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Stewart Yeoh, Wesley S. Warner, Ilyas Eli, and Mark A. Mahan

OBJECTIVE

Traditional animal models of nerve injury use controlled crush or transection injuries to investigate nerve regeneration; however, a more common and challenging clinical problem involves closed traction nerve injuries. The authors have produced a precise traction injury model and sought to examine how the pathophysiology of stretch injuries compares with that of crush and transection injuries.

METHODS

Ninety-five late-adolescent (8-week-old) male mice underwent 1 of 7 injury grades or a sham injury (n > 10 per group): elastic stretch, inelastic stretch, stretch rupture, crush, primary coaptation, secondary coaptation, and critical gap. Animals underwent serial neurological assessment with sciatic function index, tapered beam, and von Frey monofilament testing for 48 days after injury, followed by trichrome and immunofluorescent nerve histology and muscle weight evaluation.

RESULTS

The in-continuity injuries, crush and elastic stretch, demonstrated different recovery profiles, with more severe functional deficits after crush injury than after elastic stretch immediately following injury (p < 0.05). However, animals with either injury type returned to baseline performance in all neurological assessments, accompanied by minimal change in nerve histology. Inelastic stretch, a partial discontinuity injury, produced more severe neurological deficits, incomplete return of function, 47% ± 9.1% (mean ± SD) reduction of axon counts (p < 0.001), and partial neuroma formation within the nerve. Discontinuity injuries, including immediate and delayed nerve repair, stretch rupture, and critical gap, manifested severe, long-term neurological deficits and profound axonal loss, coupled with intraneural scar formation. Although repaired nerves demonstrated axon regeneration across the gap, rupture and critical gap injuries demonstrated negligible axon crossing, despite rupture injuries having healed into continuity.

CONCLUSIONS

Stretch-injured nerves present unique pathology and functional deficits compared with traditional nerve injury models. Because of the profound neuroma formation, stretch injuries represent an opportunity to study the pathophysiology associated with clinical injury mechanisms. Further validation for comparison with human injuries will require evaluation in a large-animal model.

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Gmaan Alzhrani, Yair M. Gozal, Ilyas Eli, Walavan Sivakumar, Amol Raheja, Douglas L. Brockmeyer, and William T. Couldwell

OBJECTIVE

Surgical treatment of pathological processes involving the ventral craniocervical junction (CCJ) traditionally involves anterior and posterolateral skull base approaches. In cases of bilateral extension, when lesions extend beyond the midline to the contralateral side, a unilateral corridor may result in suboptimal resection. In these cases, the lateral extent of the tumor will prevent extirpation of the lesion via anterior surgical approaches. The authors describe a unilateral operative corridor developed along an extreme lateral trajectory to the anterior aspect of the clival and upper cervical dura, allowing exposure and resection of tumor on the contralateral side. This approach is used when the disease involves the bone structures inherent to stability at the anterior CCJ.

METHODS

To achieve exposure of the ventral CCJ, an extreme lateral transcondylar transodontoid (ELTO) approach was performed with transposition of the ipsilateral vertebral artery, followed by drilling of the C1 anterior arch. Resection of the odontoid process allowed access to the contralateral component of lesions across the midline to the region of the extracranial contralateral vertebral artery, maximizing resection.

RESULTS

Exposure and details of the surgical procedure were derived from anatomical cadavers. At the completion of cadaveric dissection, morphometric measurements of the relevant anatomical landmarks were obtained. Illustrative case examples for approaching ventral CCJ chordomas via the ELTO approach are presented.

CONCLUSIONS

The ELTO approach provides a safe and direct surgical corridor to treat complex lesions at the ventral CCJ with bilateral extension through a single operative corridor. This approach can be combined with other lateral approaches or posterior infratemporal approaches to remove more extensive lesions involving the rostral clivus, jugular foramen, and temporal bone.

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Vijay M. Ravindra, Ilyas M. Eli, Meic H. Schmidt, and Douglas L. Brockmeyer

Spinal column tumors are rare in children and young adults, accounting for only 1% of all spine and spinal cord tumors combined. They often present diagnostic and therapeutic challenges. In this article, the authors review the current management of primary osseous tumors of the pediatric spinal column and highlight diagnosis, management, and surgical decision making.

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Michael Karsy, Jian Guan, Hussam Abou-Al-Shaar, Ilyas M. Eli, Bornali Kundu, Erica F. Bisson, William T. Couldwell, and Rimal H. Dossani

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Bob S. Carter and Fred G. Barker II

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Michael Karsy, Jian Guan, Ilyas Eli, Andrea A. Brock, Sarah T. Menacho, and Min S. Park

OBJECTIVE

Hypovitaminosis D is prevalent in neurocritical care patients, but the potential to improve patient outcome by replenishing vitamin D has not been investigated. This single-center, double-blinded, placebo-controlled, randomized (1:1) clinical trial was designed to assess the effect on patient outcome of vitamin D supplementation in neurocritical care patients with hypovitaminosis D.

METHODS

From October 2016 until April 2018, emergently admitted neurocritical care patients with vitamin D deficiency (≤ 20 ng/ml) were randomized to receive vitamin D3 (cholecalciferol, 540,000 IU) (n = 134) or placebo (n = 133). Hospital length of stay (LOS) was the primary outcome; secondary outcomes included intensive care unit (ICU) LOS, repeat vitamin D levels, patient complications, and patient disposition. Exploratory analysis evaluated specific subgroups of patients by LOS, Glasgow Coma Scale (GCS) score, and Simplified Acute Physiology Score (SAPS II).

RESULTS

Two-hundred seventy-four patients were randomized (intent-to-treat) and 267 were administered treatment within 48 hours of admission (as-treated; 61.2% of planned recruitment) and monitored. The mean age of as-treated patients was 54.0 ± 17.2 years (56.9% male, 77.2% white). After interim analysis suggested a low conditional power for outcome difference (predictive power 0.12), the trial was halted. For as-treated patients, no significant difference in hospital LOS (10.4 ± 14.5 days vs 9.1 ± 7.9 days, p = 0.4; mean difference 1.3, 95% CI −1.5 to 4.1) or ICU LOS (5.8 ± 7.5 days vs 5.4 ± 6.4 days, p = 0.4; mean difference 0.4, 95% CI −1.3 to 2.1) was seen between vitamin D3 and placebo groups, respectively. Vitamin D3 supplementation significantly improved repeat serum levels compared with placebo (20.8 ± 9.3 ng/ml vs 12.8 ± 4.8 ng/ml, p < 0.001) without adverse side effects. No subgroups were identified by exclusion of LOS outliers or segregation by GCS score, SAPS II, or severe vitamin D deficiency (≤ 10 ng/ml).

CONCLUSIONS

Despite studies showing that vitamin D can predict prognosis, supplementation in vitamin D–deficient neurocritical care patients did not result in appreciable improvement in outcomes and likely does not play a role in acute clinical recovery.

Clinical trial registration no.: NCT02881957 (clinicaltrials.gov)

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Jian Guan, Michael Karsy, Andrea A. Brock, Ilyas M. Eli, Holly K. Ledyard, Gregory W. J. Hawryluk, and Min S. Park

OBJECTIVE

Hypovitaminosis D is highly prevalent among the general population. Studies have shown an association between hypovitaminosis D and multiple negative outcomes in critical care patients, but there has been no prospective evaluation of vitamin D in the neurological critical care population. The authors examined the impact of vitamin D deficiency on in-hospital mortality and a variety of secondary outcomes.

METHODS

The authors prospectively collected 25-hydroxy vitamin D levels of all patients admitted to the neurocritical care unit (NCCU) of a quaternary-care center over a 3-month period. Demographic data, illness acuity, in-hospital mortality, infection, and length of hospitalization were collected. Univariate and multivariable logistic regression were used to examine the effects of vitamin D deficiency.

RESULTS

Four hundred fifteen patients met the inclusion criteria. In-hospital mortality was slightly worse (9.3% vs 4.5%; p = 0.059) among patients with deficient vitamin D (≤ 20 ng/dl). There was also a higher rate of urinary tract infection in patients with vitamin D deficiency (12.4% vs 4.2%; p = 0.002). For patients admitted to the NCCU on an emergency basis (n = 285), higher Simplified Acute Physiology Score II (OR 13.8, 95% CI 1.7–110.8; p = 0.014), and vitamin D deficiency (OR 3.0, 95% CI 1.0–8.6; p = 0.042) were significantly associated with increased in-hospital mortality after adjusting for other factors.

CONCLUSIONS

In the subset of patients admitted to the NCCU on an emergency basis, vitamin D deficiency is significantly associated with higher in-hospital mortality. Larger studies are needed to confirm these findings and to investigate the role of vitamin D supplementation in these patients.

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Brandon Sherrod, Michael Karsy, Jian Guan, Andrea A. Brock, Ilyas M. Eli, Erica F. Bisson, and Andrew T. Dailey

OBJECTIVE

The objective of this study was to investigate the effect of hospital type and patient transfer during the treatment of patients with vertebral fracture and/or spinal cord injury (SCI).

METHODS

The National Inpatient Sample (NIS) database was queried to identify patients treated in Utah from 2001 to 2011 for vertebral column fracture and/or SCI (ICD-9-CM codes 805, 806, and 952). Variables related to patient transfer into and out of the index hospital were evaluated in relation to patient disposition, hospital length of stay, mortality, and cost.

RESULTS

A total of 53,644 patients were seen (mean [± SEM] age 55.3 ± 0.1 years, 46.0% females, 90.2% white), of which 10,620 patients were transferred from another institution rather than directly admitted. Directly admitted (vs transferred) patients showed a greater likelihood of routine disposition (54.4% vs 26.0%) and a lower likelihood of skilled nursing facility disposition (28.2% vs 49.2%) (p < 0.0001). Directly admitted patients also had a significantly shorter length of stay (5.6 ± 6.7 vs 7.8 ± 9.5 days, p < 0.0001) and lower total charges ($26,882 ± $37,348 vs $42,965 ± $52,118, p < 0.0001). A multivariable analysis showed that major operative procedures (hazard ratio [HR] 1.7, 95% confidence interval [CI] 1.4–2.0, p < 0.0001) and SCI (HR 2.1, 95% CI 1.6–2.8, p < 0.0001) were associated with reduced survival whereas patient transfer was associated with better survival rates (HR 0.4, 95% CI 0.3–0.5, p < 0.0001). A multivariable analysis of cost showed that disposition (β = 0.1), length of stay (β = 0.6), and major operative procedure (β = 0.3) (p < 0.0001) affected cost the most.

CONCLUSIONS

Overall, transferred patients had lower mortality but greater likelihood for poor outcomes, longer length of stay, and higher cost compared with directly admitted patients. These results suggest some significant benefits to transferring patients with acute injury to facilities capable of providing appropriate treatment, but also support the need to further improve coordinated care of transferred patients, including surgical treatment and rehabilitation.

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Spencer Twitchell, Hussam Abou-Al-Shaar, Jared Reese, Michael Karsy, Ilyas M. Eli, Jian Guan, Philipp Taussky, and William T. Couldwell

OBJECTIVE

With the continuous rise of health care costs, hospitals and health care providers must find ways to reduce costs while maintaining high-quality care. Comparing surgical and endovascular treatment of intracranial aneurysms may offer direction in reducing health care costs. The Value-Driven Outcomes (VDO) database at the University of Utah identifies cost drivers and tracks changes over time. In this study, the authors evaluate specific cost drivers for surgical clipping and endovascular management (i.e., coil embolization and flow diversion) of both ruptured and unruptured intracranial aneurysms using the VDO system.

METHODS

The authors retrospectively reviewed surgical and endovascular treatment of ruptured and unruptured intracranial aneurysms from July 2011 to January 2017. Total cost (as a percentage of each patient’s cost to the system), subcategory costs, and potential cost drivers were evaluated and analyzed.

RESULTS

A total of 514 aneurysms in 469 patients were treated; 273 aneurysms were surgically clipped, 102 were repaired with coiling, and 139 were addressed with flow diverter placements. Middle cerebral artery aneurysms accounted for the largest portion of cases in the clipping group (29.7%), whereas anterior communicating artery aneurysms were most frequently involved in the coiling group (30.4%) and internal carotid artery aneurysms were the majority in the flow diverter group (63.3%). Coiling (mean total cost 0.25% ± 0.20%) had a higher cost than flow diversion (mean 0.20% ± 0.16%) and clipping (mean 0.17 ± 0.14%; p = 0.0001, 1-way ANOVA). Coiling cases cost 1.5 times as much as clipping and flow diversion costs 1.2 times as much as clipping. Facility costs were the most significant contributor to intracranial clipping costs (60.2%), followed by supplies (18.3%). Supplies were the greatest cost contributor to coiling costs (43.2%), followed by facility (40.0%); similarly, supplies were the greatest portion of costs in flow diversion (57.5%), followed by facility (28.5%). Cost differences for aneurysm location, rupture status, American Society of Anesthesiologists (ASA) grade, and discharge disposition could be identified, with variability depending on surgical procedure. A multivariate analysis showed that rupture status, surgical procedure type, ASA status, discharge disposition, and year of surgery all significantly affected cost (p < 0.0001).

CONCLUSIONS

Facility utilization and supplies constitute the majority of total costs in aneurysm treatment strategies, but significant variation exists depending on surgical approach, rupture status, and patient discharge disposition. Developing and implementing approaches and protocols to improve resource utilization are important in reducing costs while maintaining high-quality patient care.

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Michael Karsy, Mohammed A. Azab, Hussam Abou-Al-Shaar, Jian Guan, Ilyas Eli, Randy L. Jensen, and D. Ryan Ormond

Meningiomas are among the most common intracranial pathological conditions, accounting for 36% of intracranial lesions treated by neurosurgeons. Although the majority of these lesions are benign, the classical categorization of tumors by histological type or World Health Organization (WHO) grade has not fully captured the potential for meningioma progression and recurrence. Many targeted treatments have failed to generate a long-lasting effect on these tumors. Recently, several seminal studies evaluating the genomics of intracranial meningiomas have rapidly changed the understanding of the disease. The importance of NF2 (neurofibromin 2), TRAF7 (tumor necrosis factor [TNF] receptor–associated factor 7), KLF4 (Kruppel-like factor 4), AKT1, SMO (smoothened), PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha), and POLR2 (RNA polymerase II subunit A) demonstrates that there are at least 6 distinct mutational classes of meningiomas. In addition, 6 methylation classes of meningioma have been appreciated, enabling improved prediction of prognosis compared with traditional WHO grades. Genomic studies have shed light on the nature of recurrent meningioma, distinct intracranial locations and mutational patterns, and a potential embryonic cancer stem cell–like origin. However, despite these exciting findings, the clinical relevance of these findings remains elusive. The authors review the key findings from recent genomic studies in meningiomas, specifically focusing on how these findings relate to clinical insights for the practicing neurosurgeon.