601 research outputs found
Surgical management of skull base tumors
AimTo present a review of the contemporary surgical management of skull base tumors.BackgroundOver the last two decades, the treatment of skull base tumors has evolved from observation, to partial resection combined with other therapy modalities, to gross total resection and no adjuvant treatment with good surgical results and excellent clinical outcomes.Materials and methodsThe literature review of current surgical strategies and management of skull base tumors was performed and complemented with the experience of Barrow Neurological Institute.ResultsSkull base tumors include meningiomas, pituitary tumors, sellar/parasellar tumors, vestibular and trigeminal schwannomas, esthesioneuroblastomas, chordomas, chondrosarcomas, and metastases. Surgical approaches include the modified orbitozygomatic, pterional, middle fossa, retrosigmoid, far lateral craniotomy, midline suboccipital craniotomy, and a combination of these approaches. The selection of an appropriate surgical approach depends on the characteristics of the patient and the tumor, as well as the experience of the neurosurgeon.ConclusionModern microsurgical techniques, diagnostic imaging, intraoperative neuronavigation, and endoscopic technology have remarkably changed the concept of skull base surgery. These refinements have extended the boundaries of tumor resection with minimal morbidity
Sulforhodamine 101 selectively labels human astrocytoma cells in an animal model of glioblastoma
AbstractSulforhodamine 101 (SR101) is a useful tool for immediate staining of astrocytes. We hypothesized that if the selectivity of SR101was maintained in astrocytoma cells, it could prove useful for glioma research. Cultured astrocytoma cells and acute slices from orthotopic human glioma (n=9) and lymphoma (n=6) xenografts were incubated with SR101 and imaged with confocal microscopy. A subset of slices (n=18) were counter-immunostained with glial fibrillary acidic protein and CD20 for stereological assessment of SR101 co-localization. SR101 differentiated astrocytic tumor cells from lymphoma cells. In acute slices, SR101 labeled 86.50% (±1.86; p<0.0001) of astrocytoma cells and 2.19% (±0.47; p<0.0001) of lymphoma cells. SR101-labeled astrocytoma cells had a distinct morphology when compared with in vivo astrocytes. Immediate imaging of human astrocytoma cells in vitro and in ex vivo rodent xenograft tissue labeled with SR101 can identify astrocytic tumor cells and help visualize the tumor margin. These features are useful in studying astrocytoma in the laboratory and may have clinical applications
Impact of molecular profiling on overall survival of patients with advanced ovarian cancer
OBJECTIVE: Patients with recurrent epithelial ovarian cancer (EOC) have limited treatment options. Studies have reported that biomarker profiling may help predict patient response to available treatments. This study sought to determine the value of biomarker profiling in recurrent EOC. RESULTS: Patients in the Matched cohort had a median OS of 36 months compared to 27 months for patients in the Unmatched cohort (HR 0.62, 95% CI 0.41-0.96; p < 0.03). Individual biomarkers were analyzed, with TUBB3, and PGP prognostic for survival. Biomarker analysis also identified a molecular subtype (positive for at least two of the following markers: ERCC1, RRM1, TUBB3, PGP) with particularly poor overall survival. METHODS: 224 patients from a commercial registry (NCT02678754) with stage IIIC/IV EOC at diagnosis, or restaged to IIIC/IV EOC at the time of molecular profiling, were retrospectively divided into two cohorts based on whether or not the drugs they received matched their profile recommendations. The Matched cohort received no drugs predicted to be lack-of-benefit while the Unmatched cohort received at least one drug predicted to be lack-of-benefit. Profile biomarker/drug associations were based on multiple test platforms including immunohistochemistry, fluorescent in situ hybridization and DNA sequencing. CONCLUSIONS: This report demonstrates the ability of multi-platform molecular profiling to identify EOC patients at risk of inferior survival. It also suggests a potential beneficial role of avoidance of lack-of-benefit therapies which, when administered, resulted in decreased survival relative to patients who received only therapies predicted to be of benefit
Extracellular microRNAs in blood differentiate between ischaemic and haemorrhagic stroke subtypes.
Rapid identification of patients suffering from cerebral ischaemia, while excluding intracerebral haemorrhage, can assist with patient triage and expand patient access to chemical and mechanical revascularization. We sought to identify blood-based, extracellular microRNAs 15 (ex-miRNAs) derived from extracellular vesicles associated with major stroke subtypes using clinical samples from subjects with spontaneous intraparenchymal haemorrhage (IPH), aneurysmal subarachnoid haemorrhage (SAH) and ischaemic stroke due to cerebral vessel occlusion. We collected blood from patients presenting with IPH (n = 19), SAH (n = 17) and ischaemic stroke (n = 21). We isolated extracellular vesicles from plasma, extracted RNA cargo, 20 sequenced the small RNAs and performed bioinformatic analyses to identify ex-miRNA biomarkers predictive of the stroke subtypes. Sixty-seven miRNAs were significantly variant across the stroke subtypes. A subset of exmiRNAs differed between haemorrhagic and ischaemic strokes, and LASSO analysis could distinguish SAH from the other subtypes with an accuracy of 0.972 ± 0.002. Further analyses predicted 25 miRNA classifiers that stratify IPH from ischaemic stroke with an accuracy of 0.811 ± 0.004 and distinguish haemorrhagic from ischaemic stroke with an accuracy of 0.813 ± 0.003. Blood-based, ex-miRNAs have predictive value, and could be capable of distinguishing between major stroke subtypes with refinement and validation. Such a biomarker could one day aid in the triage of patients to expand the pool eligible for effective treatment
Extracellular microRNAs in blood differentiate between ischaemic and haemorrhagic stroke subtypes
Rapid identification of patients suffering from cerebral ischaemia, while excluding intracerebral haemorrhage, can assist with patient triage and expand patient access to chemical and mechanical revascularization. We sought to identify blood-based, extracellular microRNAs 15 (ex-miRNAs) derived from extracellular vesicles associated with major stroke subtypes using clinical samples from subjects with spontaneous intraparenchymal haemorrhage (IPH), aneurysmal subarachnoid haemorrhage (SAH) and ischaemic stroke due to cerebral vessel occlusion. We collected blood from patients presenting with IPH (n = 19), SAH (n = 17) and ischaemic stroke (n = 21). We isolated extracellular vesicles from plasma, extracted RNA cargo, 20 sequenced the small RNAs and performed bioinformatic analyses to identify ex-miRNA biomarkers predictive of the stroke subtypes. Sixty-seven miRNAs were significantly variant across the stroke subtypes. A subset of exmiRNAs differed between haemorrhagic and ischaemic strokes, and LASSO analysis could distinguish SAH from the other subtypes with an accuracy of 0.972 +/- 0.002. Further analyses predicted 25 miRNA classifiers that stratify IPH from ischaemic stroke with an accuracy of 0.811 +/- 0.004 and distinguish haemorrhagic from ischaemic stroke with an accuracy of 0.813 +/- 0.003. Blood-based, ex-miRNAs have predictive value, and could be capable of distinguishing between major stroke subtypes with refinement and validation. Such a biomarker could one day aid in the triage of patients to expand the pool eligible for effective treatment.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]
Analyzing international medical graduate research productivity for application to US neurosurgery residency and beyond: A survey of applicants, program directors, and institutional experience
BackgroundThe authors investigated perceived discrepancies between the neurosurgical research productivity of international medical graduates (IMGs) and US medical graduates (USMGs) through the perspective of program directors (PDs) and successfully matched IMGs.MethodsResponses to 2 separate surveys on neurosurgical applicant research productivity in 115 neurosurgical programs and their PDs were analyzed. Neurosurgical research participation was analyzed using an IMG survey of residents who matched into neurosurgical residency within the previous 8 years. Productivity of IMGs conducting dedicated research at the study institution was also analyzed.ResultsThirty-two of 115 (28%) PDs responded to the first research productivity survey and 43 (37%) to the second IMG research survey. PDs expected neurosurgery residency applicants to spend a median of 12–24 months on research (Q1-Q3: 0–12 to 12–24; minimum time: 0–24; maximum time: 0–48) and publish a median of 5 articles (Q1-Q3: 2–5 to 5–10; minimum number: 0–10; maximum number: 4–20). Among 43 PDs, 34 (79%) ranked “research institution or associated personnel” as the most important factor when evaluating IMGs' research. Forty-two of 79 (53%) IMGs responding to the IMG-directed survey reported a median of 30 months (Q1-Q3: 18–48; range: 4–72) of neurosurgical research and 12 published articles (Q1-Q3: 6–24; range: 1–80) before beginning neurosurgical residency. Twenty-two PDs (69%) believed IMGs complete more research than USMGs before residency. Of 20 IMGs conducting dedicated neuroscience/neurosurgery research at the study institution, 16 of 18 who applied matched or entered a US neurosurgical training program; 2 applied and entered a US neurosurgical clinical fellowship.ConclusionThe research work of IMGs compared to USMGs who apply to neurosurgery residency exceeds PDs' expectations regarding scientific output and research time. Many PDs perceive IMG research productivity before residency application as superior to USMGs. Although IMGs comprise a small percentage of trainees, they are responsible for a significant amount of US-published neurosurgical literature. Preresidency IMG research periods may be improved with dedicated mentoring and advising beginning before the research period, during the period, and within a neurosurgery research department, providing a formal structure such as a research fellowship or graduate program for IMGs aspiring to train in the US
Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade.
The genomes of cancers deficient in mismatch repair contain exceptionally high numbers of somatic mutations. In a proof-of-concept study, we previously showed that colorectal cancers with mismatch repair deficiency were sensitive to immune checkpoint blockade with antibodies to programmed death receptor-1 (PD-1). We have now expanded this study to evaluate the efficacy of PD-1 blockade in patients with advanced mismatch repair-deficient cancers across 12 different tumor types. Objective radiographic responses were observed in 53% of patients, and complete responses were achieved in 21% of patients. Responses were durable, with median progression-free survival and overall survival still not reached. Functional analysis in a responding patient demonstrated rapid in vivo expansion of neoantigen-specific T cell clones that were reactive to mutant neopeptides found in the tumor. These data support the hypothesis that the large proportion of mutant neoantigens in mismatch repair-deficient cancers make them sensitive to immune checkpoint blockade, regardless of the cancers\u27 tissue of origin
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Extracellular RNAs: development as biomarkers of human disease
Ten ongoing studies designed to test the possibility that extracellular RNAs may serve as biomarkers in human disease are described. These studies, funded by the NIH Common Fund Extracellular RNA Communication Program, examine diverse extracellular body fluids, including plasma, serum, urine and cerebrospinal fluid. The disorders studied include hepatic and gastric cancer, cardiovascular disease, chronic kidney disease, neurodegenerative disease, brain tumours, intracranial haemorrhage, multiple sclerosis and placental disorders. Progress to date and the plans for future studies are outlined
Meeting report: discussions and preliminary findings on extracellular RNA measurement methods from laboratories in the NIH Extracellular RNA Communication Consortium
Extracellular RNAs (exRNAs) have been identified in all tested biofluids and have been associated with a variety of extracellular vesicles, ribonucleoprotein complexes and lipoprotein complexes. Much of the interest in exRNAs lies in the fact that they may serve as signalling molecules between cells, their potential to serve as biomarkers for prediction and diagnosis of disease and the possibility that exRNAs or the extracellular particles that carry them might be used for therapeutic purposes. Among the most significant bottlenecks to progress in this field is the lack of robust and standardized methods for collection and processing of biofluids, separation of different types of exRNA-containing particles and isolation and analysis of exRNAs. The Sample and Assay Standards Working Group of the Extracellular RNA Communication Consortium is a group of laboratories funded by the U.S. National Institutes of Health to develop such methods. In our first joint endeavour, we held a series of conference calls and in-person meetings to survey the methods used among our members, placed them in the context of the current literature and used our findings to identify areas in which the identification of robust methodologies would promote rapid advancements in the exRNA field
In Memoriam: A Memoir for Our Fallen "Heroes"
This article is made available for unrestricted research re-use and secondary analysis in any form or be any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.Even though neurosurgeons exercise these enormous and versatile skills, the COVID-19 pandemic has shaken the fabrics of the global neurosurgical family, jeopardizing human lives, and forcing the entire world to be locked down. We stand on the shoulders of the giants and will not forget their examples and their teachings. We will work to the best of our ability to honor their memory. Professor Harvey Cushing said: “When to take great risks; when to withdraw in the face of unexpected difficulties; whether to force an attempted enucleation of a pathologically favorable tumor to its completion with the prospect of an operative fatality, or to abandon the procedure short of completeness with the certainty that after months or years even greater risks may have to be faced at a subsequent session—all these require surgical judgment which is a matter of long experience.” It is up to us, therefore, to keep on the noble path that we have decided to undertake, to accumulate the surgical experience that these icons have shown us, the fruit of sacrifice and obstinacy. Our tribute goes to them; we will always remember their excellent work and their brilliant careers that will continue to enlighten all of us. This memorial is intended to commemorate our colleagues who succumbed during the first 4 months
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