-limited settings.




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Prevalence of Rathke Cleft and Other Incidental Pituitary Gland Findings on Contrast-Enhanced 3D Fat-Saturated T1 MPRAGE at 7T MRI [CLINICAL PRACTICE]

BACKGROUND AND PURPOSE:

A cleftlike nonenhancing hypointensity was observed repeatedly in the pituitary gland at the adenohypophysis/neurohypophysis border on contrast-enhanced 3D fat-saturated T1-MPRAGE using clinical 7T MRI. Our primary goal was to assess the prevalence of this finding. The secondary goals were to evaluate the frequency of other incidental pituitary lesions, MRI artifacts, and their effect on pituitary imaging on the contrast-enhanced 3D fat-saturated T1 MPRAGE at 7T.

MATERIALS AND METHODS:

One hundred patients who underwent 7T neuroimaging between October 27, 2021, and August 10, 2023, were included. Each case was evaluated for cleftlike pituitary hypointensity, pituitary masses, and artifacts on contrast-enhanced 3D fat-saturated T1 MPRAGE. Follow-up examinations were evaluated if present. The average prevalence for each finding was calculated, as were descriptive statistics for age and sex.

RESULTS:

A cleftlike hypointensity was present in 66% of 7T MRIs. There were no significant differences between the "cleftlike present" and "cleftlike absent" groups regarding sex (P = .39) and age (P = .32). The cleftlike hypointensity was demonstrated on follow-up MRIs in 3/3 patients with 7T, 1/12 with 3T, and 1/5 with 1.5T. A mass was found in 22%, while 75% had no mass and 3% were indeterminate. A mass was found in 18 (27%) of the cleftlike present and 4 (13%) of the cleftlike absent groups. The most common mass types were Rathke cleft cyst in 7 (31.8%) patients, "Rathke cleft cyst versus entrapped CSF" in 6 (27.3%), and microadenoma in 6 (22.2%) in the cleftlike present group. There were no significant differences in the mass types between the cleftlike present and cleftlike absent groups (P = .23). Susceptibility and/or motion artifacts were frequent using contrast-enhanced 3D fat-saturated T1 MPRAGE (54%). Artifact-free scans were significantly more frequent in the cleftlike present group (P = .03).

CONCLUSIONS:

A cleftlike nonenhancing hypointensity was frequently seen on the contrast-enhanced 3D fat-saturated T1 MPRAGE images at 7T MRI, which most likely represents a normal embryologic Rathke cleft remnant and cannot be seen in lower-field-strength MRIs. Susceptibility and motion artifacts are common in the sella. They may affect image quality, and the artifacts at 7T may lead to an underestimation of the prevalence of the Rathke cleft and other incidental findings.




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An Extended Follow-up of Spinal Instrumentation Rescue with Cement Augmentation [CLINICAL PRACTICE]

BACKGROUND AND PURPOSE:

Percutaneous cement augmentation has been reported as an effective salvage procedure for frail patients with spinal instrumentation failure, such as screw loosening, hardware breakage, cage subsidence, and fractures within or adjacent to stabilized segments. Favorable results were reported during a median follow-up period of 16 months in a retrospective analysis of 31 consecutive procedures performed in 29 patients. In the present study, the long-term effectiveness of this treatment in avoiding or postponing revision surgery is reported.

MATERIALS AND METHODS:

Clinical and radiologic data of our original cohort of patients were retrospectively collected and reviewed to provide an extended follow-up assessment. The need for revision spinal surgery was assessed as the primary outcome, and the radiologic stability of the augmented spinal implants was considered as the secondary outcome.

RESULTS:

An extended radiologic follow-up was available in 27/29 patients with an average of 50.9 months. Overall, 18 of 27 (66.7%) patients, originally candidates for revision surgery, avoided a surgical intervention after a cement augmentation rescue procedure. In the remaining patients, the average interval between the rescue cement augmentation and the revision surgery was 22.5 months. Implant mobilization occurred in 2/27 (7.4%) patients; rod breakage, in 1/27 (3.7%); a new fracture within or adjacent to the instrumented segment occurred in 4/27 (14.8%) patients; and screw loosening at rescued levels occurred in 5/27 (18.5%) patients.

CONCLUSIONS:

In this cohort, cement augmentation rescue procedures were found to be effective in avoiding or postponing revision surgery during long-term follow-up.




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Probabilistic Presurgical Language fMRI Atlas of Patients with Brain Tumors [CLINICAL PRACTICE]

BACKGROUND AND PURPOSE:

Patients with brain tumors have high intersubject variation in putative language regions, which may limit the utility of straightforward application of healthy subject brain atlases in clinical scenarios. The purpose of this study was to develop a probabilistic functional brain atlas that consolidates language functional activations of sentence completion and Silent Word Generation language paradigms using a large sample of patients with brain tumors.

MATERIALS AND METHODS:

The atlas was developed using retrospectively collected fMRI data from patients with brain tumors who underwent their first standard-of-care presurgical language fMRI scan at our institution between July 18, 2015, and May 13, 2022. Three hundred seventeen patients (861 fMRI scans) were used to develop the language functional atlas. An independent presurgical language fMRI data set of 39 patients with brain tumors from a previous study was used to evaluate our atlas. Family-wise error–corrected binary functional activation maps from sentence completion, letter fluency, and category fluency presurgical fMRI were used to create probability overlap maps and pooled probabilistic overlap maps in Montreal Neurological Institute standard space. The Wilcoxon signed-rank test was used to determine a significant difference in the maximum Dice coefficient for our atlas compared with a meta-analysis-based template with respect to expert-delineated primary language area activations.

RESULTS:

Probabilities of activating the left anterior primary language area and left posterior primary language area in the temporal lobe were 87.9% and 91.5%, respectively, for sentence completion, 88.5% and 74.2%, respectively, for letter fluency, and 83.6% and 67.6%, respectively, for category fluency. Maximum Dice coefficients for templates derived from our language atlas were significantly higher than the meta-analysis-based template in the left anterior primary language area (0.351 and 0.326, respectively, P < .05) and the left posterior primary language area in the temporal lobe (0.274 and 0.244, respectively, P < .005).

CONCLUSIONS:

Brain tumor patient- and paradigm-specific probabilistic language atlases were developed. These atlases had superior spatial agreement with fMRI activations in individual patients compared with the meta-analysis-based template.




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Enzyme Replacement Therapy for CLN2 Disease: MRI Volumetry Shows Significantly Slower Volume Loss Compared with a Natural History Cohort [CLINICAL PRACTICE]

BACKGROUND AND PURPOSE:

Neuronal ceroid lipofuscinoses are a group of neurodegenerative disorders. Recently, enzyme replacement therapy (ERT) was approved for neuronal ceroid lipofuscinosis type 2 (CLN2), a subtype of neuronal ceroid lipofuscinoses. The aim of this study was to quantify brain volume loss in CLN2 disease in patients on ERT in comparison with a natural history cohort using MRI.

MATERIALS AND METHODS:

Nineteen (14 female, 5 male) patients with CLN2 disease at 1 UK center were studied using serial 3D T1-weighted MRI (follow-up time, 1–9 years). Brain segmentation was performed using FreeSurfer. Volume measurements for supratentorial gray and white matter, deep gray matter (basal ganglia/thalami), the lateral ventricles, and cerebellar gray and white matter were recorded. The volume change with time was analyzed using a linear mixed-effects model excluding scans before treatment onset. Comparison was made with a published natural history cohort of 12 patients (8 female, 4 male), which was re-analyzed using the same method.

RESULTS:

Brain volume loss of all segmented brain regions was much slower in treated patients compared with the natural history cohort. For example, supratentorial gray matter volume in treated patients decreased by a mean of 3% (SD, 0.74%) (P < .001) annually compared with an annual volume loss of a mean of 16.8% (SD, 1.5%) (P < .001) in the natural history cohort.

CONCLUSIONS:

Our treatment cohort showed a significantly slower rate of brain parenchymal volume loss compared with a natural history cohort in several anatomic regions. Our results complement prior clinical data that found a positive response to ERT. We demonstrate that automated MRI volumetry is a sensitive tool to monitor treatment response in children with CLN2 disease.




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Arterial Spin-Labeling Perfusion Lightbulb Sign: An Imaging Biomarker of Pediatric Posterior Fossa Hemangioblastoma [CLINICAL PRACTICE]

BACKGROUND AND PURPOSE:

Hemangioblastoma is a rare vascular tumor that occurs within the central nervous system in children. Differentiating hemangioblastoma from other posterior fossa tumors can be challenging on imaging, and preoperative diagnosis can change the neurosurgical approach. We hypothesize that a "lightbulb sign" on the arterial spin-labeling (ASL) sequence (diffuse homogeneous intense hyperperfusion within the solid component of the tumor) will provide additional imaging finding to differentiate hemangioblastoma from other posterior fossa tumors.

MATERIALS AND METHODS:

In this retrospective comparative observational study, we only included pathology-proved cases of hemangioblastoma, while the control group consisted of other randomly selected pathology-proved posterior fossa tumors from January 2022 to January 2024. Two blinded neuroradiologists analyzed all applicable MRI sequences, including ASL sequence if available. ASL was analyzed for the lightbulb sign. Disagreements between the radiologists were resolved by a third pediatric neuroradiologist. 2 and Fisher exact test were used to analyze the data.

RESULTS:

Ninety-five patients were enrolled in the study; 57 (60%) were boys. The median age at diagnosis was 8 years old (interquartile range: 3–14). Of the enrolled patients, 8 had hemangioblastoma, and 87 had other posterior fossa tumors, including medulloblastoma (n = 31), pilocytic astrocytoma (n = 23), posterior fossa ependymoma type A (n = 16), and other tumors (n = 17). The comparison of hemangioblastoma versus nonhemangioblastoma showed that peripheral edema (P = .02) and T2-flow void (P = .02) favor hemangioblastoma, whereas reduced diffusion (low ADC) (P = .002) and ventricular system extension (P = .001) favor nonhemangioblastoma tumors. Forty-two cases also had ASL perfusion sequences. While high perfusion favors hemangioblastoma (P = .03), the lightbulb sign shows a complete distinction because all the ASL series of hemangioblastoma cases (n = 4) showed the lightbulb sign, whereas none of the nonhemangioblastoma cases (n = 38) showed the sign (P < .001).

CONCLUSIONS:

Lightbulb-like intense and homogeneous hyperperfusion patterns on ASL are helpful in diagnosing posterior fossa hemangioblastoma in children.




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Diffusion Analysis of Intracranial Epidermoid, Head and Neck Epidermal Inclusion Cyst, and Temporal Bone Cholesteatoma [CLINICAL PRACTICE]

BACKGROUND AND PURPOSE:

Intracranial epidermoids temporal bone cholesteatomas, and head and neck epidermal inclusion cysts are typically slow-growing, benign conditions arising from ectodermal tissue. They exhibit increased signal on DWI. While much of the imaging literature describes these lesions as showing diffusion restriction, we investigated these qualitative signal intensities and interpretations of restricted diffusion with respect to normal brain structures. This study aimed to quantitatively evaluate the ADC values and histogram features of these lesions.

MATERIALS AND METHODS:

This retrospective study included children with histologically confirmed diagnoses of intracranial epidermoids, temporal bone cholesteatomas, or head and neck epidermal inclusion cysts. Lesions were segmented, and voxelwise calculation of ADC values was performed along with histogram analysis. ADC calculations were validated with a second analysis software to ensure accuracy. Normal brain ROIs—including the cerebellum, white matter, and thalamus—served as normal comparators. Correlational analysis and Bland-Altman plots assessed agreement among software tools for ADC calculations. Differences in the distribution of values between the lesions and normal brain tissues were assessed using the Wilcoxon rank sum and Kruskal-Wallis tests.

RESULTS:

Forty-eight pathology-proved cases were included in this study. Among them, 13 (27.1%) patients had intracranial epidermoids 14 (29.2%) had head and neck epidermal inclusion cysts, and 21 (43.7%) had temporal bone cholesteatomas. The mean age was 8.67 (SD, 5.30) years, and 27 (56.3%) were female. The intraclass correlation for absolute agreement for lesional ADC between the 2 software tools was 0.997 (95% CI, 0.995–0.998). The intracranial epidermoid head and neck epidermal inclusion cyst, and temporal bone cholesteatoma median ADC values were not significantly different (973.7 versus 875.7 versus 933.2 x 10–6 mm2/s, P = .265). However, the ADCs of the 3 types of lesions were higher than those of 3 normal brain tissue types (933 versus 766, x 10–6 mm2/s, P < .001).

CONCLUSIONS:

The ADC values of intracranial epidermoids, temporal bone cholesteatomas, and head and neck epidermal inclusion cysts are higher than those of normal brain regions. It is not accurate to simply classify these lesions as exhibiting restricted diffusion or reduced diffusivity without considering the tissue used for comparison. The observed hyperintensity on DWI compared with the brain is likely attributable to a relatively higher contribution of the T2 shinethrough effect.




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Utility of Early Postoperative DWI to Assess the Extent of Resection of Adult-Type World Health Organization Grade 2 and 3 Diffuse Gliomas [CLINICAL PRACTICE]

BACKGROUND AND PURPOSE:

World Health Organization (WHO) grade 2 and 3 diffuse gliomas account for approximately 5% of primary brain tumors. They are invasive and infiltrative tumors and have considerable morbidity, causing progressive neurologic deterioration. The mean survival time is <10 years from diagnosis. Surgical debulking represents first-line management. The extent of resection is associated with progression-free and overall survival. Radiologic assessment of the extent of resection is challenging. This can be underestimated on early postoperative MRI, meaning that accurate assessment may be achieved only on delayed follow-up imaging. We hypothesized that DWI may help facilitate more reliable estimates of the extent of resection on early postoperative MRI. This study aimed to assess the utility of DWI in early postoperative MRI to evaluate the extent of resection.

MATERIALS AND METHODS:

A single-center observational cohort study was performed. All patients with histologically confirmed WHO grade 2 and 3 gliomas managed with surgical debulking between January 2015 and December 2020 were identified. Preoperative, early postoperative, and follow-up imaging were reviewed independently by 2 consultant neuroradiologists. The extent of resection was estimated with and without DWI sequences for each case.

RESULTS:

Two hundred twenty-four patients with WHO grade 2 and 3 gliomas were managed with surgical debulking between 2015 and 2020. DWI was not performed on early postoperative MRI in 2 patients. With the use of DWI, the extent of resection was upgraded in 30% of cases (n = 66/222) and classified as "complete" or "supramaximal" in 58% of these patients (n = 38/66). In cases in which the extent of resection was upgraded with the use of DWI, signal abnormality was stable or reduced at follow-up in 78% (n = 49/63). In cases with worsening signal abnormality, 64% were deemed to be secondary to adjuvant radiation therapy (n = 9/14). Eight percent (n = 5/63) of patients with an increased estimated extent of resection using DWI demonstrated signal progression attributed to true disease progression at follow-up.

CONCLUSIONS:

DWI is a helpful and reliable adjunct in differentiating residual tumor from marginal ischemia in early postoperative MRI in WHO grade 2 and 3 diffuse gliomas and increases the accuracy in assessing the extent of resection. It should be used routinely in these cases.




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Comparative Evaluation of Lower Gadolinium Doses for MR Imaging of Meningiomas: How Low Can We Go? [CLINICAL PRACTICE]

BACKGROUND AND PURPOSE:

Gadolinium-based contrast agents are widely used for meningioma imaging; however, concerns exist regarding their side effects, cost, and environmental impact. At the standard gadolinium dose, most meningiomas show avid contrast enhancement, suggesting that administering a smaller dose may be feasible. The purpose of this study was to evaluate the impact of a lower gadolinium dose on the differentiation between meningiomas and adjacent intracranial tissues.

MATERIALS AND METHODS:

One hundred eight patients with presumed or confirmed meningiomas who underwent a brain MRI at multiple doses of gadolinium were included in the study. The patients’ MRIs were categorized into 3 groups based on the gadolinium dose administered: micro (approximately 25% of the standard dose), low (approximately 62% of the standard dose), and standard dose. Multireader qualitative visual assessment and quantitative relative signal differences calculations were performed to evaluate tumor differentiation from the cortex and from the dural venous sinus. The relative signal differences for each dose were analyzed by using ANOVA for quantitative assessment and the McNemar test for qualitative assessment. Additionally, noninferiority testing was used to compare the low and micro doses to the standard dose.

RESULTS:

Decreasing the gadolinium dose to a low dose or micro dose resulted in a statistically significant decrease in signal difference between the tumor and the adjacent brain tissue (P < .02). However, on visual assessment, the low dose was noninferior to the standard dose. The proportion of cases with suboptimal differentiation was significantly higher for the micro dose than for the standard dose, both for the differentiation between the tumor and the cortex (P = .041) and the differentiation between the tumor and the sinus (P < .001).

CONCLUSIONS:

Reducing the gadolinium dose to 62% of the standard level still allows for sufficient visual delineation of meningiomas from surrounding tissues. However, further reduction to 25% substantially compromises the ability to distinguish the tumor from adjacent structures and is, therefore, not advisable.




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Neuroimaging Correlates with Clinical Severity in Wilson Disease: A Multiparametric Quantitative Brain MRI [RESEARCH]

BACKGROUND AND PURPOSE:

Previous studies have reported metal accumulation and microstructure changes in deep gray nuclei (DGN) in Wilson disease (WD). However, there are limited studies that investigate whether there is metal accumulation and microstructure changes in DGN of patients with WD with normal-appearing routine MRI. This study aimed to evaluate multiparametric changes in DGN of WD and whether the findings correlate with clinical severity in patients with WD.

MATERIALS AND METHODS:

The study enrolled 28 patients with WD (19 with neurologic symptoms) and 25 controls. Fractional anisotropy (FA), mean diffusivity (MD), and magnetic susceptibility in globus pallidus, pontine tegmentum, dentate nucleus, red nucleus, head of caudate nucleus, putamen, substantia nigra, and thalamus were extracted. Correlations between imaging data and the Unified Wilson’s Disease Rating Scale (UWDRS) neurologic subitems were explored.

RESULTS:

FA, MD, and susceptibility values were higher in multiple DGN of patients with WD than controls (P < .05). Patients with WD without abnormal signals in DGN on routine MRI also had higher FA, MD, and susceptibility values than controls (P < .017). We found that UWDRS neurologic subscores correlated with FA and susceptibility values of DGN (P < .05). In addition, we also found that FA and susceptibility values in specific structures correlated with specific neurologic symptoms of WD (ie, tremor, parkinsonism, dysarthria, dystonia, and ataxia) (P < .05).

CONCLUSIONS:

Patients with WD have increased FA, MD, and susceptibility values even before the lesion is morphologically apparent on routine MRI. The increased FA and susceptibility values correlate with clinical severity of WD.




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Differences in Cervical Spine Fractures in Patients Younger or Older Than 65 Years of Age: Implications for the Canadian C-Spine Rule [CLINICAL PRACTICE]

BACKGROUND AND PURPOSE:

There has been a distinction made in the 2001 Canadian C-Spine Rule regarding patients 65 and older and younger than 65 years of age as far as indications for cervical spine CT scanning. We sought to determine if there are differences in the symptoms, mechanisms of injury, fracture locations, and types that are still relevant in 2024.

MATERIALS AND METHODS:

The institutional review board approved this retrospective study of cervical spine CT emergency department results from 2 hospitals in our health system after reviewing 5 years of data in patients experiencing trauma. In addition to the primary variable of age (younger than 65 years and 65 years and older), we looked at injury mechanism, fracture types, sites, symptoms, and operative or medical treatments. Because the demographics of our home site is different from most towns in the United States, we provide race/ethnicity data.

RESULTS:

Of 21,986 cervical spine CTs, 190/9455 (2.0%) participants 65 years of age and older and 199/12,531 (1.6%) participants younger than 65 years of age had fractures (total, 389/21,986, 1.8%). There were more cases of falls from standing (106, 55.8%) and falls from a height (46, 4.2%) in those 65 years and older and this mechanism was associated with a higher risk of C1 and C2 fractures (52, 27.4%; and 78, 41.1%, respectively). Among the C1 fractures, anterior and posterior arch fractures predominated (37, 19.5%). For C2 fractures, types 2 and 3 odontoid fractures (39, 20.5%; and 12, 6.3%) were more common in the older cohort. Motor vehicle collisions were more common in the younger cohort (89, 44.7%), and they were associated with more C5–C7 fractures (47, 23.6%; 60, 30.2%; and 66, 33.2%, respectively) including the facets (49, 24.6%), spinous processes (31, 15.6%), and transverse processes (52, 26.1%). Overall, the rates of instability, surgical intervention, and asymptomatic fractures were similar in the 2 age groups.

CONCLUSIONS:

Cervical spine fractures appear in about 1.8% of the CT scans performed in a busy emergency department environment. Fractures in the elderly occur more commonly due to falls, are located at C1 and C2, and may involve ligamentous injuries. Younger patients incur trauma more commonly due to motor vehicle collisions, and they are more likely to affect the posterior elements, especially C5–C7. The differences in trends for fractures in the 65 years of age and older and younger than 65 years of age groups have persisted since the Canadian C-Spine Rule 1996–1998 data were collected.




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Predictors and Outcomes of Periprocedural Intracranial Hemorrhage after Stenting for Symptomatic Intracranial Atherosclerotic Stenosis [CLINICAL PRACTICE]

BACKGROUND AND PURPOSE:

Periprocedural intracranial hemorrhage is one of common complications after stent placement for symptomatic intracranial atherosclerotic stenosis. This study was conducted to demonstrate predictors and long-term outcomes of periprocedural intracranial hemorrhage after stent placement for symptomatic intracranial atherosclerotic stenosis.

MATERIALS AND METHODS:

We retrospectively analyzed patients with symptomatic intracranial atherosclerotic stenosis stent placement in a prospective cohort at a high-volume stroke center. Clinical, radiologic, and periprocedural characteristics and long-term outcomes were reviewed. Periprocedural intracranial hemorrhage was classified as procedure-related hemorrhage (PRH) and non-procedure-related hemorrhage (NPRH). The long-term outcomes were compared between patients with PRH and NPRH, and the predictors of NPRH were explored.

RESULTS:

Among 1849 patients, 24 (1.3%) had periprocedural intracranial hemorrhage, including PRH (4) and NPRH (20). The postprocedural 30-day mRS was 0–2 in 9 (37.5%) cases, 3–5 in 5 (20.8%) cases, and 6 in 10 (41.7%) cases. For the 14 survivors, the long-term (median of 78 months) mRS were 0–2 in 10 (76.9%) cases and 3–5 in 3 (23.1%) cases. The proportion of poor long-term outcomes (mRS ≥3) in patients with NPRH was significantly higher than those with PRH (68.4% versus 0%, P = .024). Anterior circulation (P = .002), high preprocedural stenosis rate (P < .001), and cerebral infarction within 30 days (P = .006) were independent predictors of NPRH after stent placement.

CONCLUSIONS:

Patients with NPRH had worse outcomes than those with PRH after stent placement for symptomatic ICAS. Anterior circulation, severe preprocedural stenosis, and recent infarction are independent predictors of NPRH.




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Cyclic Aspiration in Mechanical Thrombectomy: Influencing Factors and Experimental Validation [RESEARCH]

BACKGROUND AND PURPOSE:

Mechanical thrombectomy is a fundamental intervention for acute ischemic stroke treatment. While conventional techniques are effective, cyclic aspiration (CyA) shows potential for better recanalization rates. We aim to investigate factors affecting CyA and compare them with static aspiration (StA).

MATERIALS AND METHODS:

StA setup consisted of an aspiration pump connected to pressure transducer. CyA was tested with 5 subsequent iterations: single solenoid valve with air plus saline (i1) or saline alone (i2) as aspiration medium; 2 solenoid valves with air plus saline (i3) as aspiration medium; complete air removal and saline feeding (i4); and pressurized saline feeding (i5). To assess the efficacy of clot ingestion, the pressure transducer was replaced with a distal aspiration catheter. Moderately stiff clot analogs (15 mm) were used to investigate the ingestion quantified as clot relative weight loss. Additionally, the aspiration flow rate was assessed for each setup.

RESULTS:

With CyA i1, the amplitude of the achieved negative pressure waves declined with increasing frequencies but progressively increased with each subsequent iteration, achieving a maximum amplitude of 81 kPa for i5 at 1 Hz. Relative clot weight loss was significantly higher with i5 at 5 Hz than with StA (100% versus 37.8%; P = .05). Aspiration flow rate was lower with CyA than with StA (i5 at 5 Hz: 199.8 mL/min versus StA: 311 mL/min; P < .01).

CONCLUSIONS:

CyA with the appropriate setup may represent an encouraging innovation in mechanical thrombectomy, offering a promising pathway for improving efficacy in clot ingestion and recanalization. The observed benefits warrant confirmation in a clinical setting.




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Stent Retriever AssIsted Lysis Technique with Tirofiban: A Potential Bailout Alternative to Angioplasty and Stenting [CLINICAL PRACTICE]

BACKGROUND AND PURPOSE:

Angioplasty and stent placement have been described as a bailout technique in individuals with failed thrombectomy. We aimed to investigate Stent retriever AssIsted Lysis (SAIL) with tirofiban before angioplasty and stent placement.

MATERIALS AND METHODS:

Patients from 2 comprehensive stroke centers were reviewed (2020–2023). We included patients with failed thrombectomy and/or underlying intracranial stenosis who received SAIL with tirofiban before the intended angioplasty and stent placement. SAIL consisted of deploying a stent retriever through the occluding lesion to create a bypass channel and infuse 10 mL of tirofiban for 10 minutes either intra-arterially or IV. The stent retriever was re-sheathed before retrieval. The primary end points were successful reperfusion (expanded TICI 2b–3) and symptomatic intracerebral hemorrhage. Additional end points included 90-day mRS 0–2 and mortality.

RESULTS:

After a median of 3 (interquartile range, 2–4) passes, 44 patients received the SAIL bridging protocol with tirofiban, and later they were considered potential candidates for angioplasty and stent placement bailout (43.2%, intra-arterial SAIL). Post-SAIL successful reperfusion was obtained in 79.5%. A notable residual stenosis (>50%) after successful SAIL was observed in 45.7%. No significant differences were detected according to post-SAIL: successful reperfusion (intra-arterial SAIL, 80.0% versus IV-SAIL, 78.9%; P = .932), significant stenosis (33.3% versus 55.0%; P = .203), early symptomatic re-occlusion (0% versus 8.0%; P = .207), or symptomatic intracerebral hemorrhage (5.3% versus 8.0%; P = .721). Rescue angioplasty and stent placement were finally performed in 15 (34.1%) patients (intra-arterial SAIL 21.0% versus IV-SAIL 44%; P = .112). At 90 days, mRS 0–2 (intra-arterial SAIL 50.0% versus IV-SAIL 43.5%; P = .086) and mortality (26.3% versus 12.0%; P = .223) were also similar.

CONCLUSIONS:

In patients with stroke in which angioplasty and stent placement are considered, SAIL with tirofiban, either intra-arterial or IV, seems to safely induce sustained recanalization, offering a potential alternative to definitive angioplasty and stent placement.




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Optimal Endovascular Therapy Technique for Isolated Intracranial Atherothrombotic Stroke-Related Large-Vessel Occlusion in the Acute-to-Subacute Stage [CLINICAL PRACTICE]

BACKGROUND AND PURPOSE:

Reocclusion after treatment is a concern in endovascular therapy for isolated intracranial atherothrombotic stroke-related large-vessel occlusion (AT-LVO). However, the optimal endovascular therapy technique for AT-LVO has not yet been investigated. This study evaluated the optimal endovascular therapy technique for AT-LVO in a real-world setting.

MATERIALS AND METHODS:

We conducted a historical, multicenter registry study at 51 centers that enrolled patients with AT-LVO. We divided the patients into 3 groups based on the endovascular therapy technique: mechanical thrombectomy alone, percutaneous transluminal angioplasty (PTA), and stent deployment. Mechanical thrombectomy alone was classified into the mechanical thrombectomy-only group; PTA and mechanical thrombectomy–PTA, into the PTA group; and mechanical thrombectomy–stent deployment, mechanical thrombectomy–PTA–stent deployment, PTA–stent deployment, and stent deployment–only into the stent group. The primary outcome was incidence of reocclusion of the treated vessels within 90 days of endovascular therapy completion.

RESULTS:

We enrolled 770 patients and analyzed 509 patients. The rates in the mechanical thrombectomy-only, PTA, and stent deployment groups were 40.7%, 44.4%, and 14.9%, respectively. Incidence rate of residual stenosis >70% of final angiography was significantly higher in the mechanical thrombectomy-only group than in the PTA and stent deployment groups (mechanical thrombectomy-only versus PTA versus stent deployment: 34.5% versus 26.3% versus 13.2%, P = .002). Reocclusion rate was significantly lower in the PTA group than in the mechanical thrombectomy-only group (adjusted hazard ratio, 0.48; 95% CI, 0.29–0.80). Of the patients, 83.5% experienced reocclusion within 10 days after endovascular therapy. Alarmingly, a substantial subset (approximately 62.0%) of patients experienced reocclusion within 2 days of endovascular therapy. Incidence of mRS scores of 0–2 ninety days after endovascular therapy was not significantly different among the 3 groups. Incidences of symptomatic intracranial hemorrhage, any other intracranial hemorrhage, and death were not significantly different.

CONCLUSIONS:

Incidence rate of reocclusion was significantly lower in the PTA group than in the mechanical thrombectomy-only group. We found no meaningful difference in reocclusion rates between the stent deployment and mechanical thrombectomy-only groups. In Japan, glycoprotein IIb/IIIa inhibitors are not reimbursed. Therefore, PTA might be the preferred choice for AT-LVOs due to the higher reocclusion risk with mechanical thrombectomy-only. Reocclusion was likely to occur within 10 days, particularly within 2 days post-endovascular therapy.




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Prognosis of Proximal and Distal Vertebrobasilar Artery Stent Placement [CLINICAL PRACTICE]

BACKGROUND AND PURPOSE:

Vertebrobasilar artery stent placement (VBS) is potentially effective in preventing recurrent posterior circulation strokes; however, the incidences of in-stent restenosis and stented-territory ischemic events based on the location of stent placement have rarely been investigated. We aimed to investigate the characteristics and prognosis of VBS between intracranial and extracranial.

MATERIALS AND METHODS:

This study was single-center retrospective cohort study, and we obtained medical records of patients who underwent VBS. We compared clinical and periprocedural factors between extracranial and intracranial VBS. The primary outcomes included the incidence of in-stent restenosis (>50% reduction in lumen diameter) and stented-territory ischemic events. We compared the incidence of in-stent restenosis and stented-territory ischemic events by using Kaplan-Meier curves.

RESULTS:

Of the 105 patients, 41 (39.0%) underwent extracranial VBS, and 64 (61.0%) underwent intracranial VBS. During the follow-up, the incidences of in-stent restenosis and stented-territory ischemic events were 15.2% and 22.9%, respectively. The procedure time was longer (47.7 ± 19.5 minutes versus 74.5 ± 35.2 minutes, P < .001), and the rate of residual stenosis (≥30%) just after VBS was higher (2 [4.9%] versus 24 [37.5%], P < .001) in intracranial VBS than in extracranial VBS. Also, the incidences of in-stent restenosis were significantly higher in intracranial VBS than in extracranial VBS (4.9% versus 21.9%, P = .037). On the other hand, the incidences of stented-territory ischemic events (7.3% versus 32.8%, P < .001) were significantly higher in intracranial VBS than in extracranial VBS. The main mechanisms of stroke were artery-to-artery embolism (2 [66.7%]) in extracranial VBS, and artery-to-artery embolism (9 [42.9%]) and branch atheromatous disease (8 [38.1%]) in intracranial VBS. The Kaplan-Meier curve demonstrated a higher incidence of in-stent restenosis and stented-territory ischemic events in intracranial VBS than in extracranial VBS (P = .008 and P = .002, respectively).

CONCLUSIONS:

During the follow-up, the incidence of in-stent restenosis and stented-territory ischemic events was higher in patients with intracranial VBS than in those with extracranial VBS. The higher rates of postprocedural residual stenosis might have contributed to the increased risk of in-stent restenosis. Furthermore, prolonged procedure time and additional stroke mechanism, including branch atheromatous disease, might be associated with a higher risk of stented-territory ischemic events in intracranial VBS.




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Clinical and Pathophysiologic Correlates of Basilar Artery Measurements in Fabry Disease [CLINICAL PRACTICE]

BACKGROUND AND PURPOSE:

Alterations of the basilar artery (BA) anatomy have been suggested as a possible MRA feature of Fabry disease (FD). Nonetheless, no information about their clinical or pathophysiologic correlates is available, limiting our comprehension of the real impact of vessel remodeling in FD.

MATERIALS AND METHODS:

Brain MRIs of 53 subjects with FD (mean age, 40.7 [SD, 12.4] years; male/female ratio = 23:30) were collected in this single-center study. Mean BA diameter and its tortuosity index were calculated on MRA. Possible correlations between these metrics and clinical, laboratory, and advanced imaging variables of the posterior circulation were tested. In a subgroup of 20 subjects, a 2-year clinical and imaging follow-up was available, and possible longitudinal changes of these metrics and their ability to predict clinical scores were also probed.

RESULTS:

No significant association was found between MRA metrics and any clinical, laboratory, or advanced imaging variable (P values ranging from –0.006 to 0.32). At the follow-up examination, no changes were observed with time for the mean BA diameter (P = .84) and the tortuosity index (P = .70). Finally, baseline MRA variables failed to predict the clinical status of patients with FD at follow-up (P = .42 and 0.66, respectively).

CONCLUSIONS:

Alterations of the BA in FD lack of any meaningful association with clinical, laboratory, or advanced imaging findings collected in this study. Furthermore, this lack of correlation seems constant across time, suggesting stability over time. Taken together, these results suggest that the role of BA dolichoectasia in FD should be reconsidered.




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High-Resolution MRA Cerebrovascular Findings in a Tri-Ethnic Population [CLINICAL PRACTICE]

BACKGROUND AND PURPOSE:

Incidental findings on brain MRI and variations of the circle of Willis (CoW) are relatively common among the general population. Ethnic differences have been described before, but few studies have explored the prevalence of incidental intracranial cerebrovascular findings and CoW variants in the setting of a single multiethnic cohort. The purpose of this investigation was to describe both incidental cerebrovascular findings and the morphology of the CoW on high-resolution 3T TOF-MRA in a UK tri-ethnic population-based cohort and to present updated prevalence estimates and morphologic reference values.

MATERIALS AND METHODS:

We studied participants from the UK Southall and Brent REvisited study who underwent 3T brain MRI between 2014 and 2018. TOF-MRA images were assessed for the presence of incidental cerebrovascular findings and used to determine CoW anatomy.

RESULTS:

Seven hundred fifty participants (mean age, 71.28 [SD, 6.46] years; range, 46–90 years; 337 women), 322 White Europeans, 253 South Asians, and 175 African Caribbeans were included. Incidental cerebrovascular findings were observed in 84 subjects (11.2%, 95% CI, 9.0%–13.7%; 36 women; 42.86%, 95% CI, 32.11%–54.12%), with cerebral aneurysms being the most frequent followed by intracranial arterial stenoses with the highest prevalence among South Asians compared with White European (OR: 2.72; 95% CI, 1.22–6.08; P = .015) and African Caribbean subjects (OR: 2.79; 95% CI, 1.00–7.82; P = .051). Other findings included arteriovenous malformations and infundibula. The CoW was found to be more often complete in women than in men (25.22% compared with 18.41%, P = .024) and in African Caribbean (34.86%) compared with White European (19.19%) and South Asian (14.23%) subjects (P < .001 each).

CONCLUSIONS:

Intracranial arterial stenoses were independently associated with ethnicity after adjusting for vascular risk factors, having the highest prevalence among South Asians. The prevalence of aneurysms was higher than that in previous population-based studies. We observed anatomic differences in the CoW configuration among women, men, and ethnicities.




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Distribution and Disparities of Industry Payments to Neuroradiologists [CLINICAL PRACTICE]

BACKGROUND AND PURPOSE:

Physician-industry relationships can be useful for driving innovation and technologic progress, though little is known about the scale or impact of industry involvement in neuroradiology. The purpose of this study was to assess the trends and distributions of industry payments to neuroradiologists.

MATERIALS AND METHODS:

Neuroradiologists were identified using a previously-validated method based on Work Relative Value Units and Neiman Imaging Types of Service classification. Data on payments from industry were obtained from the Open Payments database from the Centers for Medicare & Medicaid Services, from 2016 to 2021. Payments were grouped into 7 categories, including consulting fees, education, gifts, medical supplies, research, royalties/ownership, and speaker fees. Descriptive statistics were calculated.

RESULTS:

A total of 3019 neuroradiologists were identified in this study. Between 2016 and 2021, 48% (1440/3019) received at least 1 payment from industry, amounting to a total number of 21,967 payments. Each year, among those receiving payments from industry, each unique neuroradiologist received between a mean of 5.49–7.42 payments and a median of 2 payments, indicating a strong rightward skew to the distribution of payments. Gifts were the most frequent payment type made (60%, 13,285/21,967) but accounted for only 4.1% ($689,859/$17,010,546) of payment value. The greatest aggregate payment value came from speaker fees, which made up 36% ($6,127,484/$17,010,546) of the total payment value. The top 5% highest paid neuroradiologists received 42% (9133/21,967) of payments, which accounted for 84% ($14,284,120/$17,010,546) of the total dollar value. Since the start of the coronavirus 2019 (COVID-19) pandemic, the number of neuroradiologists receiving industry payments decreased from a mean of 671 neuroradiologists per year prepandemic (2016–2019) to 411 in the postpandemic (2020–2021) era (P = .030). The total number of payments to neuroradiologists decreased from 4177 per year prepandemic versus 2631 per year postpandemic (P = .011).

CONCLUSIONS:

Industry payments to neuroradiologists are highly concentrated among top earners, particularly among the top 5% of payment recipients. The number of payments decreased during the COVID-19 pandemic, though the dollar value of payments was offset by coincidental increases in royalty payments. Further investigation is needed in subsequent years to determine if the postpandemic changes in industry payment trends continue.




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Ependymal Tumors: Overview of the Recent World Health Organization Histopathologic and Genetic Updates with an Imaging Characteristic [CLINICAL PRACTICE]

SUMMARY:

The 2021 World Health Organization Classification of Tumors of the Central Nervous System (CNS5), introduced significant changes, impacting tumors ranging from glial to ependymal neoplasms. Ependymal tumors were previously classified and graded based on histopathology, which had limited clinical and prognostic utility. The updated CNS5 classification now divides ependymomas into 10 subgroups based on anatomic location (supratentorial, posterior fossa, and spinal compartment) and genomic markers. Supratentorial tumors are defined by zinc finger translocation associated (ZFTA) (formerly v-rel avian reticuloendotheliosis viral oncogene [RELA]), or yes-associated protein 1 (YAP1) fusion; posterior fossa tumors are classified into groups A (PFA) and B (PFB), spinal ependymomas are defined by MYCN amplification. Subependymomas are present across all these anatomic compartments. The new classification kept an open category of "not elsewhere classified" or "not otherwise specified" if no pathogenic gene fusion is identified or if the molecular diagnosis is not feasible. Although there is significant overlap in the imaging findings of these tumors, a neuroradiologist needs to be familiar with updated CNS5 classification to understand tumor behavior, for example, the higher tendency for tumor recurrence along the dural flap for ZFTA fusion-positive ependymomas. On imaging, supratentorial ZFTA-fused ependymomas are preferentially located in the cerebral cortex, carrying predominant cystic components. YAP1-MAMLD1-fused ependymomas are intra- or periventricular with prominent multinodular solid components and have significantly better prognosis than ZFTA-fused counterparts. PFA ependymomas are aggressive paramedian masses with frequent calcification, seen in young children, originating from the lateral part of the fourth ventricular roof. PFB ependymomas are usually midline, noncalcified solid-cystic masses seen in adolescents and young adults arising from the fourth ventricular floor. PFA has a poorer prognosis, higher recurrence, and higher metastatic rate than PFB. Myxopapillary spinal ependymomas are now considered grade II due to high recurrence rates. Spinal-MYCN ependymomas are aggressive tumors with frequent leptomeningeal spread, relapse, and poor prognosis. Subependymomas are noninvasive, intraventricular, slow-growing benign tumors with an excellent prognosis. Currently, the molecular classification does not enhance the clinicopathologic understanding of subependymoma and myxopapillary categories. However, given the molecular advancements, this will likely change in the future. This review provides an updated molecular classification of ependymoma, discusses the individual imaging characteristics, and briefly outlines the latest targeted molecular therapies.




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Academic Neuroradiology: 2023 Update on Turnaround Time, Financial Recruitment, and Retention Strategies [CLINICAL PRACTICE]

SUMMARY:

The ASNR Neuroradiology Division Chief Working Group's 2023 survey, with responses from 62 division chiefs, provides insights into turnaround times, faculty recruitment, moonlighting opportunities, and academic funds. In emergency cases, 61% aim for a turnaround time of less than 45–60 minutes, with two-thirds meeting this expectation more than 75% of the time. For inpatient CT and MR imaging scans, 54% achieve a turnaround time of 4–8 hours, with three-quarters meeting this expectation at least 50% of the time. Outpatient scans have an expected turnaround time of 24–48 hours, which is met in 50% of cases. Faculty recruitment strategies included 35% offering sign-on bonuses, with a median of $30,000. Additionally, 23% provided bonuses to fellows during fellowship to retain them in the practice upon completion of their fellowship. Internal moonlighting opportunities for faculty were offered by 70% of divisions, with a median pay of $250 per hour. The median annual academic fund for a full-time neuroradiology faculty member was $6000, typically excluding license fees but including American College of Radiology and American Board of Radiology membership, leaving $4000 for professional expenses. This survey calls for further dialogue on adapting and innovating academic institutions to meet evolving needs in neuroradiology.




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Clinical and functional analysis of the germline TP53 p.K164E acetylation site variant [RESEARCH ARTICLE]

TP53 plays a critical role as a tumor suppressor by controlling cell cycle progression, DNA repair, and apoptosis. Post-translational modifications such as acetylation of specific lysine residues in the DNA binding and carboxy-terminus regulatory domains modulate its tumor suppressor activities. In this study, we addressed the functional consequences of the germline TP53 p.K164E (NM_000546.5: c.490A>G) variant identified in a patient with early-onset breast cancer and a significant family history of cancer. K164 is a conserved residue located in the L2 loop of the p53 DNA binding domain that is post-translationally modified by acetylation. In silico, in vitro, and in vivo analyses demonstrated that the glutamate substitution at K164 marginally destabilizes the p53 protein structure but significantly impairs sequence-specific DNA binding, transactivation, and tumor cell growth inhibition. Although p.K164E is currently considered a variant of unknown significance by different clinical genetic testing laboratories, the clinical and laboratory-based findings presented here provide strong evidence to reclassify TP53 p.K164E as a likely pathogenic variant.




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Collaborative discussions between GPs and pharmacists to optimise patient medication: a qualitative study within a UK primary care clinical trial

BackgroundThere has been significant investment in pharmacists working in UK general practice to improve the effective and safe use of medicines. However, evidence of how to optimise collaboration between GPs and pharmacists in the context of polypharmacy (multiple medication) is lacking.AimTo explore GP and pharmacist views and experiences of in-person, interprofessional collaborative discussions (IPCDs) as part of a complex intervention to optimise medication use for patients with polypharmacy in general practice.Design and settingA mixed-method process evaluation embedded within the Improving Medicines use in People with Polypharmacy in Primary Care (IMPPP) trial conducted in Bristol and the West Midlands, between February 2021 and September 2023.MethodAudio-recordings of IPCDs between GPs and pharmacists, along with individual semi-structured interviews to explore their reflections on these discussions, were used. All recordings were transcribed verbatim and analysed thematically.ResultsA total of 14 practices took part in the process evaluation from February 2022 to September 2023; 17 IPCD meetings were audio-recorded, discussing 30 patients (range 1–6 patients per meeting). In all, six GPs and 13 pharmacists were interviewed. The IPCD was highly valued by GPs and pharmacists who described benefits, including: strengthening their working relationship; gaining in confidence to manage more complex patients; and learning from each other. It was often challenging, however, to find time for the IPCDs.ConclusionThe model of IPCD used in this study provided protected time for GPs and pharmacists to work together to deliver whole-patient care, with both professions finding this beneficial. Protected time for interprofessional liaison and collaboration, and structured interventions may facilitate improved patient care.




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Primary care health professionals&#x2019; approach to clinical coding: a qualitative interview study




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[PERSPECTIVES] New Paradigms in the Clinical Management of Li-Fraumeni Syndrome

Approximately 8.5%–16.2% of childhood cancers are associated with a pathogenic/likely pathogenic germline variant—a prevalence that is likely to rise with improvements in phenotype recognition, sequencing, and variant validation. One highly informative, classical hereditary cancer predisposition syndrome is Li–Fraumeni syndrome (LFS), associated with germline variants in the TP53 tumor suppressor gene, and a >90% cumulative lifetime cancer risk. In seeking to improve outcomes for young LFS patients, we must improve the specificity and sensitivity of existing cancer surveillance programs and explore how to complement early detection strategies with pharmacology-based risk-reduction interventions. Here, we describe novel precision screening technologies and clinical strategies for cancer risk reduction. In particular, we summarize the biomarkers for early diagnosis and risk stratification of LFS patients from birth, noninvasive and machine learning–based cancer screening, and drugs that have shown the potential to be repurposed for cancer prevention.




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[PERSPECTIVES] Addressing Biological Questions with Preclinical Cancer Imaging

The broad application of noninvasive imaging has transformed preclinical cancer research, providing a powerful means to measure dynamic processes in living animals. While imaging technologies are routinely used to monitor tumor growth in model systems, their greatest potential lies in their ability to answer fundamental biological questions. Here we present the broad range of potential imaging applications according to the needs of a cancer biologist with a focus on some of the common biological processes that can be used to visualize and measure. Topics include imaging metastasis; biophysical properties such as perfusion, diffusion, oxygenation, and stiffness; imaging the immune system and tumor microenvironment; and imaging tumor metabolism. We also discuss the general ability of each approach and the level of training needed to both acquire and analyze images. The overall goal is to provide a practical guide for cancer biologists interested in answering biological questions with preclinical imaging technologies.




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Management of opioid use disorder: 2024 update to the national clinical practice guideline [Guideline]

Background

In an evolving landscape of practices and policies, reviewing and incorporating the latest scientific evidence is necessary to ensure optimal clinical management for people with opioid use disorder. We provide a synopsis of the 2024 update of the 2018 National Guideline for the Clinical Management of Opioid Use Disorder, from the Canadian Research Initiative in Substance Matters.

Methods

For this update, we followed the United States Institute of Medicine’s Standards for Developing Trustworthy Clinical Practice Guidelines and used the Appraisal of Guidelines Research and Evaluation—Recommendation Excellence tool to ensure guideline quality. We carried out a comprehensive systematic literature review, capturing the relevant literature from Jan. 1, 2017, to Sept. 14, 2023. We drafted and graded recommendations according to the Grading of Recommendations, Assessments, Development and Evaluation approach. A multidisciplinary external national committee, which included people with living or lived experience of opioid use disorder, provided input that was incorporated into the guideline.

Recommendations

From the initial 11 recommendations in the 2018 guideline, 3 remained unchanged, and 8 were updated. Specifically, 4 recommendations were consolidated into a single revised recommendation; 1 recommendation was split into 2; another recommendation was moved to become a special consideration; and 2 recommendations were revised. Key changes have arisen from substantial evidence supporting that methadone and buprenorphine are similarly effective, particularly in reducing opioid use and adverse events, and both are now considered preferred first-line treatment options. Slow-release oral morphine is recommended as a second-line option. Psychosocial interventions can be offered as adjunctive treatment but should not be mandatory. The guideline reaffirms the importance of avoiding withdrawal management as a standalone intervention and of incorporating evidence-based harm reduction services along the continuum of care.

Interpretation

This guideline update presents new recommendations based on the latest literature for standardized management of opioid use disorder. The aim is to establish a robust foundation upon which provincial and territorial bodies can develop guidance for optimal care.




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Controversies in the clinical management of chronic pulmonary aspergillosis

Chronic pulmonary aspergillosis has a range of manifestations from indolent nodules to semi-invasive infection. Patients may be asymptomatic or have chronic symptoms such as cough and weight loss or present with life-threatening haemoptysis. The physician can choose from a range of available therapies including medical therapy with antifungals, minimally invasive therapy with intracavitary antifungal therapy and surgery involving open thoracotomy or video-assisted thoracoscopic surgery. The patients with the most severe forms of pulmonary infection may not be surgical candidates due to their underlying pulmonary condition. The management of haemoptysis can include tranexamic acid, bronchial artery embolisation, antifungals or surgery. There are few controlled studies to inform clinicians managing complex cases, so a multidisciplinary approach may be helpful.




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Spatial lung imaging in clinical and translational settings

For many severe lung diseases, non-invasive biomarkers from imaging could improve early detection of lung injury or disease onset, establish a diagnosis, or help follow-up disease progression and treatment strategies. Imaging of the thorax and lung is challenging due to its size, respiration movement, transferred cardiac pulsation, vast density range and gravitation sensitivity. However, there is extensive ongoing research in this fast-evolving field. Recent improvements in spatial imaging have allowed us to study the three-dimensional structure of the lung, providing both spatial architecture and transcriptomic information at single-cell resolution. This fast progression, however, comes with several challenges, including significant image file storage and network capacity issues, increased costs, data processing and analysis, the role of artificial intelligence and machine learning, and mechanisms to combine several modalities. In this review, we provide an overview of advances and current issues in the field of spatial lung imaging.




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Even Exxon’s CEO Doesn’t Want Trump to Pull Out of the Paris Climate Agreement



The head of one of the world's largest oil companies has had it with government flip-flopping.






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RPG Cast – Episode 577: “Eclipse, I Love You, but GO AWAY”

It's a slightly quieter week after the mass dump of games that was February and the first week of March. Kelley doesn't want her mom to think she's watching hentai, while Anna Marie insists our reviewers don't hate every game. Josh will one day be free of the epic grip of Cold Steel IV, but not before Chris convinces him if he just lifts a truck, he can find a new orbment.

The post RPG Cast – Episode 577: “Eclipse, I Love You, but GO AWAY” appeared first on RPGamer.




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You can now make video clips using Steam's built-in game recording feature, as an update rolls it out to all users

Steam's built-in game recording feature has been usable in beta since the summer, but it has now been properly launched for every user, following a client update to Steam yesterday. It's basically another method of capturing funny ragdoll glitches and posting them on the "lol-games-are-dumb" channel of your friend's Discord. Or for posting that flukey knife throw in Call Of Duty to Twitter, as if you really meant to kill the man from across the map all along. Or saving a clip for your personal records, like the footage of that time you yeeted an innocent citizen off the 50-foot wall of a castle town in Dragon's Dogma 2. We all do that, right? Right?

Read more




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First breathtaking images from Euclid telescope's map of the universe

The Euclid space telescope's massive “cosmic atlas” promises to shed light on fundamental questions in physics and cosmology




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What preparing for an asteroid strike teaches us about climate change

Averting an asteroid strike will need many of the same skills we must hone to tackle climate change and future pandemics




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Video Friday: Quadruped Ladder Climbing



Video Friday is your weekly selection of awesome robotics videos, collected by your friends at IEEE Spectrum robotics. We also post a weekly calendar of upcoming robotics events for the next few months. Please send us your events for inclusion.

IROS 2024: 14–18 October 2024, ABU DHABI, UAE
ICSR 2024: 23–26 October 2024, ODENSE, DENMARK
Cybathlon 2024: 25–27 October 2024, ZURICH
Humanoids 2024: 22–24 November 2024, NANCY, FRANCE

Enjoy today’s videos!

Not even ladders can keep you safe from quadruped robots anymore.

[ ETH Zürich Robot Systems Lab ]

Introducing Azi (right), the new desktop robot from Engineered Arts Ltd. Azi and Ameca are having a little chat, demonstrating their wide range of expressive capabilities. Engineered Arts desktop robots feature 32 actuators, 27 for facial control alone, and 5 for the neck. They include AI conversational ability including GPT-4o support which makes them great robotic companions.

[ Engineered Arts ]

Quadruped robots that individual researchers can build by themselves are crucial for expanding the scope of research due to their high scalability and customizability. In this study, we develop a metal quadruped robot MEVIUS, that can be constructed and assembled using only materials ordered through e-commerce. We have considered the minimum set of components required for a quadruped robot, employing metal machining, sheet metal welding, and off-the-shelf components only.

[ MEVIUS from JSK Robotics Laboratory ]

Thanks Kento!

Avian perching maneuvers are one of the most frequent and agile flight scenarios, where highly optimized flight trajectories, produced by rapid wing and tail morphing that generate high angular rates and accelerations, reduce kinetic energy at impact. Here, we use optimal control methods on an avian-inspired drone with morphing wing and tail to test a recent hypothesis derived from perching maneuver experiments of Harris’ hawks that birds minimize the distance flown at high angles of attack to dissipate kinetic energy before impact.

[ EPFL Laboratory of Intelligent Systems ]

The earliest signs of bearing failures are inaudible to you, but not to Spot . Introducing acoustic vibration sensing—Automate ultrasonic inspections of rotating equipment to keep your factory humming.

The only thing I want to know is whether Spot is programmed to actually do that cute little tilt when using its acoustic sensors.

[ Boston Dynamics ]

Hear from Jonathan Hurst, our co-founder and Chief Robot Officer, why legs are ideally suited for Digit’s work.

[ Agility Robotics ]

I don’t think “IP67” really does this justice.

[ ANYbotics ]

This paper presents a teleportation system with floating robotic arms that traverse parallel cables to perform long-distance manipulation. The system benefits from the cable-based infrastructure, which is easy to set up and cost-effective with expandable workspace range.

[ EPFL ]

It seems to be just renderings for now, but here’s the next version of Fourier’s humanoid.

[ Fourier ]

Happy Oktoberfest from Dino Robotics!

[ Dino Robotics ]

This paper introduces a learning-based low-level controller for quadcopters, which adaptively controls quadcopters with significant variations in mass, size, and actuator capabilities. Our approach leverages a combination of imitation learning and reinforcement learning, creating a fast-adapting and general control framework for quadcopters that eliminates the need for precise model estimation or manual tuning.

[ HiPeR Lab ]

Parkour poses a significant challenge for legged robots, requiring navigation through complex environments with agility and precision based on limited sensory inputs. In this work, we introduce a novel method for training end-to-end visual policies, from depth pixels to robot control commands, to achieve agile and safe quadruped locomotion.

[ SoloParkour ]




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Some scientists say blocking the sun could slow climate change — just like on The Simpsons

Scientists say geoengineering, or doing things like intentionally increasing Earth’s reflectivity or blocking the sun, is a “really big deal” in slowing down climate change. Here are the ideas they are proposing.




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Trump picks former national intelligence head John Ratcliffe for CIA

President-elect Donald Trump announced Tuesday that John Ratcliffe, a former Texas congressman and director of national intelligence, will serve as the director of the Central Intelligence Agency in his administration.




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Trump picks John Ratcliffe for CIA, expected to name Gov. Kristi Noem for Homeland Security

President-elect Donald Trump announced a flurry of appointments Tuesday for key posts in his new administration, including former Director of National Intelligence John Ratcliffe to lead the CIA and the expected nomination of South Dakota Gov. Kristi Noem to head the Department of Homeland Security.




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Quadruped robot climbs ladders, creeps us out

A Swiss-engineered robot can climb ladders, showing why it's at the cutting edge of autonomous robotic solutions for harsh industrial settings.



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Is just reading that sketchy scammer’s email dangerous or do I have to click on a link to get in trouble?

Tech expert Kurt “CyberGuy" Knutsson says opening emails is safe, but risks arise from interacting with links, attachments or HTML content.



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Texas children’s hospital and clinics see sharp rise in Salmonella cases

Various Cook Children’s locations are experiencing a spike in cases of salmonella, but the Texas Department of State Health Services has not reported an outbreak.     Since July, the Emergency Department at Cook Children’s Medical Center – Fort Worth has also reported increased numbers of patients with salmonella.   “In... Continue Reading




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Germany sees outbreaks decline, but cases increase

Germany has reported a decline in outbreaks for 2023, but more people were sick than in the previous year. In 2023, the Federal Office of Consumer Protection and Food Safety (BVL) and the Robert Koch Institute (RKI) received 190 reports of foodborne outbreaks that caused 2,248 illnesses, 283 hospitalizations, and... Continue Reading




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Trump picks former intel director John Ratcliffe to head the CIA

John Ratcliffe, who previously served as President-elect Trump's principal intelligence advisor, has now been picked by Trump to serve as director of the CIA.



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It’s Time to Redefine What a Megafire Is in the Climate Change Era

It's not the reach of a fire that matters most; it's the speed. Understanding this can help society better prepare.