Citations

Abstract Thromboembolic complications during aneurysm coiling are rare, with higher rates noted in ruptured aneurysms as patients are not usually premedicated with dual antiplatelet therapy. 1,2 Management includes a series of escalating strategies, including medical therapy and intra-arterial thrombolysis. 3-6 Additional strategies include mechanical thrombectomy with suction aspiration and stent retrievers. 3 Intracranial stenting can be used as a last resource, especially in ruptured cases given the need for dual antiplatelets to prevent stent thrombosis. 2 We present the case of a 42-yr-old man with a ruptured left internal carotid artery aneurysm with associated intracranial and intraventricular hemorrhage. The patient was initially presented to an outside facility after he was found in bed unable to speak and with right hemiparesis. The patient consented for surgery and underwent external ventricular drain (EVD) placement for the treatment of obstructive hydrocephalus, followed by diagnostic cerebral angiogram and aneurysm coiling. After the deployment of the last coil, control angiogram showed a small filling defect at the interface between the aneurysm neck and the distal vessel. The patient received intravenous heparin for therapeutic ACT and aspirin load. After progressive enlargement of the thrombus, the patient received intra-arterial glycoprotein (GP) IIB/IIIA inhibitors with a microcatheter positioned proximal to the thrombus. As the thrombus mass continued to enlarge, mechanical thrombectomy with an aspiration catheter was performed twice. Follow-up angiogram 20 min after the second aspiration demonstrated near-complete resolution of the thrombus. The patient recovered from his right hemiparesis, and he was discharged to rehabilitation on POD #21.

Abstract Intracranial atherosclerosis disease (IAD) is the cause of stroke in up to 10% of cases. Symptomatic IAD results mainly from hypoperfusion, embolic phenomenon, and occlusion. Treatment consists of conservative management with aggressive medical treatment, surgery, and endovascular therapy. 1,2 This video is about a 62-yr-old male who presented with left-sided hemiparesis and right gaze preference secondary to an acute ischemic stroke in the right middle cerebral artery (MCA) territory treated initially with tissue plasminogen activator (tPA). Head computed tomography (CT) angiography (CTA) revealed occlusion of the extracranial and cavernous segments of the internal carotid artery (ICA). CT perfusion (CTP) showed hypoperfusion in the MCA territory and magnetic resonance imaging (MRI) revealed multifocal, wedge-shaped areas of restricted diffusion in the right hemisphere. During his hospitalization, he experienced worsening of his symptoms in the setting of hypoperfusion (hypotension). The patient underwent a cerebral angiogram with thrombectomy and submaximal angioplasty (SA). Successful revascularization of the right ICA was obtained. No procedure-related complications occurred, and the patient's neurological exam improved. SA can be as efficient and a safer option than conventional angioplasty or angioplasty and stenting for symptomatic IAD. The patient consented for the procedure and for the video production.

Introduction: The NHLBI National MDS Study (NCT02775383) is a prospective cohort study conducted at 92 community hospitals and 29 academic centers. It enrolls patients undergoing work up for suspected MDS to understand the genetic, epigenetic, and biological factors associated with the initiation and progression of the disease. Previously untreated, cytopenic participants undergo both local and centralized pathology review and are assigned a diagnosis, including MDS, MDS/MPN, AML with blasts < 30%, and "Other". Emerging data suggests that Next Generation Sequencing (NGS), along with cytogenetics and clinical variables, may improve MDS diagnostic precision. Given that our study relies on central review (with additional tertiary pathology review used to adjudicate disagreements), we examined whether targeted gene sequencing data could be used to increase the agreement between local and central pathologic diagnosis of MDS vs. Other. Methods: Peripheral blood and bone marrow (BM) biopsy specimens from cytopenic patients, along with clinical history, CBC, and other results including karyotyping, FISH and pathology reports from local pathologists were reviewed by central pathologists. The updated 2016 WHO classifications were used to diagnose MDS. Targeted exon sequencing of 96 genes was performed using BM specimens. A subset of 648 individuals that were classified as MDS (n=212) or Other (n=436, including 90 CCUS and 89 individuals with other cancers) by pathology assessments were selected. A mean coverage of 1,317X was achieved and variants had a minimum variant allele frequency (VAF) of 2% (except FLT3). Variants for 596 subjects were manually reviewed to retain likely disease-causing variants to build a binary classifier (MDS vs. Other) using the maximum VAF per gene as input (Figure 1). Subjects diagnosed with MDS or Other by both central and local pathology were used for training, validation, and testing, and were considered "gold standard" (GS) cases (n=546). These subjects were split into 4 random groups with equal proportions of MDS cases. 75% of the GS cases were used to train and validate lasso-regularized logistic regression models using 3-fold cross validation. ROC curve analysis was carried out using the remaining 25% of GS cases (Test Set 1) on the best model to identify an optimal probability cut off point for classifying subjects as MDS. Model performance was then tested on 50 subjects for which the central and local pathology diagnosis disagreed (Test Set 2), as well as on 52 additional subjects irrespective of agreement (Test Set 3). Results : The best performing logistic regression model retained 7 genes as most informative in a discriminating diagnosis of MDS from Other based on their VAFs, in order of impact: TP53, SF3B1, U2AF1, ASXL1, TET2,STAG2, and SRSF2. We used this model to assign probabilities for each of the subjects in Test Set 1 and to estimate the performance using ROC analysis (Figure 1), resulting in a high area under the curve (AUC) of 0.89. We chose a probability cut-off of ≥0.17, being associated with a high percentage of correct classification of MDS with a sensitivity and specificity of 0.90 and 0.81, respectively. Among the cohort of 50 subjects with a discordant local and central pathology diagnosis (Test Set 2), the classifier accurately reassigned 37 subjects (accuracy = 74%) from the local to the central pathology. The blinded tertiary pathology reviewer agreed with central in all Test Set 2 cases. This included 24/34 MDS cases that had been labeled as Other by local pathology (positive predictive value [PPV]=0.89). 3/16 final pathology-classified Other cases were mis-classified as MDS by the local pathologist (negative predictive value [NPV] = 0.57). Next, we assessed the ability of the model to predict MDS vs. Other for 52 additional independent subjects using the third pathologist's diagnosis to break any ties (Test Set 3). The classifier correctly predicted 15/21 MDS cases (PPV=0.83) and misclassified 6/31 Others as MDS (NPV=0.82). The overall accuracy was 83%. Conclusions: We identified that VAFs for 7 genes can correctly re-classify subjects as either MDS or Other in 74% of cases that were misclassified between local and central pathology review. Further assessment on an independent cohort showed an accuracy of 83% of the model. Taken together, these data suggest that complementing pathology reviews with targeted sequencing of 7 genes could improve MDS diagnosis. Disclosures Lindsley: MedImmune: Research Funding; Jazz Pharmaceuticals: Consultancy, Research Funding; Bluebird Bio: Consultancy; Takeda Pharmaceuticals: Consultancy. Bejar:Aptose Biosciences: Current Employment; AbbVie/Genentech: Honoraria; Astex/Otsuka: Honoraria; Takeda: Honoraria, Research Funding; Celgene/BMS: Honoraria, Research Funding; Daiichi-Sankyo: Honoraria; Forty-Seven/Gilead: Honoraria; Genoptix/NeoGenomics: Honoraria. DeZern:MEI: Consultancy; Astex: Research Funding; Abbvie: Consultancy; Celgene: Consultancy, Honoraria. Foran:H3Biosciences: Research Funding; Aptose: Research Funding; Kura Oncology: Research Funding; Trillium: Research Funding; Takeda: Research Funding; Revolution Medicine: Consultancy; Xencor: Research Funding; Agios: Honoraria, Research Funding; Aprea: Research Funding; Actinium: Research Funding; Servier: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Abbvie: Research Funding; BMS: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Boehringer Ingelheim: Research Funding. Gore:Abbvie: Consultancy, Honoraria, Research Funding. Komrokji:Acceleron: Honoraria; Incyte: Honoraria; Abbvie: Honoraria; Agios: Speakers Bureau; BMS: Honoraria, Speakers Bureau; Jazz: Honoraria, Speakers Bureau; Geron: Honoraria; Novartis: Honoraria. Maciejewski:Alexion, BMS: Speakers Bureau; Novartis, Roche: Consultancy, Honoraria. Padron:Novartis: Honoraria; BMS: Research Funding; Incyte: Research Funding; Kura: Research Funding. Starczynowski:Captor Therapeutics: Consultancy; Tolero Therapeutics: Research Funding; Kurome Therapeutics: Consultancy, Current equity holder in private company, Research Funding. Sekeres:BMS: Consultancy; Takeda/Millenium: Consultancy; Pfizer: Consultancy.

Abstract Initially developed for large and giant wide-necked aneurysms of the internal carotid artery, flow diverter devices are now used in almost every location safely and with effectiveness. 1-5 This video demonstrates a unique case of a giant aneurysm of the right petrous internal carotid artery in a 20-yr-old patient. This is an extremely rare location, and most of patients are asymptomatic. 3-6 Signs of compression of the seventh and eight cranial nerves can be present and even Horner syndrome and lower cranial nerves neuropathies. Nevertheless, rupture can lead to epistaxis and otorrhagia, and ultimately to hemorrhagic shock. The patient in the current report was otherwise healthy but presented with lightheadedness and dizziness for 10 d. The patient consented to the procedure. There was no history of major trauma or head and neck infection. A transradial endovascular flow diversion embolization of a giant aneurysm of the petrous internal carotid artery is herein demonstrated in a stepwise manner. A triaxial system was used to deploy 3 overlapping devices. Concepts of J-wire technique, multiple coverage, 1 and the so-called weld technique are emphasized. The role of adjunctive coiling and main reasons for failure are also discussed. 7,8 Brief cases of flow diversion embolization of aneurysms of different morphologies at different locations are used to highlight the importance of assessing vessel wall apposition and follow-up imaging.

This review extensively summarized the properties and synthesis methods for phosphorene nanosheets, quantum dots, nanoribbons and their most-recent biomedical applications in bone, nerve, skin, brain, kidney, biosensor, and cancer related fields.

The NCCN Guidelines for Acute Myeloid Leukemia (AML) provide recommendations for the diagnosis and treatment of adults with AML based on clinical trials that have led to significant improvements in treatment, or have yielded new information regarding factors with prognostic importance, and are intended to aid physicians with clinical decision-making. These NCCN Guidelines Insights focus on recent select updates to the NCCN Guidelines, including familial genetic alterations in AML, postinduction or postremission treatment strategies in low-risk acute promyelocytic leukemia or favorable-risk AML, principles surrounding the use of venetoclax-based therapies, and considerations for patients who prefer not to receive blood transfusions during treatment.

AbstractNeuromuscular ultrasound is a rapidly evolving specialty with direct application for patient care. Competency assessment is an essential standard needed to ensure quality for practitioners, particularly for those newly acquiring skills with the technique. Our aim was to survey experts' opinions regarding physician competency assessment of neuromuscular ultrasound and to identify minimal competency of knowledge and skills. The opinions of 18 experts were obtained through the Delphi method using two consecutive electronic surveys. A high degree of consensus was achieved on items regarding framework and the conduct of neuromuscular ultrasound assessment and the knowledge and skills that a candidate needs to attain minimal competency in neuromuscular ultrasound. In this study, a group of neuromuscular ultrasound experts developed a general framework for neuromuscular ultrasound competency assessment and recommended testable areas of knowledge and skills suitable for establishing minimal competency.

Abstract Background The survival benefit of combination antifungal therapy for invasive mucormycosis (IM) in patients with hematologic malignancy (HM) and hematopoietic cell transplant (HCT) is not well defined. Methods This multicenter, retrospective study included HM and HCT recipients with proven or probable IM between January 1, 2007 and December 31, 2017 from 10 transplant centers across North America. Results Sixty-four patients with proven (n = 47) or probable (n = 17) IM defined by 2008 European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) consensus definitions were included. Thirty-nine (61%) were HCT recipients (95% allogeneic). Sites of infection included rhino-orbital-cerebral (33), pulmonary (30%), disseminated (19%), gastrointestinal (3%), and cutaneous (3%). Surgical debridement was performed in 66%. Initial antifungal treatment consisted of the following: lipid formulation of amphotericin B (AmB) alone (44%), AmB + posaconazole (25%), AmB + echinocandin (13%), AmB + isavuconazole (8%), posaconazole alone (5%), and isavuconazole alone (3%). All-cause mortality at 30 days and 1 year were 38% and 66%, respectively. Initial treatment with AmB plus posaconazole or isavuconazole (n = 28) was associated with a trend toward lower treatment failure compared with AmB (n = 21) (42% vs 64%, P = .136). Conclusions Long-term survival with IM among HM and HCT populations remains poor. However, initial use of AmB + azole in conjunction with surgery may result in less treatment failure. More evidence from prospective controlled studies is needed to confirm this observation.

Abstract Primary age-related tauopathy (PART) is a neurodegenerative entity defined as Alzheimer-type neurofibrillary degeneration primarily affecting the medial temporal lobe with minimal to absent amyloid-β (Aβ) plaque deposition. The extent to which PART can be differentiated pathoanatomically from Alzheimer disease (AD) is unclear. Here, we examined the regional distribution of tau pathology in a large cohort of postmortem brains (n = 914). We found an early vulnerability of the CA2 subregion of the hippocampus to neurofibrillary degeneration in PART, and semiquantitative assessment of neurofibrillary degeneration in CA2 was significantly greater than in CA1 in PART. In contrast, subjects harboring intermediate-to-high AD neuropathologic change (ADNC) displayed relative sparing of CA2 until later stages of their disease course. In addition, the CA2/CA1 ratio of neurofibrillary degeneration in PART was significantly higher than in subjects with intermediate-to-high ADNC burden. Furthermore, the distribution of tau pathology in PART diverges from the Braak NFT staging system and Braak stage does not correlate with cognitive function in PART as it does in individuals with intermediate-to-high ADNC. These findings highlight the need for a better understanding of the contribution of PART to cognitive impairment and how neurofibrillary degeneration interacts with Aβ pathology in AD and PART.