Searched for: school:SOM
Department/Unit:Neurology
Clinical Experience of Cerebrospinal Fluid-Based Liquid Biopsy Demonstrates Superiority of Cell-Free DNA over Cell Pellet Genomic DNA for Molecular Profiling
Bale, Tejus A; Yang, Soo-Ryum; Solomon, James P; Nafa, Khedoudja; Middha, Sumit; Casanova, Jacklyn; Sadowska, Justyna; Skakodub, Anna; Ahmad, Hamza; Yu, Helena A; Riely, Greg J; Kris, Mark G; Chandarlapaty, Sarat; Rosenblum, Marc K; Gavrilovic, Igor; Karajannis, Matthias A; Pentsova, Elena; Miller, Alexandra; Boire, Adrienne; Mellinghoff, Ingo; Berger, Michael F; Zehir, Ahmet; Ladanyi, Marc; Benayed, Ryma; Arcila, Maria E
Cell-free DNA (cfDNA) from cerebrospinal fluid (CSF) offers unique opportunities for genomic profiling of tumors involving the central nervous system but remains uncommonly used in clinical practice. We describe our clinical experience using cfDNA from CSF for routine molecular testing using Memorial Sloan Kettering Integrated Mutation Profiling of Actionable Cancer Targets (targeting 468 cancer-related genes). In all, 148 cfDNA samples were assessed, comparing results of cfDNA versus genomic DNA (gDNA; gDNA from cell pellets) derived from the same CSF sample and the primary tumor. Of these, 71.6% (106/148) were successfully sequenced. Somatic alterations (mutations and fusions) were observed in 70.8% (75/106) of the samples; 97.3% (73/75) comprised variants confirming central nervous system involvement by a previously diagnosed tumor, 14.7% (11/75) had additional variants consistent with a therapy-related resistance mechanism, and 2.7% (2/75) had variants that independently diagnosed a new primary. Among samples with paired cfDNA and gDNA sequencing results, cfDNA was more frequently positive for at least one mutation [43.6% (55/126) versus 19.8% (25/126)] and harbored 1.6× more mutations (6.94 versus 4.65; P = 0.005), with higher mean variant allele fractions (41.1% versus 13.0%; P < 0.0001). Among mutation-positive cfDNAs, the corresponding gDNA was frequently negative (44.6%; 25/55) or failed sequencing (17.8%; 9/55). Routine molecular profiling of cfDNA is superior to gDNA from CSF, facilitating the capture of mutations at high variant allele frequency, even in the context of a negative cytology.
PMCID:8207471
PMID: 33781965
ISSN: 1943-7811
CID: 5671082
Mortality risk assessment in Spain and Italy, insights of the HOPE COVID-19 registry
Núñez-Gil, Iván J; Fernández-Pérez, Cristina; Estrada, Vicente; Becerra-Muñoz, VÃctor M; El-Battrawy, Ibrahim; Uribarri, Aitor; Fernández-Rozas, Inmaculada; Feltes, Gisela; Viana-Llamas, María C; Trabattoni, Daniela; López-PaÃs, Javier; Pepe, Martino; Romero, Rodolfo; Castro-MejÃa, Alex F; Cerrato, Enrico; Astrua, Thamar Capel; D'Ascenzo, Fabrizio; Fabregat-Andres, Oscar; Moreu, José; Guerra, Federico; Signes-Costa, Jaime; MarÃn, Francisco; Buosenso, Danilo; BardajÃ, Alfredo; Raposeiras-RoubÃn, Sergio; Elola, Javier; Molino, Ãngel; Gómez-Doblas, Juan J; Abumayyaleh, Mohammad; Aparisi, Ãlvaro; Molina, María; Guerri, Asunción; Arroyo-Espliguero, Ramón; Assanelli, Emilio; Mapelli, Massimo; García-Acuña, José M; Brindicci, Gaetano; Manzone, Edoardo; Ortega-Armas, María E; Bianco, Matteo; Trung, Chinh Pham; Núñez, María José; Castellanos-Lluch, Carmen; García-Vázquez, Elisa; Cabello-Clotet, NoemÃ; Jamhour-Chelh, Karim; Tellez, María J; Fernández-Ortiz, Antonio; Macaya, Carlos
Recently the coronavirus disease (COVID-19) outbreak has been declared a pandemic. Despite its aggressive extension and significant morbidity and mortality, risk factors are poorly characterized outside China. We designed a registry, HOPE COVID-19 (NCT04334291), assessing data of 1021 patients discharged (dead or alive) after COVID-19, from 23 hospitals in 4 countries, between 8 February and 1 April. The primary end-point was all-cause mortality aiming to produce a mortality risk score calculator. The median age was 68 years (IQR 52-79), and 59.5% were male. Most frequent comorbidities were hypertension (46.8%) and dyslipidemia (35.8%). A relevant heart or lung disease were depicted in 20%. And renal, neurological, or oncological disease, respectively, were detected in nearly 10%. Most common symptoms were fever, cough, and dyspnea at admission. 311 patients died and 710 were discharged alive. In the death-multivariate analysis, raised as most relevant: age, hypertension, obesity, renal insufficiency, any immunosuppressive disease, 02 saturation < 92% and an elevated C reactive protein (AUC = 0.87; Hosmer-Lemeshow test, p > 0.999; bootstrap-optimist: 0.0018). We provide a simple clinical score to estimate probability of death, dividing patients in four grades (I-IV) of increasing probability. Hydroxychloroquine (79.2%) and antivirals (67.6%) were the specific drugs most commonly used. After a propensity score adjustment, the results suggested a slight improvement in mortality rates (adjusted-ORhydroxychloroquine 0.88; 95% CI 0.81-0.91, p = 0.005; adjusted-ORantiviral 0.94; 95% CI 0.87-1.01; p = 0.115). COVID-19 produces important mortality, mostly in patients with comorbidities with respiratory symptoms. Hydroxychloroquine could be associated with survival benefit, but this data need to be confirmed with further trials. Trial Registration: NCT04334291/EUPAS34399.
PMCID:7649104
PMID: 33165755
ISSN: 1970-9366
CID: 4717182
Evaluation of diazepam nasal spray in patients with epilepsy concomitantly using maintenance benzodiazepines: An interim subgroup analysis from a phase 3, long-term, open-label safety study
Segal, Eric B; Tarquinio, Daniel; Miller, Ian; Wheless, James W; Dlugos, Dennis; Biton, Victor; Cascino, Gregory D; Desai, Jay; Hogan, R Edward; Liow, Kore; Sperling, Michael R; Vazquez, Blanca; Cook, David F; Rabinowicz, Adrian L; Carrazana, Enrique
OBJECTIVE:Diazepam nasal spray (Valtoco), indicated for acute treatment of frequent seizure activity (seizure clusters) in patients with epilepsy ≥6 years of age, is designed to be a rapid, noninvasive, socially acceptable route of administration. This interim analysis evaluated the safety profile of diazepam nasal spray in patients with and without concomitant use of benzodiazepines, with use of a second dose for a seizure cluster as a proxy for effectiveness. METHODS:A long-term, phase 3, open-label safety study enrolled patients with epilepsy who had seizures despite a stable antiseizure medication regimen. RESULTS:Among 175 patients enrolled by October 31, 2019, a total of 158 were treated with diazepam nasal spray (aged 6-65 years; 53.8% female). Of those, 119 (75.3%) received concomitant benzodiazepines (60, chronic; 59, intermittent); 39 (24.7%) did not. Use of a second dose was similar in patients using chronic concomitant benzodiazepines (second dose in 11.1% [144/1299]) and those with no concomitant benzodiazepines (second dose in 10.3% [41/398]). Treatment emergent adverse events (TEAEs) occurred for 80.0% with chronic use of concomitant benzodiazepines and 61.5% without. Cardiorespiratory depression was not reported, and no serious TEAEs were treatment related. Study retention was high: 83.3% in the chronic benzodiazepine group and 76.9% in the no-benzodiazepine group. Findings were similar in a sub-analysis of patients who were (n = 44) or were not (n = 75) taking clobazam. SIGNIFICANCE/CONCLUSIONS:This analysis of patients from a long-term study shows a similar safety profile of diazepam nasal spray in patients with and without concomitant benzodiazepines, and consistent with the established profile for diazepam. Use of a single dose of diazepam nasal spray and high study retention rates suggest the effectiveness of diazepam nasal spray in patients irrespective of chronic daily benzodiazepine use. Results were similar in the clobazam sub-analysis. These results support the safety and effectiveness of diazepam nasal spray in patients with concomitant benzodiazepine use.
PMID: 33942315
ISSN: 1528-1167
CID: 4897982
Cross-validation of a forced-choice validity indicator to enhance the clinical utility of the Rey Auditory Verbal Learning Test
Soble, Jason R; Sharp, Dillon W; Carter, Dustin A; Jennette, Kyle J; Resch, Zachary J; Ovsiew, Gabriel P; Critchfield, Edan A
A forced-choice (FC) recognition trial was recently developed as an embedded validity indicator for the Rey Auditory Verbal Learning Test (RAVLT), although it has not been replicated outside of the initial validation study. This study cross-validated the RAVLT FC trial for detecting invalid neuropsychological test performance and assessed the degree to which material-specific verbal memory impairment severity impacts its classification accuracy as a performance validity test (PVT). This cross-sectional study included 172 neuropsychiatric patients who completed the RAVLT and 4 independent criterion PVTs, which were used to classify validity groups (134 valid/38 invalid). Overall results showed the RAVLT FC had excellent classification accuracy for detecting invalid performance at a ≤13 cut-score (66% sensitivity/87% specificity). When patients were subdivided by memory impairment status, FC retained excellent classification accuracy among the normal memory and mild memory impairment groups with 66%-82% sensitivity and ≥89% specificity. Accuracy decreased among those with severe memory impairment, but remained significant with a lower, alternative cut-score of ≤11 (37% sensitivity/88% specificity). Findings were consistent with FC trials developed for other memory measures and support the utility of this novel RAVLT FC index for reliably identifying invalid performance, even in the context of significant verbal memory impairment. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
PMID: 33900098
ISSN: 1939-134x
CID: 5593032
Cost-Effectiveness of Advanced Neuroimaging for Transient and Minor Neurological Events in the Emergency Department
Liberman, Ava L; Zhang, Hui; Rostanski, Sara K; Cheng, Natalie T; Esenwa, Charles C; Haranhalli, Neil; Singh, Puneet; Labovitz, Daniel L; Lipton, Richard B; Prabhakaran, Shyam
Background Accurate diagnosis of patients with transient or minor neurological events can be challenging. Recent studies suggest that advanced neuroimaging can improve diagnostic accuracy in low-risk patients with transient or minor neurological symptoms, but a cost-effective emergency department diagnostic evaluation strategy remains uncertain. Methods and Results We constructed a decision-analytic model to evaluate 2 diagnostic evaluation strategies for patients with low-risk transient or minor neurological symptoms: (1) obtain advanced neuroimaging (magnetic resonance imaging brain and magnetic resonance angiography head and neck) on every patient or (2) current emergency department standard-of-care clinical evaluation with basic neuroimaging. Main probability variables were: proportion of patients with true ischemic events, strategy specificity and sensitivity, and recurrent stroke rate. Direct healthcare costs were included. We calculated incremental cost-effectiveness ratios, conducted sensitivity analyses, and evaluated various diagnostic test parameters primarily using a 1-year time horizon. Cost-effectiveness standards would be met if the incremental cost-effectiveness ratio was less than willingness to pay. We defined willingness to pay as $100Â 000 US dollars per quality-adjusted life year. Our primary and sensitivity analyses found that the advanced neuroimaging strategy was more cost-effective than emergency department standard of care. The incremental effectiveness of the advanced neuroimaging strategy was slightly less than the standard-of-care strategy, but the standard-of-care strategy was more costly. Potentially superior diagnostic approaches to the modeled advanced neuroimaging strategy would have to be >92% specific, >70% sensitive, and cost less than or equal to standard-of-care strategy's cost. Conclusions Obtaining advanced neuroimaging on emergency department patient with low-risk transient or minor neurological symptoms was the more cost-effective strategy in our model.
PMID: 34056914
ISSN: 2047-9980
CID: 4890962
Systemic Inflammatory Response Syndrome is Associated with Hematoma Expansion in Intracerebral Hemorrhage
Melmed, Kara R; Carroll, Elizabeth; Lord, Aaron S; Boehme, Amelia K; Ishida, Koto; Zhang, Cen; Torres, Jose L; Yaghi, Shadi; Czeisler, Barry M; Frontera, Jennifer A; Lewis, Ariane
OBJECTIVES/OBJECTIVE:Systemic inflammatory response syndrome (SIRS) and hematoma expansion are independently associated with worse outcomes after intracerebral hemorrhage (ICH), but the relationship between SIRS and hematoma expansion remains unclear. MATERIALS AND METHODS/METHODS:We performed a retrospective review of patients admitted to our hospital from 2013 to 2020 with primary spontaneous ICH with at least two head CTs within the first 24 hours. The relationship between SIRS and hematoma expansion, defined as ≥6 mL or ≥33% growth between the first and second scan, was assessed using univariable and multivariable regression analysis. We assessed the relationship of hematoma expansion and SIRS on discharge mRS using mediation analysis. RESULTS:Of 149 patients with ICH, 83 (56%; mean age 67±16; 41% female) met inclusion criteria. Of those, 44 (53%) had SIRS. Admission systolic blood pressure (SBP), temperature, antiplatelet use, platelet count, initial hematoma volume and rates of infection did not differ between groups (all p>0.05). Hematoma expansion occurred in 15/83 (18%) patients, 12 (80%) of whom also had SIRS. SIRS was significantly associated with hematoma expansion (OR 4.5, 95% CI 1.16 - 17.39, p= 0.02) on univariable analysis. The association remained statistically significant after adjusting for admission SBP and initial hematoma volume (OR 5.72, 95% CI 1.40 - 23.41, p= 0.02). There was a significant indirect effect of SIRS on discharge mRS through hematoma expansion. A significantly greater percentage of patients with SIRS had mRS 4-6 at discharge (59 vs 33%, p=0.02). CONCLUSION/CONCLUSIONS:SIRS is associated with hematoma expansion of ICH within the first 24 hours, and hematoma expansion mediates the effect of SIRS on poor outcome.
PMID: 34077823
ISSN: 1532-8511
CID: 4891632
"Diversity Matters Series" - The ALBA Network [Editorial]
Helmreich, Dana L; Bovolenta, Paola; Adamantidis, Antoine; Foxe, John J; Smith, Yoland; Vaidya, Vidita A
PMID: 34051001
ISSN: 1460-9568
CID: 4890602
Recalled and momentary virtual portions created of snacks predict actual intake under laboratory stress condition
Hamm, Jeon D; Klatzkin, Rebecca R; Herzog, Musya; Tamura, Shoran; Brunstrom, Jeffrey M; Kissileff, Harry R
Virtual portion tasks have been used to predict food intake in healthy individuals, severity of illness in individuals with anorexia nervosa, and weight loss in bariatric surgery patients. Whether portion creation in response to a recalled interpersonal stress ("recalled stress portions") could be used as a proxy for ad lib intake, after a stressor, remains untested, and the mechanism supporting this relationship is unclear. The present study's goals were: 1) to validate virtual portion tasks as proxies for actual food intake in a stressful context and 2) to test a causal pathway in which these virtual stress portions predict ad lib intake after stress. We proposed that this relationship is mediated by virtual portions created the moment after laboratory stress or rest manipulation (momentary portions), and before the participant actually ate food. At screening, 29 healthy undergraduate white women created virtual portions of eight snacks (apples, olives, potato chips, pretzels, caramel popcorn, milk chocolate) that they typically eat and also portions they recall eating in response to a stressful interpersonal situation. In addition, after a Trier Social Stress Test, or a rest period, on separate days in counterbalanced order, participants created 'momentary' virtual portions of the same snacks presented during screening, and then were given potato chips, mini golden Oreos, and M&Ms to eat. Recalled stress (b = 0.07 ± 0.02, p = 0.003), and momentary stress (b = 0.12 ± 0.02, p = 0.00001), portions of milk chocolate accounted for 29% and 51%, respectively, of the variance in ad lib stress intake of M&Ms. Typical (b = 0.15 ± 0.07, p = 0.03), and momentary rest (b = 0.21 ± 0.06, p = 0.002), portions of chips accounted for 16% and 31%, respectively, of the variance in ad lib rest intake of chips. The causal pathway from recalled stress portion to ad lib stress snack intake was completely mediated by momentary stress portion for milk chocolate and M&Ms (β = 0.04 ± 0.02, z = 2.4, p = 0.0154). These findings illustrate the planning and recall components of eating in response to stress, but not necessarily under rest conditions. This recalled stress virtual portion paradigm has clinical and research value in that it can detect those who overconsume in response to stress.
PMID: 34058220
ISSN: 1873-507x
CID: 4891032
Making the hard problem of consciousness easier
Melloni, Lucia; Mudrik, Liad; Pitts, Michael; Koch, Christof
PMID: 34045342
ISSN: 1095-9203
CID: 4924342
Diagnosis of Guillain-Barré Syndrome After Total Hip Arthroplasty: A Case Report
Tesoriero, Paul; Feng, James E; Anoushiravani, Afshin A; Kiprovski, Kiril; Marwin, Scott; Wiznia, Daniel
CASE REPORT:A 67-year-old man presented with signs of acute periprosthetic infection after total hip arthroplasty (THA). Surgical debridement, antibiotics, and a head and liner exchange were performed. After showing no improvement, a single-stage revision was conducted. Postoperatively, he developed back pain and lower extremity weakness. Electrodiagnostic studies showed a Guillain-Barré syndrome (GBS) variant. Intravenous immunoglobulin was administered to halt disease progression. After 1 year, he still demonstrated neuromuscular deficits and required a cane for ambulation. CONCLUSION:This case highlights GBS after THA. A high degree of clinical suspicion is essential to prevent misinterpretation as a postsurgical complication. LEVEL OF EVIDENCE:V, case report.
PMID: 34038913
ISSN: 2160-3251
CID: 4887982