The mutational landscape of melanoma brain metastases presenting as the first visceral site of recurrence

Brain metastases are a major cause of melanoma-related mortality and morbidity. We undertook whole-exome sequencing of 50 tumours from patients undergoing surgical resection of brain metastases presenting as the first site of visceral disease spread and validated our findings in an independent dataset of 18 patients. Brain metastases had a similar driver mutational landscape to cutaneous melanomas in TCGA. However, KRAS was the most significantly enriched driver gene, with 4/50 (8%) of brain metastases harbouring non-synonymous mutations. Hotspot KRAS mutations were mutually exclusive from BRAF^V600, NRAS and HRAS mutations and were associated with a reduced overall survival from the resection of brain metastases (HR 10.01, p = 0.001). Mutations in KRAS were clonal and concordant with extracranial disease, suggesting that these mutations are likely present within the primary. Our analyses suggest that KRAS mutations could help identify patients with primary melanoma at higher risk of brain metastases who may benefit from more intensive, protracted surveillance.Subject terms: CNS cancer, Metastasis, Melanoma, Tumour biomarkers, Cancer     

Tractography of the Cerebellar Peduncles in Second- and Third-Trimester Fetuses

BACKGROUND AND PURPOSE:Little is known about microstructural development of cerebellar white matter in vivo. This study aimed to investigate developmental changes of the cerebellar peduncles in second- and third-trimester healthy fetuses using motion-corrected DTI and tractography.MATERIALS AND METHODS:3T data of 81 healthy fetuses were reviewed. Structural imaging consisted of multiplanar T2-single-shot sequences; DTI consisted of a series of 12-direction diffusion. A robust motion-tracked section-to-volume registration algorithm reconstructed images. ROI-based deterministic tractography was performed using anatomic landmarks described in postnatal tractography. Asymmetry was evaluated qualitatively with a perceived difference of >25% between sides. Linear regression evaluated gestational age as a predictor of tract volume, ADC, and fractional anisotropy.RESULTS:Twenty-four cases were excluded due to low-quality reconstructions. Fifty-eight fetuses with a median gestational age of 30.6 weeks (interquartile range, 7 weeks) were analyzed. The superior cerebellar peduncle was identified in 39 subjects (69%), and it was symmetric in 15 (38%). The middle cerebellar peduncle was identified in all subjects and appeared symmetric; in 13 subjects (22%), two distinct subcomponents were identified. The inferior cerebellar peduncle was not found in any subject. There was a significant increase in volume for the superior cerebellar peduncle and middle cerebellar peduncle (both, P < .05), an increase in fractional anisotropy (both, P < .001), and a decrease in ADC (both, P < .001) with gestational age. The middle cerebellar peduncle had higher volume (P < .001) and fractional anisotropy (P = .002) and lower ADC (P < .001) than the superior cerebellar peduncle after controlling for gestational age.CONCLUSIONS:A robust motion-tracked section-to-volume registration algorithm enabled deterministic tractography of the superior cerebellar peduncle and middle cerebellar peduncle in vivo and allowed characterization of developmental changes.

In the second half of pregnancy, the cerebellum is growing rapidly and is extremely vulnerable.¹ Despite the increasingly recognized association of antenatal and perinatal cerebellar injury with adverse motor and neurologic outcomes later in life,^2-5 little is known about normal cerebellar developmental in the later part of gestation, in particular with regard to changes in microstructure. In fact, most existing fetal MR imaging data addresses primarily changes in cerebellar volume with gestational age (GA) or changes in volume and their association with specific diseases such as congenital heart disease.^6-8In vivo evaluation of cerebellar microstructure using fetal MR imaging has been limited by the technical challenges related to imaging the gravid abdomen, particularly patient motion. However, data from ex vivo MR imaging studies are promising. For instance, Takahashi et al^9,10 performed high-resolution ex vivo DTI of fetal specimens and demonstrated the feasibility of using tractography to outline the cerebellar peduncles prenatally. Even though tractography of the cerebellar peduncles has been sporadically reported in vivo in technical articles or general review articles on fetal DTI,¹¹ the GA-related microstructural changes that occur in the cerebellar peduncles in the second half of pregnancy remain largely unexplored.Recent advances in hardware and software have improved fetal MR imaging substantially. The use of 3T magnets, which have been shown to be safe, results in improvement of the SNR and spatial resolution, which is advantageous to image the small structures of the fetal brain.^12,13 In addition, postprocessing algorithms that enable reconstruction of motion-corrected fetal DTI data are increasingly available and have been used by several groups to characterize the development of the supratentorial white matter tracts in vivo.^14-16 We hypothesize that fetal DTI performed at 3T and processed with a robust section-to-volume motion-correction and registration¹⁴ algorithm will enable tractography of the cerebellar peduncles in fetuses in the second and third trimesters of pregnancy. We aimed to characterize fetal cerebellar tract microstructure and to investigate tract-specific developmental changes.     

Anatomic Snuffbox (Distal Radial Artery) and Radial Artery Access for Treatment of Intracranial Aneurysms with FDA-Approved Flow Diverters

BACKGROUND AND PURPOSE:Transradial access for neurointerventional procedures has been proved a safer and more comfortable alternative to femoral artery access. We present our experience with transradial (distal radial/anatomic snuffbox and radial artery) access for treatment of intracranial aneurysms using all 3 FDA-approved flow diverters.MATERIALS AND METHODS:This was a high-volume, dual-center, retrospective analysis of each institution’s data base between June 2018 and June 2020 and a collection of all patients treated with flow diversion via transradial access. Patient demographic information and procedural and radiographic data were obtained.RESULTS:Seventy-four patients were identified (64 female patients) with a mean age of 57.5 years with a total of 86 aneurysms. Most aneurysms were located in the anterior circulation (93%) and within the intracranial ICA (67.4%). The mean aneurysm size was 5.5 mm. Flow diverters placed included the Pipeline Embolization Device (Flex) (PED, n = 65), the Surpass Streamline Flow Diverter (n = 8), and the Flow-Redirection Endoluminal Device (FRED, n = 1). Transradial access was successful in all cases, but femoral crossover was required in 3 cases (4.1%) due to tortuous anatomy and inadequate support of the catheters in 2 cases and an inability to navigate to the target vessel in a patient with an aberrant right subclavian artery. All 71 other interventions were successfully performed via the transradial approach (95.9%). No access site complications were encountered. Asymptomatic radial artery occlusion was encountered in 1 case (3.7%).CONCLUSIONS:Flow diverters can be successfully placed via the transradial approach with high technical success, low access site complications, and a low femoral crossover rate.

The transradial access (TRA), including distal radial artery (dRA) access in the anatomic snuffbox and radial artery (RA) access at the palmar surface of the wrist, is being increasingly used as primary vascular access for neurointerventional procedures. In prior years, large randomized trials in the field of interventional cardiology and more recent articles in neurointerventional surgery have shown higher patient preference for the TRA, cost reduction, as well as lower morbidity and mortality compared with the traditional transfemoral access (TFA).^1-11 Reduction in access site complications has been a particular advantage of wrist over femoral access and is an important consideration for vascular access choice in the treatment of intracranial aneurysms using flow diversion. Patients undergoing flow diversion are required to take dual-antiplatelet agents and receive heparin during the procedure, all of which increase the risk of bleeding from the access site.¹² Also, flow diverters (FDs) may require large-bore catheter assemblies for delivery and deployment, which may increase the risk of radial artery occlusion, access site bleeding, or vascular injury.^13,14To date, only a limited number of case reports and case series have described the safety and feasibility of TRA for the treatment of intracranial aneurysms using flow diverters.^15-22Recently, a large, retrospective multicenter study reported the safety of TRA for flow diversion, showing a lower access site (P = .039) and overall complication rate (P = .035).¹² This study, however, did not cover catheter systems, patient functional outcome, and aneurysm occlusion. Here, we report our experience with TRA (dRA [anatomic snuffbox] and RA) for the treatment of intracranial aneurysms using all 3 FDA-approved flow diverters, including technical feasibility, procedural safety, patient outcome, and aneurysm occlusion on follow-up. Additionally, we reviewed the current literature on use of flow diverters via TRA.     

Analysis of Stroke Detection during the COVID-19 Pandemic Using Natural Language Processing of Radiology Reports

BACKGROUND AND PURPOSE:The coronavirus disease 2019 (COVID-19) pandemic has led to decreases in neuroimaging volume. Our aim was to quantify the change in acute or subacute ischemic strokes detected on CT or MR imaging during the pandemic using natural language processing of radiology reports.MATERIALS AND METHODS:We retrospectively analyzed 32,555 radiology reports from brain CTs and MRIs from a comprehensive stroke center, performed from March 1 to April 30 each year from 2017 to 2020, involving 20,414 unique patients. To detect acute or subacute ischemic stroke in free-text reports, we trained a random forest natural language processing classifier using 1987 randomly sampled radiology reports with manual annotation. Natural language processing classifier generalizability was evaluated using 1974 imaging reports from an external dataset.RESULTS:The natural language processing classifier achieved a 5-fold cross-validation classification accuracy of 0.97 and an F1 score of 0.74, with a slight underestimation (−5%) of actual numbers of acute or subacute ischemic strokes in cross-validation. Importantly, cross-validation performance stratified by year was similar. Applying the classifier to the complete study cohort, we found an estimated 24% decrease in patients with acute or subacute ischemic strokes reported on CT or MR imaging from March to April 2020 compared with the average from those months in 2017–2019. Among patients with stroke-related order indications, the estimated proportion who underwent neuroimaging with acute or subacute ischemic stroke detection significantly increased from 16% during 2017–2019 to 21% in 2020 (P = .01). The natural language processing classifier performed worse on external data.CONCLUSIONS:Acute or subacute ischemic stroke cases detected by neuroimaging decreased during the COVID-19 pandemic, though a higher proportion of studies ordered for stroke were positive for acute or subacute ischemic strokes. Natural language processing approaches can help automatically track acute or subacute ischemic stroke numbers for epidemiologic studies, though local classifier training is important due to radiologist reporting style differences.

There is much concern regarding the impact of the coronavirus disease 2019 (COVID-19) pandemic on the quality of stroke care, including issues with hospital capacity, clinical resource re-allocation, and the safety of patients and clinicians.^1,2 Previous reports have shown that there have been substantial decreases in stroke neuroimaging volume during the pandemic.^3,4 In addition, acute ischemic infarcts have been found on neuroimaging studies in many hospitalized patients with COVID-19, though the causal relationship is unclear.^5,6 Studies like these and other epidemiologic analyses usually rely on the creation of manually curated databases, in which identification of cases can be time-consuming and difficult to update in real-time. One way to facilitate such research is to use natural language processing (NLP), which has shown utility for automated analysis of radiology report data.⁷ NLP algorithms have been developed previously for the classification of neuroradiology reports for the presence of ischemic stroke findings and acute ischemic stroke subtypes.^8,9 Thus, NLP has the potential to facilitate COVID-19 research.In this study, we developed an NLP machine learning model that classifies radiology reports for the presence or absence of acute or subacute ischemic stroke (ASIS), as opposed to chronic stroke. We used this model to quantify the change in ASIS detected on all CT or MR imaging studies performed at a large comprehensive stroke center during the COVID-19 pandemic in the United States. We also evaluated NLP model generalizability and different training strategies using a sample of radiology reports from a second stroke center.     

Twelve tips for developing and implementing a medical education Twitter chat

Abstract

Live discussions on the social media site Twitter or Twitter chats are gaining popularity as powerful tools for engaging a broad audience in an interactive discussion. Medical education, in particular, is experiencing an increase in the use of this modality to support informal learning, as a means to encourage collaboration and share best practices, and as a platform for large-scale mentorship. Despite this growth in popularity, there are limited data to guide medical educators on the fundamentals of organizing a Twitter chat. In this Twelve Tips article, we discuss strategies relevant to potential Twitter chat organizers. We have arranged the tips chronologically, beginning with a discussion of initial considerations when planning and formulating a chat topic and publicizing the chat to potentially interested people and groups, followed by practical considerations while hosting the chat, and finally strategies for evaluating and extending a Twitter chat’s impact.     

Does ablation of atrial fibrillation at the time of septal myectomy improve survival of patients with obstructive hypertrophic cardiomyopathy?

ObjectiveTo evaluate the outcomes after septal myectomy in patients with obstructive hypertrophic cardiomyopathy according to atrial fibrillation and surgical ablation of atrial fibrillation.MethodsWe reviewed patients with obstructive hypertrophic cardiomyopathy who underwent septal myectomy at the Mayo Clinic from 2001 to 2016. History of atrial fibrillation was obtained from patient histories and electrocardiograms. All-cause mortality was the primary end point.ResultsA total of 2023 patients underwent septal myectomy, of whom 394 (19.5%) had at least 1 episode of atrial fibrillation preoperatively. Among patients with atrial fibrillation, 76 (19.3%) had only 1 known episode, 278 (70.6%) had recurrent paroxysmal atrial fibrillation, and 40 (10.2%) had persistent atrial fibrillation. Surgical ablation was performed in 190 patients at the time of septal myectomy, including 148 with pulmonary vein isolation and 42 with the classic maze procedure. Among all patients, operative mortality was 0.4%, and there were no early deaths in patients undergoing surgical ablation. Over a median follow-up of 5.6 years, patients with preoperative atrial fibrillation had increased mortality (hazard ratio, 1.36; 95% confidence interval, 0.97-1.91; P = .070) after multivariable adjustment for comorbidities. When considering the impact of atrial fibrillation with or without surgical treatment, the adjusted hazard ratio for mortality in patients undergoing ablation compared with no ablation was 0.93 (95% confidence interval, 0.52-1.69; P = .824).ConclusionsAtrial fibrillation is present preoperatively in one-fifth of patients with obstructive hypertrophic cardiomyopathy undergoing myectomy and showed a trend toward higher all-cause mortality. Survival of patients undergoing septal myectomy with preoperative atrial fibrillation was similar between those who did and did not receive concomitant surgical ablation.     

Comparison of Patch Materials for Pulmonary Artery Reconstruction

Graphical abstract summarizing the overall results of our study comparing reintervention for a main or central branch pulmonary artery reconstruction site and various patch materials. Autologous pericardium was associate with the lowest reintervention and was free. Multivariable analysis demonstrated lack of superiority of homograft branch patch, which clearly has a much higher cost.

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Patterns of Use of Induction Therapy for T2N0 Esophageal Cancer

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A Diagnostic Algorithm for Posterior Fossa Tumors in Children: A Validation Study

BACKGROUND AND PURPOSE:Primary posterior fossa tumors comprise a large group of neoplasias with variable aggressiveness and short and long-term outcomes. This study aimed to validate the clinical usefulness of a radiologic decision flow chart based on previously published neuroradiologic knowledge for the diagnosis of posterior fossa tumors in children.MATERIALS AND METHODS:A retrospective study was conducted (from January 2013 to October 2019) at 2 pediatric referral centers, Children''s Hospital of Philadelphia, United States, and Great Ormond Street Hospital, United Kingdom. Inclusion criteria were younger than 18 years of age and histologically and molecularly confirmed posterior fossa tumors. Subjects with no available preoperative MR imaging and tumors located primarily in the brain stem were excluded. Imaging characteristics of the tumors were evaluated following a predesigned, step-by-step flow chart. Agreement between readers was tested with the Cohen κ, and each diagnosis was analyzed for accuracy.RESULTS:A total of 148 cases were included, with a median age of 3.4 years (interquartile range, 2.1–6.1 years), and a male/female ratio of 1.24. The predesigned flow chart facilitated identification of pilocytic astrocytoma, ependymoma, and medulloblastoma sonic hedgehog tumors with high sensitivity and specificity. On the basis of the results, the flow chart was adjusted so that it would also be able to better discriminate atypical teratoid/rhabdoid tumors and medulloblastoma groups 3 or 4 (sensitivity = 75%–79%; specificity = 92%–99%). Moreover, our adjusted flow chart was useful in ruling out ependymoma, pilocytic astrocytomas, and medulloblastoma sonic hedgehog tumors.CONCLUSIONS:The modified flow chart offers a structured tool to aid in the adjunct diagnosis of pediatric posterior fossa tumors. Our results also establish a useful starting point for prospective clinical studies and for the development of automated algorithms, which may provide precise and adequate diagnostic tools for these tumors in clinical practice.

In the past 10 years, there has been an exponential increase in knowledge of the molecular characteristics of pediatric brain tumors, which was only partially incorporated in the 2016 World Health Organization Classification of Tumors of the Central Nervous System.¹ The main update in the 2016 Classification was the introduction of the molecular profile of a tumor as an important factor for predicting different biologic behaviors of entities which, on histology, look very similar or even indistinguishable.² A typical example is the 4 main groups of medulloblastoma: wingless (WNT), sonic hedgehog (SHH) with or without the p53 mutation, group 3, and group 4. Although they may appear similar on microscopy, these categories have distinct molecular profiles, epidemiology, prognosis, and embryologic origin.³Subsequent to the publication of the 2016 World Health Organization Classification, further studies have identified even more molecular subgroups of medulloblastoma with possible prognostic implications⁴ and also at least 3 new molecular subgroups of atypical teratoid/rhabdoid tumor (AT/RT)⁵ and several subgroups of ependymoma.⁶ MR imaging shows promise as a technique for differentiating histologic tumors and their molecular subgroups. This capability relies on not only various imaging characteristics but also the location and spatial extension of the tumor, evident on MR imaging, which can be traced to the embryologic origin of the neoplastic cells.^5,7-10One approach to the challenge of identifying imaging characteristics of different tumors in children is to use artificial intelligence. Yet despite this exciting innovation, correctly identifying the location of the mass and its possible use as an element for differential diagnosis still requires the expertise of an experienced radiologist. Previously, D''Arco et al¹¹ proposed a flow chart (Fig 1) for the differential diagnosis of posterior fossa tumors in children based on epidemiologic, imaging signal, and location characteristics of the neoplasm. The aims of the current study were the following: 1) to validate, in a retrospective, large cohort of posterior fossa tumors from 2 separate pediatric tertiary centers, the diagnostic accuracy of that flow chart, which visually represents the neuroadiologist''s mental process in making a diagnosis of posterior fossa tumors in children, 2) to describe particular types of posterior fossa lesions that are not correctly diagnosed by the initial flow chart, and 3) to provide an improved, clinically accessible flow chart based on the results.Open in a separate windowFIG 1.Predesigned radiologic flow chart created according to the literature before diagnostic accuracy analysis. The asterisk indicates brain stem tumors excluded from the analysis. Double asterisks indicate relative to gray matter. Modified with permission from D''Arco et al.¹¹