RESUMO
Over the past 10 years, the drive to improve outcomes from epilepsy surgery has stimulated widespread interest in methods to quantitatively guide epilepsy surgery from intracranial EEG (iEEG). Many patients fail to achieve seizure freedom, in part due to the challenges in subjective iEEG interpretation. To address this clinical need, quantitative iEEG analytics have been developed using a variety of approaches, spanning studies of seizures, interictal periods, and their transitions, and encompass a range of techniques including electrographic signal analysis, dynamical systems modeling, machine learning and graph theory. Unfortunately, many methods fail to generalize to new data and are sensitive to differences in pathology and electrode placement. Here, we critically review selected literature on computational methods of identifying the epileptogenic zone from iEEG. We highlight shared methodological challenges common to many studies in this field and propose ways that they can be addressed. One fundamental common pitfall is a lack of open-source, high-quality data, which we specifically address by sharing a centralized high-quality, well-annotated, multicentre dataset consisting of >100 patients to support larger and more rigorous studies. Ultimately, we provide a road map to help these tools reach clinical trials and hope to improve the lives of future patients.
Assuntos
Eletrocorticografia , Epilepsia , Humanos , Eletrocorticografia/métodos , Eletroencefalografia/métodos , Epilepsia/cirurgia , Epilepsia/patologia , Convulsões/diagnóstico , Convulsões/cirurgia , Projetos de PesquisaRESUMO
OBJECTIVE: Evaluate the independent effect of age on baseline neurocognitive performance. STUDY DESIGN: Baseline ImPACT scores from tests taken by 7454 athletes aged 12-22 from 2009 to 2019 were split into three age cohorts: 12-14 years (3244), 15-17 years (3732), and 18-22 years (477). Linear regression analyses were used to evaluate the effect of age on ImPACT composite scores while controlling for demographic differences, medication-use, and symptom burden. Significance values have been set at p < 0.05. RESULTS: Linear regression analyses demonstrated that increased age does not significantly affect symptom score (ß = 0.06, p = 0.54) but does improve impulse control (ß = -0.45, p < 0.0001), verbal memory (ß = 0.23, p = 0.03), visualmotor (ß = 0.77, p < 0.0001), and reaction time (ß = -0.008, p < 0.0001) scores. However, age did not have an effect on visual memory scores (ß = -0.25, p = 0.07). CONCLUSIONS: Age was shown to be an independent modifier of impulse control, verbal memory, visual motor, and reaction time scores but not visual memory or symptom scores. This underscores the previous literature showing developmental differences as age increases among the adolescent athlete population. This data also indicates the need for repeat neurocognitive baseline testing every other year as baseline scoring is likely to change as athletes become older.
Assuntos
Traumatismos em Atletas , Concussão Encefálica , Adolescente , Humanos , Traumatismos em Atletas/diagnóstico , Concussão Encefálica/psicologia , Testes Neuropsicológicos , Tempo de Reação , Atletas/psicologiaRESUMO
Epigenetic clocks allow us to accurately predict the age and future health of individuals based on the methylation status of specific CpG sites in the genome and are a powerful tool to measure the effectiveness of longevity interventions. There is a growing need for methods to efficiently construct epigenetic clocks. The most common approach is to create clocks using elastic net regression modelling of all measured CpG sites, without first identifying specific features or CpGs of interest. The addition of feature selection approaches provides the opportunity to optimise the identification of predictive CpG sites. Here, we apply novel feature selection methods and combinatorial approaches including newly adapted neural networks, genetic algorithms, and 'chained' combinations. Human whole blood methylation data of ~470,000 CpGs was used to develop clocks that predict age with R2 correlation scores of greater than 0.73, the most predictive of which uses 35 CpG sites for a R2 correlation score of 0.87. The five most frequent sites across all clocks were modelled to build a clock with a R2 correlation score of 0.83. These two clocks are validated on two external datasets where they maintain excellent predictive accuracy. When compared with three published epigenetic clocks (Hannum, Horvath, Weidner) also applied to these validation datasets, our clocks outperformed all three models. We identified gene regulatory regions associated with selected CpGs as possible targets for future aging studies. Thus, our feature selection algorithms build accurate, generalizable clocks with a low number of CpG sites, providing important tools for the field.
Assuntos
Metilação de DNA , Epigênese Genética , Envelhecimento/genética , Ilhas de CpG/genética , Metilação de DNA/genética , Epigênese Genética/genética , Epigenômica , Humanos , Longevidade/genéticaRESUMO
Over 15 million epilepsy patients worldwide have drug-resistant epilepsy. Successful surgery is a standard of care treatment but can only be achieved through complete resection or disconnection of the epileptogenic zone, the brain region(s) where seizures originate. Surgical success rates vary between 20% and 80%, because no clinically validated biological markers of the epileptogenic zone exist. Localizing the epileptogenic zone is a costly and time-consuming process, which often requires days to weeks of intracranial EEG (iEEG) monitoring. Clinicians visually inspect iEEG data to identify abnormal activity on individual channels occurring immediately before seizures or spikes that occur interictally (i.e. between seizures). In the end, the clinical standard mainly relies on a small proportion of the iEEG data captured to assist in epileptogenic zone localization (minutes of seizure data versus days of recordings), missing opportunities to leverage these largely ignored interictal data to better diagnose and treat patients. IEEG offers a unique opportunity to observe epileptic cortical network dynamics but waiting for seizures increases patient risks associated with invasive monitoring. In this study, we aimed to leverage interictal iEEG data by developing a new network-based interictal iEEG marker of the epileptogenic zone. We hypothesized that when a patient is not clinically seizing, it is because the epileptogenic zone is inhibited by other regions. We developed an algorithm that identifies two groups of nodes from the interictal iEEG network: those that are continuously inhibiting a set of neighbouring nodes ('sources') and the inhibited nodes themselves ('sinks'). Specifically, patient-specific dynamical network models were estimated from minutes of iEEG and their connectivity properties revealed top sources and sinks in the network, with each node being quantified by source-sink metrics. We validated the algorithm in a retrospective analysis of 65 patients. The source-sink metrics identified epileptogenic regions with 73% accuracy and clinicians agreed with the algorithm in 93% of seizure-free patients. The algorithm was further validated by using the metrics of the annotated epileptogenic zone to predict surgical outcomes. The source-sink metrics predicted outcomes with an accuracy of 79% compared to an accuracy of 43% for clinicians' predictions (surgical success rate of this dataset). In failed outcomes, we identified brain regions with high metrics that were untreated. When compared with high frequency oscillations, the most commonly proposed interictal iEEG feature for epileptogenic zone localization, source-sink metrics outperformed in predictive power (by a factor of 1.2), suggesting they may be an interictal iEEG fingerprint of the epileptogenic zone.
Assuntos
Epilepsia , Convulsões , Humanos , Estudos Retrospectivos , Eletrocorticografia/métodos , Epilepsia/diagnóstico , Epilepsia/cirurgia , BiomarcadoresRESUMO
OBJECTIVE/ BACKGROUND: Chronic headaches and sports-related concussions are among the most common neurological morbidities in adolescents and young adults. Given that the two can overlap in presentation, studying the effects of one on another has proven difficult. In this longitudinal study, we sought to assess the relationship between chronic headaches and concussions, analyzing the role of historic concussions on chronic headaches, as well as that of premorbid headaches on future concussion incidence, severity, and recovery. METHODS: This multi-center, longitudinal cohort study followed 7,453 youth athletes who were administered demographic and clinical surveys as well as a total of 25,815 Immediate Post-concussion Assessment and Cognitive Testing (ImPACT) assessments between 2009 and 2019. ImPACT was administered at baseline. Throughout the season concussions were examined by physicians and athletic trainers, followed by re-administration of ImPACT post-injury (PI), and at follow-up (FU), a median of 7 days post-concussion. Concussion incidence was calculated as the total number of concussions per patient years. Concussion severity and recovery were calculated as standardized deviations from baseline to PI and then FU in Symptom Score and the four neurocognitive composite ImPACT scores: Verbal Memory, Visual Memory, Processing Speed, and Reaction Time. Data were collected prospectively in a well-organized electronic format supervised by a national research-oriented organization with rigorous quality assurance. Analysis was preformed retrospectively. RESULTS: Of the eligible athletes, 1,147 reported chronic headaches (CH) at the start of the season and 6,306 reported no such history (NH). Median age of the cohort was 15.4 ± 1.6 years, and students were followed for an average of 1.3 ± 0.6 years. A history of concussions (OR 2.31, P < 0.0001) was associated with CH. Specifically, a greater number of past concussions (r2 = 0.95) as well as concussions characterized by a loss of consciousness (P < 0.0001) were associated with more severe headache burden. The CH cohort had a greater future incidence of concussion than the NH cohort (55.6 vs. 43.0 per 100 patient-years, P < 0.0001). However, multivariate analysis controlling for demographic, clinical, academic, and sports-related variables yielded no such effect (OR 0.99, P = 0.85). On multivariable analysis the CH cohort did have greater deviations from baseline to PI and FU in Symptom Score (PI OR per point 1.05, P = 0.01, FU OR per point 1.11, P = 0.04) and Processing Speed (OR per point 1.08, P = 0.04), suggesting greater concussion severity and impaired symptomatic recovery as compared to the NH cohort. CONCLUSION: A history of concussions was a significant contributor to headache burden among American adolescents and young adults. However, those with chronic headaches were not more likely to be diagnosed with a concussion, despite presenting with more severe concussions that had protracted recovery. Our findings not only suggest the need for conservative management among youth athletes with chronic headaches, they also indicate a potential health care gap in this population, in that those with chronic headaches may be referred for concussion diagnosis and management at lower rates than those with no such comorbidity.
Assuntos
Traumatismos em Atletas , Concussão Encefálica , Transtornos da Cefaleia , Adulto Jovem , Humanos , Adolescente , Estados Unidos/epidemiologia , Concussão Encefálica/complicações , Concussão Encefálica/epidemiologia , Concussão Encefálica/diagnóstico , Estudos Longitudinais , Traumatismos em Atletas/complicações , Traumatismos em Atletas/epidemiologia , Estudos Retrospectivos , Cefaleia/epidemiologia , Cefaleia/complicações , Atletas , Testes Neuropsicológicos , Transtornos da Cefaleia/complicaçõesRESUMO
Numerous studies have shown that epigenetic age-an individual's degree of aging based on patterns of DNA methylation-can be computed and is associated with an array of factors including diet, lifestyle, genetics, and disease. One can expect that still further associations will emerge with additional aging research, but to what end? Prediction of age was an important first step, but-in our view-the focus must shift from chasing increasingly accurate age computations to understanding the links between the epigenome and the mechanisms and physiological changes of aging. Here, we outline emerging areas of epigenetic aging research that prioritize biological understanding and clinical application. First, we survey recent progress in epigenetic clocks, which are beginning to predict not only chronological age but aging outcomes such as all-cause mortality and onset of disease, or which integrate aging signals across multiple biological processes. Second, we discuss research that exemplifies how investigation of the epigenome is building a mechanistic theory of aging and informing clinical practice. Such examples include identifying methylation sites and the genes most strongly predictive of aging-a subset of which have shown strong potential as biomarkers of neurodegenerative disease and cancer; relating epigenetic clock predictions to hallmarks of aging; and using longitudinal studies of DNA methylation to characterize human disease, resulting in the discovery of epigenetic indications of type 1 diabetes and the propensity for psychotic experiences.
Assuntos
Epigênese Genética , Doenças Neurodegenerativas , Envelhecimento/genética , Biomarcadores , Ilhas de CpG , Metilação de DNA , Epigenômica , Humanos , Doenças Neurodegenerativas/genéticaRESUMO
BACKGROUND: High altitude may affect concussion, but prior studies are limited . We tested whether high altitude affects sport-related concussion (SRC) incidence, severity, and recovery. METHODS: Twenty-five thousand eight hundred fifteen baseline and post-injury Immediate Post-Concussion Assessment and Cognitive Testing results were compiled from Florida and Colorado, low (27 m or 62 m) and high (1,640 m or 1,991 m) altitude locations, respectively. Incidence, severity, and recovery of injury were compared between altitudes. RESULTS: High altitude was associated with increased suspected concussion incidence (adjusted OR, 2.04 [95% CI, 1.86 to 2.24];P < .0001). However, high altitude was associated with lower concussion severity measured by Severity Index (SI) (adjusted OR, 0.42 [95% CI, 0.37 to 0.49];P < .0001). High altitude was associated with decreased recovery from post-concussive symptoms in the migraine (ß, -2.72 [95% CI, -3.31 to -2.13]; P < .0001), cognitive (ß, -1.88 [95% CI, -2.40 to -1.36]; P < .0001), and sleep symptom clusters (ß, -0.30 [95% CI, -0.52 to -0.08]; P = .007). Athletes with initial SI≥8 showed prolonged neurocognitive dysfunction at high altitude (HR, 1.38 [95% CI, 1.06 to 1.81]; P = .02). CONCLUSIONS: High altitude was associated with increased suspected concussions and prolonged recovery but less severe initial injury.
Assuntos
Traumatismos em Atletas , Concussão Encefálica , Altitude , Atletas , Traumatismos em Atletas/complicações , Traumatismos em Atletas/diagnóstico , Traumatismos em Atletas/epidemiologia , Concussão Encefálica/complicações , Concussão Encefálica/diagnóstico , Concussão Encefálica/epidemiologia , Humanos , Incidência , Testes NeuropsicológicosRESUMO
INTRODUCTION: Gender differences in neurocognitive function have been reported over the past few decades. However, multiple studies that report gender differences in Immediate Post-Concussion Assessment and Cognitive Tests composite scores ignore potential confounders which may lead to inaccurate results. METHODS: A total of 4829 male and 2477 female baseline Immediate Post-Concussion Assessment and Cognitive Tests from 2009 to 2019 of subjects ages 12-18 years were used to evaluate gender differences in baseline neurocognitive scores and symptom severity ratings. Regression analyses were used to assess the effects of gender on neurocognitive performance at baseline while controlling for a number of potential confounders including symptom burden at the time of testing. RESULTS: Differences in 3 of 5 composite scores as well as severity rating scores were maintained in multivariate analysis. Females had increased Post-Concussion Symptom Scale (ß = 3.54, 95% confidence interval, 2.91 to 4.16, P < .0001) along with higher verbal memory (ß = 1.82, 95% confidence interval, 1.15 to 2.50, P < .0001) and visual motor (ß = 1.29, 95% confidence interval, 0.85-1.72, P < .0001) scores. CONCLUSIONS: Statistically significant gender differences were found in baseline neurocognitive function. This study clarifies for the first time that gender differences in these neurocognitive domains are not simply an artifact of differences in symptom burden. However, the small effect sizes call into question the clinical relevance of these differences.
Assuntos
Traumatismos em Atletas , Concussão Encefálica , Adolescente , Atletas/psicologia , Traumatismos em Atletas/diagnóstico , Concussão Encefálica/diagnóstico , Concussão Encefálica/psicologia , Criança , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Fatores Sexuais , EstudantesRESUMO
OBJECTIVE/BACKGROUND: Despite the prevalence of concussions in young athletes, the impact of headaches on neurocognitive function at baseline is poorly understood. We analyze the effects of a history of headache treatment on baseline ImPACT composite scores in young athletes. METHODS: A total of 11,563 baseline ImPACT tests taken by 7,453 student-athletes ages 12-22 between 2009 and 2019 were reviewed. The first baseline test was included. There were 960 subjects who reported a history of treatment for headache and/or migraine (HA) and 5,715 controls (CT). The HA cohort included all subjects who self-reported a history of treatment for migraine or other type of headache on the standardized questionnaire. Chi-squared tests were used to compare demographic differences. Univariate and multivariate regression analyses were used to assess differences in baseline composite scores between cohorts while controlling for demographic differences and symptom burden. RESULTS: Unadjusted analyses demonstrated that HA was associated with increased symptoms (ß=2.30, 95% CI: 2.18-2.41, p<.0001), decreased visual memory (ß=-1.35, 95% CI: -2.62 to -0.43, p=.004), and increased visual motor speed (ß=0.71, 95% CI: 0.23-1.19, p=.004) composite scores. Baseline scores for verbal memory, reaction time, and impulse control were not significantly different between cohorts. Adjusted analyses demonstrated similar results with HA patients having greater symptom burden (ß=1.40, 95% CI: 1.10-1.70, p<.0001), lower visual memory (ß=-1.25, 95% CI: -2.22 to -0.27, p=.01), and enhanced visual motor speed (ß=0.60, 95% CI: 0.11-1.10, p=.02) scores. CONCLUSION: HA affected symptom, visual motor speed, and visual memory ImPACT composite scores. Visual memory scores and symptom burden were significantly worse in the HA group while visual motor speed scores were better, which may have been due to higher stimulant use in the HA group. The effects of HA on visual motor speed and visual memory scores were independent of the effects of the increased symptom burden.
Assuntos
Traumatismos em Atletas , Transtornos de Enxaqueca , Adolescente , Adulto , Atletas/psicologia , Traumatismos em Atletas/complicações , Traumatismos em Atletas/diagnóstico , Traumatismos em Atletas/epidemiologia , Criança , Cefaleia/complicações , Humanos , Transtornos de Enxaqueca/complicações , Transtornos de Enxaqueca/tratamento farmacológico , Transtornos de Enxaqueca/epidemiologia , Testes Neuropsicológicos , Adulto JovemRESUMO
OBJECTIVE: To examine the effects of recurrent concussions on the incidence, severity, and recovery of significant neurocognitive dysfunction (SND) in young athletes. SETTING: Various US youth sports organizations that utilize Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) for baseline and postinjury concussion testing. PARTICIPANTS: Data from 11 563 ImPACT baseline evaluations of US student-athletes aged 12 to 22 years were separated into 2 cohorts: subjects reporting 2 or more previous concussions (PC; n = 976 baseline evaluations) at baseline and a control group reporting zero previous concussions (CT; n = 7743 baseline evaluations). Subjects reporting 1 prior concussion were excluded. DESIGN: Retrospective cohort. MAIN MEASURES: Differences in SND incidence, severity, and recovery between the 2 cohorts were assessed using chi-squared tests, t tests, survival analyses, and multivariate regressions. RESULTS: The PC cohort had a higher incidence of head injury leading to ImPACT (436.7 per 1000 person-years vs 194.4 per 1000 person-years, P < .0001) and a higher incidence of SND (140.4 vs 71.8, P < .0001) than controls. However, the Severity Index (SI) demonstrated that SND severity was lower in the PC group (7.55 vs 8.59, P = .04). Adjusted analyses similarly demonstrated that the PC cohort had increased SND incidence (odds ratio = 1.93; 95% CI, 1.61 to 2.31; P < .0001), decreased SI (ß = -1.37; 95% CI, -2.40 to -0.34; P = .009), and equivalent recovery (hazard ratio = 0.98; 95% CI, 0.76 to 1.72; P = .90). CONCLUSION: Participants with a history of concussion have a higher incidence of SND but present with lower severity SND, which may be a result of increased concussion education or symptom awareness. Recurrent concussion has no significant impact on acute neurocognitive recovery. Together, these results provide evidence against the supposition that a history of concussion increases the severity of future SND.
Assuntos
Traumatismos em Atletas , Concussão Encefálica , Adolescente , Atletas , Traumatismos em Atletas/diagnóstico , Traumatismos em Atletas/epidemiologia , Concussão Encefálica/diagnóstico , Concussão Encefálica/epidemiologia , Humanos , Incidência , Testes Neuropsicológicos , Estudos Retrospectivos , EstudantesRESUMO
Background: Reduction of surgical site infections (SSIs) is important in improving cervical spine surgery outcomes. Plastic surgery involvement and an enhanced modified prophylaxis protocol may reduce infection rates. Methods: A total of 962 cervical spine operations were conducted by a single surgeon (TFC). An enhanced modified prophylaxis protocol and plastic surgery were used in some operations. Differences in infection rates, surgical approach, previous operations, prophylaxis use, and plastic surgery involvement were compared using Fisher's exact tests and multivariate linear regression. Results: Four patients (0.42%) experienced SSIs. All 4 infections involved the standard protocol, posterior approach, and did not involve plastic surgery. The infection rate was lower in the enhanced protocol group when compared to the standard protocol (ß -0.78, 95% CI -1.23 to -0.33, P = .0008). The enhanced protocol group had an increased percentage of operations with plastic surgery (ß 0.19, 95% CI 0.10 to 0.28, P < .0001). The infection rate among the plastics group was 0.00% compared to 0.60% for the non-plastics group (P = .32). The plastics group had a lower rate of anterior approach when compared to the non-plastics group (ß -0.20, 95% CI -0.24 to -0.15, P = .049). Among the posterior approach group, procedures with plastic surgery had an infection rate of 0.00% compared to 2.53% without plastic surgery (P = .13). Conclusion: The enhanced protocol was associated with a lower SSI rate and increased plastic surgery involvement. Posterior approaches were associated with increased infection rates and the likelihood of utilizing plastic surgery. Both the enhanced protocol and plastic surgery may decrease infection.
Contexte: La réduction des infections du site opératoire est importante pour améliorer les résultats de la chirurgie de la colonne cervicale. L'implication de la chirurgie plastique et d'un protocole amélioré de prophylaxie modifiée peuvent réduire les taux d'infection. Méthodes: Un total de 962 opérations sur la colonne cervicale a été effectué par un seul chirurgien (TFC). Un protocole amélioré de prophylaxie modifiée et la chirurgie plastique ont été utilisés au cours de certaines interventions. Les différences dans les taux d'infection, l'abord chirurgical, les opérations précédentes, l'utilisation de la prophylaxie et l'implication de la chirurgie plastique ont été évalués au moyen de tests exacts de Fisher et d'une régression linéaire multifactorielle. Résultats: Quatre patients (0.42%) ont présenté une infection de la cicatrice opératoire (ICO). Les quatre infections impliquaient le protocole standard, l'abord postérieur et l'absence de chirurgie plastique. Le taux d'infection a été moindre dans le groupe de protocole amélioré, comparativement au protocole standard (ß −0.78, IC à 95%: −1.23 à −0.33, P = .0008). Le pourcentage d'opérations avec chirurgie plastique était augmenté dans le groupe au protocole amélioré (ß 0.19, IC à 95%: 0.10 à 0.28, P < .0001). La fréquence des infections dans le groupe de chirurgie plastique était de 0.00%, comparée à 0.60% dans le groupe sans chirurgie plastique (P = .32). Le groupe avec chirurgie plastique avait un taux d'abord antérieur inférieur comparativement au groupe sans chirurgie plastique (ß −0.20, IC à 95%: −0.24 à −0.15, P = .049). Dans le groupe avec abord postérieur, le taux d'infections était de 0.00% avec chirurgie plastique contre 2.53% sans chirurgie plastique (P = .13). Conclusion: Le protocole amélioré a été associé à un taux d'OCI inférieur et à une plus grande implication de la chirurgie plastique. Un abord postérieur a été associé à des taux augmentés d'infection et à une plus grande probabilité d'utilisation de la chirurgie plastique. Le protocole amélioré et la chirurgie plastique peuvent tous deux réduire les infections.
RESUMO
This study aims to analyze changes in health-related quality of life (HRQoL) and safety in patients with generalized anxiety disorder (GAD) prescribed a homogenous selection of cannabis-based medicinal products (CBMPs). Patients prescribed Adven CBMPs (Curaleaf International, UK) for GAD were identified from the UK Medical Cannabis Registry. Primary outcomes were changes in patient-reported outcome measures (PROMs) from baseline up to 12 months, including GAD-7, Single-Item Sleep Quality Scale (SQS), and EQ-5D-5L. Adverse events were recorded using CTCAE version 4.0. A total of 120 patients were identified for inclusion, of which 38 (31.67%), 52 (43.33%), and 30 (25.00%) were prescribed oils, dried flower, and both formulations of CBMP. Associated improvements in GAD-7, SQS, and EQ-5D-5L at 1, 3, 6, and 12 months were observed compared to baseline (Pâ <â 0.010). There were 24 (20.00%) patients who reported 442 (368.33%) adverse events, most of which were mild (nâ =â 184, 41.63%) and moderate (nâ =â 197, 44.57%). This study reports an association between initiation of a homogeneous CBMP therapy and improvements in anxiety severity and HRQoL in individuals with GAD. Moreover, therapy was well-tolerated at 12 months follow-up. Further investigation through randomized controlled trials will ultimately be required to determine causation.
RESUMO
DNA methylation marks have recently been used to build models known as "epigenetic clocks" which predict calendar age. As methylation of cytosine promotes C-to-T mutations, we hypothesized that the methylation changes observed with age should reflect the accrual of somatic mutations, and the two should yield analogous aging estimates. In analysis of multimodal data from 9,331 human individuals, we find that CpG mutations indeed coincide with changes in methylation, not only at the mutated site but also with pervasive remodeling of the methylome out to ±10 kilobases. This one-to-many mapping enables mutation-based predictions of age that agree with epigenetic clocks, including which individuals are aging faster or slower than expected. Moreover, genomic loci where mutations accumulate with age also tend to have methylation patterns that are especially predictive of age. These results suggest a close coupling between the accumulation of sporadic somatic mutations and the widespread changes in methylation observed over the course of life.
RESUMO
OBJECTIVE: To investigate the role of seasonality on postoperative complications after spinal surgery. METHODS: Data were obtained from the American College of Surgeons National Surgical Quality Improvement Program database from 2011 to 2018. Current Procedural Terminology codes were used to identify the following procedures: posterior cervical decompression and fusion, cervical laminoplasty, posterior lumbar fusion, lumbar laminectomy, and spinal deformity surgery. The database was queried for deep vein thrombosis (DVT), pulmonary embolism, pneumonia, sepsis, septic shock, Clostridium difficile infection, stroke, cardiac arrest, myocardial infarction, urinary tract infection (UTI), and early unplanned hospital readmission (readmission). Warm season was defined as April-September, whereas cold season was defined as October-March. Statistical analysis included computing overall complication rates and comparison between seasons using univariate analysis and multivariable logistic regression. RESULTS: A total of 208,291 individuals underwent spinal surgery from 2011 to 2018. There was a statistically significant increase in UTI (odds ratio [OR], 1.16; 95% confidence interval [CI], 1.07-1.26; P = 0.0002) and readmission (OR, 1.06; 95% CI, 1.02-1.11, P = 0.007) in the warm season compared with the cold season. An investigation into the July effect showed increases in DVT (OR, 1.24; 95% CI, 1.03-1.48; P = 0.020) and thromboembolic events (OR 1.17; 95% CI, 1.01-1.35; P = 0.032) in July-September compared with the preceding 3 months. CONCLUSIONS: The results showed a higher incidence of UTI and readmission among spine surgery patients in the warm season and a higher incidence of DVT and thromboembolic events from July to September. In both cases, the effect of seasonality is statistically significant, but the absolute difference is small and may not suggest policy changes.
Assuntos
Embolia Pulmonar , Fusão Vertebral , Humanos , Estações do Ano , Complicações Pós-Operatórias/epidemiologia , Procedimentos Neurocirúrgicos/efeitos adversos , Laminectomia , Embolia Pulmonar/epidemiologia , Embolia Pulmonar/etiologia , Readmissão do Paciente , Fusão Vertebral/efeitos adversos , Fusão Vertebral/métodos , Fatores de Risco , Estudos RetrospectivosRESUMO
BACKGROUND: Flexion-extension magnetic resonance imaging (MRI) has potential to identify cervical pathology not detectable on conventional static MRI. Our study evaluated standard quantitative and novel subjective grading scales for assessing the severity of cervical spondylotic myelopathy in dynamic sagittal MRI as well as in static axial and sagittal images. METHODS: Forty-five patients underwent both conventional and flexion-extension MRI prior to anterior cervical discectomy and fusion from C4 through C7. In addition to measuring Cobb angles and cervical canal diameter, grading scales were developed for assessment of vertebral body translation, loss of disc height, change in disc contour, deformation of cord contour, and cord edema. Data were collected at all levels from C2-C3 through C7-T1. Variations in measurements between cervical levels and from flexion through neutral to extension were assessed using Mann-Whitney, Kruskal-Wallis, and two-way ANOVA tests. RESULTS: Cervical canal diameter, vertebral translation, and posterior disc opening changed significantly from flexion to neutral to extension positions (P < 0.01). When comparing operative versus nonoperative cervical levels, significant differences were found when measuring sagittal cervical canal dimensions, vertebral translation, and posterior disc opening (P < 0.01). Degenerative loss of disc height, disc dehydration, deformation of ventral cord contour, and cord edema were all significantly increased at operative levels versus nonoperative levels (P < 0.01). CONCLUSIONS: Flexion-extension MRI demonstrated significant changes not available from conventional MRI. Subjective scales for assessing degenerative changes were significantly more severe at levels with operative cervical spondylotic myelopathy. The utility of these scales for planning surgical intervention at specific and adjacent levels is currently under investigation.
Assuntos
Doenças da Medula Espinal , Humanos , Doenças da Medula Espinal/diagnóstico por imagem , Doenças da Medula Espinal/cirurgia , Doenças da Medula Espinal/patologia , Imageamento por Ressonância Magnética/métodos , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Vértebras Cervicais/patologia , Pescoço/cirurgia , DiscotomiaRESUMO
OBJECTIVE: Bibliometrics assessing academic productivity plays a significant role in neurosurgeons' career advancement. This study aimed to evaluate the influence of multiple author profiles on Scopus on neurosurgeon author-level metrics (h-index, document number, citation number). METHODS: A list of 1671 academic neurosurgeons was compiled through public searches of hospital and faculty websites for 115 neurosurgical residency training programs. The h-index, document number, and citation number for each neurosurgeon were collected using the Scopus algorithm. For surgeons with multiple profiles, total document number and citation number were calculated by summing results of each profile. Cumulative h-indices were calculated manually. Comparisons were made between surgeons with a single Scopus profile and surgeons with multiple profiles. RESULTS: A total of 124 neurosurgeons with multiple profiles were identified. Gender distribution (P = 0.47), years in practice (P = 0.06), subspecialty (P = 0.32), and academic rank (P = 0.16) between neurosurgeons with a single profile versus multiple profiles were similar. Primary profile h-index median was 16 (interquartile range [IQR]: 8-34), combined profiles median was 20 (IQR: 11-36), and percent loss median was 17.3% (IQR: 3%-33%) (P < 0.001). For document number, primary profile median was 46 (IQR: 16-127), combined profiles median was 55 (IQR: 22-148), and percent loss median was 16.2% (IQR: 7%-36%) (P < 0.001). For citation number, primary profile median was 1030 (IQR: 333-4082), combined profiles median was 1319 (IQR: 546-4439), and percent loss median was 14.1% (IQR: 4%-32%) (P < 0.001). CONCLUSIONS: U.S. academic neurosurgeons with multiple existing profiles on Scopus experience a 17.3% loss in h-index, a 16.2% loss in document number, and a 14.1% loss in citations, heavily undercounting their perceived academic productivity.
Assuntos
Neurocirurgia , Cirurgiões , Estados Unidos , Humanos , Neurocirurgiões , Neurocirurgia/educação , Bibliometria , EficiênciaRESUMO
BACKGROUND: Athletes who are diagnosed with attention-deficit/hyperactivity disorder (ADHD) are at increased risk of concussion compared to other athletes. Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) is a widely used concussion tool, but it relies on pre-injury baseline testing that can be affected by psychiatric conditions. This research aims to determine if there are differences in pre-injury testing composite scores in student-athletes with ADHD compared to those without ADHD diagnosis. METHODS: We obtained 11,563 pre-season ImPACT assessments of 7,454 student-athletes (ages: 12-22) from 2009 to 2019. After exclusions, there were 6,920 control and 276 ADHD subjects. Multivariable linear regression analyses compared the independent effect of ADHD on the six ImPACT composite score metrics with Bonferroni correction for multiple comparisons with a = 0.008. RESULTS: Univariate analyses indicated ADHD is associated with more symptoms as measured by the Post-Concussion Symptom Scale (PCSS) (ß = 2.67, 95% CI: 1.47-3.87, p < .0001) and worse Impulse Control scores (ß = 0.93, 95% CI: 0.33-1.53, p = .002). In multivariate analysis, this association was the same for symptom score (ß = 2.48, 95% CI: 1.22-3.74, p < .0001), but Impulse Control was not significantly different after multiple comparison adjustment (ß = 0.87, 95% CI: 0.22-1.15, p = .009). CONCLUSIONS: The ADHD subjects reported worse symptoms at baseline and had worse Impulse Control in univariate analysis, but not multivariate analysis. These results can further guide clinicians in concussion diagnosis and test interpretations for student-athletes with ADHD, considering the symptom burden at baseline.
RESUMO
BACKGROUND: International medical graduates (IMGs) comprise â¼25% of physicians in the United States. Differences in promotion rates from assistant to associate to full professorship based on medical school location have been understudied. We aim to stratify odds of professional advancement by 3 categories: IMG with U.S. residency, IMG with international residency, and U.S. medical with U.S. residency training. METHODS: We created and queried a database after exclusions of 1334 neurosurgeons including multiple demographic factors: academic productivity and promotion rates. Stratified logistic regression modeled odds of promotion including the variables: decades out of training, Scopus h-index, gender, and training location. Odds ratios (ORs) and 95% confidence intervals (CIs) for each variable were calculated. RESULTS: Significant predictors of increased associate versus assistant professorship included decades out of training (OR = 2.519 [95% CI: 2.07-3.093], P < 0.0001) and Scopus h-index (OR = 1.085 [95% CI: 1.064-1.108], P < 0.0001) while international medical school with U.S. residency (OR = 0.471 [95% CI: 0.231-0.914], P = 0.0352) was associated with decreased promotion. Significant predictors of associate versus full professorship were decades out of training (OR = 2.781 [95% CI: 2.268-3.444], P < 0.0001) and Scopus h-index (OR = 1.064 [95% CI: 1.049-1.080], P < 0.0001). Attending medical school or residency internationally was not associated with odds of full professorship. CONCLUSIONS: Time out of residency and Scopus h-index were associated with higher academic rank regardless of career level. Attending medical school internationally with U.S. residency was associated with lower odds of associate professorship promotion over 10 years. There was no relationship between IMG and full professorship promotion. IMGs who attended residency internationally did not have lower promotion rates. These findings suggest it may be harder for IMGs to earn promotion from assistant to associate professor in neurosurgery.
RESUMO
SARS-CoV-2 harbors a unique S1/S2 furin cleavage site within its spike protein, which can be cleaved by furin and other proprotein convertases. Proteolytic activation of SARS-CoV-2 spike protein at the S1/S2 boundary facilitates interaction with host ACE2 receptor for cell entry. To address this, high titer antibody was generated against the SARS-CoV-2-specific furin motif. Using a series of innovative ELISA-based assays, this furin site blocking antibody displayed high sensitivity and specificity for the S1/S2 furin cleavage site, including with a P681R mutation, and demonstrated effective blockage of both enzyme-mediated cleavage and spike-ACE2 interaction. The results suggest that immunological blocking of the furin cleavage site may afford a suitable approach to stem proteolytic activation of SARS-CoV-2 spike protein and curtail viral infectivity.
Assuntos
Enzima de Conversão de Angiotensina 2/metabolismo , Anticorpos Antivirais/imunologia , Furina/metabolismo , Glicoproteína da Espícula de Coronavírus/imunologia , Motivos de Aminoácidos/genética , Motivos de Aminoácidos/imunologia , Anticorpos Antivirais/farmacologia , Humanos , Mutação , Nariz/enzimologia , Pró-Proteína Convertases/metabolismo , Ligação Proteica/efeitos dos fármacos , Proteólise/efeitos dos fármacos , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/genética , SARS-CoV-2/metabolismo , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/metabolismoRESUMO
The availability of thousands of assays of epigenetic activity necessitates compressed representations of these data sets that summarize the epigenetic landscape of the genome. Until recently, most such representations were cell type-specific, applying to a single tissue or cell state. Recently, neural networks have made it possible to summarize data across tissues to produce a pan-cell type representation. In this work, we propose Epi-LSTM, a deep long short-term memory (LSTM) recurrent neural network autoencoder to capture the long-term dependencies in the epigenomic data. The latent representations from Epi-LSTM capture a variety of genomic phenomena, including gene-expression, promoter-enhancer interactions, replication timing, frequently interacting regions, and evolutionary conservation. These representations outperform existing methods in a majority of cell types while yielding smoother representations along the genomic axis due to their sequential nature.