li An Extended Follow-up of Spinal Instrumentation Rescue with Cement Augmentation [CLINICAL PRACTICE] By www.ajnr.org Published On :: 2024-11-07T15:14:12-08:00 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. Full Article
li Probabilistic Presurgical Language fMRI Atlas of Patients with Brain Tumors [CLINICAL PRACTICE] By www.ajnr.org Published On :: 2024-11-07T15:14:12-08:00 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. Full Article
li Enzyme Replacement Therapy for CLN2 Disease: MRI Volumetry Shows Significantly Slower Volume Loss Compared with a Natural History Cohort [CLINICAL PRACTICE] By www.ajnr.org Published On :: 2024-11-07T15:14:12-08:00 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. Full Article
li Arterial Spin-Labeling Perfusion Lightbulb Sign: An Imaging Biomarker of Pediatric Posterior Fossa Hemangioblastoma [CLINICAL PRACTICE] By www.ajnr.org Published On :: 2024-11-07T15:14:12-08:00 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. Full Article
li Diffusion Analysis of Intracranial Epidermoid, Head and Neck Epidermal Inclusion Cyst, and Temporal Bone Cholesteatoma [CLINICAL PRACTICE] By www.ajnr.org Published On :: 2024-11-07T15:14:12-08:00 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. Full Article
li 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] By www.ajnr.org Published On :: 2024-11-07T15:14:12-08:00 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. Full Article
li Comparative Evaluation of Lower Gadolinium Doses for MR Imaging of Meningiomas: How Low Can We Go? [CLINICAL PRACTICE] By www.ajnr.org Published On :: 2024-11-07T15:14:12-08:00 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. Full Article
li Neuroimaging Correlates with Clinical Severity in Wilson Disease: A Multiparametric Quantitative Brain MRI [RESEARCH] By www.ajnr.org Published On :: 2024-11-07T15:14:12-08:00 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. Full Article
li Differences in Cervical Spine Fractures in Patients Younger or Older Than 65 Years of Age: Implications for the Canadian C-Spine Rule [CLINICAL PRACTICE] By www.ajnr.org Published On :: 2024-11-07T15:14:12-08:00 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. Full Article
li Predictors and Outcomes of Periprocedural Intracranial Hemorrhage after Stenting for Symptomatic Intracranial Atherosclerotic Stenosis [CLINICAL PRACTICE] By www.ajnr.org Published On :: 2024-11-07T15:14:12-08:00 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. Full Article
li Cyclic Aspiration in Mechanical Thrombectomy: Influencing Factors and Experimental Validation [RESEARCH] By www.ajnr.org Published On :: 2024-11-07T15:14:12-08:00 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. Full Article
li Stent Retriever AssIsted Lysis Technique with Tirofiban: A Potential Bailout Alternative to Angioplasty and Stenting [CLINICAL PRACTICE] By www.ajnr.org Published On :: 2024-11-07T15:14:12-08:00 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. Full Article
li Optimal Endovascular Therapy Technique for Isolated Intracranial Atherothrombotic Stroke-Related Large-Vessel Occlusion in the Acute-to-Subacute Stage [CLINICAL PRACTICE] By www.ajnr.org Published On :: 2024-11-07T15:14:12-08:00 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. Full Article
li Prognosis of Proximal and Distal Vertebrobasilar Artery Stent Placement [CLINICAL PRACTICE] By www.ajnr.org Published On :: 2024-11-07T15:14:12-08:00 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. Full Article
li Intra-Aneurysmal High-Resolution 4D MR Flow Imaging for Hemodynamic Imaging Markers in Intracranial Aneurysm Instability [RESEARCH] By www.ajnr.org Published On :: 2024-11-07T15:14:12-08:00 BACKGROUND AND PURPOSE: Prediction of aneurysm instability is crucial to guide treatment decisions and to select appropriate patients with unruptured intracranial aneurysms (IAs) for preventive treatment. High-resolution 4D MR flow imaging and 3D quantification of aneurysm morphology could offer insights and new imaging markers for aneurysm instability. In this cross-sectional study, we aim to identify 4D MR flow imaging markers for aneurysm instability by relating hemodynamics in the aneurysm sac to 3D morphologic proxy parameters for aneurysm instability. MATERIALS AND METHODS: In 35 patients with 37 unruptured IAs, a 3T MRA and a 7T 4D MRI flow scan were performed. Five hemodynamic parameters—peak-systolic wall shear stress (WSSMAX) and time-averaged wall shear stress (WSSMEAN), oscillatory shear index (OSI), mean velocity, and velocity pulsatility index—were correlated to 6 3D morphology proxy parameters of aneurysm instability—major axis length, volume, surface area (all 3 size parameters), flatness, shape index, and curvedness—by Pearson correlation with 95% CI. Scatterplots of hemodynamic parameters that correlated with IA size (major axis length) were created. RESULTS: WSSMAX and WSSMEAN correlated negatively with all 3 size parameters (strongest for WSSMEAN with volume (r = –0.70, 95% CI –0.83 to –0.49) and OSI positively (strongest with major axis length [r = 0.87, 95% CI 0.76–0.93]). WSSMAX and WSSMEAN correlated positively with shape index (r = 0.61, 95% CI 0.36–0.78 and r = 0.49, 95% CI 0.20–0.70, respectively) and OSI negatively (r = –0.82, 95% CI –0.9 to –0.68). WSSMEAN and mean velocity correlated negatively with flatness (r = –0.35, 95% CI –0.61 to –0.029 and r = –0.33, 95% CI –0.59 to 0.007, respectively) and OSI positively (r = 0.54, 95% CI 0.26–0.74). Velocity pulsatility index did not show any statistically relevant correlation. CONCLUSIONS: Out of the 5 included hemodynamic parameters, WSSMAX, WSSMEAN, and OSI showed the strongest correlation with morphologic 3D proxy parameters of aneurysm instability. Future studies should assess these promising new imaging marker parameters for predicting aneurysm instability in longitudinal cohorts of patients with IA. Full Article
li Clinical and Pathophysiologic Correlates of Basilar Artery Measurements in Fabry Disease [CLINICAL PRACTICE] By www.ajnr.org Published On :: 2024-11-07T15:14:12-08:00 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. Full Article
li High-Resolution MRA Cerebrovascular Findings in a Tri-Ethnic Population [CLINICAL PRACTICE] By www.ajnr.org Published On :: 2024-11-07T15:14:12-08:00 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. Full Article
li Deep Learning-Based Reconstruction of 3D T1 SPACE Vessel Wall Imaging Provides Improved Image Quality with Reduced Scan Times: A Preliminary Study [ARTIFICIAL INTELLIGENCE] By www.ajnr.org Published On :: 2024-11-07T15:14:12-08:00 BACKGROUND AND PURPOSE: Intracranial vessel wall imaging is technically challenging to implement, given the simultaneous requirements of high spatial resolution, excellent blood and CSF signal suppression, and clinically acceptable gradient times. Herein, we present our preliminary findings on the evaluation of a deep learning–optimized sequence using T1-weighted imaging. MATERIALS AND METHODS: Clinical and optimized deep learning–based image reconstruction T1 3D Sampling Perfection with Application optimized Contrast using different flip angle Evolution (SPACE) were evaluated, comparing noncontrast sequences in 10 healthy controls and postcontrast sequences in 5 consecutive patients. Images were reviewed on a Likert-like scale by 4 fellowship-trained neuroradiologists. Scores (range, 1–4) were separately assigned for 11 vessel segments in terms of vessel wall and lumen delineation. Additionally, images were evaluated in terms of overall background noise, image sharpness, and homogeneous CSF signal. Segment-wise scores were compared using paired samples t tests. RESULTS: The scan time for the clinical and deep learning–based image reconstruction sequences were 7:26 minutes and 5:23 minutes respectively. Deep learning–based image reconstruction images showed consistently higher wall signal and lumen visualization scores, with the differences being statistically significant in most vessel segments on both pre- and postcontrast images. Deep learning–based image reconstruction had lower background noise, higher image sharpness, and uniform CSF signal. Depiction of intracranial pathologies was better or similar on the deep learning–based image reconstruction. CONCLUSIONS: Our preliminary findings suggest that deep learning–based image reconstruction–optimized intracranial vessel wall imaging sequences may be helpful in achieving shorter gradient times with improved vessel wall visualization and overall image quality. These improvements may help with wider adoption of intracranial vessel wall imaging in clinical practice and should be further validated on a larger cohort. Full Article
li Artificial Intelligence Efficacy as a Function of Trainee Interpreter Proficiency: Lessons from a Randomized Controlled Trial [RESEARCH] By www.ajnr.org Published On :: 2024-11-07T15:14:12-08:00 BACKGROUND AND PURPOSE: Recently, artificial intelligence tools have been deployed with increasing speed in educational and clinical settings. However, the use of artificial intelligence by trainees across different levels of experience has not been well-studied. This study investigates the impact of artificial intelligence assistance on the diagnostic accuracy for intracranial hemorrhage and large-vessel occlusion by medical students and resident trainees. MATERIALS AND METHODS: This prospective study was conducted between March 2023 and October 2023. Medical students and resident trainees were asked to identify intracranial hemorrhage and large-vessel occlusion in 100 noncontrast head CTs and 100 head CTAs, respectively. One group received diagnostic aid simulating artificial intelligence for intracranial hemorrhage only (n = 26); the other, for large-vessel occlusion only (n = 28). Primary outcomes included accuracy, sensitivity, and specificity for intracranial hemorrhage/large-vessel occlusion detection without and with aid. Study interpretation time was a secondary outcome. Individual responses were pooled and analyzed with the t test; differences in continuous variables were assessed with ANOVA. RESULTS: Forty-eight participants completed the study, generating 10,779 intracranial hemorrhage or large-vessel occlusion interpretations. With diagnostic aid, medical student accuracy improved 11.0 points (P < .001) and resident trainee accuracy showed no significant change. Intracranial hemorrhage interpretation time increased with diagnostic aid for both groups (P < .001), while large-vessel occlusion interpretation time decreased for medical students (P < .001). Despite worse performance in the detection of the smallest-versus-largest hemorrhages at baseline, medical students were not more likely to accept a true-positive artificial intelligence result for these more difficult tasks. Both groups were considerably less accurate when disagreeing with the artificial intelligence or when supplied with an incorrect artificial intelligence result. CONCLUSIONS: This study demonstrated greater improvement in diagnostic accuracy with artificial intelligence for medical students compared with resident trainees. However, medical students were less likely than resident trainees to overrule incorrect artificial intelligence interpretations and were less accurate, even with diagnostic aid, than the artificial intelligence was by itself. Full Article
li Distribution and Disparities of Industry Payments to Neuroradiologists [CLINICAL PRACTICE] By www.ajnr.org Published On :: 2024-11-07T15:14:12-08:00 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. Full Article
li Ependymal Tumors: Overview of the Recent World Health Organization Histopathologic and Genetic Updates with an Imaging Characteristic [CLINICAL PRACTICE] By www.ajnr.org Published On :: 2024-11-07T15:14:12-08:00 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. Full Article
li Academic Neuroradiology: 2023 Update on Turnaround Time, Financial Recruitment, and Retention Strategies [CLINICAL PRACTICE] By www.ajnr.org Published On :: 2024-11-07T15:14:12-08:00 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. Full Article
li The diagnostic odyssey of a patient with dihydropyrimidinase deficiency: a case report and review of the literature [RESEARCH REPORT] By molecularcasestudies.cshlp.org Published On :: 2024-01-10T08:13:38-08:00 Dihydropyrimidinase (DHP) deficiency is an autosomal recessive metabolic disorder caused by biallelic pathogenic variants of DPYS. Patients with DHP deficiency exhibit a broad spectrum of phenotypes, ranging from severe neurological and gastrointestinal involvement to cases with no apparent symptoms. The biochemical diagnosis of DHP deficiency is based on the detection of a significant amount of dihydropyrimidines in urine, plasma, and cerebrospinal fluid samples. Molecular genetic testing, specifically the identification of biallelic pathogenic variants in DPYS, has proven instrumental in confirming the diagnosis and facilitating family studies. This case study documents the diagnostic journey of an 18-yr-old patient with DHP deficiency, highlighting features at the severe end of the clinical spectrum. Notably, our patient exhibited previously unreported skeletal features that positively responded to bisphosphonate treatment, contributing valuable insights to the clinical characterization of DHP deficiency. Additionally, a novel DPYS variant was identified and confirmed pathogenicity through metabolic testing, further expanding the variant spectrum of the gene. Our case emphasizes the importance of a comprehensive diagnostic approach using genetic sequencing and metabolic testing for accurate diagnosis. Full Article
li PD-L1+ diffuse large B-cell lymphoma with extremely high mutational burden and microsatellite instability due to acquired PMS2 mutation [RESEARCH REPORT] By molecularcasestudies.cshlp.org Published On :: 2024-01-10T08:13:38-08:00 We present a unique case of a single patient presenting with two mutationally distinct, PD-L1+ diffuse large B-cell lymphomas (DLBCLs). One of these DLBCLs demonstrated exceptionally high mutational burden (eight disease-associated variants and 41 variants of undetermined significance) with microsatellite instability (MSI) and an acquired PMS2 mutation with loss of PMS2 protein expression, detected postchemotherapy. This report, while highlighting the extent of possible tumor heterogeneity across separate clonal expansions as well as possible syndromic B-cell neoplasia, supports the notion that, although rare, PD-L1 expression and associated states permissive of high mutational burden (such as mismatch repair gene loss of function/MSI) should be more routinely considered in DLBCLs. Appropriate testing may be predictive of outcome and inform the utility of targeted therapy in these genetically diverse and historically treatment-refractory malignancies. Full Article
li Pazopanib elicits remarkable response in metastatic porocarcinoma: a functional precision medicine approach [RESEARCH REPORT] By molecularcasestudies.cshlp.org Published On :: 2024-01-10T08:13:38-08:00 Metastatic porocarcinomas (PCs) are vanishingly rare, highly aggressive skin adnexal tumors with mortality rates exceeding 70%. Their rarity has precluded the understanding of their disease pathogenesis, let alone the conduct of clinical trials to evaluate treatment strategies. There are no effective agents for unresectable PCs. Here, we successfully demonstrate how functional precision medicine was implemented in the clinic for a metastatic PC with no known systemic treatment options. Comprehensive genomic profiling of the tumor specimen did not yield any actionable genomic aberrations. However, ex vivo drug testing predicted pazopanib efficacy, and indeed, administration of pazopanib elicited remarkable clinicoradiological response. Pazopanib and its class of drugs should be evaluated for efficacy in other cases of PC, and the rationale for efficacy should be determined when PC tumor models become available. A functional precision medicine approach could be useful to derive effective treatment options for rare cancers. Full Article
li ITPR1-associated spinocerebellar ataxia with craniofacial features--additional evidence for germline mosaicism [RESEARCH ARTICLE] By molecularcasestudies.cshlp.org Published On :: 2024-01-10T08:13:38-08:00 Inositol 1,4,5-triphosphate receptor type 1 (ITPR1) is an endoplasmic reticulum–bound intracellular inositol triphosphate receptor involved in the regulation of intracellular calcium. Pathogenic variants in ITPR1 are associated with spinocerebellar ataxia (SCA) types 15/16 and 29 and have recently been implicated in a facial microsomia syndrome. In this report, we present a family with three affected individuals found to have a heterozygous missense c.800C > T (predicted p.Thr267Met) who present clinically with a SCA29-like syndrome. All three individuals presented with varying degrees of ataxia, developmental delay, and apparent intellectual disability, as well as craniofacial involvement—an uncommon finding in patients with SCA29. The variant was identified using clinical exome sequencing and validated with Sanger sequencing. It is presumed to be inherited via parental germline mosaicism. We present our findings to provide additional evidence for germline mosaic inheritance of SCA29, as well as to expand the clinical phenotype of the syndrome. Full Article
li Clinical and functional analysis of the germline TP53 p.K164E acetylation site variant [RESEARCH ARTICLE] By molecularcasestudies.cshlp.org Published On :: 2024-01-10T08:13:38-08:00 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. Full Article
li Synchronous T-lymphoblastic lymphoma and neuroblastoma in a 3-yr-old with novel germline SMARCA4 and EZH2 variants [RAPID CANCER COMMUNICATION] By molecularcasestudies.cshlp.org Published On :: 2024-01-10T08:13:38-08:00 T-lymphoblastic lymphoma (T-LLy) is the most common lymphoblastic lymphoma in children and often presents with a mediastinal mass. Lymphomatous suprarenal masses are possible but rare. Here, we discuss the case of a previously healthy 3-yr-old male who presented with mediastinal T-LLy with bilateral suprarenal masses. Following initial treatment, surgical biopsy of persisting adrenal masses revealed bilateral neuroblastoma (NBL). A clinical genetics panel for germline cancer predisposition did not identify any pathogenic variants. Combination large panel (864 genes) profiling analysis in the context of a precision oncology study revealed two novel likely pathogenic heterozygous variants: SMARCA4 c.1420-1G > T p.? and EZH2 c.1943G > C p.(Ile631Phefs*44). Somatic analysis revealed potential second hits/somatic variants in EZH2 (in the T-LLy) and a segmental loss in Chromosome 19p encompassing SMARCA4 (in the NBL). Synchronous cancers, especially at a young age, warrant genetic evaluation for cancer predisposition; enrollment in a precision oncology program assessing germline and tumor DNA can fulfill that purpose, particularly when standard first-line genetic testing is negative and in the setting of tumors that are not classic for common cancer predisposition syndromes. Full Article
li Phosphate-Buffered Saline (PBS), pH 7.4 By cshprotocols.cshlp.org Published On :: 2024-11-01T06:46:10-07:00 Full Article
li Phosphate-Buffered Saline with Tween and BSA (PBSTB) By cshprotocols.cshlp.org Published On :: 2024-11-01T06:46:10-07:00 Full Article
li Phosphate-Buffered Saline with Tween (0.1%) (PBST) By cshprotocols.cshlp.org Published On :: 2024-11-01T06:46:10-07:00 Full Article
li Phosphate-Buffered Saline with 1% BSA (PBSB) By cshprotocols.cshlp.org Published On :: 2024-11-01T06:46:10-07:00 Full Article
li Selection of Affibody Molecules Using Escherichia coli Display By cshprotocols.cshlp.org Published On :: 2024-11-01T06:46:10-07:00 Affibody molecules are small (6-kDa) affinity proteins generated by directed evolution for specific binding to various target molecules. The first step in this workflow involves the generation of an affibody library, which can then be used for selection via multiple display methods. This protocol describes selection from affibody libraries by Escherichia coli cell surface display. With this method, high-diversity libraries of 1011 can be displayed on the cell surface. The method involves two steps for selection of binders from high-diversity libraries: magnetic-activated cell sorting (MACS) and fluorescence-activated cell sorting (FACS). MACS is used first to enrich the library in target-binding clones and to decrease diversity to a size that can be effectively screened and sorted in the flow cytometer in a reasonable time (typically <107 cells). The protocol is based on methodology using an AIDA-I autotransporter for display on the outer membrane, but the general procedures can also be adjusted and used for other types of autotransporters or alternative E. coli display methods. Full Article
li Cloning of Affibody Libraries for Display Methods By cshprotocols.cshlp.org Published On :: 2024-11-01T06:46:10-07:00 Affibody molecules are small (6-kDa) affinity proteins folded in a three-helical bundle and generated by directed evolution for specific binding to various target molecules. The most advanced affibody molecules are currently tested in the clinic, and data from more than 300 subjects show excellent activity and safety profiles. The generation of affibody molecules against a particular target starts with the generation of an affibody library, which can then be used for panning using multiple methods and selection systems. This protocol describes the molecular cloning of DNA-encoded affibody libraries to a display vector of choice, for either phage, Escherichia coli, or Staphylococcus carnosus display. The DNA library can come from different sources, such as error-prone polymerase chain reaction (PCR), molecular shuffling of mutations from previous selections, or, more commonly, from DNA synthesis using various methods. Restriction enzyme-based subcloning is the most common strategy for affibody libraries of higher diversity (e.g., >107 variants) and is described here. Full Article
li Healthcare avoidance during the early stages of the COVID-19 pandemic and all-cause mortality: a longitudinal community-based study By bjgp.org Published On :: 2024-10-31T16:05:26-07:00 BackgroundDuring the COVID-19 pandemic, global trends of reduced healthcare-seeking behaviour were observed. This raises concerns about the consequences of healthcare avoidance for population health.AimTo determine the association between healthcare avoidance during the early stages of the COVID-19 pandemic and all-cause mortality.Design and settingThis was a 32-month follow-up within the population-based Rotterdam Study, after sending a COVID-19 questionnaire at the onset of the pandemic in April 2020 to all communty dwelling participants (n = 6241/8732, response rate 71.5%).MethodCox proportional hazards models assessed the risk of all-cause mortality among respondents who avoided health care because of the COVID-19 pandemic. Mortality status was collected through municipality registries and medical records.ResultsOf 5656 respondents, one-fifth avoided health care because of the COVID-19 pandemic (n = 1143). Compared with non-avoiders, those who avoided health care more often reported symptoms of depression (n = 357, 31.2% versus n = 554, 12.3%) and anxiety (n = 340, 29.7% versus n = 549, 12.2%), and more often rated their health as poor to fair (n = 336, 29.4% versus n = 457, 10.1%) . Those who avoided health care had an increased adjusted risk of all-cause mortality (hazard ratio [HR] 1.30, 95% confidence interval [CI] = 1.01 to 1.67), which remained nearly identical after adjustment for history of any non-communicable disease (HR 1.20, 95% CI = 0.93 to 1.54). However, this association attenuated after additional adjustment for mental and physical self-perceived health factors (HR 0.93, 95% CI = 0.71 to 1.20).ConclusionThis study found an increased risk of all-cause mortality among individuals who avoided health care during COVID-19. These individuals were characterised by poor mental and physical self-perceived health. Therefore, interventions should be targeted to these vulnerable individuals to safeguard their access to primary and specialist care to limit health disparities, inside and beyond healthcare crises. Full Article
li Geographic inequalities in need and provision of social prescribing link workers a retrospective study in primary care By bjgp.org Published On :: 2024-10-31T16:05:26-07:00 BackgroundLong-term health conditions are major challenges for care systems. Social prescribing link workers have been introduced via primary care networks (PCNs) across England since 2019 to address the wider determinants of health by connecting individuals to activities, groups, or services within their local community.AimTo assess whether the rollout of social prescribing link workers was in areas with the highest need.Design and settingA retrospective study of social prescribing link workers in England from 2019 to 2023.MethodWorkforce, population, survey, and area-level data at the PCN-level from April 2020 to October 2023 were combined. Population need before the rollout of link workers was measured using reported lack of support from local services in the 2019 General Practice Patient Survey. To assess if rollout reflected need, linear regression was used to relate provision of link workers (measured by full-time equivalent [FTE] per 10 000 patients) in each quarter to population need for support.ResultsPopulations in urban, more deprived areas and with higher proportions of people from minority ethnic groups had the highest reported lack of support. Geographically these were in the North West and London. Initially, there was no association between need and provision; then from July 2022, this became negative and significant. By October 2023, a 10-percentage point higher need for support was associated with a 0.035 (95% confidence interval = −0.634 to −0.066) lower FTE per 10 000 patients.ConclusionRollout of link workers has not been sufficiently targeted at areas with the highest need. Future deployments should be targeted at those areas. Full Article
li Weight management with orlistat in type 2 diabetes: an electronic health records study By bjgp.org Published On :: 2024-10-31T16:05:26-07:00 BackgroundOrlistat is recommended as an adjunct to diet and exercise for weight loss in the treatment of type 2 diabetes mellitus (T2DM).AimTo explore associations between patient characteristics and orlistat prescribing, and to determine associations of orlistat with weight loss in T2DM and prediabetes.Design and settingCohort study using anonymised health records from a UK database of general practice.MethodThe UK Clinical Practice Research Datalink (CPRD) Aurum database was searched to compile a cohort of patients aged ≥18 years, first diagnosed with T2DM or prediabetes in 2016 or 2017. Once the data had been collated, multivariable logistic regression models were used to determine associations with starting orlistat and stopping it early (<12 weeks of prescriptions) and orlistat’s associations with weight loss in those who had not been prescribed second-line antidiabetic medications.ResultsOut of 100 552 patients with incident T2DM or prediabetes, 655 (0.8%) patients with T2DM and 128 (0.7%) patients with prediabetes were prescribed orlistat. Younger people, females, those in areas of deprivation, current smokers, those coprescribed metformin, and those recorded as having hypertension were statistically significantly more likely to be prescribed orlistat; higher baseline glycated haemoglobin levels were associated with early stopping. In comparison with patients not on orlistat, those who continued using it for ≥12 weeks were more likely to lose ≥5% weight (adjusted odds ratio [AOR] 1.69, 95% confidence interval [CI] = 1.07 to 2.67) but those who stopped orlistat early were less likely to lose ≥5% weight (AOR 0.56, 95% CI = 0.29 to 1.09).ConclusionOrlistat was significantly associated with weight loss in patients with T2DM and prediabetes when taken for at least 12 weeks; however, it was infrequently prescribed and often taken for <12 weeks. Orlistat may be a useful adjunct to lifestyle modifications for patients with T2DM and prediabetes, but barriers to continued use means it may not be effective for everyone in managing weight loss. Full Article
li Prescribing benzodiazepines in young adults with anxiety: a qualitative study of GP perspectives By bjgp.org Published On :: 2024-10-31T16:05:26-07:00 BackgroundIncident benzodiazepine prescriptions in primary care for anxiety decreased between 2003 and 2018. However, from 2008, incident prescribing of benzodiazepines for anxiety increased among those aged 18–34 years. There are increasing concerns around prescribing of benzodiazepines. Further, although guidelines state benzodiazepines should only be prescribed short term, in 2017, 44% of incident prescriptions were prescribed for longer than the recommended duration of 2–4 weeks.AimTo understand when and why GPs prescribe benzodiazepines for anxiety in young adults.Design and settingA qualitative study was undertaken using in-depth interviews with 17 GPs from 10 general practices in South West England.MethodInterviews were conducted by telephone or videocall. A topic guide was used to ensure consistency across interviews. Interviews were audio-recorded, transcribed verbatim, and data analysed using reflexive thematic analysis.ResultsGPs described caution in prescribing benzodiazepines for anxiety in young adults, but thought they had an important role in acute situations. GPs described caution in prescribing duration, but some thought longer-term prescriptions could be appropriate. In light of these views, some GPs questioned whether primary care needs to revisit how clinicians are using benzodiazepines. GPs perceived that some young adults requested benzodiazepines and suggested this might be because they wanted quick symptom relief. GPs noted that refusing to prescribe felt uncomfortable and that the number of young adults presenting to general practice, already dependent on benzodiazepines, had increased.ConclusionPatient-driven factors for prescribing benzodiazepines suggest there are current unmet treatment needs among young adults with anxiety. Given increases in prescribing in this age group, it may be timely to revisit the role of benzodiazepines in the management of people with anxiety in primary care. Full Article
li GPs’ views of prescribing beta- blockers for people with anxiety disorders: a qualitative study By bjgp.org Published On :: 2024-10-31T16:05:26-07:00 BackgroundBetween 2003 and 2018, incident prescriptions of beta-blockers for anxiety increased substantially, particularly for young adults. National Institute for Health and Care Excellence guidance for anxiety does not recommend beta-blockers, probably due to a lack of evidence to support such use. Recent reports have highlighted the potential risks of beta-blockers.AimTo understand when and why GPs prescribe beta-blockers for people with anxiety.Design and settingIn-depth interviews with 17 GPs in Bristol and the surrounding areas.MethodInterviews were held by telephone or video call. A topic guide was used to ensure consistency across interviews. Interviews were audio-recorded, transcribed verbatim, and analysed thematically.ResultsMany GPs viewed beta-blockers as ‘low risk’, particularly for young adults. Some GPs viewed beta-blockers as an alternative to benzodiazepines, acting quickly and not leading to dependence. GPs reflected that some patients appeared to want an ‘immediate fix’ to their symptoms, which GPs thought beta-blockers could potentially offer. This is salient in light of substantial waiting lists for talking therapies and delays in antidepressants taking effect. GPs described how some patients seemed more willing to try beta-blockers than antidepressants, as patients did not perceive them as ‘mental health drugs’ and therefore viewed them as potentially more acceptable and less stigmatising. Further, GPs viewed beta-blockers as ‘patient-led’, with patients managing their own dose and frequency, without GP input.ConclusionMany GPs believe that beta-blockers have a role to play in the management of anxiety. Given recent increases in the prescribing of these drugs in primary care, there is a need to assess their safety and effectiveness as a treatment for people with anxiety disorders. Full Article
li Collaborative discussions between GPs and pharmacists to optimise patient medication: a qualitative study within a UK primary care clinical trial By bjgp.org Published On :: 2024-10-31T16:05:26-07:00 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. Full Article
li Books: The Political Economy of Health Care: Where the NHS Came From and Where it Could Lead By bjgp.org Published On :: 2024-10-31T16:05:26-07:00 Full Article
li General practice should tackle healthcare inequalities but not health inequalities By bjgp.org Published On :: 2024-10-31T16:05:26-07:00 Full Article
li The Ealing domestic abuse initiative: a success story By bjgp.org Published On :: 2024-10-31T16:05:26-07:00 Full Article
li Primary care health professionals’ approach to clinical coding: a qualitative interview study By bjgp.org Published On :: 2024-10-31T16:05:26-07:00 Full Article
li Unpicking influence and conflicts of interest in prescribing By bjgp.org Published On :: 2024-10-31T16:05:26-07:00 Full Article
li Cross-Sectional Study of Cesarean Delivery and Safety Culture by Family Medicine Presence [Annals Journal Club] By www.annfammed.org Published On :: 2024-09-23T14:00:14-07:00 Full Article
li Improving Access to Disability Assessment for US Citizenship Applicants in Primary Care: An Embedded Neuropsychological Assessment Innovation [Innovations in Primary Care] By www.annfammed.org Published On :: 2024-09-23T14:00:14-07:00 Full Article
li Using the Electronic Health Record to Facilitate Patient-Physician Relationship While Establishing Care [Innovations in Primary Care] By www.annfammed.org Published On :: 2024-09-23T14:00:14-07:00 Full Article