Publications by authors named "Thomas Snyder"

59 Publications

T-cell receptor sequencing identifies prior SARS-CoV-2 infection and correlates with neutralizing antibody titers and disease severity.

medRxiv 2021 Mar 22. Epub 2021 Mar 22.

Measuring the adaptive immune response to SARS-CoV-2 can enable the assessment of past infection as well as protective immunity and the risk of reinfection. While neutralizing antibody (nAb) titers are one measure of protection, such assays are challenging to perform at a large scale and the longevity of the SARS-CoV-2 nAb response is not fully understood. Here, we apply a T-cell receptor (TCR) sequencing assay that can be performed on a small volume standard blood sample to assess the adaptive T-cell response to SARS-CoV-2 infection. Samples were collected from a cohort of 302 individuals recovered from COVID-19 up to 6 months after infection. Previously published findings in this cohort showed that two commercially available SARS-CoV-2 serologic assays correlate well with nAb testing. We demonstrate that the magnitude of the SARS-CoV-2-specific T-cell response strongly correlates with nAb titer, as well as clinical indicators of disease severity including hospitalization, fever, or difficulty breathing. While the depth and breadth of the T-cell response declines during convalescence, the T-cell signal remains well above background with high sensitivity up to at least 6 months following initial infection. Compared to serology tests detecting binding antibodies to SARS-CoV-2 spike and nucleoprotein, the overall sensitivity of the TCR-based assay across the entire cohort and all timepoints was approximately 5% greater for identifying prior SARS-CoV-2 infection. Notably, the improved performance of T-cell testing compared to serology was most apparent in recovered individuals who were not hospitalized and were sampled beyond 150 days of their initial illness, suggesting that antibody testing may have reduced sensitivity in individuals who experienced less severe COVID-19 illness and at later timepoints. Finally, T-cell testing was able to identify SARS-CoV-2 infection in 68% (55/81) of convalescent samples having nAb titers below the lower limit of detection, as well as 37% (13/35) of samples testing negative by all three antibody assays. These results demonstrate the utility of a TCR-based assay as a scalable, reliable measure of past SARS-CoV-2 infection across a spectrum of disease severity. Additionally, the TCR repertoire may be useful as a surrogate for protective immunity with additive clinical value beyond serologic or nAb testing methods.
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http://dx.doi.org/10.1101/2021.03.19.21251426DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010755PMC
March 2021

A Prospective Study of Neurologic Disorders in Hospitalized Patients With COVID-19 in New York City.

Neurology 2021 01 5;96(4):e575-e586. Epub 2020 Oct 5.

From the New York University Grossman School of Medicine (J.A.F., S.S., R.L., T.F., B.F., P.M.-V., T.S., S.B., D.Y., A.G., N.M., P.P., J.G., K.M., S.A., M.B., A.A., E.V., M.O., A.K., K.L., Daniel Friedman, David Friedman, M.H., J.H., S.T., J.H., N.A.-F., P.K., A.L., A.S.L., T.Z., D.E.K., B.M.C., J.T., S.Y., K.I., E.S., D.P., M.L., T.W., A.B.T., L.B., S.G.), New YorkUniversity of Pittsburgh School of Medicine (S.H.-Y.C., E.L.F.), PAThe Ohio State University (M.M., S.M.), ColumbusMedical University of Innsbruck (R.H.), AustriaThe Johns Hopkins University School of Medicine (C.R., J.I.S., W.Z.), Baltimore, MDUniversity of Utah School of Medicine (M.S., A.d.H.), Salt Lake CityUniversity of Cambridge (D.M.), UK.

Objective: To determine the prevalence and associated mortality of well-defined neurologic diagnoses among patients with coronavirus disease 2019 (COVID-19), we prospectively followed hospitalized severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive patients and recorded new neurologic disorders and hospital outcomes.

Methods: We conducted a prospective, multicenter, observational study of consecutive hospitalized adults in the New York City metropolitan area with laboratory-confirmed SARS-CoV-2 infection. The prevalence of new neurologic disorders (as diagnosed by a neurologist) was recorded and in-hospital mortality and discharge disposition were compared between patients with COVID-19 with and without neurologic disorders.

Results: Of 4,491 patients with COVID-19 hospitalized during the study timeframe, 606 (13.5%) developed a new neurologic disorder in a median of 2 days from COVID-19 symptom onset. The most common diagnoses were toxic/metabolic encephalopathy (6.8%), seizure (1.6%), stroke (1.9%), and hypoxic/ischemic injury (1.4%). No patient had meningitis/encephalitis or myelopathy/myelitis referable to SARS-CoV-2 infection and 18/18 CSF specimens were reverse transcriptase PCR negative for SARS-CoV-2. Patients with neurologic disorders were more often older, male, white, hypertensive, diabetic, intubated, and had higher sequential organ failure assessment (SOFA) scores (all < 0.05). After adjusting for age, sex, SOFA scores, intubation, history, medical complications, medications, and comfort care status, patients with COVID-19 with neurologic disorders had increased risk of in-hospital mortality (hazard ratio [HR] 1.38, 95% confidence interval [CI] 1.17-1.62, < 0.001) and decreased likelihood of discharge home (HR 0.72, 95% CI 0.63-0.85, < 0.001).

Conclusions: Neurologic disorders were detected in 13.5% of patients with COVID-19 and were associated with increased risk of in-hospital mortality and decreased likelihood of discharge home. Many observed neurologic disorders may be sequelae of severe systemic illness.
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http://dx.doi.org/10.1212/WNL.0000000000010979DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905791PMC
January 2021

Special considerations in the assessment of catastrophic brain injury and determination of brain death in patients with SARS-CoV-2.

J Neurol Sci 2020 10 8;417:117087. Epub 2020 Aug 8.

NYU Langone Medical Center, Department of Neurology, New York, NY 10016, United States of America; NYU Langone Medical Center, Department of Neurosurgery, New York, NY 10016, United States of America.

Introduction: The coronavirus disease 2019 (Covid-19) pandemic has led to challenges in provision of care, clinical assessment and communication with families. The unique considerations associated with evaluation of catastrophic brain injury and death by neurologic criteria in patients with Covid-19 infection have not been examined.

Methods: We describe the evaluation of six patients hospitalized at a health network in New York City in April 2020 who had Covid-19, were comatose and had absent brainstem reflexes.

Results: Four males and two females with a median age of 58.5 (IQR 47-68) were evaluated for catastrophic brain injury due to stroke and/or global anoxic injury at a median of 14 days (IQR 13-18) after admission for acute respiratory failure due to Covid-19. All patients had hypotension requiring vasopressors and had been treated with sedative/narcotic drips for ventilator dyssynchrony. Among these patients, 5 had received paralytics. Apnea testing was performed for 1 patient due to the decision to withdraw treatment (n = 2), concern for inability to tolerate testing (n = 2) and observation of spontaneous respirations (n = 1). The apnea test was aborted due to hypoxia and hypotension. After ancillary testing, death was declared in three patients based on neurologic criteria and in three patients based on cardiopulmonary criteria (after withdrawal of support (n = 2) or cardiopulmonary arrest (n = 1)). A family member was able to visit 5/6 patients prior to cardiopulmonary arrest/discontinuation of organ support.

Conclusion: It is feasible to evaluate patients with catastrophic brain injury and declare brain death despite the Covid-19 pandemic, but this requires unique considerations.
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http://dx.doi.org/10.1016/j.jns.2020.117087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7414304PMC
October 2020

Magnitude and Dynamics of the T-Cell Response to SARS-CoV-2 Infection at Both Individual and Population Levels.

medRxiv 2020 Aug 4. Epub 2020 Aug 4.

T cells are involved in the early identification and clearance of viral infections and also support the development of antibodies by B cells. This central role for T cells makes them a desirable target for assessing the immune response to SARS-CoV-2 infection. Here, we combined two high-throughput immune profiling methods to create a quantitative picture of the T-cell response to SARS-CoV-2. First, at the individual level, we deeply characterized 3 acutely infected and 58 recovered COVID-19 subjects by experimentally mapping their CD8 T-cell response through antigen stimulation to 545 Human Leukocyte Antigen (HLA) class I presented viral peptides (class II data in a forthcoming study). Then, at the population level, we performed T-cell repertoire sequencing on 1,015 samples (from 827 COVID-19 subjects) as well as 3,500 controls to identify shared "public" T-cell receptors (TCRs) associated with SARS-CoV-2 infection from both CD8 and CD4 T cells. Collectively, our data reveal that CD8 T-cell responses are often driven by a few immunodominant, HLA-restricted epitopes. As expected, the T-cell response to SARS-CoV-2 peaks about one to two weeks after infection and is detectable for several months after recovery. As an application of these data, we trained a classifier to diagnose SARS-CoV-2 infection based solely on TCR sequencing from blood samples, and observed, at 99.8% specificity, high early sensitivity soon after diagnosis (Day 3-7 = 83.8% [95% CI = 77.6-89.4]; Day 8-14 = 92.4% [87.6-96.6]) as well as lasting sensitivity after recovery (Day 29+/convalescent = 96.7% [93.0-99.2]). These results demonstrate an approach to reliably assess the adaptive immune response both soon after viral antigenic exposure (before antibodies are typically detectable) as well as at later time points. This blood-based molecular approach to characterizing the cellular immune response has applications in vaccine development as well as clinical diagnostics and monitoring.
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http://dx.doi.org/10.1101/2020.07.31.20165647DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7418734PMC
August 2020

A large-scale database of T-cell receptor beta (TCRβ) sequences and binding associations from natural and synthetic exposure to SARS-CoV-2.

Res Sq 2020 Aug 4. Epub 2020 Aug 4.

We describe the establishment and current content of the ImmuneCODE™ database, which includes hundreds of millions of T-cell Receptor (TCR) sequences from over 1,400 subjects exposed to or infected with the SARS-CoV-2 virus, as well as over 135,000 high-confidence SARS-CoV-2-specific TCRs. This database is made freely available, and the data contained in it can be downloaded and analyzed online or offline to assist with the global efforts to understand the immune response to the SARS-CoV-2 virus and develop new interventions.
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http://dx.doi.org/10.21203/rs.3.rs-51964/v1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7418738PMC
August 2020

Stroke Treatment Delay Limits Outcome After Mechanical Thrombectomy: Stratification by Arrival Time and ASPECTS.

J Neuroimaging 2020 09 27;30(5):625-630. Epub 2020 Jun 27.

Department of Neurology, New York Langone Medical Center, New York, NY.

Background And Purpose: Mechanical thrombectomy (MT) has helped many patients achieve functional independence. The effect of time-to-treatment based in specific epochs and as related to Alberta Stroke Program Early CT Score (ASPECTS) has not been established. The goal of the study was to evaluate the association between last known normal (LKN)-to-puncture time and good functional outcome.

Methods: We conducted a retrospective cohort study of prospectively collected acute ischemic stroke patients undergoing MT for large vessel occlusion. We used binary logistic regression models adjusted for age, Modified Treatment in Cerebral Ischemia score, initial National Institutes of Health Stroke Scale, and noncontrast CT ASPECTS to assess the association between LKN-to-puncture time and favorable outcome defined as Modified Rankin Score 0-2 on discharge.

Results: Among 421 patients, 328 were included in analysis. Increased LKN-to-puncture time was associated with decreased probability of good functional outcome (adjusted odds ratio [aOR] ratio per 15-minute delay = .98; 95% confidence interval [CI], .97-.99; P = .001). This was especially true when LKN-puncture time was 0-6 hours (aOR per 15-minute delay = .94; 95% CI, .89-.99; P = .05) or ASPECTS 8-10 (aOR = .98; 95% CI, .97-.99; P = .002) as opposed to when LKN-puncture time was 6-24 hours (aOR per 15-minute delay = .99; 95% CI, .97-1.00; P = .16) and ASPECTS <8 (aOR = .98; 95% CI, .93-1.03; P = .37).

Conclusion: Decreased LKN-groin puncture time improves outcome particularly in those with good ASPECTS presenting within 6 hours. Strategies to decrease reperfusion times should be investigated, particularly in those in the early time window and with good ASPECTS.
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http://dx.doi.org/10.1111/jon.12729DOI Listing
September 2020

Quantifying neurologic disease using biosensor measurements in-clinic and in free-living settings in multiple sclerosis.

NPJ Digit Med 2019 11;2:123. Epub 2019 Dec 11.

Verily Life Sciences, South San Francisco, CA USA.

Technological advances in passive digital phenotyping present the opportunity to quantify neurological diseases using new approaches that may complement clinical assessments. Here, we studied multiple sclerosis (MS) as a model neurological disease for investigating physiometric and environmental signals. The objective of this study was to assess the feasibility and correlation of wearable biosensors with traditional clinical measures of disability both in clinic and in free-living in MS patients. This is a single site observational cohort study conducted at an academic neurological center specializing in MS. A cohort of 25 MS patients with varying disability scores were recruited. Patients were monitored in clinic while wearing biosensors at nine body locations at three separate visits. Biosensor-derived features including aspects of gait (stance time, turn angle, mean turn velocity) and balance were collected, along with standardized disability scores assessed by a neurologist. Participants also wore up to three sensors on the wrist, ankle, and sternum for 8 weeks as they went about their daily lives. The primary outcomes were feasibility, adherence, as well as correlation of biosensor-derived metrics with traditional neurologist-assessed clinical measures of disability. We used machine-learning algorithms to extract multiple features of motion and dexterity and correlated these measures with more traditional measures of neurological disability, including the expanded disability status scale (EDSS) and the MS functional composite-4 (MSFC-4). In free-living, sleep measures were additionally collected. Twenty-three subjects completed the first two of three in-clinic study visits and the 8-week free-living biosensor period. Several biosensor-derived features significantly correlated with EDSS and MSFC-4 scores derived at visit two, including mobility stance time with MSFC-4 z-score (Spearman correlation -0.546;  = 0.0070), several aspects of turning including turn angle (0.437;  = 0.0372), and maximum angular velocity (0.653;  = 0.0007). Similar correlations were observed at subsequent clinic visits, and in the free-living setting. We also found other passively collected signals, including measures of sleep, that correlated with disease severity. These findings demonstrate the feasibility of applying passive biosensor measurement techniques to monitor disability in MS patients both in clinic and in the free-living setting.
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http://dx.doi.org/10.1038/s41746-019-0197-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6906296PMC
December 2019

Immunoglobulin somatic hypermutation has clinical impact in DLBCL and potential implications for immune checkpoint blockade and neoantigen-based immunotherapies.

J Immunother Cancer 2019 10 22;7(1):272. Epub 2019 Oct 22.

Hematopathology Division, Department of Pathology, Duke University School of Medicine, Durham, NC, 27710, USA.

Background: Diffuse large B-cell lymphoma (DLBCL) harbors somatic hypermutation (SHM) in the immunoglobulin heavy chain and light chain variable region genes, IGHV and IGK/LV. Recent studies have revealed that IGV SHM creates neoantigens that activate T-cell responses against B-cell lymphoma.

Methods: To determine the clinical relevance of IGV SHM in DLBCL treated with standard immunochemotherapy, we performed next-generation sequencing of the immunoglobulin variable regions and complementarity determining region 3 (CDR3) for 378 patients with de novo DLBCL. The prognostic effects of IGV SHM and ongoing SHM or intra-clonal heterogeneity were analyzed in the training (192 patients), validation (186 patients), and overall DLBCL cohorts. To gain mechanistic insight, we analyzed the predicted IG-derived neoantigens' immunogenicity potential, determined by the major histocompatibility complex-binding affinity and the frequency-of-occurrence of T cell-exposed motifs (TCEMs) in a TCEM repertoire derived from human proteome, microbiome, and pathogen databases. Furthermore, IGV SHM was correlated with molecular characteristics of DLBCL and PD-1/L1 expression in the tumor microenvironment assessed by fluorescent multiplex immunohistochemistry.

Results: SHM was commonly found in IGHV and less frequently in IGK/LV. High levels of clonal IGHV SHM (SHM) were associated with prolonged overall survival in DLBCL patients, particularly those without BCL2 or MYC translocation. In contrast, long heavy chain CDR3 length, the presence of IGHV ongoing SHM in DLBCL, and high clonal IGK/LV SHM in germinal center B-cell-like (GCB)-DLBCL were associated with poor prognosis. These prognostic effects were significant in both the training and validation sets. By prediction, the SHM groups harbored more potentially immune-stimulatory neoantigens with high binding affinity and rare TCEMs. PD-1/L1 expression in CD8 T cells was significantly lower in IGHV SHM than in SHM patients with activated B-cell-like DLBCL, whereas PD-1 expression in CD4 T cells and PD-L1 expression in natural killer cells were higher in IGK/LV SHM than in SHM patients with GCB-DLBCL. PD-L1/L2 (9p24.1) amplification was associated with high IGHV SHM and ongoing SHM.

Conclusions: These results show for the first time that IGV SHM and ongoing SHM have prognostic effects in DLBCL and potential implications for PD-1/PD-L1 blockade and neoantigen-based immunotherapies.
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http://dx.doi.org/10.1186/s40425-019-0730-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6806565PMC
October 2019

Deep learning predicts hip fracture using confounding patient and healthcare variables.

NPJ Digit Med 2019 30;2:31. Epub 2019 Apr 30.

2Institute for Next Generation Healthcare, Icahn School of Medicine at Mount Sinai, New York, NY USA.

Hip fractures are a leading cause of death and disability among older adults. Hip fractures are also the most commonly missed diagnosis on pelvic radiographs, and delayed diagnosis leads to higher cost and worse outcomes. Computer-aided diagnosis (CAD) algorithms have shown promise for helping radiologists detect fractures, but the image features underpinning their predictions are notoriously difficult to understand. In this study, we trained deep-learning models on 17,587 radiographs to classify fracture, 5 patient traits, and 14 hospital process variables. All 20 variables could be individually predicted from a radiograph, with the best performances on scanner model (AUC = 1.00), scanner brand (AUC = 0.98), and whether the order was marked "priority" (AUC = 0.79). Fracture was predicted moderately well from the image (AUC = 0.78) and better when combining image features with patient data (AUC = 0.86, DeLong paired AUC comparison,  = 2e-9) or patient data plus hospital process features (AUC = 0.91,  = 1e-21). Fracture prediction on a test set that balanced fracture risk across patient variables was significantly lower than a random test set (AUC = 0.67, DeLong unpaired AUC comparison,  = 0.003); and on a test set with fracture risk balanced across patient and hospital process variables, the model performed randomly (AUC = 0.52, 95% CI 0.46-0.58), indicating that these variables were the main source of the model's fracture predictions. A single model that directly combines image features, patient, and hospital process data outperforms a Naive Bayes ensemble of an image-only model prediction, patient, and hospital process data. If CAD algorithms are inexplicably leveraging patient and process variables in their predictions, it is unclear how radiologists should interpret their predictions in the context of other known patient data. Further research is needed to illuminate deep-learning decision processes so that computers and clinicians can effectively cooperate.
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http://dx.doi.org/10.1038/s41746-019-0105-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6550136PMC
April 2019

CANDI: an R package and Shiny app for annotating radiographs and evaluating computer-aided diagnosis.

Bioinformatics 2019 05;35(9):1610-1612

Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Motivation: Radiologists have used algorithms for Computer-Aided Diagnosis (CAD) for decades. These algorithms use machine learning with engineered features, and there have been mixed findings on whether they improve radiologists' interpretations. Deep learning offers superior performance but requires more training data and has not been evaluated in joint algorithm-radiologist decision systems.

Results: We developed the Computer-Aided Note and Diagnosis Interface (CANDI) for collaboratively annotating radiographs and evaluating how algorithms alter human interpretation. The annotation app collects classification, segmentation, and image captioning training data, and the evaluation app randomizes the availability of CAD tools to facilitate clinical trials on radiologist enhancement.

Availability And Implementation: Demonstrations and source code are hosted at (https://candi.nextgenhealthcare.org), and (https://github.com/mbadge/candi), respectively, under GPL-3 license.

Supplementary Information: Supplementary material is available at Bioinformatics online.
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http://dx.doi.org/10.1093/bioinformatics/bty855DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6499410PMC
May 2019

Experience of psychogenic nonepileptic seizures in the Canadian league against epilepsy: A survey describing current practices by neurologists and epileptologists.

Seizure 2018 Oct 2;61:227-233. Epub 2018 Sep 2.

Saskatchewan Epilepsy Program, College of Medicine, Division of Neurology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada. Electronic address:

Purpose: Psychogenic nonepileptic seizures (PNES) are one of the most common differential diagnoses of epilepsy. Our objective is to describe current medical care in Canada and identify patterns of practice and service gaps.

Methods: In 2015, a 36-question survey was sent via email to the 131 members of the Canadian League Against Epilepsy. The questions were designed after literature review and discussion with the ILAE PNES Task Force. Questions were separated into 5 sections: 1) the role of the respondent and their exposure to PNES, 2) diagnostic methods, 3) management of PNES, 4) etiological factors, and 5) problems accessing health care.

Results: Sixty-two questionnaires were analyzed (response rate: 47%). Most respondents were epileptologists (76%). The majority of respondents personally diagnosed PNES and communicated the diagnosis to the patient, but only 55% provided follow-up within their practice and only 50% recommended or arranged treatment. Many (35%) were either unfamiliar with the diagnosis of PNES or inexperienced in arranging or offering treatment. Most (79%) provided follow-up to patients with concomitant epilepsy, but when PNES was the sole diagnosis follow-up rates were low. Although 84% of respondents felt that individualized psychological therapy was the most effective treatment, 40% of patients were not referred to psychotherapy and in most cases availability such therapy was low (30-60%).

Conclusions: Canadian health professionals' understanding of PNES mostly reflects current international expert opinion. Once diagnosis is made however, the majority of patients are discharged from neurological services without appropriate psychological care.
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http://dx.doi.org/10.1016/j.seizure.2018.08.025DOI Listing
October 2018

Seizure outcome in pediatric medically refractory temporal lobe epilepsy surgery: selective amygdalohippocampectomy versus anterior temporal lobectomy.

J Neurosurg Pediatr 2018 09 22;22(3):276-282. Epub 2018 Jun 22.

4Pediatric Neurology, University of Alberta, Edmonton, Alberta, Canada.

OBJECTIVE The aim of this study was to investigate long-term seizure outcome, rate of reoperation, and postoperative neuropsychological performance following selective amygdalohippocampectomy (SelAH) or anterior temporal lobectomy (ATL) in pediatric patients with medically refractory temporal lobe epilepsy (TLE). METHODS The authors performed a retrospective review of cases of medically refractory pediatric TLE treated initially with either SelAH or ATL. Standardized pre- and postoperative evaluation included seizure charting, surface and long-term video-electroencephalography, 1.5-T MRI, and neuropsychological testing. RESULTS A total of 79 patients treated initially with SelAH (n = 18) or ATL (n = 61) were included in this study, with a mean follow-up of 5.3 ± 4 years (range 1-16 years). The patients' average age at initial surgery was 10.6 ± 5 years, with an average surgical delay of 5.7 ± 4 years between seizure onset and surgery. Seizure freedom (Engel I) following the initial operation was significantly more likely following ATL (47/61, 77%) than SelAH (8/18, 44%; p = 0.017, Fisher's exact test). There was no statistically significant difference in the proportion of patients with postoperative neuropsychological deficits following SelAH (8/18, 44%) or ATL (21/61, 34%). However, reoperation was significantly more likely following SelAH (8/18, 44%) than after ATL (7/61, 11%; p = 0.004) and was more likely to result in Engel I outcome for ATL after failed SelAH (7/8, 88%) than for posterior extension after failed ATL (1/7, 14%; p = 0.01). Reoperation was well tolerated without significant neuropsychological deterioration. Ultimately, including 15 reoperations, 58 of 79 (73%) patients were free from disabling seizures at the most recent follow-up. CONCLUSIONS SelAH among pediatric patients with medically refractory unilateral TLE yields significantly worse rates of seizure control compared with ATL. Reoperation is significantly more likely following SelAH, is not associated with incremental neuropsychological deterioration, and frequently results in freedom from disabling seizures. These results are significant in that they argue against using SelAH for pediatric TLE surgery.
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http://dx.doi.org/10.3171/2018.4.PEDS17607DOI Listing
September 2018

A Public Database of Memory and Naive B-Cell Receptor Sequences.

PLoS One 2016 11;11(8):e0160853. Epub 2016 Aug 11.

Adaptive Biotechnologies, Seattle, United States of America.

The vast diversity of B-cell receptors (BCR) and secreted antibodies enables the recognition of, and response to, a wide range of epitopes, but this diversity has also limited our understanding of humoral immunity. We present a public database of more than 37 million unique BCR sequences from three healthy adult donors that is many fold deeper than any existing resource, together with a set of online tools designed to facilitate the visualization and analysis of the annotated data. We estimate the clonal diversity of the naive and memory B-cell repertoires of healthy individuals, and provide a set of examples that illustrate the utility of the database, including several views of the basic properties of immunoglobulin heavy chain sequences, such as rearrangement length, subunit usage, and somatic hypermutation positions and dynamics.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0160853PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4981401PMC
August 2017

Dynamics of the cytotoxic T cell response to a model of acute viral infection.

J Virol 2015 Apr 4;89(8):4517-26. Epub 2015 Feb 4.

Adaptive Biotechnologies, Seattle, Washington, USA Fred Hutchinson Cancer Research Center, Seattle, Washington, USA

Unlabelled: A detailed characterization of the dynamics and breadth of the immune response to an acute viral infection, as well as the determinants of recruitment to immunological memory, can greatly contribute to our basic understanding of the mechanics of the human immune system and can ultimately guide the design of effective vaccines. In addition to neutralizing antibodies, T cells have been shown to be critical for the effective resolution of acute viral infections. We report the first in-depth analysis of the dynamics of the CD8(+) T cell repertoire at the level of individual T cell clonal lineages upon vaccination of human volunteers with a single dose of YF-17D. This live attenuated yellow fever virus vaccine yields sterile, long-term immunity and has been previously used as a model to understand the immune response to a controlled acute viral infection. We identified and enumerated unique CD8(+) T cell clones specifically induced by this vaccine through a combined experimental and statistical approach that included high-throughput sequencing of the CDR3 variable region of the T cell receptor β-chain and an algorithm that detected significantly expanded T cell clones. This allowed us to establish that (i) on average, ∼ 2,000 CD8(+) T cell clones were induced by YF-17D, (ii) 5 to 6% of the responding clones were recruited to long-term memory 3 months postvaccination, (iii) the most highly expanded effector clones were preferentially recruited to the memory compartment, and (iv) a fraction of the YF-17D-induced clones could be identified from peripheral blood lymphocytes solely by measuring clonal expansion.

Importance: The exhaustive investigation of pathogen-induced effector T cells is essential to accurately quantify the dynamics of the human immune response. The yellow fever vaccine (YFV) has been broadly used as a model to understand how a controlled, self-resolving acute viral infection induces an effective and long-term protective immune response. Here, we extend this previous work by reporting the identity of activated effector T cell clones that expand in response to the YFV 2 weeks postvaccination (as defined by their unique T cell receptor gene sequence) and by tracking clones that enter the memory compartment 3 months postvaccination. This is the first study to use high-throughput sequencing of immune cells to characterize the breadth of the antiviral effector cell response and to determine the contribution of unique virus-induced clones to the long-lived memory T cell repertoire. Thus, this study establishes a benchmark against which future vaccines can be compared to predict their efficacy.
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http://dx.doi.org/10.1128/JVI.03474-14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4442358PMC
April 2015

Correlations between Limbic White Matter and Cognitive Function in Temporal-Lobe Epilepsy, Preliminary Findings.

Front Aging Neurosci 2014 30;6:142. Epub 2014 Jun 30.

Division of Neurology, University of Alberta , Edmonton, AB , Canada.

The limbic system is presumed to have a central role in cognitive performance, in particular memory. The purpose of this study was to investigate the relationship between limbic white matter microstructure and neuropsychological function in temporal-lobe epilepsy (TLE) patients using diffusion tensor imaging (DTI). Twenty-one adult TLE patients, including 7 non-lesional (nlTLE) and 14 with unilateral mesial temporal sclerosis (uTLE), were studied with both DTI and hippocampal T2 relaxometry. Correlations were performed between fractional anisotropy (FA) of the bilateral fornix and cingulum, hippocampal T2, neuropsychological tests. Positive correlations were observed in the whole group for the left fornix and processing speed index. In contrast, memory tests did not show significant correlations with DTI findings. Subgroup analysis demonstrated an association between the left fornix and processing speed in nlTLE but not uTLE. No correlations were observed between hippocampal T2 and test scores in either the TLE group as a whole or after subgroup analysis. Our findings suggest that integrity of the left fornix specifically is an important anatomical correlate of cognitive function in TLE patients, in particular patients with nlTLE.
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http://dx.doi.org/10.3389/fnagi.2014.00142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4075095PMC
July 2014

Circulating cell-free DNA enables noninvasive diagnosis of heart transplant rejection.

Sci Transl Med 2014 Jun;6(241):241ra77

Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.

Monitoring allograft health is an important component of posttransplant therapy. Endomyocardial biopsy is the current gold standard for cardiac allograft monitoring but is an expensive and invasive procedure. Proof of principle of a universal, noninvasive diagnostic method based on high-throughput screening of circulating cell-free donor-derived DNA (cfdDNA) was recently demonstrated in a small retrospective cohort. We present the results of a prospective cohort study (65 patients, 565 samples) that tested the utility of cfdDNA in measuring acute rejection after heart transplantation. Circulating cell-free DNA was purified from plasma and sequenced (mean depth, 1.2 giga-base pairs) to quantify the fraction of cfdDNA. Through a comparison with endomyocardial biopsy results, we demonstrate that cfdDNA enables diagnosis of acute rejection after heart transplantation, with an area under the receiver operating characteristic curve of 0.83 and sensitivity and specificity that are comparable to the intrinsic performance of the biopsy itself. This noninvasive genome transplant dynamics approach is a powerful and informative method for routine monitoring of allograft health without incurring the risk, discomfort, and expense of an invasive biopsy.
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http://dx.doi.org/10.1126/scitranslmed.3007803DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4326260PMC
June 2014

A follow-up study of cognitive function in young adults who had resective epilepsy surgery in childhood.

Epilepsy Behav 2014 Mar 7;32:79-83. Epub 2014 Feb 7.

Division of Neurology, Children's Hospital of Eastern Ontario, Ottawa, ON K1H 8L1, Canada.

This study examined cognitive function in young adults who had epilepsy surgery in childhood. Thirty-seven individuals with medically intractable epilepsy with onset at 16 years or younger who had resective epilepsy surgery at least two years in the past (mean follow-up duration of 8.5 years) were assessed; of these, 13 had seizures within the year prior to the study, and the remainder had none. A comparison group of 16 individuals with childhood-onset intractable epilepsy who had not had surgery, all of whom had experienced at least one seizure in the past 12 months, was also included. The cognitive tests included measures of vocabulary, visuoconstructive ability, memory, and concept formation. Group differences were found only for the vocabulary and verbal memory tests, with the surgical group with seizures having the lowest performance. A subset of the surgical patients had preoperative data available on comparable tests, allowing for an examination of performance over time. Vocabulary scores were higher at follow-up, a finding which was present irrespective of seizure status. The results suggest that after epilepsy surgery in childhood or adolescence, few improvements in cognitive skills related to surgery or seizure outcome are to be expected.
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http://dx.doi.org/10.1016/j.yebeh.2014.01.006DOI Listing
March 2014

Feasibility of computerized adaptive testing for collection of patient-reported outcomes after inpatient rehabilitation.

Arch Phys Med Rehabil 2014 May 16;95(5):882-91. Epub 2014 Jan 16.

Department of Outcome Measurement Systems and Analysis, Rehabilitation Institute of Chicago, Chicago, IL.

Objective: To evaluate the feasibility of computer adaptive testing (CAT) using an Internet or telephone interface to collect patient-reported outcomes after inpatient rehabilitation and to examine patient characteristics associated with completion of the CAT-administered measure and mode of administration.

Design: Prospective cohort study of patients contacted approximately 4 weeks after discharge from inpatient rehabilitation. Patients selected an Internet or telephone interface.

Setting: Rehabilitation hospital.

Participants: Patients (N=674) with diagnoses of neurologic, orthopedic, or medically complex conditions.

Interventions: None.

Main Outcome Measure: CAT version of the Community Participation Indicators (CAT-CPI).

Results: From an eligible pool of 3221 patients, 674 (21%) agreed to complete the CAT-CPI. Patients who agreed to complete the CAT-CPI were younger and reported slightly higher satisfaction with overall care than those who did not participate. Among these patients, 231 (34%) actually completed the CAT-CPI; 141 (61%) selected telephone administration, and 90 (39%) selected Internet administration. Decreased odds of completing the CAT-CPI were associated with black and other race; stroke, brain injury, or orthopedic and other impairments; and being a Medicaid beneficiary, whereas increased odds of completing the CAT-CPI were associated with longer length of stay and higher discharge FIM cognition measure. Decreased odds of choosing Internet administration were associated with younger age, retirement status, and being a woman, whereas increased odds of choosing Internet administration were associated with higher discharge FIM motor measure.

Conclusions: CAT administration by Internet and telephone has limited feasibility for collecting postrehabilitation outcomes for most rehabilitation patients, but it is feasible for a subset of patients. Providing alternative ways of answering questions helps assure that a larger proportion of patients will respond.
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http://dx.doi.org/10.1016/j.apmr.2013.12.024DOI Listing
May 2014

Inflammasome induction in Rasmussen's encephalitis: cortical and associated white matter pathogenesis.

J Neuroinflammation 2013 Dec 13;10:152. Epub 2013 Dec 13.

Department of Psychiatry, University of Alberta, Edmonton, AB, Canada.

Background: Rasmussen's encephalitis (RE) is an inflammatory encephalopathy of unknown cause defined by seizures with progressive neurological disabilities. Herein, the pathogenesis of RE was investigated focusing on inflammasome activation in the brain.

Methods: Patients with RE at the University of Alberta, Edmonton, AB, Canada, were identified and analyzed by neuroimaging, neuropsychological, molecular, and pathological tools. Primary human microglia, astrocytes, and neurons were examined using RT-PCR, enzyme-linked immunosorbent assay (ELISA), and western blotting.

Results: Four patients with RE were identified at the University of Alberta. Magnetic resonance imaging (MRI) disclosed increased signal intensities in cerebral white matter adjacent to cortical lesions of RE patients, accompanied by a decline in neurocognitive processing speed (P <0.05). CD3ϵ, HLA-DRA, and TNFα together with several inflammasome-associated genes (IL-1β, IL-18, NLRP1, NLRP3, and CASP1) showed increased transcript levels in RE brains compared to non-RE controls (n = 6; P <0.05). Cultured human microglia displayed expression of inflammasome-associated genes and responded to inflammasome activators by releasing IL-1β, which was inhibited by the caspase inhibitor, zVAD-fmk. Major histocompatibility complex (MHC) class II, IL-1β, caspase-1, and alanine/serine/cysteine (ASC) immunoreactivity were increased in RE brain tissues, especially in white matter myeloid cells, in conjunction with mononuclear cell infiltration and gliosis. Neuroinflammation in RE brains was present in both white matter and adjacent cortex with associated induction of inflammasome components, which was correlated with neuroimaging and neuropsychological deficits.

Conclusion: Inflammasome activation likely contributes to the disease process underlying RE and offers a mechanistic target for future therapeutic interventions.
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http://dx.doi.org/10.1186/1742-2094-10-152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3881507PMC
December 2013

Temporal response of the human virome to immunosuppression and antiviral therapy.

Cell 2013 Nov;155(5):1178-87

Departmets of Bioengineering and Applied Physics, Stanford University and the Howard Hughes Medical Institute, Stanford, CA 94305, USA.

There are few substantive methods to measure the health of the immune system, and the connection between immune strength and the viral component of the microbiome is poorly understood. Organ transplant recipients are treated with posttransplant therapies that combine immunosuppressive and antiviral drugs, offering a window into the effects of immune modulation on the virome. We used sequencing of cell-free DNA in plasma to investigate drug-virome interactions in a cohort of organ transplant recipients (656 samples, 96 patients) and find that antivirals and immunosuppressants strongly affect the structure of the virome in plasma. We observe marked virome compositional dynamics at the onset of the therapy and find that the total viral load increases with immunosuppression, whereas the bacterial component of the microbiome remains largely unaffected. The data provide insight into the relationship between the human virome, the state of the immune system, and the effects of pharmacological treatment and offer a potential application of the virome state to predict immunocompetence.
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http://dx.doi.org/10.1016/j.cell.2013.10.034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4098717PMC
November 2013

CASE REPORT Anomalies Associated With Congenitally Corrected Transposition of Great Arteries: Expect the Unexpected.

Eplasty 2013 24;13:e6. Epub 2013 Jan 24.

Departments of Internal Medicine.

Objective: Congenitally corrected transposition of great arteries (CCTGA) is characterized by atrioventricular and ventriculoarterial discordance. Characterizations of these anomalies are important because they may influence surgical approach and management.

Methods: We present a case of newly diagnosed CCTGA at the age of 50. He presented with sudden onset of shortness of breath for the first time and was diagnosed with CCTGA. Echocardiogram, magnetic resonance imaging, and cardiac catheterization were utilized to elucidate the pathology.

Results: Intraoperatively, patient's CCTGA and ventricularization of the right ventricle were confirmed. The severe systemic atrioventricular valve regurgitation was replaced with a bioprosthetic valve (Medtronic Mosaic No. 29) with placement of epicardial ventricular leads for possible future placement of automatic implantable cardioverter defibrillators. Pathology report confirmed a degeneration of the systemic atrioventricular valve.

Conclusions: Significant coronary artery anomalies have also been described in literature with CCTGA. The variances encountered in this case are excellent examples of the intricacies associated in diagnosis and surgical care in patients with CCTGA.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3556635PMC
February 2013

Depth electrodes in pediatric epilepsy surgery.

Can J Neurol Sci 2013 Jan;40(1):48-55

Comprehensive Epilepsy Program, University of Alberta Hospital, Edmonton, Alberta, Canada.

Background: The surgical removal of the epileptogenic zone in medically intractable seizures depends on accurate localization to minimize the neurological sequelae and prevent future seizures. To date, few studies have demonstrated the use of depth electrodes in a pediatric epilepsy population. Here, we report our study of pediatric epilepsy patients at our epilepsy center who were successfully operated for medically intractable seizures following the use of intracranial depth electrodes. In addition, we detail three individuals with distinct clinical scenarios in which depth electrodes were helpful and describe our technical approach to implantation and surgery.

Methods: We retrospectively reviewed 18 pediatric epilepsy patients requiring depth electrode studies who presented at the University of Alberta Comprehensive Epilepsy Program between 1999 and 2010 with medically intractable epilepsy. Patients underwent cortical resection following depth electrode placement according to the Comprehensive Epilepsy Program surgical protocols after failure of surface electroencephalogram and magnetic resonance imaging to localize ictal onset zone.

Result: The ictal onset zone was successfully identified in all 18 patients. Treatment of all surgical patients resulted in successful seizure freedom (Engel class I) without neurological complications.

Conclusion: Intracranial depth electrode use is safe and able to provide sufficient information for the identification of the epileptogenic zone in pediatric epilepsy patients previously not considered for epilepsy surgery.
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http://dx.doi.org/10.1017/s0317167100012944DOI Listing
January 2013

Clonal evolution of preleukemic hematopoietic stem cells precedes human acute myeloid leukemia.

Sci Transl Med 2012 Aug;4(149):149ra118

Program in Cancer Biology, Cancer Institute, Institute for Stem Cell Biology and Regenerative Medicine, and Ludwig Center, Stanford University School of Medicine, Palo Alto, CA 94305, USA.

Given that most bone marrow cells are short-lived, the accumulation of multiple leukemogenic mutations in a single clonal lineage has been difficult to explain. We propose that serial acquisition of mutations occurs in self-renewing hematopoietic stem cells (HSCs). We investigated this model through genomic analysis of HSCs from six patients with de novo acute myeloid leukemia (AML). Using exome sequencing, we identified mutations present in individual AML patients harboring the FLT3-ITD (internal tandem duplication) mutation. We then screened the residual HSCs and detected some of these mutations including mutations in the NPM1, TET2, and SMC1A genes. Finally, through single-cell analysis, we determined that a clonal progression of multiple mutations occurred in the HSCs of some AML patients. These preleukemic HSCs suggest the clonal evolution of AML genomes from founder mutations, revealing a potential mechanism contributing to relapse. Such preleukemic HSCs may constitute a cellular reservoir that should be targeted therapeutically for more durable remissions.
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http://dx.doi.org/10.1126/scitranslmed.3004315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4045621PMC
August 2012

Quality of life in young adults who underwent resective surgery for epilepsy in childhood.

Epilepsia 2012 Sep 19;53(9):1577-86. Epub 2012 Jul 19.

Division of Neurology, The Hospital for Sick Children, Toronto, Ontario, Canada.

Purpose: This study investigated quality of life (QOL) in young adults who had undergone epilepsy surgery before the age of 16 years. The contribution to QOL of seizure status in the prior year, sex, number of antiepileptic drugs, and mood were evaluated.

Methods: Sixty-nine young adults who had undergone surgery were subdivided into those who were seizure-free in the past year (n = 38) and those who had seizures (n = 31) in that time. A nonsurgical comparison group of young adults (n = 29) with childhood-onset medically intractable epilepsy was also studied. All groups completed measures of QOL and mood.

Key Findings: After accounting for mood, sex, and number of antiepileptic drugs, the seizure-free group reported better cognitive and physical function and overall QOL, experienced less seizure worry, and had better self-perception. Mood was the most consistently predictive covariate, and was independently predictive of many aspects of QOL.

Significance: Seizure freedom associated with surgery in childhood is associated with improved QOL in certain domains. Findings highlight the importance of mood in determining self-perception of QOL.
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http://dx.doi.org/10.1111/j.1528-1167.2012.03594.xDOI Listing
September 2012

Cortical tubers, cognition, and epilepsy in tuberous sclerosis.

Pediatr Neurol 2011 May;44(5):328-32

Comprehensive Epilepsy Program, University of Alberta Hospital, Edmonton, Alberta, Canada.

Tuberous sclerosis complex is an autosomal-dominant genetic disorder characterized by hamartomatous growth in various organs. Patients who have this disorder exhibit a high rate of epilepsy and cognitive problems. We investigated number of tubers, location, seizure types, and cognitive outcome, and we analyzed the relationships among them in our tuberous sclerosis patients in the Comprehensive Epilepsy Program at the University of Alberta. We also examined the seizure outcome after tuber resection. Our study cohort included 24 patients with tuberous sclerosis complex. We obtained seizure history, electroencephalogram, and neuropsychologic parameters. Magnetic resonance imaging was used to examine tuber numbers and locations. Ten patients underwent surgical removal of tubers responsible for intractable epilepsy. A negative correlation was found between the number of tubers and intelligent quotient score. Epilepsy surgery led to freedom from seizures in this patient group. We demonstrated that the total number and location of cortical tubers play a significant role in the extent of mental retardation in patients with tuberous sclerosis complex. In addition, patients with intractable seizures and well-defined epileptic focus had excellent surgical outcome.
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http://dx.doi.org/10.1016/j.pediatrneurol.2011.01.001DOI Listing
May 2011

Universal noninvasive detection of solid organ transplant rejection.

Proc Natl Acad Sci U S A 2011 Apr 28;108(15):6229-34. Epub 2011 Mar 28.

Department of Applied Physics, Stanford University, Stanford, The Howard Hughes Medical Institute, CA 94305, USA.

It is challenging to monitor the health of transplanted organs, particularly with respect to rejection by the host immune system. Because transplanted organs have genomes that are distinct from the recipient's genome, we used high throughput shotgun sequencing to develop a universal noninvasive approach to monitoring organ health. We analyzed cell-free DNA circulating in the blood of heart transplant recipients and observed significantly increased levels of cell-free DNA from the donor genome at times when an endomyocardial biopsy independently established the presence of acute cellular rejection in these heart transplant recipients. Our results demonstrate that cell-free DNA can be used to detect an organ-specific signature that correlates with rejection, and this measurement can be made on any combination of donor and recipient. This noninvasive test holds promise for replacing the endomyocardial biopsy in heart transplant recipients and may be applicable to other solid organ transplants.
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http://dx.doi.org/10.1073/pnas.1013924108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3076856PMC
April 2011

Self-reported symptoms of psychological well-being in young adults who underwent resective epilepsy surgery in childhood.

Epilepsia 2011 May 22;52(5):891-9. Epub 2011 Mar 22.

University of Toronto Mississauga, Mississauga, Ontario, Canada.

Purpose: This study investigated the relationship of childhood resective surgery for lesional epilepsy and recent seizure history on self-reported symptoms of mood and psychological distress in young adults (aged 18-30).

Methods: Ninety-eight individuals with epilepsy of childhood onset were divided into three groups: a seizure-free surgical group (n = 39), a surgical group still experiencing seizures (n = 31), and a nonsurgical epilepsy comparison group (n = 28). Participants completed two standardized questionnaires about current mood state and psychological and psychiatric symptoms: the Profile of Mood States (POMS) and the Symptom Checklist-90 Revised (SCL-90R).

Key Findings: Forty-eight percent of all participants reported a history of psychological problems. The percentage of the seizure-free surgical group who met the SCL-90R criteria for current clinically significant distress was statistically less than in the other groups. Those who were seizure free also reported significantly fewer total symptoms on the SCL-90R. The current number of antiepileptic medications was related to scores on a number of the scales.

Significance: These results provide modest support for the contention that seizure freedom after pediatric epilepsy surgery is associated with reduced risk for psychological distress during early adulthood.
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http://dx.doi.org/10.1111/j.1528-1167.2011.03026.xDOI Listing
May 2011

Left atrial appendage lipoma: an unusual location of cardiac lipomas.

Echocardiography 2011 May 17;28(5):E91-3. Epub 2011 Feb 17.

Department of Cardiology, Staten Island University Hospital, New York, New York, USA.

Cardiac lipomas are benign neoplasms of the heart and accounts for 8.4% of all primary tumors. They can occur sporadically at any age with no sex preference. The tumor originates mostly in the subendocardium and subepicardium but very rarely within the myocardium. Clinically this tumor is asymptomatic and found incidentally in the vast majority of cases. On occasion large lesions can lead to mechanical obstruction and pericardial effusions if located in the epicardium. Although lipomas can occur at different atrial or ventricular locations, it was never reported at the level of the left atrial appendage (LAA). Usually a mass in the LAA represents a thrombus, however there are few case reports of LAA tumors mainly representing fibroelastomas, myxomas, hemangiomas, and malignant tumors. To our knowledge there are no reported cases of left atrial appendage lipomas (LAAL) in the medical literature. We report the first case of LAAL discovered incidentally on transesophageal echocardiogram during off pump coronary artery bypass grafting.
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http://dx.doi.org/10.1111/j.1540-8175.2010.01334.xDOI Listing
May 2011

Intelligence quotient is not affected by epilepsy surgery in childhood.

Pediatr Neurol 2011 Feb;44(2):117-21

Comprehensive Epilepsy Program, University of Alberta Hospital, Edmonton, Alberta, Canada.

Epilepsy surgery is known to help children with intractable seizures. The effect of epilepsy surgery itself on cognition in childhood is less well studied. We report our experience at the University of Alberta Hospital on the effects of epilepsy surgery on cognition. All children undergoing epilepsy surgery at the Comprehensive Epilepsy Program from 1990-2005 were examined. Sixty-seven patients received both preoperative and postoperative neuropsychologic evaluations. We compared verbal, performance, and full scale intelligent quotients and the Child Behavioral Checklist preoperatively and postoperatively. Forty-eight patients demonstrated excellent surgical outcomes, with significant reductions in disabling seizures. Overall, no significant change occurred in neuropsychologic parameters examined after surgery. Epilepsy surgery in childhood offers excellent surgical outcomes for seizure control, and does not adversely affect intelligence quotient.
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http://dx.doi.org/10.1016/j.pediatrneurol.2010.10.011DOI Listing
February 2011