Publications by authors named "Alfredo Quiñones-Hinojosa"

494 Publications

Single-level awake transforaminal lumbar interbody fusion: a Mayo Clinic institutional experience and national analysis.

Neurosurg Focus 2021 Dec;51(6):E4

2Department of Neurosurgery, Mayo Clinic, Rochester; and.

Objective: Awake transforaminal lumbar interbody fusion (TLIF) is a novel technique for performing spinal fusions in patients under conscious sedation. Whether awake TLIF can reduce operative times and decrease the hospital length of stay (LOS) remains to be shown. In this study, the authors sought to assess the differences in clinical outcomes between patients who underwent awake TLIF and those who underwent TLIF under general anesthesia by using institutional experience at the Mayo Clinic and the National Surgical Quality Improvement Program (NSQIP) database.

Methods: Chart review was performed for a consecutive series of patients who underwent single-level minimally invasive surgery (MIS)-TLIF performed by a single surgeon (K.A.I.) at a single institution. Additionally, the NSQIP database was queried from 2016 to 2019 for patients who underwent awake TLIF as well as propensity score-matched patients who underwent TLIF under general anesthesia.

Results: A total of 20 patients at Mayo Clinic underwent awake single-level MIS-TLIF. The mean operative time was 122 ± 16.68 minutes, and the mean estimated blood loss was 39 ± 30.24 ml. No intraoperative complications were reported. A total of 96 patients who underwent TLIF (24 awake and 72 under general anesthesia) were analyzed from the NSQIP database. The mean LOS was less in the awake cohort (1.4 ± 1.381 days) than the general anesthesia cohort (3 ± 2.274 days) (p = 0.002).

Conclusions: Evidence from the authors' institutional experience and national analysis has demonstrated that awake MIS-TLIF is efficient and can reduce hospital LOS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3171/2021.9.FOCUS21457DOI Listing
December 2021

Spinal versus general anesthesia for minimally invasive transforaminal lumbar interbody fusion: implications on operating room time, pain, and ambulation.

Neurosurg Focus 2021 Dec;51(6):E3

1Department of Neurosurgery, Mayo Clinic, Jacksonville.

Objective: There has been increasing interest in the use of spinal anesthesia (SA) for spine surgery, especially within Enhanced Recovery After Surgery (ERAS) protocols. Despite the wide adoption of SA by the orthopedic practices, it has not gained wide acceptance in lumbar spine surgery. Studies investigating SA versus general anesthesia (GA) in lumbar laminectomy and discectomy have found that SA reduces perioperative costs and leads to a reduction in analgesic use, as well as to shorter anesthesia and surgery time. The aim of this retrospective, case-control study was to compare the perioperative outcomes of patients who underwent minimally invasive surgery (MIS)-transforaminal lumbar interbody fusion (TLIF) after administration of SA with those who underwent MIS-TLIF under GA.

Methods: Overall, 40 consecutive patients who underwent MIS-TLIF by a single surgeon were analyzed; 20 patients received SA and 20 patients received GA. Procedure time, intraoperative adverse events, postoperative adverse events, postoperative length of stay, 3-hour postanesthesia care unit (PACU) numeric rating scale (NRS) pain score, opioid medication, and time to first ambulation were collected for each patient.

Results: The two groups were homogeneous for clinical characteristics. A decrease in total operating room (OR) time was found for patients who underwent MIS-TLIF after administration of SA, with a mean OR time of 156.5 ± 18.9 minutes versus 213.6 ± 47.4 minutes for patients who underwent MIS-TLIF under GA (p < 0.0001), a reduction of 27%. A decrease in total procedure time was also observed for SA versus GA (122 ± 16.7 minutes vs 175.2 ± 10 minutes; p < 0.0001). No significant differences were found in intraoperative and postoperative adverse events. There was a difference in the mean maximum NRS pain score during the first 3 hours in the PACU as patients who received SA reported a lower pain score compared with those who received GA (4.8 ± 3.5 vs 7.3 ± 2.7; p = 0.018). No significant difference was observed in morphine equivalents received by the two groups. A difference was also observed in the mean overall NRS pain score, with 2.4 ± 2.1 for the SA group versus 4.9 ± 2.3 for the GA group (p = 0.001). Patients who received SA had a shorter time to first ambulation compared with those who received GA (385.8 ± 353.8 minutes vs 855.9 ± 337.4 minutes; p < 0.0001).

Conclusions: The results of this study have pointed to some important observations in this patient population. SA offers unique advantages in comparison with GA for performing MIS-TLIF, including reduced OR time and postoperative pain, and faster postoperative mobilization.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3171/2021.9.FOCUS21265DOI Listing
December 2021

Comparison of Outcomes between Cage Materials Used for Patients Undergoing Anterior Cervical Discectomy and Fusion with Stand-Alone Cages: A Systematic Review and Meta-Analysis.

World Neurosurg 2021 Nov 24. Epub 2021 Nov 24.

Neuro-Informatics Laboratory, Mayo Clinic College of Medicine and Science, Rochester, MN, USA; Department of Neurological Surgery, Mayo Clinic, Rochester, MN, USA; Departments of Orthopedic Surgery and Health Services Research, Mayo Clinic College of Medicine and Science, Rochester, MN, USA. Electronic address:

Introduction: Interbody cages are currently being used to address diseases of the vertebra requiring surgical stabilization. Titanium cages were first introduced in 1988. Polyetheretherketone (PEEK) cages are utilized frequently as one of the alternatives to titanium cages in current practice. This study aimed to compare available cage materials by reviewing the surgical and radiographic outcomes following anterior cervical discectomy and fusion (ACDF).

Methods: A comprehensive search of several electronic databases was conducted following the PRISMA guidelines. Baseline characteristics, operative outcomes, arthrodesis rates, subsidence rates and complications were collected from included studies. Collected outcomes were further stratified according to the procedure type, the number of levels operated, and graft used to compare cage materials.

Results: Following the screening for inclusion criteria, a total of 37 studies with 2,363 patients were included. The median age was 49.5 years and the median follow-up was 26 months. Overall, no significant differences were found between PEEK and titanium cages regarding fusion, neurologic deficit, subsidence rates, or "good and excellent" outcome according to Odom criteria. However, the standalone comparison between PEEK, titanium, and PMMA cages showed a significantly lower fusion rate for PMMA. (PEEK: 94%, PMMA: 56%, Titanium: 95%, p < 0.01).

Conclusion: In the present systematic review and meta-analysis, a comparison of the long-term patient reported and the radiographic outcomes associated with the use of titanium and PEEK, intervertebral body cages showed similar findings. However, there were significantly lower fusion rates for PMMA cages when using a standalone cage without graft material.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.wneu.2021.10.084DOI Listing
November 2021

Protein kinase C and SRC signaling define reciprocally related subgroups of glioblastoma with distinct therapeutic vulnerabilities.

Cell Rep 2021 Nov;37(8):110054

Department of Cancer Biology, Mayo Clinic, Jacksonville, FL 32224, USA. Electronic address:

We report that atypical protein kinase Cι (PKCι) is an oncogenic driver of glioblastoma (GBM). Deletion or inhibition of PKCι significantly impairs tumor growth and prolongs survival in murine GBM models. GBM cells expressing elevated PKCι signaling are sensitive to PKCι inhibitors, whereas those expressing low PKCι signaling exhibit active SRC signaling and sensitivity to SRC inhibitors. Resistance to the PKCι inhibitor auranofin is associated with activated SRC signaling and response to a SRC inhibitor, whereas resistance to a SRC inhibitor is associated with activated PKCι signaling and sensitivity to auranofin. Interestingly, PKCι- and SRC-dependent cells often co-exist in individual GBM tumors, and treatment of GBM-bearing mice with combined auranofin and SRC inhibitor prolongs survival beyond either drug alone. Thus, we identify PKCι and SRC signaling as distinct therapeutic vulnerabilities that are directly translatable into an improved treatment for GBM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.celrep.2021.110054DOI Listing
November 2021

The impact of multiple lesions on progression-free survival of meningiomas: a 10-year multicenter experience.

J Neurosurg 2021 Nov 19:1-9. Epub 2021 Nov 19.

11Neurology, Mayo Clinic, Jacksonville, Florida.

Objective: Multiple meningiomas (MMs) occur in as many as 18% of patients with meningioma, and data on progression-free survival (PFS) are scarce. The objective of this study was to explore the influence of the number of lesions and clinical characteristics on PFS in patients with WHO grade I meningiomas.

Methods: The authors retrospectively reviewed the records of all adults diagnosed with a meningioma at their three main sites from January 2009 to May 2020. Progression was considered the time from diagnosis until radiographic growth of the originally resected meningioma. A secondary analysis was performed to evaluate the time of diagnosis until the time to second intervention (TTSI). Univariable and multivariable analyses were conducted to assess whether the number of lesions or any associated variables (age, sex, race, radiation treatment, tumor location, and extent of resection) had a significant impact on PFS and TTSI.

Results: Eight hundred thirty-eight patients were included. Use of a log-rank test to evaluate PFS and TTSI between a single and multiple lesions showed a significantly shorter progression for MM (p < 0.001 and p < 0.001, respectively). Multivariable Cox regression analysis showed significantly inferior PFS on MM compared to a single lesion (hazard ratio [HR] 2.262, 95% confidence interval [CI] 1.392-3.677, p = 0.001) and a significantly inferior TTSI for patients with MM when compared to patients with a single meningioma (HR 2.377, 95% CI 1.617-3.494, p = 0.001). By testing the number of meningiomas as a continuous variable, PFS was significantly inferior for each additional meningioma (HR 1.350, 95% CI 1.074-1.698, p = 0.010) and TTSI was significantly inferior as well (HR 1.428, 95% CI 1.189-1.716, p < 0.001). African American patients had an inferior PFS when compared to non-Hispanic White patients (HR 3.472, 95% CI 1.083-11.129, p = 0.036).

Conclusions: The PFS of meningiomas appears to be influenced by the number of lesions present. Patients with MM also appear to be more prone to undergoing a second intervention for progressive disease. Hence, a closer follow-up may be warranted in patients who present with multiple lesions. These results show a decreased PFS for each additional lesion present, as well as a shorter PFS for MM compared to a single lesion. When assessing associated risk factors, African American patients showed an inferior PFS, whereas older age and adjuvant therapy with radiation showed an improved PFS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3171/2021.8.JNS211252DOI Listing
November 2021

Minimally Invasive Transforaminal Lumbar Interbody Fusion: Cost of a Surgeon's Learning Curve.

World Neurosurg 2021 Nov 13. Epub 2021 Nov 13.

Department of Neurologic Surgery, Mayo Clinic, Jacksonville, Florida, USA. Electronic address:

Background: Minimally invasive transforaminal interbody fusion has become an increasingly common approach in adult degenerative spine disease but is associated with a steep learning curve.

Objective: To evaluate the impact of the learning experience on mean procedure time and mean cost associated with each procedure.

Methods: We studied the first one-hundred consecutive minimally invasive transforaminal interbody fusion procedures of a single surgeon. We performed multivariable linear regression models, modelling operating time and costs in function of the procedure order adjusted for patients' age, gender and number of surgical levels. The number of procedures necessary to attain proficiency was determined through a k-means cluster analysis. Finally, the total excess operative time and total excess cost until obtaining proficiency was evaluated.

Results: Procedure order was found to impact procedure time and mean costs, with each successive case being associated with progressively less procedure time and cost. On average, each successive case was associated with a reduction in procedure time of 0.97 minutes (95% CI=0.54-1.40; p<0.001) and an average adjusted reduction in overall costs of $82.75 (95% CI=$35.93-129.57; p<0.001). An estimated 58 procedures were needed to attain proficiency, translating into an excess procedure time of 2604.2 minutes (average of 45 minutes per case), overall costs associated with the learning experience of $226,563.8 (average of $3974.80 per case), and excess surgical cost of $125,836.6 (average of $2207.66 per case).

Conclusion: Successive cases were associated with progressively less procedure time and mean overall and surgical costs, until a proficiency threshold was attained.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.wneu.2021.11.039DOI Listing
November 2021

What Is the Learning Curve for Lumbar Spine Surgery Under Spinal Anesthesia?

World Neurosurg 2021 Nov 1. Epub 2021 Nov 1.

Department of Neurosurgery, Mayo Clinic, Jacksonville, Florida, USA. Electronic address:

Background: Spinal anesthesia (SA) is routinely used in obstetrics and orthopedic surgery but has not been widely adopted in lumbar spine surgery (LSS). One perceived barrier is the learning curve for the neurosurgical and anesthesia team associated with managing a patient in the prone position under SA.

Methods: A retrospective cohort of 34 LSS cases under SA at our institution was examined. Operative time, corrected operative time per level, and complications were analyzed. The learning curve was assessed using a curve-fit regression analysis.

Results: Of patients, 62% were female, with mean (SD) age and body mass index of 60.7 (10.8) years and 29.9 (4.6) kg/m, respectively. The mean (SD) for each time segment was operating room arrival to incision 35.7 (8.1) minutes, total surgical time 100.4 (35.8) minutes, and procedure finish to operating room exit 3.4 (2.5) minutes. When the times were normalized to procedure type and analyzed sequentially, the mean (SD) slope of all trendlines was 0.003 (0.005) with correlation coefficients of R = 0.0002-0.01, indicating no appreciable learning curve. Normalized postanesthesia care unit time was significantly shorter for overnight stay versus same-day discharge (0.64 vs. 1.36, P = 0.0005).

Conclusions: Our data demonstrate the lack of a learning curve when SA is implemented in LSS cases by an anesthetic team already familiar with SA techniques for other procedures. Importantly, the surgical team was already familiar with the minimally invasive surgery approaches used in conjunction with SA. This study highlights that the barriers to transitioning to SA for LSS may be fewer than perceived.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.wneu.2021.10.172DOI Listing
November 2021

Building and implementing an institutional registry for a data-driven national neurosurgical practice: experience from a multisite medical center.

Neurosurg Focus 2021 11;51(5):E9

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

In an era when healthcare "value" remains a much-emphasized concept, measuring and reporting the quality of neurosurgical care and costs remains a challenge for large multisite health systems. Ensuring cohesion in outcomes across multiple sites is important to the development of a holistic competitive marketing strategy that seeks to promote "brand" performance characterized by a superior quality of patient care. This requires mechanisms for data collection and development of a single uniform outcomes measurement system site wide. Operationalizing a true multidisciplinary effort in this space requires intersection of a vast array of information technology and administrative resources along with the neurosurgeons who provide subject-matter expertise relevant to patient care. To measure neurosurgical quality and safety as well as improve payor contract negotiations, a practice analytics dashboard was created to allow summary visualization of operational indicators such as case volumes, quality outcomes, and relative value units and financial indicators such as total hospital costs and charges in order to provide a comprehensive overview of the "value" of surgical care. The current version of the dashboard summarizes these metrics by site, surgeon, and procedure for nearly 30,000 neurosurgical procedures that have been logged into the Mayo Clinic Enterprise Neurosurgery Registry since transition to the Epic electronic health record (EHR) system. In this article, the authors sought to review their experience in launching this EHR-linked data-driven neurosurgical practice initiative across a large, national multisite academic medical center.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3171/2021.8.FOCUS21381DOI Listing
November 2021

Adipose-Derived Stem Cells Therapy for Radiation-Induced Skin Injury.

Ann Plast Surg 2021 12;87(6):639-649

From the Division of Plastic Surgery.

Background: Radiation-induced skin injuries have been treated with different medical therapies and have shown diverse outcomes. We aim to evaluate the effect of adipose-derived stem cells (ADSCs) therapy on radiation-induced skin injury.

Methods: We performed a review by querying PubMed, Ovid MEDLINE, and EMBASE databases from inception to April 2020 following Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. The MeSH terms "adipose-derived stem cells," "wound healing," "radiation," and synonyms in combinations determined our search strategy. Experimental peer-reviewed articles describing the protocol and comparing the results with controls were included. Non-English studies were excluded.

Results: Our search recorded a total of 137 articles. Only 8 studies met our inclusion criteria and were included in this review. Five studies evaluated the use of ADSC alone, whereas the others evaluated the efficacy of ADSC seeded in scaffolds. Adipose-derived stem cell-based therapies, either alone or seeded in scaffolds, were shown to improve wound healing in most studies when compared with controls.

Conclusions: There is evidence supporting the positive benefits from ADSC-based therapies in radiation-induced skin injury. However, further studies are needed to standardize the method of ADSC extraction, radiation-induced skin injury experimental model, and increase the time of follow-up to evaluate the results accurately.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/SAP.0000000000003039DOI Listing
December 2021

IDH-wild-type glioblastoma cell density and infiltration distribution influence on supramarginal resection and its impact on overall survival: a mathematical model.

J Neurosurg 2021 Oct 29:1-9. Epub 2021 Oct 29.

1Department of Neurosurgery, Mayo Clinic, Jacksonville, Florida.

Objective: Recent studies have proposed resection of the T2 FLAIR hyperintensity beyond the T1 contrast enhancement (supramarginal resection [SMR]) for IDH-wild-type glioblastoma (GBM) to further improve patients' overall survival (OS). GBMs have significant variability in tumor cell density, distribution, and infiltration. Advanced mathematical models based on patient-specific radiographic features have provided new insights into GBM growth kinetics on two important parameters of tumor aggressiveness: proliferation rate (ρ) and diffusion rate (D). The aim of this study was to investigate OS of patients with IDH-wild-type GBM who underwent SMR based on a mathematical model of cell distribution and infiltration profile (tumor invasiveness profile).

Methods: Volumetric measurements were obtained from the selected regions of interest from pre- and postoperative MRI studies of included patients. The tumor invasiveness profile (proliferation/diffusion [ρ/D] ratio) was calculated using the following formula: ρ/D ratio = (4π/3)2/3 × (6.106/[VT21/1 - VT11/1])2, where VT2 and VT1 are the preoperative FLAIR and contrast-enhancing volumes, respectively. Patients were split into subgroups based on their tumor invasiveness profiles. In this analysis, tumors were classified as nodular, moderately diffuse, or highly diffuse.

Results: A total of 101 patients were included. Tumors were classified as nodular (n = 34), moderately diffuse (n = 34), and highly diffuse (n = 33). On multivariate analysis, increasing SMR had a significant positive correlation with OS for moderately and highly diffuse tumors (HR 0.99, 95% CI 0.98-0.99; p = 0.02; and HR 0.98, 95% CI 0.96-0.99; p = 0.04, respectively). On threshold analysis, OS benefit was seen with SMR from 10% to 29%, 10% to 59%, and 30% to 90%, for nodular, moderately diffuse, and highly diffuse, respectively.

Conclusions: The impact of SMR on OS for patients with IDH-wild-type GBM is influenced by the degree of tumor invasiveness. The authors' results show that increasing SMR is associated with increased OS in patients with moderate and highly diffuse IDH-wild-type GBMs. When grouping SMR into 10% intervals, this benefit was seen for all tumor subgroups, although for nodular tumors, the maximum beneficial SMR percentage was considerably lower than in moderate and highly diffuse tumors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3171/2021.6.JNS21925DOI Listing
October 2021

Photocrosslinked Bioreducible Polymeric Nanoparticles for Enhanced Systemic siRNA Delivery as Cancer Therapy.

Adv Funct Mater 2021 Apr 22;31(17). Epub 2021 Feb 22.

Department of Biomedical Engineering and Institute for Nanobiotechnology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Departments of Materials Science and Engineering, Neurosurgery, Oncology, Ophthalmology, and Chemical and Biomolecular Engineering, Sidney Kimmel Comprehensive Cancer Center, The Bloomberg~Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.

Clinical translation of polymer-based nanocarriers for systemic delivery of RNA has been limited due to poor colloidal stability in the blood stream and intracellular delivery of the RNA to the cytosol. To address these limitations, this study reports a new strategy incorporating photocrosslinking of bioreducible nanoparticles for improved stability extracellularly and rapid release of RNA intracellularly. In this design, the polymeric nanocarriers contain ester bonds for hydrolytic degradation and disulfide bonds for environmentally triggered small interfering RNA (siRNA) release in the cytosol. These photocrosslinked bioreducible nanoparticles (XbNPs) have a shielded surface charge, reduced adsorption of serum proteins, and enable superior siRNA-mediated knockdown in both glioma and melanoma cells in high-serum conditions compared to non-crosslinked formulations. Mechanistically, XbNPs promote cellular uptake and the presence of secondary and tertiary amines enables efficient endosomal escape. Following systemic administration, XbNPs facilitate targeting of cancer cells and tissue-mediated siRNA delivery beyond the liver, unlike conventional nanoparticle-based delivery. These attributes of XbNPs facilitate robust siRNA-mediated knockdown in vivo in melanoma tumors colonized in the lungs following systemic administration. Thus, biodegradable polymeric nanoparticles, via photocrosslinking, demonstrate extended colloidal stability and efficient delivery of RNA therapeutics under physiological conditions, and thereby potentially advance systemic delivery technologies for nucleic acid-based therapeutics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/adfm.202009768DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8513781PMC
April 2021

Application of Human Adipose-Derived Stem cells for Bone Regeneration of the Skull in Humans.

J Craniofac Surg 2021 Oct 11. Epub 2021 Oct 11.

Division of Plastic Surgery Department of Neurological Surgery Department of Laboratory Medicine and Pathology, Transfusion Medicines and Stem Cell Therapy, Mayo Clinic, Jacksonville, FL.

Background: Archeological archives report cranioplasty as 1 of the oldest surgical procedures; however, it was not until the last century that true advances have been made. Alternative approaches are necessary to achieve optimal closure of the defect with fewer adverse effects. We aim to evaluate the use of human adipose-derived stem cells (hADSCs) alone or seeded in scaffolds as the main treatment for cranial bone defects and to assess human patient outcomes.

Methods: A systematic review was performed by querying PubMed, Ovid MEDLINE, EMBASE, and Cumulative Index to Nursing and Allied Health Literature databases with the MeSH terms: "adipose-derived stem cells," "cranial bone defect," "stromal vascular factor," "fat grafting," as well as synonyms in combinations determined by our search strategy. We included human models that used hADSCs as primary therapy. We excluded studies in languages other than English.

Results: One hundred ninety-four studies were identified after removal of duplicates. Four articles that used hADSCs as the main therapy to treat calvarial defects in humans were included. One article applied the cell therapy alone, and 3 used β-tricalcium phosphate granules as a scaffold to seed the hADSCs.

Conclusions: Bone regeneration was reached in a short and intermediate period using autologous hADSCs in humans with no major adverse effects in all 4 articles included. A long-term follow-up study (6 years) exhibited late infections and reabsorption of the β-tricalcium phosphate scaffold seeded with hADSCs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/SCS.0000000000008114DOI Listing
October 2021

Connectivity correlates to predict essential tremor deep brain stimulation outcome: Evidence for a common treatment pathway.

Neuroimage Clin 2021 Oct 4;32:102846. Epub 2021 Oct 4.

Department of Neurology, Norman Fixel Institute for Neurological Diseases, University of Florida, Gainesville, FL, USA; Department of Neurology, Mayo Clinic, Jacksonville, FL, USA; Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Background And Purpose: Deep brain stimulation (DBS) is the most common surgical treatment for essential tremor (ET), yet there is variation in outcome and stimulation targets. This study seeks to consolidate proposed stimulation "sweet spots," as well as assess the value of structural connectivity in predicting treatment outcomes.

Materials And Methods: Ninety-seven ET individuals with unilateral thalamic DBS were retrospectively included. Using normative brain connectomes, structural connectivity measures were correlated with the percentage improvement in contralateral tremor, based on the Fahn-Tolosa-Marin tremor rating scale (TRS), after parameter optimization (range 3.1-12.9 months) using a leave-one-out cross-validation in 83 individuals. The predictive feature map was used for cross-validation in a separate cohort of 14 ET individuals treated at another center. Lastly, estimated volumes of tissue activated (VTA) were used to assess a treatment "sweet spot," which was compared to seven previously reported stimulation sweet spots and their relationship to the tract identified by the predictive feature map.

Results: In the training cohort, structural connectivity between the VTA and dentato-rubro-thalamic tract (DRTT) correlated with contralateral tremor improvement (R = 0.41; p < 0.0001). The same connectivity profile predicted outcomes in a separate validation cohort (R = 0.59; p = 0.028). The predictive feature map represented the anatomical course of the DRTT, and all seven analyzed sweet spots overlapped the predictive tract (DRTT).

Conclusions: Our results strongly support the possibility that structural connectivity is a predictor of contralateral tremor improvement in ET DBS. The results suggest the future potential for a patient-specific functionally based surgical target. Finally, the results showed convergence in "sweet spots" suggesting the importance of the DRTT to the outcome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.nicl.2021.102846DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8503569PMC
October 2021

Use of adipose-derived stem cells in lymphatic tissue engineering and regeneration.

Arch Plast Surg 2021 Sep 15;48(5):559-567. Epub 2021 Sep 15.

Department of Neurosurgery, Mayo Clinic, Jacksonville, FL, USA.

The potential to differentiate into different cell lines, added to the easy and cost-effective method of extraction, makes adipose-derived stem cells (ADSCs) an object of interest in lymphedema treatment. Our study's goal was to conduct a comprehensive systematic review of the use of ADSCs in lymphatic tissue engineering and regeneration. On July 23, 2019, using PubMed/MEDLINE, Cochrane Clinical Answers, Cochrane Central Register of Controlled Trials, and Embase databases, we conducted a systematic review of published literature on the use of ADSCs in lymphatic tissue engineering and regeneration. There were no language or time frame limitations, and the following search strategy was applied: ((Adipose stem cell) OR Adipose-derived stem cell)) AND ((Lymphedema) OR Breast Cancer Lymphedema). Only original research manuscripts were included. Fourteen studies fulfilled the inclusion criteria. Eleven studies were experimental (in vitro or in vivo in animals), and only three were clinical. Publications on the topic demonstrated that ADSCs promote lymphangiogenesis, and its effect could be enhanced by modulation of vascular endothelial growth factor-C, interleukin-7, prospero homeobox protein 1, and transforming growth factor-β1. Pilot clinical studies included 11 patients with breast cancer-related lymphedema, and no significant side effects were present at 12-month follow-up. Literature on the use of ADSCs in lymphatic tissue engineering and regeneration demonstrated promising data. Clinical evidence is still in its infancy, but the scientific community agrees that ADSCs can be useful in regenerative lymphangiogenesis. Data collected in this review indicate that unprecedented advances in lymphedema treatment can be anticipated in the upcoming years.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5999/aps.2021.00339DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8490113PMC
September 2021

Three-Dimensionally Printed Surgical Simulation Tool for Brain Mapping Training and Preoperative Planning.

Oper Neurosurg (Hagerstown) 2021 Nov;21(6):523-532

Department of Neurologic Surgery, Mayo Clinic, Jacksonville, Florida, USA.

Background: Brain mapping is the most reliable intraoperative tool for identifying surrounding functional cortical and subcortical brain parenchyma. Brain mapping procedures are nuanced and require a multidisciplinary team and a well-trained neurosurgeon. Current training methodology involves real-time observation and operation, without widely available surgical simulation.

Objective: To develop a patient-specific, anatomically accurate, and electrically responsive biomimetic 3D-printed model for simulating brain mapping.

Methods: Imaging data were converted into a 2-piece inverse 3D-rendered polyvinyl acetate shell forming an anatomically accurate brain mold. Functional and diffusion tensor imaging data were used to guide wire placement to approximate the projection fibers from the arm and leg areas in the motor homunculus. Electrical parameters were generated, and data were collected and processed to differentiate between the 2 tracts. For validation, the relationship between the electrical signal and the distance between the probe and the tract was quantified. Neurosurgeons and trainees were interviewed to assess the validity of the model.

Results: Material testing of the brain component showed an elasticity modulus of 55 kPa (compared to 140 kPa of cadaveric brain), closely resembling the tactile feedback a live brain. The simulator's electrical properties approximated that of a live brain with a voltage-to-distance correlation coefficient of r2 = 0.86. Following 32 neurosurgeon interviews, ∼96% considered the model to be useful for training.

Conclusion: The realistic neural properties of the simulator greatly improve representation of a live surgical environment. This proof-of-concept model can be further developed to contain more complicated tractography, blood and cerebrospinal fluid circulation, and more in-depth feedback mechanisms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ons/opab331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8637789PMC
November 2021

Commentary: Dr Dorothy Kenke Nash: The First Woman Neurosurgeon in the United States.

Neurosurgery 2021 Nov;89(6):E318-E322

Queen's University Belfast, Belfast, UK.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/neuros/nyab338DOI Listing
November 2021

Perioperative Glycemia Management in Patients Undergoing Craniotomy for Brain Tumor Resection: A Global Survey of Neuroanesthesiologists' Perceptions and Practices.

World Neurosurg 2021 Nov 1;155:e548-e563. Epub 2021 Sep 1.

Department of Anesthesiology, Critical Care and Pain Medicine, Sapienza University of Rome, Rome, Italy.

Objective: There is a paucity of clinical evidence that guides perioperative glycemia management in patients undergoing craniotomy for brain tumor resection. The purpose of this study was to better understand global perceptions and practices related to glycemia management in these patients.

Methods: Neuroanesthesiologists throughout North America, South America, Europe, and Asia filled out a brief online questionnaire related to their perceptions and practices regarding glycemia management in patients undergoing craniotomy for brain tumor resection.

Results: Over 4 weeks, 435 participants practicing in 34 countries across 6 continents participated in this survey. Although responders in North America were found to perceive a higher risk hyperglycemia compared with those practicing in European (P = 0.024) and South Asian (P = 0.007) countries, responders practicing in South Asian countries (P = 0.030), Middle Eastern countries (P = 0.029), and South American (P = 0.005) countries were more likely than those from North America to remeasure glucose after an initial normal glucose measurement at incision. Responders from North America reported that a higher blood glucose threshold was necessary for them to delay or cancel the surgery compared with responders in Slavic (P < 0.001), European (P = 0.002), South American (P = 0.002), and Asian and Pacific (P < 0.001) countries. Responders from North America were more likely to report that they would delay or cancel the surgery because of a higher blood glucose threshold.

Conclusions: Our survey results suggest that perceptions and practices related to blood glucose management in patients undergoing brain tumor resection are variable. This study highlights the need for stronger clinical evidence and guidelines to help guide decisions for when and how to manage blood glucose derangements in these patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.wneu.2021.08.092DOI Listing
November 2021

Functional Characterization of Brain Tumor-Initiating Cells and Establishment of GBM Preclinical Models that Incorporate Heterogeneity, Therapy, and Sex Differences.

Mol Cancer Ther 2021 Dec 31;20(12):2585-2597. Epub 2021 Aug 31.

Department of Neurosurgery, Mayo Clinic, Jacksonville, Florida.

Glioblastoma (GBM) is the most common primary brain cancer in adults where tumor cell heterogeneity and sex differences influence clinical outcomes. Here, we functionally characterize three male and three female patient-derived GBM cell lines, identify protumorigenic BTICs, and create novel male and female preclinical models of GBM. Cell lines were evaluated on the following features: proliferation, stemness, migration, tumorigenesis, clinical characteristics, and sensitivity to radiation, TMZ, rh (rhTRAIL), and rh All cell lines were classified as GBM according to epigenetic subtyping, were heterogenous and functionally distinct from one another, and re-capitulated features of the original patient tumor. In establishing male and female preclinical models, it was found that two male-derived GBM cell lines (QNS108 and QNS120) and one female-derived GBM cell line (QNS315) grew at a faster rate in female mice brains. One male-derived GBM cell line (QNS108) decreased survival in female mice in comparison with male mice. However, no survival differences were observed for mice injected with a female-derived cell line (QNS315). In summary, a panel of six GBM patient-derived cell lines were functionally characterized, and it was shown that BTIC lines can be used to construct sex-specific models with differential phenotypes for additional studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1535-7163.MCT-20-0547DOI Listing
December 2021

Acute Brain Activation Patterns of High- Versus Low-Frequency Stimulation of the Anterior Nucleus of the Thalamus During Deep Brain Stimulation for Epilepsy.

Neurosurgery 2021 Oct;89(5):901-908

Department of Neurosurgery, Mayo Clinic, Jacksonville, Florida, USA.

Background: Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) is an increasingly utilized treatment of drug-resistant epilepsy. To date, the effect of high-frequency stimulation (HFS) vs low-frequency stimulation (LFS) in ANT DBS is poorly understood.

Objective: To assess differences in the acute effect of LFS vs HFS in ANT DBS utilizing blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI).

Methods: In this prospective study of 5 patients with ANT DBS for epilepsy, BOLD activation and deactivation were modeled for 145-Hz and 30-Hz ANT stimulation using an fMRI block design. Data were analyzed with a general linear model and combined via 2-stage mixed-effects analysis. Z-score difference maps were nonparametrically thresholded using cluster threshold of z > 3.1 and a (corrected) cluster significance threshold of P = .05.

Results: HFS produced significantly greater activation within multiple regions, in particular the limbic and default mode network (DMN). LFS produced minimal activation and failed to produce significant activation within these same networks. HFS produced widespread cortical and subcortical deactivation sparing most of the limbic and DMN regions. Meanwhile, LFS produced deactivation in most DMN and limbic structures.

Conclusion: Our results show that HFS and LFS produce substantial variability in both local and downstream network effects. In particular, largely opposing effects were identified within the limbic network and DMN. These findings may serve as a mechanistic basis for understanding the potential of HFS vs LFS in various epilepsy syndromes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/neuros/nyab306DOI Listing
October 2021

Minimizing OCT quantification error via a surface-tracking imaging probe.

Biomed Opt Express 2021 Jul 10;12(7):3992-4002. Epub 2021 Jun 10.

Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21215, USA.

OCT-based quantitative tissue optical properties imaging is a promising technique for intraoperative brain cancer assessment. The attenuation coefficient analysis relies on the depth-dependent OCT intensity profile, thus sensitive to tissue surface positions relative to the imaging beam focus. However, it is almost impossible to maintain a steady tissue surface during intraoperative imaging due to the patient's arterial pulsation and breathing, the operator's motion, and the complex tissue surface geometry of the surgical cavity. In this work, we developed an intraoperative OCT imaging probe with a surface-tracking function to minimize the quantification errors in optical attenuation due to the tissue surface position variations. A compact OCT imaging probe was designed and engineered to have a long working distance of ∼ 41 mm and a large field of view of 4 × 4 mm while keeping the probe diameter small (9 mm) to maximize clinical versatility. A piezo-based linear motor was integrated with the imaging probe and controlled based upon real-time feedback of tissue surface position inferred from OCT images. A GPU-assisted parallel processing algorithm was implemented, enabling detection and tracking of tissue surface in real-time and successfully suppressing more than 90% of the typical physiologically induced motion range. The surface-tracking intraoperative OCT imaging probe could maintain a steady beam focus inside the target tissue regardless of the surface geometry or physiological motions and enabled to obtain tissue optical attenuation reliably for assessing brain cancer margins in challenging intraoperative settings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1364/BOE.423233DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8367274PMC
July 2021

A multicenter analysis of the prognostic value of histone H3 K27M mutation in adult high-grade spinal glioma.

J Neurosurg Spine 2021 Aug 20:1-10. Epub 2021 Aug 20.

1Department of Neurosurgery, Mayo Clinic, Jacksonville, Florida.

Objective: High-grade spinal glioma (HGSG) is a rare but aggressive tumor that occurs in both adults and children. Histone H3 K27M mutation correlates with poor prognosis in children with diffuse midline glioma. However, the role of H3 K27M mutation in the prognosis of adults with HGSG remains unclear owing to the rarity of this mutation, conflicting reports, and the absence of multicenter studies on this topic.

Methods: The authors studied a cohort of 30 adult patients with diffuse HGSG who underwent histological confirmation of diagnosis, surgical intervention, and treatment between January 2000 and July 2020 at six tertiary academic centers. The primary outcome was the effect of H3 K27M mutation status on progression-free survival (PFS) and overall survival (OS).

Results: Thirty patients (18 males and 12 females) with a median (range) age of 50.5 (19-76) years were included in the analysis. Eighteen patients had H3 K27M mutation-positive tumors, and 12 had H3 K27M mutation-negative tumors. The median (interquartile range) PFS was 3 (10) months, and the median (interquartile range) OS was 9 (23) months. The factors associated with increased survival were treatment with concurrent chemotherapy/radiation (p = 0.006 for PFS, and p ≤ 0.001 for OS) and American Spinal Injury Association grade C or better at presentation (p = 0.043 for PFS, and p < 0.001 for OS). There were no significant differences in outcomes based on tumor location, extent of resection, sex, or H3 K27M mutation status. Analysis restricted to HGSG containing necrosis and/or microvascular proliferation (WHO grade IV histological features) revealed increased OS for patients with H3 K27M mutation-positive tumors (p = 0.017).

Conclusions: Although H3 K27M mutant-positive HGSG was associated with poor outcomes in adult patients, the outcomes of patients with H3 K27M mutant-positive HGSG were somewhat more favorable compared with those of their H3 K27M mutant-negative HGSG counterparts. Further preclinical animal studies and larger clinical studies are needed to further understand the age-dependent effects of H3 K27M mutation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3171/2021.2.SPINE201675DOI Listing
August 2021

Impact of COVID-19 on Neurosurgery in Brazil's Health System: The Reality of a Developing Country Affected by the Pandemic.

World Neurosurg 2021 11 13;155:e142-e149. Epub 2021 Aug 13.

Department of Neurosurgery, General Hospital of Fortaleza, Fortaleza, Ceará, Brazil.

Background: The coronavirus disease identified in 2019 (COVID-19) pandemic changed neurosurgery protocols to provide ongoing care for patients while ensuring the safety of health care workers. In Brazil, the rapid spread of the disease led to new challenges in the health system. Neurooncology practice was one of the most affected by the pandemic due to restricted elective procedures and new triage protocols. We aim to characterize the impact of the pandemic on neurosurgery in Brazil.

Methods: We analyzed 112 different types of neurosurgical procedures, with special detail in 11 neurooncology procedures, listed in the Brazilian Hospital Information System records in the DATASUS database between February and July 2019 and the same period in 2020. Linear regression and paired t-test analyses were performed and considered statistically significant at P < 0.05.

Results: There was an overall decrease of 21.5% (28,858 cases) in all neurosurgical procedures, impacting patients needing elective procedures (-42.46%) more than emergency surgery (-5.93%). Neurooncology procedures decreased by 14.89%. Nonetheless, the mortality rate during hospitalization increased by 21.26%. Linear regression analysis in hospitalizations (Slope = 0.9912 ± 0.07431; CI [95%] = 0.8231-1.159) and total cost (Slope = 1.03 ± 0.03501; CI [95%] = 0.9511-1.109) in the 11 different types of neurooncology procedures showed a P < 0.0001. The mean cost per type of procedure showed an 11.59% increase (P = 0.0172) between 2019 and 2020.

Conclusions: The COVID-19 pandemic has increased mortality, decreased hospitalizations, and therefore decreased overall costs, despite increased costs per procedure for a variety of neurosurgical procedures. Our study serves as a stark example of the effect of the pandemic on neurosurgical care in settings of limited resources and access to care.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.wneu.2021.08.030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8548285PMC
November 2021

Commentary: Evandro de Oliveira in the Historical Context of Brazilian Neurosurgery.

Neurosurgery 2021 Oct;89(5):E264-E265

Queen's University Belfast, Belfast, United Kingdom.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/neuros/nyab313DOI Listing
October 2021

Influence of glucose levels on clinical outcome after mechanical thrombectomy for large-vessel occlusion: a systematic review and meta-analysis.

J Neurointerv Surg 2021 Aug 6. Epub 2021 Aug 6.

Department of Neurologic Surgery, Mayo Clinic, Jacksonville, Florida, USA

Mechanical thrombectomy (MT) represents the mainstay of treatment for patients with acute ischemic stroke due to large-vessel occlusion (LVO). Intravenous thrombolysis has been associated with worse clinical outcome in patients presenting with high blood glucose levels at admission; to date the true effect of hyperglycemia in the setting of MT has not been fully elucidated. In this meta-analysis, we analyzed the influence of high blood glucose levels at admission on clinical outcome after MT. Ovid EMBASE, PubMed, Scopus, and Cochrane Library databases were searched from their dates of inception up to March 2021. An initial search identified 2118 articles representing 1235 unique studies. After applying selection criteria, three prospective and five retrospective studies were analyzed, yielding a pooled cohort of 5861 patients (2041 who presented with hyperglycemia, and 3820 who presented with normal blood glucose levels). Patients in the hyperglycemia group were less likely to have a modified Ranking Scale (mRS) score <3 (risk ratio (RR): 0.65; 95% CI 0.59 to 0.72; p<0.0001; =13%), and had an increased risk of symptomatic intracranial hemorrhage (sICH) (RR: 2.07; 95% CI 1.65 to 2.60; p<0.0001; =0%) and mortality (RR: 1.73; 95% CI 1.57 to 1.91; p<0.0001; =0%). Patients who present with hyperglycemia and undergo MT for treatment of LVO have an increased risk of unfavorable clinical outcome, sICH, and mortality. Glucose levels at admission appear to be a prognostic factor in this subset of patients. Further studies should focus on evaluating control of the glucose level at admission as a modifiable risk factor in patients undergoing MT for LVO.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/neurintsurg-2021-017771DOI Listing
August 2021

Hematologic Emergencies in the Postoperative Neurointensive Care Unit Setting: Illustrative Case Series and Differential Diagnosis.

J Stroke Cerebrovasc Dis 2021 Oct 3;30(10):106019. Epub 2021 Aug 3.

Department of Neurology, Mayo Clinic, Jacksonville, FL, US; Department of Neurologic Surgery, Mayo Clinic, Jacksonville, FL, US; Department of Critical Care, Mayo Clinic, Jacksonville, FL, US.

Objectives: Investigating the development of acute thrombocytopenia, differential etiologies, and potentially the rare manifestation of disseminated intravascular coagulation after brain tumor resection of primary and secondary malignancies.

Materials And Methods: We performed a retrospective review of a case series of post-operative neurosurgical patients which developed thrombocytopenia. We applied National Library of Medicine search engine methodology using the terms disseminated intravascular coagulation and brain tumors.

Results: We report clinical, radiographic, and laboratory data of four Neurointensive care unit patients that developed thrombocytopenia, three with disseminated intravascular coagulation after craniotomy, and one with heparin-induced thrombocytopenia masquerading as low grade disseminated intravascular coagulation. All four patients presented with cranial lesions and underwent neurosurgical resection. Underlying disorders included: high grade glioma, stage IV lung cancer with metastases, and meningioma. One patient survived and was able to recover after several days of hospitalization, while another patient was discharged to hospice. Search results illustrated that disseminated intravascular coagulation in the presence of glioblastoma multiforme is rare (only four patients) and may be due to a release of coagulation factors like tissue plasminogen activator, treated with antifibrinolytic agents. Searching the terms disseminated intravascular coagulation and brain tumors in the National Library of Medicine search engine yielded 116 results; eight were relevant to our study.

Conclusions: Correlation of thrombocytopenia after neurosurgery for glioblastoma multiforme and disseminated intravascular coagulation is rare. It is extremely challenging to manage these patients with concomitant deep vein thrombosis/pulmonary embolism and intracranial bleeding. Heparin-induced thrombocytopenia is common yet possesses a different hematological coagulation profile and has more pharmacologic options. Neurointensive care unit teams should recognize intraoperative and post-operative disseminated intravascular coagulation cases, and heparin-induced thrombocytopenia in the differential of post-operative thrombocytopenia with specific pharmacologic interventions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2021.106019DOI Listing
October 2021

Directed stimulation of the dentato-rubro-thalamic tract for deep brain stimulation in essential tremor: a blinded clinical trial.

Neuroradiol J 2021 Aug 2:19714009211036689. Epub 2021 Aug 2.

Department of Neurosurgery, Mayo Clinic, USA.

Objective: Observational studies utilising diffusion tractography have suggested a common mechanism for tremor alleviation in deep brain stimulation for essential tremor: the decussating portion of the dentato-rubro-thalamic tract. We hypothesised that directional stimulation of the dentato-rubro-thalamic tract would result in greater tremor improvement compared to sham programming, as well as comparable improvement as more tedious standard-of-care programming.

Methods: A prospective, blinded crossover trial was performed to assess the feasibility, safety and outcomes of programming based solely on dentato-rubro-thalamic tract anatomy. Using magnetic resonance imaging diffusion-tractography, the dentato-rubro-thalamic tract was identified and a connectivity-based treatment setting was derived by modelling a volume of tissue activated using directional current steering oriented towards the dentato-rubro-thalamic tract centre. A sham setting was created at approximately 180° opposite the connectivity-based treatment. Standard-of-care programming at 3 months was compared to connectivity-based treatment and sham settings that were blinded to the programmer. The primary outcome measure was percentage improvement in the Fahn-Tolosa-Marín tremor rating score compared to the preoperative baseline.

Results: Among the six patients, tremor rating scores differed significantly among the three experimental conditions (=0.030). The mean tremor rating score improvement was greater with the connectivity-based treatment settings (64.6% ± 14.3%) than with sham (44.8% ± 18.6%; =0.031) and standard-of-care programming (50.7% ± 19.2%; =0.062). The distance between the centre of the dentato-rubro-thalamic tract and the volume of tissue activated inversely correlated with the percentage improvement in the tremor rating score (R=0.24; =0.04). No significant adverse events were encountered.

Conclusions: Using a blinded, crossover trial design, we have shown the technical feasibility, safety and potential efficacy of connectivity-based stimulation settings in deep brain stimulation for treatment of essential tremor.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/19714009211036689DOI Listing
August 2021

Brain structural differences in temporal lobe and frontal lobe epilepsy patients: A voxel-based morphometry and vertex-based surface analysis.

Neuroradiol J 2021 Jul 27:19714009211034839. Epub 2021 Jul 27.

Department of Radiology, 6915Mayo Clinic, Mayo Clinic, USA.

Purpose: Exploration of the effect of chronic recurrent seizures in focal epilepsy on brain volumes has produced many conflicting reports. To determine differences in brain structure in temporal lobe epilepsy (TLE) and extratemporal epilepsy (using frontal lobe epilepsy (FLE) a surrogate) further, we performed a retrospective analysis of a large cohort of patients with seizure-onset zone proven by intracranial monitoring.

Methods: A total of 120 TLE patients, 86 FLE patients, and 54 healthy controls were enrolled in this study. An analysis of variance of voxel-based morphometry (VBM) was used to seek morphometric brain differences among TLE patients, FLE patients, and healthy controls. Additionally, a vertex-based surface analysis was utilized to analyze the hippocampus and thalamus. Significant side-specific differences in hippocampal gray matter volume were present between the left TLE (LTLE), right TLE RTLE (RTLE), and control groups (<0.05, family-wise error (FWE) corrected).

Results: Vertex analyses revealed significant volume reduction in inferior parts of the left hippocampus in the LTLE group and lateral parts of the right hippocampus in the RTLE group compared to controls (<0.05, FWE corrected). Significant differences were also detected between the LTLE and control group in the bilateral medial and inferior thalamus (<0.05, FWE corrected). FLE patients did not exhibit focal atrophy of gray matter across the brain.

Conclusion: Our results highlight the variation in morphometric lateralized changes in the brain between different epilepsy onset zones, providing critical insight into the natural history of people with drug-resistant focal epilepsies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/19714009211034839DOI Listing
July 2021

Impact of international research fellows in neurosurgery: results from a single academic center.

J Neurosurg 2021 Jul 23:1-11. Epub 2021 Jul 23.

Objective: International research fellows have been historically involved in academic neurosurgery in the United States (US). To date, the contribution of international research fellows has been underreported. Herein, the authors aimed to quantify the academic output of international research fellows in the Department of Neurosurgery at The Johns Hopkins University School of Medicine.

Methods: Research fellows with Doctor of Medicine (MD), Doctor of Philosophy (PhD), or MD/PhD degrees from a non-US institution who worked in the Hopkins Department of Neurosurgery for at least 6 months over the past decade (2010-2020) were included in this study. Publications produced during fellowship, number of citations, and journal impact factors (IFs) were analyzed using ANOVA. A survey was sent to collect information on personal background, demographics, and academic activities.

Results: Sixty-four international research fellows were included, with 42 (65.6%) having MD degrees, 17 (26.6%) having PhD degrees, and 5 (7.8%) having MD/PhD degrees. During an average 27.9 months of fellowship, 460 publications were produced in 136 unique journals, with 8628 citations and a cumulative journal IF of 1665.73. There was no significant difference in total number of publications, first-author publications, and total citations per person among the different degree holders. Persons holding MD/PhDs had a higher number of citations per publication per person (p = 0.027), whereas those with MDs had higher total IFs per person (p = 0.048). Among the 43 (67.2%) survey responders, 34 (79.1%) had nonimmigrant visas at the start of the fellowship, 16 (37.2%) were self-paid or funded by their country of origin, and 35 (81.4%) had mentored at least one US medical student, nonmedical graduate student, or undergraduate student.

Conclusions: International research fellows at the authors' institution have contributed significantly to academic neurosurgery. Although they have faced major challenges like maintaining nonimmigrant visas, negotiating cultural/language differences, and managing self-sustainability, their scientific productivity has been substantial. Additionally, the majority of fellows have provided reciprocal mentorship to US students.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3171/2021.1.JNS203824DOI Listing
July 2021

Phosphorylated WNK kinase networks in recoded bacteria recapitulate physiological function.

Cell Rep 2021 Jul;36(3):109416

Department of Cellular & Molecular Physiology, Yale School of Medicine, New Haven, CT 06520, USA; Systems Biology Institute, Yale University, West Haven, CT 06516, USA. Electronic address:

Advances in genetic code expansion have enabled the production of proteins containing site-specific, authentic post-translational modifications. Here, we use a recoded bacterial strain with an expanded genetic code to encode phosphoserine into a human kinase protein. We directly encode phosphoserine into WNK1 (with-no-lysine [K] 1) or WNK4 kinases at multiple, distinct sites, which produced activated, phosphorylated WNK that phosphorylated and activated SPAK/OSR kinases, thereby synthetically activating this human kinase network in recoded bacteria. We used this approach to identify biochemical properties of WNK kinases, a motif for SPAK substrates, and small-molecule kinase inhibitors for phosphorylated SPAK. We show that the kinase inhibitors modulate SPAK substrates in cells, alter cell volume, and reduce migration of glioblastoma cells. Our work establishes a protein-engineering platform technology that demonstrates that synthetically active WNK kinase networks can accurately model cellular systems and can be used more broadly to target networks of phosphorylated proteins for research and discovery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.celrep.2021.109416DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8379681PMC
July 2021

Long-term clinical outcome of minimally invasive versus open single-level transforaminal lumbar interbody fusion for degenerative lumbar diseases: a meta-analysis.

Spine J 2021 Dec 14;21(12):2049-2065. Epub 2021 Jul 14.

Department of Neurological Surgery, Mayo Clinic Florida, Jacksonville, FL 32224 USA. Electronic address:

Background Context: Minimally invasive surgical transforaminal lumbar interbody fusion (MIS-TLIF) was developed in addition to open-TLIF to minimize iatrogenic soft-tissue damage. A potential disadvantage of MIS-TLIF is inadequate visualization, which may lead to incomplete neural decompression and a less robust arthrodesis. This may cause long-term problems and result in decreased patient satisfaction.

Purpose: To evaluate the long-term clinical outcome, measured by patient-reported outcomes (PROMs), of patients with degenerative lumbar diseases treated with single-level TLIF (open vs. minimally invasive) with a minimum follow-up of 2-years.

Study Design: Meta-analysis.

Methods: The systematic review was conducted according to the PRISMA guidelines. Relevant studies were identified from Pubmed, MEDLINE, EMBASE, Scopus, Web of Science, and CENTRAL from the date of inception to August 2019. The inclusion criteria were (1) longitudinal comparative studies of MIS-TLIF versus open-TLIF approach for degenerative spine disease (2) outcomes reported as PROMs, (3) minimum follow-up of 2-years.

Results: Sixteen studies were included in the analysis. In total, 1,321 patients were included (660 MIS-TLIF& 661 open-TLIF). The following PROMS were analyzed: EQ-5D, SF, ODI, and VAS. Both techniques resulted in significant improvement in PROM, which remained significant at 2-years follow-up. However, no significant differences were found in all PROMs at 2-years follow-up. Both treatments resulted in a high rate of spinal fusion (80.5% vs. 91.1%; p=.29) and low rate of reoperation (3.0% vs. 2.4%; p=.50) or adjacent segment disease (12.6% vs. 12.40%; p=.50).

Conclusions: MIS-TLIF and open-TLIF have comparable long-term clinical outscomes. Both operations can significantly reduce pain and positively improve PROMs. No significant differences were found between both treatments in clinical outcomes at a follow-up of minimal 2-years. Therefore, MIS-TLIF seems to be an effective and safe alternative to traditional open-TLIF in the long-term.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.spinee.2021.07.006DOI Listing
December 2021
-->