Brain arteriovenous malformations are a relatively uncommon but important cause of hemorrhagic stroke, especially in young adults. This statement describes the current knowledge of the natural history and treatment of patients with ruptured and unruptured brain arteriovenous malformations, suggestions for management, and implications for future research.

suMMARY The cervical spine radiographs of 100 patients with early rheumatoid disease were studied annually, on a prospective basis, for a mean follow-up period of 7 years 2 months. Atlantoaxial subluxation developed in 12 patients. The subluxation was more frequent in females, more severe in patients with progressive, seropositive, erosive rheumatoid disease, and more marked in patients treated with oral corticosteroids. Subaxial subluxation, affecting upper cervical disc levels, occurred in a further 20 patients. Three patients developed vertical subluxation. The mobility of the cervical spine affects the degree of subluxation achieved, and when assessing serial films for subluxation it may be necessary to measure the cervical spine flexion before deciding whether subluxation has progressed or not. Over 80% of the patients with subluxation developed the first evidence of subluxation within 2 years of disease onset. Subluxation in the cervical spine is not, therefore, a late complication of rheumatoid disease. During the follow-up period none of the patients developed neurological signs.Cervical spine involvement in rheumatoid arthritis is common. Sharp' found that the cervical spine was affected clinically at some stage of the disease in 40% of the patients with rheumatoid arthritis attending the Rheumatism Research Centre in Manchester. Bland et al.2 found radiological evidence of cervical spine involvement in 86% of cases of classical or definite rheumatoid arthritis. In population studies Lawrence3 found the prevalence of radiological changes of rheumatoid arthritis of the cervical spine to be 4-1% in males and 4.7% in females aged 15 and over, and the prevalence increased with age to around 15 % in patients aged 65 years and over.There have been no previous prospective studies of the radiological changes which affect the cervical spine in early rheumatoid arthritis, and little is known about the development and progression of these changes. In the older patient it may be impossible, clinically and radiologically, to differentiate the effects of rheumatoid involvement

Introduction Minimal residual disease (MRD) detection in solid tumors describes isolation of circulating tumor DNA (ctDNA) molecules in plasma following definitive treatment of a cancer. Detection of MRD following surgical tumor excision categorizes patients as high risk for disease recurrence. Establishing an MRD approach to treating early-stage NSCLC will facilitate escalation of standard of care (SoC) treatment only in patients destined to relapse from their cancer and overcome challenges associated with conventional adjuvant drug-trial design. Here, we present data from the lung TRACERx study where patients with early-stage NSCLC underwent phylogenetic ctDNA profiling following resection. Methods Patient specific anchored-multiplex PCR (AMP) enrichment panels were generated for 78 lung TRACERx patients who underwent surgery for stage I-III NSCLC; 608 plasma samples were analyzed. Extensive patient-specific cfDNA enrichment panels targeted a median of 196 (range 72 to 482) clonal and subclonal variants detected in primary tumor tissue by multi-region exome sequencing. A novel MRD-caller controlled and estimated background sequencing error to maximize ctDNA detection at low mutant allele frequencies (MAFs). Analytical validation experiments benchmarked assay performance. Results Analytical validation of a 50-variant AMP-MRD assay demonstrated a sensitivity of 89% for mutant DNA at a MAF of 0.008% (with 25ng of DNA input into the assay), specificity was 100% experimentally and 99.9% (95% CI: 99.67 to 99.99%) modelled in-silico. 45 patients suffered relapse of their primary NSCLC; ctDNA was detected at or before clinical relapse in 37 of 45 patients. In these 37 patients the median ctDNA lead-time (time from ctDNA detection to clinical relapse) was 151 days (range 0 to 984 days) and the median time to relapse from surgery was 413 days (range 41 to 1242 days). In 10 of 10 patients who developed second primary cancers during follow-up no ctDNA was detected, reflecting specificity of the MRD assay toward the primary tumor. In 23 patients who remained relapse-free during a median of 1184 days of study follow-up, ctDNA was detected in 1 of 199 time-points analyzed. Analysis of SoC adjuvant surveillance imaging (CT, PET-CT or MRI, 220 encounters) revealed examples of MRD positive patients where SoC radiological surveillance was negative for impending relapse. Through application of large cfDNA enrichment panels targeting up to 483 variants per patient we observed dynamic changes in clonal composition and copy-number status prior to NSCLC relapse, categorized relapse as monoclonal or polyclonal and identified distinct subclonal dynamics during systemic intervention for disease recurrence. Conclusions ctDNA is an adjuvant biomarker capable of both detecting MRD following surgery and defining the clonality of relapsing disease. These data pave the way for clinical trials predicated on escalation of adjuvant standard of care in NSCLC patients who exhibit MRD positive status following surgery. Citation Format: Chris Abbosh, Alexander Frankell, Aaron Garnett, Thomas Harrison, Morgan Weichert, Abel Licon, Selvaraju Veeriah, Bob Daber, Mike Moreau, Adrian Chesh, Kevin Litchfield, Emilia Lim, Daniel Cooke, Clare Puttick, Maise Al Bakir, Fabio Gomes, Akshay Patel, Lizi Manzano, Ariana Huebner, Nicolas Carey, Joan Riley, Paula Roberts, Todd Druley, Jacqui A. Shaw, Nicholas McGranahan, Mariam Jamal-Hanjani, Nicolai Birkbak, Josh Stahl, Charles Swanton, Lung TRACERx consortium. Phylogenetic tracking and minimal residual disease detection using ctDNA in early-stage NSCLC: A lung TRACERx study [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT023.

IMPORTANCE Cochlear implant users generally display poor pitch perception. Flat-panel computed tomography (FPCT) has recently emerged as a modality capable of localizing individual electrode contacts within the cochlea in vivo. Significant place-pitch mismatch between the clinical implant processing settings given to patients and the theoretical maps based on FPCT imaging has previously been noted. OBJECTIVE To assess whether place-pitch mismatch is associated with poor cochlear implant-mediated pitch perception through evaluation of an individualized, image-guided approach toward cochlear implant programming on speech and music perception among cochlear implant users. DESIGN, SETTING, AND PARTICIPANTS A prospective cohort study of 17 cochlear implant users with MED-EL electrode arrays was performed at a tertiary referral center. The study was conducted from June 2016 to July 2017. INTERVENTIONS Theoretical place-pitch maps using FPCT secondary reconstructions and 3-dimensional curved planar reformation software were developed. The clinical map settings (eg, strategy, rate, volume, frequency band range) were modified to keep factors constant between the 2 maps and minimize confounding. The acclimation period to the maps was 30 minutes. MAIN OUTCOMES AND MEASURES Participants performed speech perception tasks (eg, consonant-nucleus-consonant, Bamford-Kowal-Bench Speech-in-Noise, vowel identification) and a pitch-scaling task while using the image-guided place-pitch map (intervention) and the modified clinical map (control). Performance scores between the 2 interventions were measured. RESULTS Of the 17 participants, 10 (58.8%) were women; mean (SD) was 59 (11.3) years. A significant median increase in pitch scaling accuracy was noted when using the experimental map compared with the control map (4 more correct answers; 95% CI, 0-8). Specifically, the number of pitch-scaling reversals for notes spaced at 1.65 semitones or greater decreased when an image-based approach to cochlear implant programming was used vs the modified clinical map (4 mistakes; 95% CI, 0.5-7). Although there was no observable median improvement in speech perception during use of an image-based map, the acute changes in frequency allocation and electrode channel deactivations used with the image-guided maps did not worsen consonant-nucleus-consonant (−1% correct phonemes, 95% CI, −2.5% to 6%) and Bamford-Kowal-Bench Speech-in-Noise (0.5-dB difference; 95% CI, −0.75 to 2.25 dB) median performance results relative to the clinical maps used by the patients. CONCLUSIONS AND RELEVANCE An image-based approach toward ochlear implant mapping may improve pitch perception outcomes by reducing place-pitch mismatch. Studies using a longer acclimation period with chronic stimulation over months may help assess the full range of the benefits associated with personalized image-guided cochlear implant mapping.

ACTA2 mutations have recently been shown to cause a multisystem smooth muscle dysfunction syndrome that may result in pediatric stroke. We report a case of ACTA2 mutation in a 3-year-old girl presenting with acute ischemic stroke and provide high resolution imaging of the cerebral arteries demonstrating novel findings of multiple tiny aneurysms (particularly in the posterior circulation), as well as the more characteristic imaging phenotype of straightened and narrowed proximal intracranial vessels, dilated cervical vessels and occlusion of the M1 MCA segment without lenticulostriate collateral formation. This newly identified disease should be added to the differential diagnosis of pediatric stroke and cerebral vasculopathy. Neuroradiologists, interventionalists, surgeons and neurologists should become familiar with this rare disease and its clinical sequelae.