Publications by authors named "Victor M Lu"

135 Publications

Syrinx shunts for syringomyelia: a systematic review and meta-analysis of syringosubarachnoid, syringoperitoneal, and syringopleural shunting.

J Neurosurg Spine 2021 Jul 30:1-11. Epub 2021 Jul 30.

Objective: Syringomyelia is a debilitating, progressive disease process that can lead to loss of neurological function in patients already experiencing significant compromise. Syringosubarachnoid, syringoperitoneal, and syringopleural shunts are accepted treatment options for patients with persistent syringomyelia, but direct comparisons have been lacking to date. The authors conducted a systematic review of the literature and meta-analysis to compare clinical outcomes between these three syrinx shunt modalities.

Methods: Utilizing PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines for systematic reviews, Ovid Embase, PubMed, Scopus, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, American College of Physicians Journal Club, and Database of Abstracts of Review of Effectiveness were searched to identify all potentially relevant studies published from inception until July 2020. Data were extracted and analyzed using meta-analysis of proportions. The primary study outcome was the rate of reoperation based on the initial shunt modality. Secondary outcomes included clinical improvement, clinical deterioration, and complications following shunt placement.

Results: A total of 22 articles describing 27 distinct treatment cohorts published between 1984 and 2019 satisfied the inclusion criteria. This captured 473 syrinx shunt procedures, 193 (41%) by syringosubarachnoid shunt, 153 (32%) by syringoperitoneal shunt, and 127 (27%) by syringopleural shunt, with an overall median clinical follow-up of 44 months. The pooled incidences of revision surgery were estimated as 13% for syringosubarachnoid, 28% for syringoperitoneal, and 10% for syringopleural shunts, respectively (p-interaction = 0.27). The rate of clinical improvement was estimated as 61% for syringosubarachnoid, 64% for syringoperitoneal, and 71% for syringopleural shunts. The rate of clinical deterioration following placement was estimated as 13% for syringosubarachnoid, 13% for syringoperitoneal, and 10% for syringopleural shunts.

Conclusions: The preferred modality of syrinx shunting remains a controversial topic for symptomatic syringomyelia. This study suggests that while all three modalities offer similar rates of clinical improvement and deterioration after placement, syringoperitoneal shunts have a greater rate of malfunction requiring surgical revision. These data also suggest that syringopleural shunts may offer the best rate of clinical improvement with the lowest rate of reoperation.
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http://dx.doi.org/10.3171/2020.12.SPINE201826DOI Listing
July 2021

Robotic guidance platform for laser interstitial thermal ablation and stereotactic needle biopsies: a single center experience.

J Robot Surg 2021 Jul 13. Epub 2021 Jul 13.

Department of Neurological Surgery, University of Miami Miller School of Medicine, Lois Pope Life Center, 1095 NW 14th Terrace (D4-6), Miami, FL, 33146, USA.

While laser ablation has become an increasingly important tool in the neurosurgical oncologist's armamentarium, deep seated lesions, and those located near critical structures require utmost accuracy during stereotactic laser catheter placement. Robotic devices have evolved significantly over the past two decades becoming an accurate and safe tool for stereotactic neurosurgery. Here, we present our single center experience with the MedTech ROSA ONE Brain robot for robotic guidance in laser interstitial thermal therapy (LITT) and stereotactic biopsies. We retrospectively analyzed the first 70 consecutive patients treated with ROSA device at a single academic medical center. Forty-three patients received needle biopsy immediately followed by LITT with the catheter placed with robotic guidance and 27 received stereotactic needle biopsy alone. All the procedures were performed frameless with skull bone fiducials for registration. We report data regarding intraoperative details, mortality and morbidity, diagnostic yield and lesion characteristics on MRI. Also, we describe the surgical workflow for both procedures. The mean age was 60.3 ± 15 years. The diagnostic yield was positive in 98.5% (n = 69). Sixty-three biopsies (90%) were supratentorial and seven (10%) were infratentorial. Gliomas represented 54.3% of the patients (n = 38). There were two postoperative deaths (2.8%). No permanent morbidity related to surgery were observed. We did not find intraoperative technical problems with the device. There was no need to reposition the needle after the initial placement. Stereotactic robotic guided placement of laser ablation catheters and biopsy needles is safe, accurate, and can be implemented into a neurosurgical workflow.
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http://dx.doi.org/10.1007/s11701-021-01278-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276839PMC
July 2021

Clinical utility of brain biopsy for presumed CNS relapse of systemic lymphoma.

J Neurosurg 2021 Jul 2:1-10. Epub 2021 Jul 2.

1Department of Neurosurgery and.

Objective: The objective of this study was to determine the frequency with which brain biopsy for presumed CNS relapse of systemic hematological malignancies yields new, actionable diagnostic information. Hematological malignancies represent a disparate group of genetic and histopathological disorders. Proclivity for brain involvement is dependent on the unique entity and may occur synchronously or metasynchronously with the systemic lesion. Diffuse large B-cell lymphomas (DLBCLs) have a high propensity for brain involvement. Patients in remission from systemic DLBCL may present with a lesion suspicious for brain relapse. These patients often undergo brain biopsy. The authors' a priori hypothesis was that brain biopsy in patients with a history of systemic DLBCL and a new brain MRI lesion would have lower diagnostic utility compared with patients with non-DLBCL systemic malignancies.

Methods: The authors performed a retrospective review of patients who underwent brain biopsy between 2000 and 2019. Inclusion criteria were patients ≥ 18 years of age with a prior systemic hematological malignancy in remission presenting with a new brain MRI lesion concerning for CNS relapse. Patients with a history of any CNS neoplasms, demyelinating disorders, or active systemic disease were excluded. The main outcome was the proportion of patients with a distinct histopathological brain diagnosis compared with the systemic malignancy. The authors secondarily assessed overall survival, procedure-related morbidity, and 30-day mortality.

Results: Sixty patients met inclusion criteria (40 males and 20 females); the median age at brain biopsy was 67 years (range 23-88 years). The median follow-up was 8.5 months (range 0.1-231 months). Thirty-nine (65.0%) patients had DLBCL and 21 (35%) had non-DLBCL malignancies. Thirty-five of 36 (97.2%) patients with prior systemic DLBCL and a diagnostic biopsy had histopathological confirmation of the original systemic disease versus 0 of 21 patients with non-DLBCL systemic malignancies (p < 0.001). Morbidity and 30-day mortality were 8.3% and 10.0%, respectively; 2 of 6 30-day mortalities were directly attributable to the biopsy. The median overall survival following brain biopsy was 10.8 months.

Conclusions: Patients with a history of systemic DLBCL and presumed CNS relapse gained minimal clinical benefit from brain biopsy but were at high risk of morbidity and mortality. In patients with a history of non-DLBCL systemic malignancies, brain biopsy remained critical given the high likelihood for discovery of distinct diagnostic entities. It was determined that patients with a prior systemic DLBCL and presumed brain relapse should likely receive empirical therapy obviating treatment delay and the risks of brain biopsy.
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http://dx.doi.org/10.3171/2020.12.JNS202517DOI Listing
July 2021

Perioperative Complications in Endoscopic Endonasal versus Transcranial Resections of Adult Craniopharyngiomas.

World Neurosurg 2021 Jun 18. Epub 2021 Jun 18.

Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA; Sylvester Comprehensive Cancer Center, University of Miami Health System, Miami, Florida, USA. Electronic address:

Background: Adult craniopharyngiomas are low-grade tumors of the pituitary infundibulum that can be locally aggressive and frequently present with profound visual deficits and endocrinopathies. Surgical resection remains the preferred initial treatment for these lesions, and recently endoscopic endonasal approaches (EEAs) have become increasingly used. However, minimal data exist comparing these techniques with traditional transcranial (TC) methods. The purpose of this study was to evaluate perioperative differences in EEA and TC approaches for adult craniopharyngiomas over the past several decades.

Methods: Craniopharyngioma surgeries in the Nationwide Inpatient Sample from 1998 to 2014 were identified. Complication rates, mortality rates, and annual treatment trends were stratified by procedure. Annual caseload was assessed with linear regression, and multivariate logistic regression models were created to determine predictors of inpatient mortality and perioperative complications.

Results: From 1998-2014, a significant increase in EEAs for craniopharyngiomas (+4.36/year, r = 0.80, P < 0.0001) was observed. In contrast, no increase in TC surgeries for these lesions was seen. In multivariate analysis, EEAs were more likely to experience postoperative cerebrospinal fluid leak (odds ratio = 2.61, P < 0.0001). However, EEAs were protective against all other perioperative complications including diabetes insipidus, panhypopituitarism, visual impairment, and even mortality (odds ratio = 0.41, P = 0.0007).

Conclusions: Over the past several decades, utilization of EEAs to resect adult craniopharyngiomas has increased. EEAs appear to be associated with lower rates of perioperative mortality and complications. However, long-term, prospective studies controlling for tumor size, location, and preoperative symptomatology are needed to determine when one approach should be used preferentially over the other.
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http://dx.doi.org/10.1016/j.wneu.2021.06.066DOI Listing
June 2021

The emerging role of nanotechnology in pursuit of successful drug delivery to H3K27M diffuse midline gliomas.

Nanomedicine (Lond) 2021 07 17;16(16):1343-1346. Epub 2021 May 17.

Department of Neurologic Surgery, Mayo Clinic, Rochester, MN 55905, USA.

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http://dx.doi.org/10.2217/nnm-2021-0067DOI Listing
July 2021

Current experimental therapies for atypical and malignant meningiomas.

J Neurooncol 2021 Jun 5;153(2):203-210. Epub 2021 May 5.

Department of Neurological Surgery, University of Miami Miller School of Medicine, 1095 NW 14th Terrace, Miami, FL, 33136, USA.

Introduction: Atypical (WHO grade II) and malignant meningiomas (WHO Grade III) are a rare subset of primary intracranial tumors. Given their relatively high recurrence rate after surgical resection and radiotherapy, there has been a recent push to explore other adjuvant treatment options for these treatment-refractory tumors. Recent advances in molecular sequencing of tumors have elucidated new pathways and drug targets which are currently being studied. This article provides a thorough overview of novel investigational therapeutics including targeted therapy, immunotherapy, and new technological modalities for atypical and malignant meningiomas.

Methods: We performed a comprehensive review of the available literature regarding preclinical and clinical evidence for emerging treatments for high grade meningiomas from 1980 to 2020 including contemporaneous clinical trials.

Results: There is encouraging preclinical evidence regarding the efficacy of the emerging treatments discussed in this article. Several clinical trials are currently recruiting patients to translate targeted molecular therapy for meningiomas. Several clinical studies have suggested a clinical benefit of combinatorial treatment for these treatment-refractory tumors.

Conclusion: With numerous active clinical trials for high grade meningiomas, a meaningful improvement in the outcomes for these tumors may be on the horizon.
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http://dx.doi.org/10.1007/s11060-021-03759-xDOI Listing
June 2021

Early Recurrence of an Infantile Endodermal Oculomotor Nerve Cyst following Surgical Fenestration: A Case Report.

Pediatr Neurosurg 2021 12;56(2):157-162. Epub 2021 Mar 12.

Department of Neurologic Surgery, Mayo Clinic, Rochester, Minnesota, USA.

Introduction: Infantile endodermal oculomotor nerve cyst (EONC) is an extremely rare entity. There are very few pediatric cases reported in the literature, and as expected, oculomotor palsy is the most common presenting symptom. To date however, the risk of recurrence of these lesions following surgical intervention is unclear due to a lack of long-term radiological follow-up.

Case Presentation: We present a case of a 13-month-old male patient with an EONC and detail his surgical fenestration and postoperative course. Somewhat surprisingly, re-expansion occurred within 6 months and remained stable 2 years later.

Discussion: A surgical approach to fenestration of an EONC in an infant is possible and should be performed by an expert neurosurgeon. Early recurrence is underreported in the current literature, and we encourage longer term radiological surveillance of these lesions after surgery to optimize primary and recurrent management in the future.
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http://dx.doi.org/10.1159/000511774DOI Listing
March 2021

Stimulated Raman Histology for Rapid Intraoperative Diagnosis of Gliomas.

World Neurosurg 2021 Jun 5;150:e135-e143. Epub 2021 Mar 5.

Department of Pathology, University of Miami Miller School of Medicine, Miami, Florida, USA.

Background: Intraoperative pathologic diagnosis traditionally involves frozen section histopathology, which may be labor and time intensive. Indeed, a technique that streamlines the acquisition and evaluation of intraoperative histologic data may expedite surgical decision-making and shorten operative time. Stimulated Raman histology (SRH) is an emerging technology that allows for more rapid acquisition and interpretation of intraoperative histopathologic data.

Methods: A blinded, prospective cohort study was performed for 82 patients undergoing resection for a central nervous system tumor. Of these, 21 patients were diagnosed with glioma either intraoperatively or postoperatively on permanent section histology and included in this study. Time to diagnosis (TTD) and diagnostic accuracy relative to permanent section (the gold standard) were compared between SRH-based diagnosis and conventional frozen section histology. Diagnostic concordance with permanent section was also compared between frozen histopathology and SRH diagnosis.

Results: Diagnostic accuracy was not significantly different between methods (P = 1.00). Diagnostic concordance was not significantly different between methods when comparing 95% confidence intervals for kappa values (κ = 0.215; κ = 0.297; κ = 0.369). Lastly, mean TTD was significantly shorter with SRH-based diagnosis compared with frozen section (43 vs. 9.7 minutes, P < 0.0001). SRH was able to identify key features associated with varying glioma types.

Conclusions: SRH allows for rapid intraoperative diagnosis without sacrificing diagnostic accuracy. SRH may serve as a promising adjuvant to conventional histopathology to expedite intraoperative pathology consultation and surgical decision-making.
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http://dx.doi.org/10.1016/j.wneu.2021.02.122DOI Listing
June 2021

When "Peripheral" Becomes "Central": Primary and Secondary Malignant Intracerebral Nerve Sheath Tumor: A Case Report and a Systematic Review.

Neurosurgery 2021 05;88(6):1074-1087

Department of Neurological Surgery, University of Miami Miller School of Medicine, Lois Pope Life Center, Miami, Florida, USA.

Background: The intracerebral occurrence of malignant peripheral nerve sheath tumors (MPNSTs) is exceedingly rare, and despite aggressive treatments, local recurrence and poor prognosis are very frequent. Like other brain tumors, these tumors could be primary or secondary, making the term "peripheral" an imprecise term for a primary brain tumor.

Objective: To analyze the reported cases of primary and secondary cerebral MPSNTs in terms of diagnosis, treatment, and overall survival. Additionally, we present a case of malignant intracerebral nerve sheath tumor (MINST) treated with radical surgery and radiotherapy.

Methods: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, one database (PubMed) and crossed references were queried for MPNST with brain metastasis and primary MINSTs from 1971 to 2020. Data regarding demographic features, primary tumor site, risk factors, brain location of the lesion, treatment applied, and overall survival were extracted.

Results: A total of 55 patients were selected (including the reported case): 29 patients were secondary brain MPNST and 26 patients were primary MINST. The mean age was 41.8 ± 22 and 31.2 ± 23 yr, respectively. All brain metastases of MPNST (100%) had a primary tumor elsewhere in the body at the time of diagnosis. The overall survival was significantly shorter in patients with a secondary brain MPNST compared to MINST (P = .002).

Conclusion: We present a comprehensive analysis of every reported primary and secondary intracerebral MPNST. The prognosis in terms of survival is worst in the last one despite aggressive treatment. The lack of a primary MPNST in screening tests is sufficient to confirm a MINST at time of diagnosis.
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http://dx.doi.org/10.1093/neuros/nyab043DOI Listing
May 2021

Rapid Intraoperative Diagnosis of Meningiomas using Stimulated Raman Histology.

World Neurosurg 2021 Jun 27;150:e108-e116. Epub 2021 Feb 27.

Department of Pathology, University of Miami Miller School of Medicine, Miami, Florida, USA.

Background: Frozen section is a time- and labor-intensive method for intraoperative pathologic diagnosis. As a result, there exists a need to expedite and streamline the acquisition and interpretation of diagnostic histologic data to inform surgical decision making. Stimulated Raman histology (SRH) is an emerging technology that may serve to expedite the acquisition and interpretation of histologic data in the operating room.

Methods: A blinded, prospective cohort study of 82 patients undergoing resection for tumors of the central nervous system was performed. Twenty-six patients with diagnoses of meningioma on SRH, frozen, or permanent section were included in this subanalysis. Diagnostic time and accuracy of stimulated SRH histology images were compared with the gold standard (frozen section). Agreement of SRH and frozen section diagnosis with permanent section (true) diagnosis was also compared.

Results: Mean time-to-diagnosis was significantly shorter for SRH-mediated diagnosis compared with frozen section (9.2 vs. 35.8, P < 0.0001). Diagnostic accuracy was not significantly different between methods (P = 0.15). Diagnostic agreement was not significantly different between SRH versus frozen, SRH versus permanent, or frozen versus permanent section methods (P = 0.5, P = 0.5, P = 1.00).

Conclusions: SRH is a promising adjuvant technology that may expedite intraoperative neuropathologic consult without sacrificing diagnostic accuracy.
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http://dx.doi.org/10.1016/j.wneu.2021.02.097DOI Listing
June 2021

Clinical trials using oncolytic viral therapy to treat adult glioblastoma: a progress report.

Neurosurg Focus 2021 02;50(2):E3

Objective: Adult glioblastoma (GBM) has proven refractory to decades of innovation. Oncolytic viral therapy represents a novel therapy that uses viral vectors as both a delivery and therapeutic mechanism to target GBM cells. Despite the growing body of basic science data supporting the feasibility of viral therapy to treat GBM, the reporting of clinical trial results is heterogeneous. Correspondingly, the aim of this study was to present a contemporary summary of the progress all clinical trials have made to date.

Methods: The ClinicalTrials.gov database was reviewed in August 2020 for all possible interventional clinical trials involving viral vector-based therapy to treat adult GBM. These were then screened against selection criteria to identify pertinent clinical trials.

Results: A total of 29 oncolytic viral therapy trials treating adult GBM were identified. The median start and expected completion years were 2014 and 2020, respectively. At the time of this writing, 10 (35%) trials were reported to have completed recruitment, whereas 7 (24%) were actively recruiting. The median target enrollment number was 36 (range 13-108), with the majority of trials being phase I (n = 18, 62%), and involving secondary GBM among other malignant glioma (n = 19, 66%). A total of 10 unique viral vectors were used across all trials, with the most common being adenovirus (n = 16, 55%). Only 2 (7%) phase I trials to date have reported outcomes on the ClinicalTrials.gov portal. Results of 12 additional clinical trials were found in academic publications, with median progression-free and overall survival times of 3 and 15 months, respectively, after the first viral dose at recurrence. The coordination of the large majority of trials originated from the US (n = 21, 72%), and the median number of testing sites per trial was 1 (range 1-15), via industry funding (n = 18 trials, 62%).

Conclusions: There are multiple early-stage oncolytic viral therapy clinical trials for adult GBM currently active. To date, limited results and outcomes are promising but scarce. The authors expect this to change in the near future because many trials are scheduled to have either nearly or actually reached their expected recruitment completion time. How exactly oncolytic viral therapy will fit into the current treatment paradigms for primary and secondary GBM remains to be seen, and will not be known until safety and toxicity profiles are established by these clinical trials.
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http://dx.doi.org/10.3171/2020.11.FOCUS20860DOI Listing
February 2021

Meralgia paresthetica treated by injection, decompression, and neurectomy: a systematic review and meta-analysis of pain and operative outcomes.

J Neurosurg 2021 Jan 15:1-11. Epub 2021 Jan 15.

1Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, Florida; and.

Objective: Meralgia paresthetica is caused by entrapment of the lateral femoral cutaneous nerve (LFCN) and often presents with pain. Multiple treatment options targeting the LFCN can be pursued to treat the pain should conservative measures fail, with the most common options being injection, neurolysis, and neurectomy. However, their efficacy in causing pain relief and their clinical outcomes have yet to be directly compared. The aim of this study was to interrogate the contemporary literature and quantitatively define how these options compare.

Methods: The electronic databases Ovid Embase, PubMed, SCOPUS, and the Cochrane Library were interrogated from inception to May 2020 following the PRISMA guidelines. Candidate articles were screened against prespecified criteria. Outcome data were abstracted and pooled by random-effects meta-analysis of proportions.

Results: There were 25 articles that satisfied all criteria, reporting outcomes for a total of 670 meralgia paresthetica patients, with 78 (12%) treated by injection, 496 (74%) by neurolysis, and 96 (14%) by neurectomy. The incidence of complete pain relief was 85% (95% CI 71%-96%) after neurectomy, 63% (95% CI 56%-71%) after neurolysis, and 22% (95% CI 13%-33%) after injection, which were all statistically different (p < 0.01). The incidence of revision procedures was 12% (95% CI 4%-22%) after neurolysis and 0% (95% CI 0%-2%) after neurectomy, which were significantly lower than 81% (95% CI 64%-94%) after injection (p < 0.01). The incidences of treatment complications were statistically comparable across all three treatments, ranging from 0% to 5% (p = 0.34).

Conclusions: There are multiple treatment options to target pain in meralgia paresthetica. The incidence of complete pain relief appears to be the greatest among the 3 interventions after neurectomy, accompanied by the lowest incidence of revision procedures. These findings should help inform patient preference and expectations. Greater exploration of the anatomical rationale for incomplete pain relief after surgical intervention will assist in optimizing further surgical treatment for meralgia paresthetica.
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http://dx.doi.org/10.3171/2020.7.JNS202191DOI Listing
January 2021

Efficacy and safety of bevacizumab in progressive pediatric low-grade glioma: a systematic review and meta-analysis of outcome rates.

Neurooncol Pract 2020 Jul 3;7(4):359-368. Epub 2020 Feb 3.

Department of Neurologic Surgery, Mayo Clinic, Rochester, MN, United States.

Background: Successful management of pediatric low-grade glioma (pLGG) can be complicated by eloquent anatomical location, as well as specific pathologic and molecular features. Some authors have proposed using the VEGF inhibitor bevacizumab to improve disease control, but its safety and efficacy are poorly defined. Correspondingly, our aim was to pool systematically identified clinical data in the literature to assess the clinical utility of bevacizumab for pLGG at progression.

Methods: A systematic search of 7 electronic databases from inception to June 2019 was conducted following PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines. Articles were screened against prespecified criteria. Outcomes were then pooled by random-effects meta-analyses of proportions.

Results: Seven pertinent studies described the outcomes of 110 progressive pLGG patients managed with bevacizumab in largely multiagent regimens. While on treatment, the rate of clinical response was 58% (95% CI, 43%-72%), and the rate of response on imaging was 80% (95% CI, 58%-96%). The rate of grade 3 or higher toxicity was 8% (95% CI, 2%-17%), with proteinuria the most commonly described. In the off-treatment period up to median 1 year, the rate of progression was estimated to be 51% (95% CI, 28%-74%).

Conclusions: Bevacizumab has the potential to control clinical and radiographic disease with relatively low grade 3 or higher toxicity risk in progressive pLGG patients. However, the long-term off-treatment benefits of this therapy are not yet well defined. Heterogeneity in the literature precludes any formal recommendations regarding its use until larger, more standardized investigations can be performed.
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http://dx.doi.org/10.1093/nop/npz076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7690362PMC
July 2020

Age of diagnosis clinically differentiates atypical teratoid/rhabdoid tumors diagnosed below age of 3 years: a database study.

Childs Nerv Syst 2021 04 24;37(4):1077-1085. Epub 2020 Nov 24.

Department of Neurological Surgery, University of Miami Miller School of Medicine, 1095 NW 14th Terrace, Miami, FL, 33136, USA.

Background: Atypical teratoid/rhabdoid tumor (ATRT) is a rare and largely pediatric diagnosis, with poor survival. Diagnosis below the age of 3 years is characteristically seen as a poor prognostic sign. However, elucidating if clinical differences exist within this niche age group has never been attempted before. Correspondingly, we sought to characterize clinical profile of ATRT diagnoses before the age of 3 years based on separate ages of diagnosis.

Methods: All pediatric ATRT patients aged < 3 years in the US National Cancer Database (NCDB) between 2005 and 2016 were retrospectively reviewed. Age groups were divided based on diagnoses at ages 0-1 years in group 1, 1-2 years in group 2, and 2-3 years in group 3. Data were summarized, and overall survival (OS) was modeled using Kaplan-Meier and Cox regression analyses.

Results: A total of 354 ATRT diagnoses were made before the age of 3 years, with surgery used in 316 (89%) cases, chemotherapy in 242 (68%) cases, and radiation therapy in 118 (33%) cases. In terms of diagnosis age, there were 153 (43%) in group 1, 137 (39%) in group 2, and 64 (18%) in group 3. With respect to OS, median value was 9.9 months in group 1, 28.4 months in group 2, and 15.9 months in group 3. Upon multivariate analysis, receiving radiation therapy was the only parameter shared amongst all three groups as independently prognostic of longer OS (HR 0.53, P = 0.01 in group 1; HR 0.34, P < 0.01 in group 2; HR 0.31, P < 0.01 in group 3). In group 1, surgery (HR 0.47, P < 0.01) and chemotherapy (HR 0.44, P < 0.01) were also independently prognostic of longer OS. In group 3, multiple socioeconomic parameters were identified to independently predict longer OS. There were no additional predictive parameters identified in group 2.

Conclusion: Although ATRT diagnosed before the age of 3 is typically viewed a poor prognostic age category, our findings demonstrate that the clinical profile of this pediatric niche is highly heterogeneous based on age of diagnosis. Survival of only those diagnosed between 0 and 1 years is independently prognosticated by all three treatment modalities; patients diagnosed between 1 and 2 years trend towards longest survival, and socioeconomic parameters are most influential in those diagnosed between 2 and 3 years.
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http://dx.doi.org/10.1007/s00381-020-04972-1DOI Listing
April 2021

Subarachnoid hemorrhage rebleeding in the first 24 h is associated with external ventricular drain placement and higher grade on presentation: Cohort study.

J Clin Neurosci 2020 Nov 12;81:180-185. Epub 2020 Oct 12.

Department of Neurology, Mayo Clinic, Rochester, MN, United States.

Background: Rebleeding after aneurysmal subarachnoid hemorrhage (aSAH) confers a poor prognosis; however, risk factors and differential outcomes associated with early rebleeding in the first 24 h after symptom presentation are incompletely understood.

Methods: A retrospective cohort study of all aSAH presenting to our institution between 2001 and 2016 was performed. Early rebleeding events were defined as clinical neurologic decline with radiographically confirmed acute intracranial hemorrhage within 24 h after symptom presentation. Univariate and multivariate logistic regression analyses were used to assess clinical associations, with a specific focus on baseline Glasgow Coma Score (GCS), World Federation of Neurosurgical Societies (WFNS), and modified Fisher scores.

Results: Of 471 aSAH cases, 33 (7%) experienced early rebleeding. Multivariate regression identified extraventricular drain (EVD) placement (OR = 2.16, P = 0.04) and WFNS 3-5 (OR = 2.69, P = 0.02) as significant predictors of early rebleeding. Good functional outcomes were observed in 8 patients with early rebleeding (24%), all of whom underwent aneurysm treatment. Higher SAH grade prior to rebleeding (WFNS 3-5) was significantly associated with increased odds of an unfavorable functional outcome (OR = 8.09, P < 0.01). Anticoagulation, aneurysm size and location were not significantly associated with either early rebleeding incidence or functional outcome.

Conclusions: Early rebleeding in aSAH is associated with unfavorable functional outcomes. EVD placement and higher SAH grade on presentation appear to be significantly and independently associated with increased risk of rebleeding within first 24 h, as well as unfavorable long-term functional outcome; however, the clinical benefit of hyper-acute aneurysm treatment requires further investigation.
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http://dx.doi.org/10.1016/j.jocn.2020.09.064DOI Listing
November 2020

Epigenetic-Targeted Treatments for H3K27M-Mutant Midline Gliomas.

Adv Exp Med Biol 2021 ;1283:73-84

Department of Neurosurgery, Mayo Clinic, Rochester, MN, USA.

Diffuse intrinsic pontine glioma (DIPG) is a lethal midline brainstem tumor that most commonly occurs in children and is genetically defined by substitution of methionine for lysine at site 27 of histone 3 (H3K27M) in the majority of cases. This mutation has since been shown to exert an influence on the posttranslational epigenetic landscape of this disease, with the loss of trimethylation at lysine 27 (H3K27me3) the most common alteration. Based on these findings, a number of drugs targeting these epigenetic changes have been proposed, specifically that alter histone trimethylation, acetylation, or phosphorylation. Various mechanisms have been explored, including inhibition of H327 demethylase and methyltransferase to target trimethylation, inhibition of histone deacetylase (HDAC) and bromodomain and extraterminal (BET) to target acetylation, and inhibition of phosphatase-related enzymes to target phosphorylation. This chapter reviews the current rationales and progress made to date in epigenetically targeting DIPG via these mechanisms.
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http://dx.doi.org/10.1007/978-981-15-8104-5_6DOI Listing
January 2021

Surgery versus radiosurgery for facial nerve schwannoma: a systematic review and meta-analysis of facial nerve function, postoperative complications, and progression.

J Neurosurg 2020 Oct 30:1-12. Epub 2020 Oct 30.

Departments of1Neurosurgery.

Objective: Intracranial facial nerve schwannomas (FNS) requiring treatment are frequently recommended for surgery or stereotactic radiosurgery (SRS). The objective of this study was to compare facial nerve function outcomes between these two interventions for FNS via a systematic review and meta-analysis.

Methods: A search of the Ovid EMBASE, PubMed, SCOPUS, and Cochrane databases from inception to July 2019 was conducted following PRISMA guidelines. Articles were screened against prespecified criteria. Facial nerve outcomes were classified as improved, stabilized, or worsened by last follow-up. Incidence was pooled by random-effects meta-analysis of proportions.

Results: Thirty-three articles with a pooled cohort of 519 patients with FNS satisfied all criteria. Twenty-five articles described operative outcomes in 407 (78%) patients; 10 articles reported SRS outcomes in 112 (22%). In the surgical cohort, facial nerve function improved in 23% (95% CI 15%-32%), stabilized in 41% (95% CI 32%-50%), and worsened in 30% (95% CI 21%-40%). In the SRS cohort, facial nerve function was improved in 20% (95% CI 9%-34%), stable in 66% (95% CI 54%-78%), and worsened in 9% (95% CI 3%-16%). Compared with SRS, microsurgery was associated with a significantly lower incidence of stable facial nerve function (p < 0.01) and a significantly higher incidence of worsened facial nerve function (p < 0.01). Tumor progression and complication rates were comparable. Outcome certainty assessments were very low to moderate for all parameters.

Conclusions: Unfavorable facial nerve function outcomes are associated with surgical treatment of intracranial FNS, whereas stable facial nerve function outcomes are associated with SRS. Therefore, SRS should be recommended to patients with FNS who require treatment, and surgery should be reserved for patients with another indication, such as decompression of the brainstem. Further study is required to definitively optimize and validate management strategies for these rare skull base tumors.
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http://dx.doi.org/10.3171/2020.6.JNS201548DOI Listing
October 2020

Cytotoxic lanthanum oxide nanoparticles sensitize glioblastoma cells to radiation therapy and temozolomide: an in vitro rationale for translational studies.

Sci Rep 2020 10 23;10(1):18156. Epub 2020 Oct 23.

Lowy Cancer Center, University of New South Wales, Sydney, NSW, Australia.

Glioblastoma (GBM) is a malignant brain tumour with a dismal prognosis, despite best treatment by surgical resection, radiation therapy (RT) and chemotherapy with temozolomide (TMZ). Nanoparticle (NP) therapy is an emerging consideration due to the ability of NPs to be formulated and cross the blood brain barrier. Lanthanum oxide (LaO) NPs are therapeutically advantageous due to the unique chemical properties of lanthanum making it cytotoxic to cancers, and able to enhance existing anti-cancer treatments. However, LaO NPs have yet to be thoroughly investigated in brain tumors. We show that these NPs can reach the brain after venous injection, penetrate into GBM cells via endocytosis, dissociate to be cytotoxic, and enhance the therapeutic effects of RT and TMZ. The mechanisms of cell death by LaO NPs were found to be multifaceted. Increasing NP concentration was correlated to increased intrinsic and extrinsic apoptosis pathway markers in a radical oxygen species (ROS)-dependent manner, as well as involving direct DNA damage and autophagic pathways within GBM patient-derived cell lines. NP interactions to sensitize GBM to RT and TMZ were shown to involve these pathways by enhancing ROS and apoptotic mechanisms. We therefore demonstrate the therapeutic potential of LaO NPs to treat GBM cells in vitro, and encourage translational exploration in the future.
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http://dx.doi.org/10.1038/s41598-020-75372-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7584621PMC
October 2020

Geographic and socioeconomic considerations for glioblastoma treatment in the elderly at a national level: a US perspective.

Neurooncol Pract 2020 Oct 3;7(5):522-530. Epub 2020 Jun 3.

Vivian L. Smith Department of Neurosurgery, University of Texas McGovern Medical School, Houston, Texas.

Background: Treatment for glioblastoma (GBM) in elderly (age > 65 years) patients can be affected by multiple geographic and socioeconomic parameters. Correspondingly, the aim of this study was to determine trends in treatment of elderly GBM patients in the United States.

Methods: All GBM patients in the U.S. National Cancer Database between 2005 and 2016 were retrospectively reviewed. Status of treatment by triple therapy (resection, chemotherapy, and radiation) were summarized and analyzed by U.S. Census region.

Results: There were 44 338 GBM patients included, with 21 573 (49%) elderly and 22 765 (51%) nonelderly patients with median ages 72 years (range, 65-90 years) and 47 years (range, 40-64 years), respectively. Compared to nonelderly patients, elderly patients had significantly lower odds of being treated by triple therapy (odds ratio, OR = 0.54) as a whole, and its individual elements of resection (OR = 0.78), chemotherapy (OR = 0.46), radiation therapy (OR = 0.52). This was reflected in each U.S. Census region, with the lowest odds of being treated with triple therapy, surgical resection, chemotherapy, and radiation therapy in New England (OR = 0.51) Mountain (OR = 0.66), West North Central (OR = 0.38), and the Middle Atlantic (OR = 0.44), respectively. Multivariable analysis revealed multiple socioeconomic parameters that significantly predicted lower odds of triple therapy in the elderly.

Conclusions: In the United States alone, there exists geographic disparity in the treatment outcomes of elderly GBM patients. Multiple socioeconomic parameters can influence access to treatment modalities for elderly patients compared to younger patients in different geographic regions, and public health initiatives targeting these aspects may prove beneficial conceptually to optimize and homogenize clinical outcomes.
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http://dx.doi.org/10.1093/nop/npaa029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7516121PMC
October 2020

Effects of intraoperative liposomal bupivacaine on pain control and opioid use after pediatric Chiari I malformation surgery: an initial experience.

J Neurosurg Pediatr 2020 Oct 2:1-7. Epub 2020 Oct 2.

Departments of1Neurologic Surgery and.

Objective: Pediatric Chiari I malformation decompression is a common neurosurgical procedure. Liposomal bupivacaine (LB) is a novel formulation that can have an impact on postoperative recovery for particular procedures, but its potential role in pediatric neurosurgery is largely unexplored. The authors sought to describe and assess their initial experience with LB in pediatric Chiari I malformation decompression to better define its potential role as an analgesic agent in a procedure for which the postoperative course is often remarkably painful.

Methods: A retrospective review of all pediatric Chiari procedures performed at the authors' institution between 2018 and 2020 was conducted. Patients were divided into those who were treated with a single intraoperative dose of LB (LB group) and those who were not (control group). Comparisons of total opioid use and pain control were made using chi-square and Wilcoxon rank-sum tests.

Results: A total of 18 patients were identified, 9 (50%) in the LB group and 9 (50%) in the control group. Overall, there were 13 (72%) female and 5 (28%) male patients with a mean age of 15.9 years. No surgical complications were observed over a mean length of stay of 2.7 days. Within the first 24 hours after surgery, the LB group had significantly lower total opioid use than the control group (17.5 vs 47.9 morphine milligram equivalents, respectively; p = 0.03) as well as lower mean pain scores reported by patients using a 10-point visual analog scale (3.6 vs 5.5 for the LB vs control groups, p = 0.04). However, from the first 24 postoperative hours to discharge, total opioid use (p = 0.51) and mean pain scores (p = 0.09) were statistically comparable between the two groups. There were 2/9 (22%) LB patients versus 0/9 (0%) control patients who did not require opioid analgesia at any point during hospitalization.

Conclusions: The use of a single intraoperative dose of LB in pediatric Chiari I malformation surgery appears to be safe and has the potential to reduce pain scores and opioid use when administered during the first 24 postoperative hours. From that time period to discharge, however, there may be no significant difference in total opioid use or pain scores.
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http://dx.doi.org/10.3171/2020.6.PEDS20370DOI Listing
October 2020

Presenting NIHSS predicts 90-day functional outcome after mechanical thrombectomy for basilar artery occlusion: A systematic review and meta-analysis.

Clin Neurol Neurosurg 2020 10 2;197:106199. Epub 2020 Sep 2.

Department of Neurological Surgery, Miller School of Medicine University of Miami, Miami, FL, USA.

The prediction of outcome after mechanical thrombectomy (MT) of basilar artery occlusion (BAO) remains an area of investigation. The objective of this study was to evaluate the prognostic role of presenting National Institute Health of Stroke Scale (NIHSS) scores in predicting favorable 90-day functional outcome. A survey of 7 electronic databases from inception to May 2020 was conducted following PRISMA guidelines. Articles were screened against pre-specified criteria. Multivariate odds ratios (ORs) for favorable 90-day function outcome (modified Rankin Score 0-2) were extracted and pooled by meta-analysis of proportions with random effects modeling. A total of 10 individual studies satisfied criteria for selection and described a total of 941 BAO patients managed by MT. Analysis revealed 590 (63%) males with a mean age of 66.6 years. The median presenting NIHSS was 19, and 316 (34%) patients were reported to have a favorable functional status 90-days after treatment. Lower presenting NIHSS scores independently and significantly predicted favorable 90-day functional outcome in BAO patients with a pooled OR of 0.89 (95% CI, 0.87-0.92; I = 18%; P-heterogeneity = 0.28). Meta-regression did not detect any clinical parameter that influenced this trend direction or its significance, and bias assessments were unremarkable. We confirm in this study via a consensus within the literature that the presenting NIHSS score predicts 90-day functional outcome in BAO patients treated by MT. Further, its standardized use allows more meaningful comparisons between interventions and anatomical locations.
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http://dx.doi.org/10.1016/j.clineuro.2020.106199DOI Listing
October 2020

Lanthanum nanoparticles to target the brain: proof of biodistribution and biocompatibility with adjuvant therapies.

Nanomedicine (Lond) 2020 09 1;15(22):2107-2117. Epub 2020 Sep 1.

Lowy Cancer Center, University of New South Wales, Sydney, NSW, Australia.

To determine the biodistribution of lanthanum (III) oxide (LaO) nanoparticle (NP) therapy to the brain and its biocompatibility with radiation therapy (RT) and chemotherapy (CT). Healthy balb/c nude mice were administered 4 weekly doses of LaO NP therapy via tail vein injection. Organ weights and lanthanum concentrations were evaluated. LaO NP penetrated the brain. Concentrations were found to peak in the brain at 24 h after injection and persisted at 8 weeks after injection. Neither RT nor CT affected biodistribution. No adverse events or safety concerns in other organs were noted. LaO NP can reach the brain to target neurological disease and is biocompatible with RT and CT in a biological system.
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http://dx.doi.org/10.2217/nnm-2020-0165DOI Listing
September 2020

Laser Interstitial Thermal Therapy Case Series: Choosing the Correct Number of Fibers Depending on Lesion Size.

Oper Neurosurg (Hagerstown) 2020 12;20(1):18-23

Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.

Background: Laser interstitial thermal therapy (LITT) is being used for the treatment of recurrent glioblastoma multiforme (GBM). Lesions can be treated using 1 or multiple LITT fibers depending on the preference of surgeons. Usually, more fibers are needed for coverage of larger tumors.

Objective: To investigate and analyze how tumor size affected the number of LITT fibers used.

Methods: This is a retrospective review of patients undergoing treatment of recurrent GBM. Patients were treated with up to 4 LITT fibers for adequate tumor coverage. Patient demographics, tumor characteristics, length of stay, complications, and biopsy results were recorded.

Results: A total of 43 cases were treated using LITT, and of these cases, 31 consisted of contiguous lesions. We used more fibers to treat larger tumor volumes. On average, for each 5 cc of tumor volume, a fiber was added for proper coverage (P = .554). Complications and length of stay were similar across the groups (P = .378, P = .941).

Conclusion: LITT can be used for the treatment of recurrent GBM. For each 5 cc of tumor volume, a LITT fiber can be added to the treatment plan.
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http://dx.doi.org/10.1093/ons/opaa264DOI Listing
December 2020

Understanding the trajectory of research efforts in atypical teratoid rhabdoid tumors: a bibliometric analysis of the 50 most impactful studies to date.

Childs Nerv Syst 2021 02 17;37(2):419-425. Epub 2020 Aug 17.

Department of Neurologic Surgery, Mayo Clinic, 200 First St. SW, Rochester, MN, 55905, USA.

Purpose: Atypical teratoid/rhabdoid tumor (ATRT) is a highly malignant embryonal tumor of the central nervous system (CNS) that occurs predominantly in children. More is being discovered about this disease to improve understanding and outcomes. The aim of this analysis was to evaluate citation and other bibliometric characteristics of the 50 most cited articles in the contemporary literature in order to better model the trajectory of our current efforts.

Methods: Elsevier's Scopus database was searched for the 50 most cited articles about ATRT. To look for trends, earliest 25 articles were separated from the latest 25 articles and then were compared. Various bibliometric parameters were summarized and compared using Pearson's chi-square and Mann-Whitney U tests.

Results: The 50 most cited articles were published between 1990 and 2016, from 5 unique countries in 29 unique journals, with genetic and retrospective observational cohort studies the most common design (n = 11 each). Overall median values were as follows: citation count, 145.4 citations (range, 67-626); citation rate per year, 11.7 (range, 3.5-51.4); number of authors 12 (range, 1-95); with 32 (64%) originating from the USA. Compared with older articles, newer articles had statistically lower citation counts (101.8 vs 189.0; P < 0.01), higher number of authors (17.3 vs 6.6; P < 0.01), and were less likely published from the USA (40% vs 88%; P < 0.01) CONCLUSIONS: The 50 most cited articles about ATRT were characterized in this analysis. There was a distinct focus in these studies on the genetic composition and consequences of these tumors. Trends over time suggest greater impact will be had in highly collaborative efforts worldwide. Moving forward, it will be of great interest to see how the findings of these basic science finding will translate into future clinical studies.
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http://dx.doi.org/10.1007/s00381-020-04863-5DOI Listing
February 2021

Utilizing systematic reviews and meta-analyses effectively to evaluate brain tumor biomarkers.

Biomark Med 2020 07 17;14(10):817-820. Epub 2020 Aug 17.

Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, USA.

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http://dx.doi.org/10.2217/bmm-2020-0209DOI Listing
July 2020

Effect of surgery and chemotherapy on long-term survival in infants with congenital glioblastoma: an integrated survival analysis.

J Neurosurg Pediatr 2020 Aug 14:1-9. Epub 2020 Aug 14.

1Department of Neurologic Surgery, Mayo Clinic, Rochester, Minnesota.

Objective: Glioblastoma (GBM) during infancy is rare, and the clinical outcomes of congenital GBM are not well understood. Correspondingly, the aim of this study was to present a long-term survivor case from the authors' institution, and establish an integrated cohort of cases across the published literature to better understand the clinical course of this disease in this setting.

Methods: The authors report the outcomes of an institutional case of congenital GBM diagnosed within the first 3 months of life, and performed a comprehensive literature search for published cases from 2000 onward for an integrated survival analysis. All cases were integrated into 1 cohort, and Kaplan-Meier estimations, Fisher's exact test, and logistic regression were used to interrogate the data.

Results: The integrated cohort of 40 congenital GBM cases consisted of 23 (58%) females and 17 (42%) males born at a median gestational age of 38 weeks (range 22-40 weeks). Estimates of overall survival (OS) at 1 month was 67%, at 1 year it was 59%, and at 10 years it was 45%, with statistically superior outcomes for subgroups in which patients survived to be treated by resection and chemotherapy. In the overall cohort, multivariable analysis confirmed resection (p < 0.01) and chemotherapy (p < 0.01) as independent predictors of superior OS. Gestational age > 38 weeks (p < 0.01), Apgar scores ≥ 7 at 5 minutes (p < 0.01), absence of prenatal hydrocephalus (p < 0.01), and vaginal delivery (p < 0.01) were associated with greater odds of surgical diagnosis versus autopsy diagnosis.

Conclusions: Congenital GBM can deviate from the expected poor prognosis of adult GBM in terms of OS. Both resection and chemotherapy confer statistically superior prognostic advantages in those patients who survive within the immediate postnatal period, and should be first-line considerations in the initial management of this rare disease.
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http://dx.doi.org/10.3171/2020.5.PEDS20226DOI Listing
August 2020

Telemedicine in Neurosurgery: Lessons Learned from a Systematic Review of the Literature for the COVID-19 Era and Beyond.

Neurosurgery 2020 12;88(1):E1-E12

University of Miami, Department of Neurosurgery, Miami, Florida.

Background: Evolving requirements for patient and physician safety and rapid regulatory changes have stimulated interest in neurosurgical telemedicine in the COVID-19 era.

Objective: To conduct a systematic literature review investigating treatment of neurosurgical patients via telemedicine, and to evaluate barriers and challenges. Additionally, we review recent regulatory changes that affect telemedicine in neurosurgery, and our institution's initial experience.

Methods: A systematic review was performed including all studies investigating success regarding treatment of neurosurgical patients via telemedicine. We reviewed our department's outpatient clinic billing records after telemedicine was implemented from 3/23/2020 to 4/6/2020 and reviewed modifier 95 inclusion to determine the number of face-to-face and telemedicine visits, as well as breakdown of weekly telemedicine clinic visits by subspecialty.

Results: A total of 52 studies (25 prospective and 27 retrospective) with 45 801 patients were analyzed. A total of 13 studies were conducted in the United States and 39 in foreign countries. Patient management was successful via telemedicine in 99.6% of cases. Telemedicine visits failed in 162 cases, 81.5% of which were due to technology failure, and 18.5% of which were due to patients requiring further face-to-face evaluation or treatment. A total of 16 studies compared telemedicine encounters to alternative patient encounter mediums; telemedicine was equivalent or superior in 15 studies. From 3/23/2020 to 4/6/2020, our department had 122 telemedicine visits (65.9%) and 63 face-to-face visits (34.1%). About 94.3% of telemedicine visits were billed using face-to-face procedural codes.

Conclusion: Neurosurgical telemedicine encounters appear promising in resource-scarce times, such as during global pandemics.
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http://dx.doi.org/10.1093/neuros/nyaa306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7454774PMC
December 2020

International Medical Graduates Applying to Neurosurgical Residency in the United States Through the Lenses of an Applicant Versus a Program Director.

World Neurosurg 2020 10 16;142:299-300. Epub 2020 Jul 16.

Department of Neurological Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, USA.

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http://dx.doi.org/10.1016/j.wneu.2020.07.046DOI Listing
October 2020
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