Abstract
Background
We and others have identified mutually exclusive molecular subgroups of meningiomas; however, the implications of this classification for clinical prognostication remain unclear. ...Integrated genomic and epigenomic analyses implicate unique oncogenic processes associated with each subgroup, suggesting the potential for divergent clinical courses. The aim of this study was to understand the associated clinical outcomes of each subgroup, as this could optimize treatment for patients.
Methods
We analyzed outcome data for 469 meningiomas of known molecular subgroup, including extent of resection, postoperative radiation, surveillance imaging, and time to recurrence, when applicable. Statistical relationships between outcome variables and subgroup were assessed. Features previously associated with recurrence were further investigated after stratification by subgroup. We used Kaplan–Meier analyses to compare progression-free survival, and identified factors significantly associated with recurrence using Cox proportional hazards modeling.
Results
Meningioma molecular subgroups exhibited divergent clinical courses at 2 years of follow-up, with several aggressive subgroups (NF2, PI3K, HH, tumor necrosis factor receptor–associated factor 7 TRAF7) recurring at an average rate of 22 times higher than others (KLF4, POLR2A, SMARCB1). PI3K-activated tumors recurred earlier than other subgroups but had intermediate long-term outcome. Among low-grade tumors, HH and TRAF7 meningiomas exhibited elevated recurrence compared with other subgroups. Recurrence of NF2 tumors was associated with male sex, high grade, and elevated Ki-67. Multivariate analysis identified molecular subgroup as an independent predictor of recurrence, along with grade and previous recurrence.
Conclusion
We describe distinct clinical outcomes and recurrence rates associated with meningioma molecular subgroups. Our findings emphasize the importance of genomic characterization to guide postoperative management decisions for meningiomas.
Immune‐mediated hypersensitivity reactions to ticks and other arthropods are well documented. Hypersensitivity to ixodid (hard bodied) ticks is especially important because they transmit infection to ...humans throughout the world and are responsible for most vector‐borne diseases in the United States. The causative pathogens of these diseases are transmitted in tick saliva that is secreted into the host while taking a blood meal. Tick salivary proteins inhibit blood coagulation, block the local itch response and impair host anti‐tick immune responses, which allows completion of the blood meal. Anti‐tick host immune responses are heightened upon repeated tick exposure and have the potential to abrogate tick salivary protein function, interfere with the blood meal and prevent pathogen transmission. Although there have been relatively few tick bite hypersensitivity studies in humans compared with those in domestic animals and laboratory animal models, areas of human investigation have included local hypersensitivity reactions at the site of tick attachment and generalized hypersensitivity reactions. Progress in the development of anti‐tick vaccines for humans has been slow due to the complexities of such vaccines but has recently accelerated. This approach holds great promise for future prevention of tick‐borne diseases.
Objective
While adjuvant treatment regimens have been modified for older patients with glioblastoma (GBM), surgical strategies have not been tailored.
Methods
Clinical data of 48 consecutive patients ...aged 70 years or older, who underwent surgical resection for GBM with intraoperative ultrasonography (IoUS) alone or combination with intraoperative MRI (IoMRI) at Yale New Haven Hospital were retrospectively reviewed. Variables were analyzed, and comparative analyses were performed.
Results
The addition of IoMRI was not superior to IoUS alone in terms of overall survival (OS) (P = 0.306), Karnofsky Performance Score (KPS) at postoperative 6 weeks (P = 0.704) or extent of resection (P = 0.263). Length of surgery (LOSx), however, was significantly longer (P = 0.0002) in the IoMRI group. LOSx (P = 0.015) and hospital stay (P = 0.025) were predictors of postoperative complications. Increased EOR (GTR or NTR) (P = 0.030), postoperative adjuvant treatment (P < 0.0001) and postoperative complications (P = 0.006) were predictive for OS. Patients with relatively lower preoperative KPS scores (<70) showed significant improvement at postoperative 6 weeks (P<0.0001). Patients with complications (P = 0.038) were more likely to have lower KPS at postoperative 6 weeks.
Conclusions
Aggressive management with surgical resection should be considered in older patients with GBM, even those with relatively poor KPS. The use of ioMRI in this population does not appear to confer any measurable benefit over ioUS in experienced hands, but prolongs the length of surgery significantly, which is a preventable prognostic factor for impeding care.
Purpose
As sphenoid wing meningiomas (SWMs) are associated with varying degrees of bony involvement, we sought to understand potential relationships between genomic subgroup and this feature.
Methods
...Patients treated at Yale-New Haven Hospital for SWM were reviewed. Genomic subgroup was determined via whole exome sequencing, while the extent of bony involvement was radiographically classified as no bone invasion (Type I), hyperostosis only (Type II), tumor invasion only (Type III), or both hyperostosis and tumor invasion (Type IV). Among additional clinical variables collected, a subset of tumors was identified as spheno-orbital meningiomas (SOMs). Machine-learning approaches were used to predict genomic subgroups based on pre-operative clinical features.
Results
Among 64 SWMs, 53% had Type-II, 9% had Type-III, and 14% had Type-IV bone involvement; nine SOMs were identified. Tumors with invasion (i.e., Type III or IV) were more likely to be WHO grade II (p: 0.028). Additionally, tumors with invasion were nearly 30 times more likely to harbor
NF2
mutations (OR 27.6; p: 0.004), while hyperostosis only were over 4 times more likely to have a
TRAF7
mutation (OR 4.5; p: 0.023). SOMs were a significant predictor of underlying
TRAF7
mutation (OR 10.21; p: 0.004).
Conclusions
SWMs with invasion into bone tend to be higher grade and are more likely to be
NF2
mutated, while SOMs and those with hyperostosis are associated with
TRAF7
variants. Pre-operative prediction of molecular subtypes based on radiographic bony characteristics may have significant biological and clinical implications based on known recurrence patterns associated with genomic drivers and grade.
Beckwith-Wiedemann syndrome (BWS) is an epigenetic disorder of imprinting on the chromosome 11p15 region that presents with clinical features, such as macroglossia, abdominal wall defects, neonatal ...hypoglycemia, hemihypertrophy, and embryonal tumors. Phyllodes tumors (PTs) are rare fibroepithelial tumors that account for 0.3% to 1% of breast tumors and present in women aged 35 to 55 years. Here we describe a rare case of metastatic malignant phyllodes tumor in a 27-year-old woman with BWS and uniparental disomy (UPD) of chromosome 11p15.5. To our knowledge, this is the first case report in literature to describe metastatic malignant phyllodes tumor in a woman with BWS.
Abstract
Meningiomas are the most common central nervous system tumors. Although these tumors are extra-axial, a relatively high proportion (10%–50%) of meningioma patients have seizures that can ...substantially impact the quality of life. Meningiomas are believed to cause seizures by inducing cortical hyperexcitability that results from mass effect and cortical irritation, brain invasion, or peritumoral brain edema. In general, meningiomas that are associated with seizures have aggressive features, with risk factors including atypical histology, brain invasion, and higher tumor grade. Somatic NF2 mutated meningiomas are associated with preoperative seizures, but the effect of the driver mutation is mediated through atypical features. While surgical resection is effective in controlling seizures in most patients with meningioma-related epilepsy, a history of seizures and uncontrolled seizures prior to surgery is the most significant predisposing factor for persistent postoperative seizures. Subtotal resection (STR) and relatively larger residual tumor volume are positive predictors of postoperative seizures. Other factors, including higher WHO grade, peritumoral brain edema, and brain invasion, are inconsistently associated with postoperative seizures, suggesting they might be crucial in the development of an epileptogenic focus, but do not appear to play a substantial role after seizure activity has been established. Herein, we review and summarize the current literature surrounding meningioma-related epilepsy and underscore the interaction of multiple factors that relate to seizures in patients with meningioma.
Aspiration pneumonia is a potentially preventable, aggressive type of pneumonia. Little is understood on the burden in mortality from aspiration pneumonia. Our objectives were to first examine the ...burden of mortality from aspiration pneumonia in the United States and second investigate comorbidities associated with aspiration pneumonia to understand risk factors. We conducted a case–control study of individuals who died of aspiration pneumonia matched to those who died of other causes. We analyzed all deaths in the United States using the Multiple Cause of Death Dataset from 1999 to 2017. Cases were matched with controls based on age, sex, and race. We calculated age-adjusted mortality rates, annual percentage changes in aspiration pneumonia mortality, and matched odds ratio comparisons. We identified a total of 1,112,944 deaths related to aspiration pneumonia from 1999 to 2017 or an average of 58,576 per year (age-adjusted mortality rate, 21.85 per 100,000 population; 95% confidence interval (CI) 21.78–21.92). Aspiration pneumonia was reported as the underlying cause of death in 334,712 deaths or an average of 17,616 deaths per year (30.1% of the total aspiration pneumonia-associated deaths). Individuals 75 years old or older accounted for 76.0% of aspiration pneumonia deaths and the age adjusted rate ratio was 161.0 (CI 160.5–161.5). Neurologic, upper gastrointestinal, and pulmonary conditions as well as conditions associated with sedative substances were more often associated with aspiration pneumonia-associated deaths. Aspiration pneumonia is the underlying cause or a cofactor in tens of thousands of deaths each year in the United States. Aspiration pneumonia-associated deaths are highly prevalent with advanced age and are associated with neurologic, upper gastrointestinal and pulmonary conditions.
To describe and assess the educational value of a functional neurosurgery clinical shadowing and research tutorial for pre-medical trainees.
Program participants observed functional neurosurgery ...procedures and conducted basic science and clinical research in neurosurgery fields. Former participants completed a brief online survey to evaluate their perspectives and experiences throughout the tutorial.
Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
15 pre-medical and post-baccalaureate trainees participated in the tutorial. All former tutorial participants were emailed.
11/15 former participants responded to the survey. Survey results suggest that the tutorial program increased participants' understanding of and interest in neurosurgery and related fields in neuroscience.
The functional neurosurgery medical tutorial provides valuable clinical and research exposure in neurosurgery fields for pre-medical trainees. Our work is a preliminary step in addressing the crucial challenge of training the next generation of neurosurgeon-scientists by providing a pedagogical paradigm for development of formal experiences that integrate original scientific research with clinical neurosurgery exposure.
Purpose of Review
Spontaneous coronary artery dissection (SCAD) has been increasingly recognized as a significant cause of acute myocardial infarction (AMI) in young and middle-aged women and arises ...through mechanisms independent of atherosclerosis. SCAD has a multifactorial etiology that includes environmental, individual, and genetic factors distinct from those typically associated with coronary artery disease. Here, we summarize the current understanding of the genetic factors contributing to the development of SCAD and highlight those factors which differentiate SCAD from atherosclerotic coronary artery disease.
Recent Findings
Recent studies have revealed several associated variants with varying effect sizes for SCAD, giving rise to a complex genetic architecture. Associated genes highlight an important role for arterial cells and their extracellular matrix in the pathogenesis of SCAD, as well as notable genetic overlap between SCAD and other systemic arteriopathies such as fibromuscular dysplasia and vascular connective tissue diseases. Further investigation of individual variants (including in the associated gene
PHACTR1
) along with polygenic score analysis have demonstrated an inverse genetic relationship between SCAD and atherosclerosis as distinct causes of AMI.
Summary
SCAD represents an increasingly recognized cause of AMI with opposing clinical and genetic risk factors from that of AMI due to atherosclerosis, and it is often associated with complex underlying genetic conditions. Genetic study of SCAD on a larger scale and with more diverse cohorts will not only further our evolving understanding of a newly defined genetic spectrum for AMI, but it will also inform the clinical utility of integrating genetic testing in AMI prevention and management moving forward.
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