Citations

AbstractBackgroundMucopolysaccharidoses (MPS) is a group of hereditary multisystemic lysosomal disorders. Most neuroimaging studies in MPS have focused on the supratentorial compartment and craniocervical junction abnormalities, and data regarding posterior fossa findings are scarce in the literature. Thus, our purpose is to describe posterior fossa findings on magnetic resonance imaging (MRI) of MPS patients.MethodsWe reviewed routine MRI scans of MPS patients being followed up at our institution (types I, II, III, IV, and VI), focusing on posterior fossa structures.ResultsForty‐seven MPS patients were included. MRI‐visible perivascular spaces were commonly found in the midbrain and adjacent to the dentate nuclei (85% and 55% of patients, respectively). White‐matter lesion was not identified in most cases. Its most frequent localizations were in the pons and cerebellum (34% and 30% of patients, respectively). Enlargement of cerebrospinal fluid (CSF) spaces in the posterior fossa was present in 55% of individuals and was more frequent in neuronopathic patients (73% vs 40%; P = .02). Cerebellar volume was classified as normal, apparent macrocerebellum, atrophic, and hypoplastic in 38%, 38%, 21%, and 3% of patients, respectively. A depression of the posterior fossa floor in the midline sagittal plane was found in 22 patients (47%), which was statistical significantly associated with enlargement of CSF spaces (P = .02) and with apparent macrocerebellum (P = .03).ConclusionThe present study compiled the main posterior fossa findings in MPS patients. Classically described in the supratentorial compartment, MRI‐visible perivascular spaces, white matter lesions, and enlarged perivascular spaces were also found in the posterior fossa. However, atrophy, which commonly affects cerebral hemispheres, was not the most frequent cerebellar morphology found in our study. Moreover, potential findings for future research were described.

Abstract Traditional Hardy–Weinberg equilibrium (HWE) tests (the χ2 test and the exact test) have long been used as a metric for evaluating genotype quality, as technical artifacts leading to incorrect genotype calls often can be identified as deviations from HWE. However, in data sets composed of individuals from diverse ancestries, HWE can be violated even without genotyping error, complicating the use of HWE testing to assess genotype data quality. In this manuscript, we present the Robust Unified Test for HWE (RUTH) to test for HWE while accounting for population structure and genotype uncertainty, and to evaluate the impact of population heterogeneity and genotype uncertainty on the standard HWE tests and alternative methods using simulated and real sequence data sets. Our results demonstrate that ignoring population structure or genotype uncertainty in HWE tests can inflate false-positive rates by many orders of magnitude. Our evaluations demonstrate different tradeoffs between false positives and statistical power across the methods, with RUTH consistently among the best across all evaluations. RUTH is implemented as a practical and scalable software tool to rapidly perform HWE tests across millions of markers and hundreds of thousands of individuals while supporting standard VCF/BCF formats. RUTH is publicly available at https://www.github.com/statgen/ruth.

Background. Delayed graft function (DGF) of a kidney transplant results in increased cost and complexity of management. For clinical care or a DGF trial, it would be ideal to accurately predict individual DGF risk and provide preemptive treatment. A calculator developed by Irish et al has been useful for predicting population but not individual risk. Methods. We analyzed the Irish calculator (IC) in the DeKAF prospective cohort (incidence of DGF = 20.4%) and investigated potential improvements. Results. We found that the predictive performance of the calculator in those meeting Irish inclusion criteria was comparable with that reported by Irish et al. For cohorts excluded by Irish: (a) in pump-perfused kidneys, the IC overestimated DGF risk; (b) in simultaneous pancreas kidney transplants, the DGF risk was exceptionally low. For all 3 cohorts, there was considerable overlap in IC scores between those with and those without DGF. Using a modified definition of DGF—excluding those with single dialysis in the first 24 h posttransplant—we found that the calculator had similar performance as with the traditional DGF definition. Studying whether DGF prediction could be improved, we found that recipient cardiovascular disease was strongly associated with DGF even after accounting for IC-predicted risk. Conclusions. The IC can be a useful population guide for predicting DGF in the population for which it was intended but has limited scope in expanded populations (SPK, pump) and for individual risk prediction. DGF risk prediction can be improved by inclusion of recipient cardiovascular disease.

Abstract Acute ischemic stroke is one of the leading causes of disability and mortality worldwide. There have been significant improvements to the treatment of acute ischemic stroke over the past 5 yr, specifically related to strokes caused by large vessel occlusions. Stent retrievers with and without local aspiration and direct aspiration alone have all been demonstrated as viable treatment options for this patient population. This case represents the surgical technique for direct aspiration for the treatment of large vessel occlusion. A 76-yr-old man presented with right-sided weakness and aphasia. His last known normal was 5 h ago. His NIHSS (National Institutes of Health Stroke Scale) was 18. The noncontrast computed tomography (CT) did not show a significant infarct burden and ASPECTS (Alberta Stroke Program Early CT Score) of 9. CT angiogram demonstrated a left M1 occlusion. The patient was not a candidate for tissue plasminogen activator (tPA) because of time to presentation; however, the patient was deemed to be a candidate for emergent thrombectomy. Consent was obtained per institutional guidelines for the emergent procedure and the video recording. The video demonstrates a direct aspiration thrombectomy technique for the treatment of stroke. The patient successfully underwent direct aspiration thrombectomy with a TICI 3 (thrombolysis in cerebral infarction) recanalization.

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.

AbstractThe purpose of this systematic review and meta‐analysis was to examine clinical outcomes associated with convalescent plasma therapy in COVID‐19 patients. We performed a literature search on PubMed, medRxiv, Web of Science, and Scopus to identify studies published up to December 10th, 2020 that examined the efficacy of convalescent plasma treatment for COVID‐19. The primary endpoints were mortality, clinical improvement, and hospital length of stay. We screened 859 studies that met the search criteria, performed full‐text reviews of 56 articles, and identified 15 articles that fulfilled inclusion criteria for meta‐analysis. The odds of mortality were significantly lower in the convalescent plasma group compared to the control group (OR = 0.59 [95% CI = 0.44; 0.78], P < .001), although results from two key randomized controlled trials did not support the mortality benefit. The odds of clinical improvement were significantly higher in the convalescent plasma group compared to the control group (OR = 2.02 [95% CI = 1.54; 2.65], P < .001). There was no difference in hospital length of stay between the convalescent plasma group and the control group (MD = −0.49 days [95% CI = −3.11; 2.12], P = .713). In all, these data indicate that a mortality benefit with convalescent plasma is unclear, although there remain benefits with convalescent plasma therapy for COVID‐19.

Background: The coronavirus disease 2019 (COVID-19) pandemic may have an effect on maternal anxiety and influence postpartum experience. Objective: To study the prevalence of maternal anxiety in late pregnancy in the context of the COVID-19 outbreak in Brazil and to analyze its association with maternal knowledge and concerns about the pandemic. Methods: This was a national multicenter cross-sectional study performed in 10 different public university hospitals, between 1 June and 31 August 2020, in Brazil. The inclusion criteria were: maternal age more than 18 years; gestational age more than 36 weeks at childbirth; single alive newborn without malformations; and absence of mental disorders. We applied a structured questionnaire to explore the knowledge and concerns about COVID-19. Maternal anxiety was assessed using the Beck Anxiety Inventory (BAI). Results: Of the 1662 women interviewed, the BAI score in late pregnancy indicated that 13.9% presented moderate and 9.6% severe maternal anxiety. Moderate or severe maternal anxiety was independently associated with the fear of being unaccompanied at childbirth (aOR1.12, 95% CI 1.10–1.35), and independent protective factors were confidence in knowing how to protect oneself from COVID-19 (aOR0.89, 95% CI 0.82–0.97) and how to safely breastfeed (aOR0.89, 95% CI 0.83–0.95). Conclusion: The COVID-19 pandemic has a significant impact on maternal anxiety.

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.

467 Background: Recent tumor-agnostic drug approvals have resulted in a paradigm shift in cancer treatment away from organ/histology specific indications to biomarker-guided tumor-agnostic approaches. Pralsetinib is a potent and selective RET inhibitor, which has recently been approved by the U.S. Food and Drug Administration (FDA) for the treatment of adults with metastatic RET fusion–positive non-small cell lung cancer (NSCLC) and is under New Drug Application review for RET mutant thyroid cancers by the FDA. RET fusions occur in up to approximately 7‒8% of patients with gastrointestinal malignancies, including pancreatic, liver, and colorectal cancers. There are currently no approved selective RET inhibitors for patients with RET fusion–positive solid tumors other than NSCLC and thyroid cancer. Here, we present data on the clinical activity of pralsetinib in patients with RET fusion–positive solid tumor types other than NSCLC enrolled in the Phase I/II ARROW study (NCT03037385). Methods: ARROW consists of a phase I dose escalation (30–600 mg once [QD] or twice daily) followed by a phase II expansion (400 mg QD) in patients with advanced RET-altered solid tumors. Primary objectives are overall response rate (ORR), per RECICT v1.1 and safety. Results: A total of 13 patients with RET fusion–positive thyroid cancer (12 papillary, 1 poorly differentiated; enrollment cutoff July 11, 2019) and 14 patients with RET fusion–positive solid tumors other than NSCLC and thyroid (3 pancreatic, 3 colon, 2 cholangiocarcinoma, 6 other; enrollment cutoff November 19, 2019) were enrolled in ARROW and received pralsetinib. At the February 13, 2020, data cutoff, the ORR (blinded central review) in response-evaluable patients with RET fusion–positive thyroid cancer was 91% (10/11; 95% CI: 59‒100) and disease control rate was 100% (95% CI: 72‒100). Treatment was ongoing in 7 of 11 patients. In RET fusion–positive solid tumors other than NSCLC and thyroid, ORR (investigator’s assessment) was 50% (6/12; 95% CI: 21‒79) and responses were observed in all patients with pancreatic cancer (3/3) and cholangiocarcinoma (2/2). Treatment was ongoing in 6 of 12 patients, including 2 of 3 patients with pancreatic cancer and 1 of 2 patients with cholangiocarcinoma. Responses were observed across multiple fusion genotypes. In the 27 patients with RET fusion–positive tumors other than NSCLC, most frequent treatment-related adverse events (TRAEs) were grade 1–2, and included anemia (33%), increased aspartate aminotransferase (33%), decreased white blood cell count (33%), hypertension (30%), increased alanine aminotransferase (26%), hyperphosphatemia (19%), and neutropenia (19%). No patients discontinued due to TRAEs. Conclusions: Pralsetinib demonstrated broad and durable antitumor activity across multiple advanced solid tumor types, regardless of RET fusion genotype, and was well tolerated. The study is ongoing. Clinical trial information: NCT03037385.