Publications by authors named "Evan Joyce"

20 Publications

  • Page 1 of 1

Postoperative bowel complications after non-shunt-related neurosurgical procedures: case series and review of the literature.

Neurosurg Rev 2021 Jul 23. Epub 2021 Jul 23.

Department of Neurosurgery, Clinical Neurosciences Center, University of Utah, 175 North Medical Drive East, Salt Lake City, UT, 84132, USA.

Postoperative bowel complications after non-shunt-related neurosurgical procedures are relatively rare. In an effort to identify the primary risk factors, we evaluated postoperative bowel complications in cranial, endovascular, and spinal procedures in neurosurgery patients using our own institutional case series along with a literature review.We identified severe postoperative bowel complications that occurred at our institution after non-shunt-related neurosurgical procedures between July 2016 and December 2018. We also completed a systematic review of PubMed/MEDLINE using search terms related to bowel complications.At our institution, 7 patients (average age 49.7 ± 9.5 years, range 34-60; no apparent sex predilection) had severe postoperative bowel complications after undergoing a total of 10 neurosurgical procedures. Diagnosis was on average 1 week postoperatively (range 5-13 days), and the time between radiographic/clinical diagnosis and either surgery or death was 1.3 ± 1.4 days (range 0-4 days). Bowel perforation occurred in 4 patients. Five of the patients died, 3 as a direct result of the bowel complication. In the literature review, we identified 6487 spine and 66 cranial and/or endovascular bowel complications after neurosurgical procedures.Our case series and literature review demonstrate that severe postoperative bowel complications after non-shunt-related neurosurgical procedures, while rare, carry significant morbidity/mortality despite prompt and aggressive management. These can also happen without direct injury to bowel tissue, instead occurring as sequelae of inflammatory processes, as well as from delayed mobility, extended use of opiate narcotics, and lack of standardized protocols to ensure early bowel movements that likely stems from unfamiliarity with this potentially devastating complication.
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http://dx.doi.org/10.1007/s10143-021-01609-yDOI Listing
July 2021

A multicenter validation of the condylar-C2 sagittal vertical alignment in Chiari malformation type I: a study using the Park-Reeves Syringomyelia Research Consortium.

J Neurosurg Pediatr 2021 Jun 4:1-7. Epub 2021 Jun 4.

1Division of Pediatric Neurosurgery, Primary Children's Hospital, University of Utah, Salt Lake City, Utah.

Objective: The condylar-C2 sagittal vertical alignment (C-C2SVA) describes the relationship between the occipitoatlantal joint and C2 in patients with Chiari malformation type I (CM-I). It has been suggested that a C-C2SVA ≥ 5 mm is predictive of the need for occipitocervical fusion (OCF) or ventral brainstem decompression (VBD). The authors' objective was to validate the predictive utility of the C-C2SVA by using a large, multicenter cohort of patients.

Methods: This validation study used a cohort of patients derived from the Park-Reeves Syringomyelia Research Consortium; patients < 21 years old with CM-I and syringomyelia treated from June 2011 to May 2016 were identified. The primary outcome was the need for OCF and/or VBD. After patients who required OCF and/or VBD were identified, 10 age- and sex-matched controls served as comparisons for each OCF/VBD patient. The C-C2SVA (defined as the position of a plumb line from the midpoint of the O-C1 joint relative to the posterior aspect of the C2-3 disc space), pBC2 (a line perpendicular to a line from the basion to the posteroinferior aspect of the C2 body), and clival-axial angle (CXA) were measured on sagittal MRI. The secondary outcome was the need for ≥ 2 CM-related operations.

Results: Of the 206 patients identified, 20 underwent OCF/VBD and 14 underwent repeat posterior fossa decompression. A C-C2SVA ≥ 5 mm was 100% sensitive and 86% specific for requiring OCF/VBD, with a 12.6% misclassification rate, whereas CXA < 125° was 55% sensitive and 99% specific, and pBC2 ≥ 9 was 20% sensitive and 88% specific. Kaplan-Meier analysis demonstrated that there was a significantly shorter time to second decompression in children with C-C2SVA ≥ 5 mm (p = 0.0039). The mean C-C2SVA was greater (6.13 ± 1.28 vs 3.13 ± 1.95 mm, p < 0.0001), CXA was lower (126° ± 15.4° vs 145° ± 10.7°, p < 0.05), and pBC2 was similar (7.65 ± 1.79 vs 7.02 ± 1.26 mm, p = 0.31) among those who underwent OCF/VBD versus decompression only. The intraclass correlation coefficient for the continuous measurement of C-C2SVA was 0.52; the kappa value was 0.47 for the binary categorization of C-C2SVA ≥ 5 mm.

Conclusions: These results validated the C-C2SVA using a large, multicenter, external cohort with 100% sensitivity, 86% specificity, and a 12.6% misclassification rate. A C-C2SVA ≥ 5 mm is highly predictive of the need for OCF/VBD in patients with CM-I. The authors recommend that this measurement be considered among the tools to identify the "high-risk" CM-I phenotype.
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http://dx.doi.org/10.3171/2020.12.PEDS20809DOI Listing
June 2021

Analyzing the Safety and Efficacy of Flow-Diverting Stents in Pediatric Aneurysms: A Systematic Review.

Neurosurgery 2021 07;89(2):154-163

Department of Neurosurgery, Clinical Neurosciences Center, University of Utah, Salt Lake City, Utah, USA.

Ruptured intracranial aneurysms cause 50% of spontaneous subarachnoid hemorrhages in children, resulting in up to 65% mortality when left untreated. Although flow-diverting stents are especially suited to treat the fusiform and giant aneurysms more commonly found in children, the US Food and Drug Administration (FDA) has only approved their use in patients ≥22 years of age. Our objective was to assess the safety of flow-diverting stents in the treatment of pediatric patients with aneurysms through a systematic literature review using the PRISMA criteria. We used PubMed, Embase, and Web of Science to identify all published cases of pediatric aneurysms treated or retreated using flow-diverting stents from 2007 through 2019. Two independent researchers developed a consensus regarding the inclusion of all articles. Patient data were extracted from the identified articles and used to calculate the incidence rate of complications. From 1396 journal articles identified, 24 articles contained data on 37 pediatric patients that met the inclusion criteria. Of these 37 patients, 8 (21.6%) had a complication by last follow-up (death: 2; residual aneurysm: 2; parent artery occlusion: 4). This resulted in an incidence rate of 0.018 complications per patient at-risk month (95% CI 0.008-0.035). These data suggest that the use of flow-diverting stents for treatment of aneurysms in children may be safe and that FDA approval for this use should be evaluated. Although this analysis is comprised of case reports and case series, it represents the best attempt thus far to quantify the risk of using flow-diverting stents in children.
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http://dx.doi.org/10.1093/neuros/nyab120DOI Listing
July 2021

Stereotactic Electroencephalography Is Associated With Reduced Pain and Opioid Use When Compared with Subdural Grids: A Case Series.

Oper Neurosurg (Hagerstown) 2021 06;21(1):6-13

Department of Neurosurgery, Clinical Neurosciences Center, University of Utah, Salt Lake City, USA.

Background: Minimally invasive surgery (MIS) has been shown to decrease length of hospital stay and opioid use.

Objective: To identify whether surgery for epilepsy mapping via MIS stereotactically placed electroencephalography (SEEG) electrodes decreased overall opioid use when compared with craniotomy for EEG grid placement (ECoG).

Methods: Patients who underwent surgery for epilepsy mapping, either SEEG or ECoG, were identified through retrospective chart review from 2015 through 2018. The hospital stay was separated into specific time periods to distinguish opioid use immediately postoperatively, throughout the rest of the stay and at discharge. The total amount of opioids consumed during each period was calculated by transforming all types of opioids into their morphine equivalents (ME). Pain scores were also collected using a modification of the Clinically Aligned Pain Assessment (CAPA) scale. The 2 surgical groups were compared using appropriate statistical tests.

Results: The study identified 43 patients who met the inclusion criteria: 36 underwent SEEG placement and 17 underwent craniotomy grid placement. There was a statistically significant difference in median opioid consumption per hospital stay between the ECoG and the SEEG placement groups, 307.8 vs 71.5 ME, respectively (P = .0011). There was also a significant difference in CAPA scales between the 2 groups (P = .0117).

Conclusion: Opioid use is significantly lower in patients who undergo MIS epilepsy mapping via SEEG compared with those who undergo the more invasive ECoG procedure. As part of efforts to decrease the overall opioid burden, these results should be considered by patients and surgeons when deciding on surgical methods.
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http://dx.doi.org/10.1093/ons/opab040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8203422PMC
June 2021

Middle meningeal artery embolization treatment of nonacute subdural hematomas in the elderly: a multiinstitutional experience of 151 cases.

Neurosurg Focus 2020 10;49(4):E5

1Department of Neurosurgery, Clinical Neuroscience Center, University of Utah, Salt Lake City, Utah.

Objective: The incidence of already common chronic subdural hematomas (CSDHs) and other nonacute subdural hematomas (NASHs) in the elderly is expected to rise as the population ages over the coming decades. Surgical management is associated with recurrence and exposes elderly patients to perioperative and operative risks. Middle meningeal artery (MMA) embolization offers the potential for a minimally invasive, less morbid treatment in this age group. The clinical and radiographic outcomes after MMA embolization treatment for NASHs have not been adequately described in elderly patients. In this paper, the authors describe the clinical and radiographic outcomes after 151 cases of MMA embolization for NASHs among 121 elderly patients.

Methods: In a retrospective review of a prospectively maintained database across 15 US academic centers, the authors identified patients aged ≥ 65 years who underwent MMA embolization for the treatment of NASHs between November 2017 and February 2020. Patient demographics, comorbidities, clinical and radiographic factors, treatment factors, and clinical outcomes were abstracted. Subgroup analysis was performed comparing elderly (age 65-79 years) and advanced elderly (age > 80 years) patients.

Results: MMA embolization was successfully performed in 98% of NASHs (in 148 of 151 cases) in 121 patients. Seventy elderly patients underwent 87 embolization procedures, and 51 advanced elderly patients underwent 64 embolization procedures. Elderly and advanced elderly patients had similar rates of embolization for upfront (46% vs 61%), recurrent (39% vs 33%), and prophylactic (i.e., with concomitant surgical intervention; 15% vs 6%) NASH treatment. Transfemoral access was used in most patients, and the procedure time was approximately 1 hour in both groups. Particle embolization with supplemental coils was most common, used in 51% (44/87) and 44% (28/64) of attempts for the elderly and advanced elderly groups, respectively. NASH thickness decreased significantly from initial thickness to 6 weeks, with additional decrease in thickness observed in both groups at 90 days. At longest follow-up, the treated NASHs had stabilized or improved in 91% and 98% of the elderly and advanced elderly groups, respectively, with > 50% improvement seen in > 60% of patients for each group. Surgical rescue was necessary in 4.6% and 7.8% of cases, and the overall mortality was 8.6% and 3.9% for elderly and advanced elderly patients, respectively.

Conclusions: MMA embolization can be used safely and effectively as an alternative or adjunctive minimally invasive treatment for NASHs in elderly and advanced elderly patients.
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http://dx.doi.org/10.3171/2020.7.FOCUS20518DOI Listing
October 2020

Prolonged Length of Stay and Risk of Unplanned 30-Day Readmission After Elective Spine Surgery: Propensity Score-Matched Analysis of 33,840 Patients.

Spine (Phila Pa 1976) 2020 Sep;45(18):1260-1268

Department of Neurosurgery, Clinical Neurosciences Center, University of Utah, Salt Lake City, Utah.

Study Design: Retrospective database study.

Objective: To assess the association between prolonged length of hospital stay (pLOS) (≥4 d) and unplanned readmission in patients undergoing elective spine surgery by controlling the clinical and statistical confounders.

Summary Of Background Data: pLOS has previously been cited as a risk factor for unplanned hospital readmission. This potentially modifiable risk factor has not been distinguished as an independent risk factor in a large-scale, multi-institutional, risk-adjusted study.

Methods: Data were collected from the American College of Surgeons National Surgical Quality Improvement Program database. A retrospective propensity score-matched analysis was used to reduce baseline differences between the cohorts. Univariate and multivariate analyses were performed to assess the degree of association between pLOS and unplanned readmission.

Results: From the 99,575 patients that fit the inclusion criteria, propensity score matching yielded 16,920 well-matched pairs (mean standard propensity score difference = 0.017). The overall 30-day unplanned readmission rate of these 33,840 patients was 5.5%. The mean length of stay was 2.0 ± 0.9 days and 6.0 ± 4.5 days (P ≤ 0.001) for the control and pLOS groups, respectively. In our univariate analysis, pLOS was associated with postoperative complications, especially medical complications (22.7% vs. 8.3%, P < 0.001). Multivariate analysis of the propensity score-matched population, which adjusted identified confounders (P < 0.02 and ≥10 occurrences), showed pLOS was associated with an increased risk of 30-day unplanned readmission (odds ratio [OR] 1.423, 95% confidence interval [CI] 1.290-1.570, P < 0.001).

Conclusion: Patients who undergo elective spine procedures who have any-cause pLOS (≥4 d) are at greater risk of having unplanned 30-day readmission compared with patients with shorter hospital stays.

Level Of Evidence: 4.
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http://dx.doi.org/10.1097/BRS.0000000000003520DOI Listing
September 2020

Predicting Death After Thrombectomy in the Treatment of Acute Stroke.

Front Surg 2020 8;7:16. Epub 2020 Apr 8.

Department of Neurosurgery, Clinical Neurosciences Center, University of Utah, Salt Lake City, UT, United States.

Treatments for acute stroke have significantly improved in the past decade, with emergent thrombectomy emerging as the standard of care. Despite these advancements, death after successful thrombectomy continues to pose a significant problem. Identifying patients least likely to benefit from thrombectomy would improve use of a limited resource and management of patient expectations. We retrospectively reviewed the medical records of patients who underwent emergent thrombectomy of either anterior or posterior circulation strokes between January 2012 and January 2017. Relevant patient clinical data was collected and analyzed in a multivariable regression with a primary outcome of death at 90 days. A total of 134 patients underwent emergent endovascular thrombectomy during the study period; sufficient clinical data was available in 111 of the them. Of these, 42 patients died during the 90 day post-procedural period and 69 patients survived this period. The mean NIHSS score at presentation was 14.9 in surviving patients and 19.6 in non-surviving patients ( < 0.002). Surviving patients were less likely to have a history of cancer (4.4% vs. 26.2%, < 0.002), achieved higher rates of revascularization (78.3% vs. 50.0%, < 0.003), had a lower rate of hemorrhagic conversion (21.7% vs. 47.6%, < 0.004), and experienced fewer technical complications during their treatment (7.4% vs. 26.2%, < 0.01). Overall, there were 16 intraprocedural complications and no procedural deaths. As emergent thrombectomy for the treatment of acute stroke becomes more prevalent, appropriate patient selection will be crucial in the utilization of a limited and costly intervention. Death within 90 days after thrombectomy appears to be more prevalent among patients with higher NIHSS at presentation, those with postprocedural hemorrhage or intraprocedural complications, and those with a history of cancer.
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http://dx.doi.org/10.3389/fsurg.2020.00016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7156540PMC
April 2020

Spontaneous near-complete resolution of direct carotid-cavernous fistula resulting from ruptured cavernous internal carotid artery aneurysm.

BMJ Case Rep 2020 Apr 15;13(4). Epub 2020 Apr 15.

Department of Neurosurgery, University of Utah Health Clinical Neurosciences Center, Salt Lake City, Utah, USA

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http://dx.doi.org/10.1136/bcr-2020-234875DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7199100PMC
April 2020

The Impact of Preoperative Mindfulness-Based Stress Reduction on Postoperative Outcomes in Lumbar Spine Degenerative Disease: 3-Month and 12-Month Results of a Pilot Study.

World Neurosurg 2020 07 9;139:e230-e236. Epub 2020 Apr 9.

Department of Neurosurgery, Clinical Neurosciences Center, University of Utah Health Sciences Center, Salt Lake City, Utah, USA.

Background: We previously reported inpatient and 30-day postoperative patient-reported outcomes (PROs) of a controlled, noncrossover pilot study using preoperative mindfulness-based stress reduction (MBSR) training for lumbar spine surgery. Our goal here was to assess 3-month and 12-month postoperative PROs of preoperative MBSR in lumbar spine surgery for degenerative disease.

Methods: Intervention group participants were prospectively enrolled in a preoperative online MBSR course. A comparison standard care only group was one-to-one matched retrospectively by age, sex, surgery type, and prescription opioid use. Three-month and 12-month postoperative PROs for pain, disability, quality of life, and opioid use were compared within and between groups. Regression models were used to assess whether MBSR use predicted outcomes.

Results: Twenty-four participants were included in each group. At 3 months, follow-up was 87.5% and 95.8% in the comparison and intervention groups, respectively. In the intervention group, mean Patient-Reported Outcomes Measurement Information System-Physical Function (PROMIS-PF) was significantly higher, whereas mean Patient-Reported Outcomes Measurement Information System-Pain Interference (PROMIS-PI) and Oswestry Disability Index were significantly lower. The change from baseline in mean PROMIS-PF and PROMIS-PI was significantly greater than in the comparison group. At 12 months, follow-up was 58.3% and 83.3% in the comparison and intervention groups, respectively. In the intervention group, mean PROMIS-PI was significantly lower and change in mean PROMIS-PI from baseline was significantly greater. MBSR use was a significant predictor of change in PROMIS-PF at 3 months and in PROMIS-PI at 12 months. No adverse events were reported.

Conclusions: Three-month and 12-month results suggest that preoperative MBSR may have pain control benefits in lumbar spine surgery.
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http://dx.doi.org/10.1016/j.wneu.2020.03.186DOI Listing
July 2020

Extreme Lateral Transodontoid Approach for Resection of Clival Chordoma: 2-Dimensional Operative Video.

Oper Neurosurg (Hagerstown) 2020 Sep;19(3):E298

Department of Neurosurgery, Clinical Neurosciences Center, University of Utah, Salt Lake City, Utah.

This 15-yr-old girl presented with nasal obstruction and dysphagia of duration 3 mo and 8 to 10 pounds of weight loss. On examination, she had a hoarse voice and left tongue deviation without weakness or myelopathy. Computed tomography (CT) demonstrated an erosive lesion arising from the clivus and left occipital condyle. Magnetic resonance imaging (MRI) demonstrated a T1-isointense, T2-hyperintense, enhancing mass centered at the occipital condyle and extending into the craniovertebral junction (CVJ), causing severe brainstem compression and extending inferiorly to C2 and anteriorly into the retropharyngeal space. The patient underwent transoral biopsy to confirm the diagnosis of chordoma and complete tumor resection via a left extreme lateral transodontoid (ELTO) approach. This approach was chosen because it provides bilateral exposure to the ventral CVJ and retropharyngeal space and allows for complete tumor removal using a single approach, although it requires an experienced surgeon. The ELTO incision should provide adequate exposure for occipitocervical fusion (OCF) after the destabilization of the CVJ. Transposition of the vertebral artery and odontoidectomy are key maneuvers that provide exposure to the ventral CVJ bilaterally. Dural closure is performed primarily and augmented with fat, fibrin glue, and temporary cerebrospinal fluid diversion. Postoperative MRI showed a gross-total resection and decompression of the brainstem at the CVJ. The patient remained in a cervical collar until OCF. Postoperatively, she had left vocal cord paralysis and moderate weakness with left arm abduction at the deltoid. At 2-mo follow-up, she had improved lower cranial neuropathies, tolerated oral intake, and was scheduled to begin proton beam therapy. The patient provided consent for publication.
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http://dx.doi.org/10.1093/ons/opz411DOI Listing
September 2020

End-of-Treatment Intracerebral and Ventricular Hemorrhage Volume Predicts Outcome: A Secondary Analysis of MISTIE III.

Stroke 2020 02 17;51(2):652-654. Epub 2019 Dec 17.

Neurosurgery (E.J., P.T., R.G.), Clinical Neurosciences Center, University of Utah, Salt Lake City.

Background and Purpose- Trials have shown potential clinical benefit for minimally invasive clot evacuation of intracerebral hemorrhage (ICH). Prior research showing an association between ICH size and functional outcome did not fully address the spectrum of hematoma volumes seen after clot evacuation. Methods- In this secondary analysis of the MISTIE III trial (Minimally Invasive Surgery Plus Alteplase for Intracerebral Hemorrhage Evacuation III), we included patients randomized to the surgical arm. The primary outcome was good outcome (modified Rankin Scale score 0-3 at 1 year from study enrollment). The primary predictors were the end-of-treatment (EoT) ICH and intraventricular hemorrhage volumes and an end-of-treatment ICH stratification scale called the EoT ICH volume score. Results- In 246 patients, the end-of-treatment computed tomography was performed an average of 5 days from onset. For patients with good versus poor outcomes, the mean end-of-treatment ICH and intraventricular hemorrhage volumes were 12.9 versus 18.0 mL (=0.002) and 0.5 versus 2.3 mL (<0.001), respectively. The probability of a good outcome decreased from 73% for EoT ICH volume 3 (<5 mL) to 28% for EoT ICH volume 0 (>20 mL; =0.001). Conclusions- After surgical clot evacuation, both ICH and intraventricular hemorrhage volumes have a strong association with good neurological outcome. The EoT ICH volume score needs independent verification, but such an approach could be used for prognostication and therapeutic planning.
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http://dx.doi.org/10.1161/STROKEAHA.119.028199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7000178PMC
February 2020

The Impact of Preoperative Mindfulness-Based Stress Reduction on Postoperative Patient-Reported Pain, Disability, Quality of Life, and Prescription Opioid Use in Lumbar Spine Degenerative Disease: A Pilot Study.

World Neurosurg 2019 Jan 9;121:e786-e791. Epub 2018 Oct 9.

Department of Neurosurgery, Clinical Neurosciences Center, University of Utah Health Sciences Center, Salt Lake City, Utah, USA.

Background: Prescription opioid medications negatively affect postoperative outcomes after lumbar spine surgery. Furthermore, opioid-related overdose death rates in the United States increased by 200% between 2000 and 2014. Thus, alternatives are imperative. Mindfulness-based stress reduction (MBSR), a mind-body therapy, has been associated with improved activity and mood in opioid-using patients with chronic pain. This study assessed whether preoperative MBSR is an effective adjunct to standard postoperative care in adult patients undergoing lumbar spine surgery for degenerative disease.

Methods: The intervention group underwent a preoperative online MBSR course. The comparison group was matched retrospectively in a 1:1 ratio by age, sex, type of surgery, and preoperative opioid use. Prescription opioid use during hospital admission and at 30 days postoperatively were compared with preoperative use. Thirty-day postoperative patient-reported outcomes for pain, disability, and quality of life were compared with preoperative patient-reported outcomes. Dose-response effect of mindfulness courses was assessed using Mindful Attention Awareness Scale scores.

Results: In this pilot study, 24 participants were included in each group. Most intervention patients (70.83%) completed 1 session, and the mean Mindful Attention Awareness Scale score was 4.28 ± 0.71 during hospital admission. At 30 days, mean visual analog scale back pain score was lower in the intervention group (P = 0.004) but other patient-reported outcomes did not differ.

Conclusions: During hospital admission, no significant dose-response effect of mindfulness techniques was found. At 30 days postoperatively, MBSR use was associated with less back pain. Further research is needed to assess the effectiveness of preoperative MBSR on postoperative outcomes in lumbar spine surgery for degenerative disease.
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http://dx.doi.org/10.1016/j.wneu.2018.09.223DOI Listing
January 2019

Multifocal cavernous hemangioma of the jugular foramen: a rare skull base vascular malformation.

J Neurosurg 2018 Jul;131(1):109-113

1Department of Neurosurgery, Clinical Neurosciences Center.

Jugular foramen cavernous hemangiomas are extremely rare vascular malformations, and, to the best of the authors' knowledge, their occurrence as multifocal lesions involving both intra- and extracranial compartments has never been reported before. Here, the authors describe the case of a 60-year-old woman with a complex multifocal jugular foramen cavernous hemangioma. The patient presented with signs and symptoms concerning for jugular foramen syndrome, as well as a right neck mass. Surgical extirpation of the lesion was achieved by a multidisciplinary team via a right infratemporal fossa approach (Fisch type A) with concurrent high neck dissection and a closure buttressed with an autologous fat graft and a temporoparietal fascial flap. Although rare, cavernous hemangiomas should be included in the differential diagnosis of jugular foramen masses.
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http://dx.doi.org/10.3171/2018.1.JNS172934DOI Listing
July 2018

Clinical presentation and treatment paradigms of brain arteriovenous malformations in patients with hereditary hemorrhagic telangiectasia.

J Clin Neurosci 2018 May 23;51:22-28. Epub 2018 Feb 23.

Department of Neurosurgery, Clinical Neurosciences Center, University of Utah School of Medicine, Salt Lake City, UT, United States; University of Utah Hereditary Hemorrhagic Telangiectasia Center of Excellence, Salt Lake City, UT, United States. Electronic address:

Hereditary hemorrhagic telangiectasia (HHT) is characterized by recurrent spontaneous epistaxis, mucocutaneous telangiectases, and multisystem arteriovenous malformations (AVMs). Brain AVMs typically present at birth and are identified in approximately 10-20% of patients with HHT. A retrospective review was undertaken of all HHT patients with known single or multiple brain AVMs treated at our institution. Thirty-nine patients with brain AVM(s) were diagnosed with HHT. Most patients presented with at least one Curaçao criterion. A total of 78 brain AVMs were identified in 39 patients. Two-thirds of patients had solitary brain AVMs, whereas 33% of patients harbored at least two lesions (range: 2-16). Brain AVMs of the supratentorial cerebral hemispheres comprised 83% of all lesions, whereas infratentorial lesions accounted for only 17%. Of the 55 brain AVMs assigned Spetzler-Martin grading, the majority of patients were Grade 1 (73%), and 23% and 4% were Grades 2 and 3, respectively. Patients were treated with surgery alone (51%), embolization alone (6%), embolization followed by surgery (9%), stereotactic radiosurgery (11%), stereotactic radiosurgery followed by surgery (3%), or observation (20%). Of patients who underwent genetic analysis, 62% possessed mutations in ENG (HHT type 1), whereas 38% had mutations in ACVRL1 (HHT type 2). This robust patient cohort of brain AVMs in 39 patients with HHT advances the collective understanding of this disease's varied presentation, diagnostic workup, genetic underpinnings, and available treatment options.
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http://dx.doi.org/10.1016/j.jocn.2018.01.019DOI Listing
May 2018

Clinical presentation and treatment paradigms in patients with hereditary hemorrhagic telangiectasia and spinal vascular malformations.

J Clin Neurosci 2018 Apr 3;50:51-57. Epub 2018 Feb 3.

Department of Neurosurgery, Clinical Neurosciences Center, University of Utah School of Medicine, Salt Lake City, UT, United States. Electronic address:

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder that causes angiodysplasia and results in mucocutaneous telangiectasias and arteriovenous malformations of organs. Although central nervous system vascular malformations can occur anywhere along the neuraxis, spinal vascular malformations are rare. We present our experience with the presentation and management of spinal vascular malformations in patients with HHT. Of the more than 800 patients with the diagnosis of HHT screened at our institution from 1995 through 2017, four patients with spinal vascular malformations (age range 1 month-77 years; 2 male, 2 female) were identified, three of whom came to clinical attention after significant neurological deterioration from previously unknown malformations. A review of the literature including our patients demonstrated 29 total spinal arteriovenous fistulas (AVFs) in 28 HHT patients (69% male). The lesions were located predominantly in the thoracic spine (65.5%). Three lesions were not treated, 17 were treated with embolization, 6 were surgically resected, and 3 were treated with embolization and surgery. In 14 cases, the patients presented with hemorrhage of the AVF. Overall, 79% of patients achieved complete or near-complete occlusion, with 75% reporting improvement in neurological function. Discovery of spinal lesions often occurs after neurological decline because current screening protocols do not include evaluation of the patient for spinal lesions. Most patients benefit from intervention, which is tailored to the characteristics of the patient and their malformation. Given the often-severe neurological deficit encountered at presentation, we favor a protocol that screens HHT patients for spinal vascular malformations.
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http://dx.doi.org/10.1016/j.jocn.2018.01.010DOI Listing
April 2018

Acute repair of traumatic pan-brachial plexus injury: technical considerations and approaches.

Neurosurg Focus 2018 01;44(VideoSuppl1):V4

Particularly challenging after complete brachial plexus avulsion is reestablishing effective hand function, due to limited neurological donors to reanimate the arm. Acute repair of avulsion injuries may enable reinnervation strategies for achieving hand function. This patient presented with pan-brachial plexus injury. Given its irreparable nature, the authors recommended multistage reconstruction, including contralateral C-7 transfer for hand function, multiple intercostal nerves for shoulder/triceps function, shoulder fusion, and spinal accessory nerve-to-musculocutaneous nerve transfer for elbow flexion. The video demonstrates distal contraction from electrical stimulation of the avulsed roots. Single neurorrhaphy of the contralateral C-7 transfer was performed along with a retrosternocleidomastoid approach. The video can be found here: https://youtu.be/GMPfno8sK0U .
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http://dx.doi.org/10.3171/2018.1.FocusVid.17569DOI Listing
January 2018

Biomaterials selectively modulate interactions between human blood-derived polymorphonuclear leukocytes and monocytes.

Am J Pathol 2013 Jun;182(6):2180-90

Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin-Madison, Madison, Wisconsin 53705, USA.

Implantation of a biomaterial into the body elicits a host foreign body response, during which polymorphonuclear leukocytes (PMNs) and then monocytes (MCs) are recruited to the site of implantation. MCs and MC-derived macrophages are central players in this response because they secrete proinflammatory and/or pro-wound-healing cytokines and growth factors that influence subsequent healing events. Although mechanisms of MC response to biomaterials are often studied in in vitro monoculture models, few studies have investigated how biomaterials modulate PMN-MC paracrine and juxtacrine interactions. To address this, we cultured human blood-derived MCs alone or in the presence of autologous PMN-conditioned medium (PCM) on poly(ethylene glycol) hydrogels, poly(dimethyl siloxane), and tissue culture polystyrene. We also directly co-cultured autologous PMNs and MCs on these biomaterials. PCM increased MC adhesion/viability and expression of IL-1β and tumor necrosis factor-α in a biomaterial- and time-dependent manner when compared with MCs that were not cultured in PCM. There were also biomaterial- and time-dependent differences in cell adhesion/viability, apoptosis, and expression of IL-6 and IL-8 in the PMN-MC direct co-cultures when compared with the sums of these activities in PMN and MC monocultures. In conclusion, these data suggest that biomaterials selectively modulate PMN-MC paracrine and juxtacrine interactions to influence MC and/or PMN adhesion/viability, apoptosis, and cytokine expression.
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http://dx.doi.org/10.1016/j.ajpath.2013.02.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3668020PMC
June 2013

Active leukocyte detachment and apoptosis/necrosis on PEG hydrogels and the implication in the host inflammatory response.

Biomaterials 2012 Jan 2;33(1):29-37. Epub 2011 Oct 2.

Department of Biomedical Engineering, College of Engineering, University of Wisconsin-Madison, WI, USA.

Monocytes/Macrophages have long been recognized as key players in inflammation and wound healing and are often employed in vitro to gain an understanding of the inflammatory response to biomaterials. Previous work has demonstrated a drastic decrease in primary monocyte adherent density on biomaterial surfaces coupled with a change in monocyte behavior over time. However, the mechanism responsible for this decrease remains unclear. In this study, we explored active detachment and cellular death as possible regulating factors. Specifically, extracellular TNF-α and ROS production were analyzed as potential endogenous stimulators of cell death. MMPs, but not calpains, were found to play a key role in active monocyte detachment. Monocyte death was found to peak at 24 h and occur by both apoptosis and necrosis as opposed to polymorphonuclear leukocyte death which mainly occurred through apoptosis. Finally, TNF-α and ROS production were not found to have a causal relationship with monocyte death on TCPS or PEG surfaces. The occurrence of primary monocyte apoptosis/necrosis as well as active detachment from a material surface has implications not only in in vitro study, but also in the translation of the in vitro inflammatory response of these cells to in vivo applications.
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http://dx.doi.org/10.1016/j.biomaterials.2011.09.044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3281311PMC
January 2012

Fetal bovine serum xenoproteins modulate human monocyte adhesion and protein release on biomaterials in vitro.

Acta Biomater 2011 Feb 15;7(2):515-25. Epub 2010 Sep 15.

School of Pharmacy, University of Wisconsin-Madison, Madison, WI 53705, USA.

Monocyte-derived macrophages are critical in the host-foreign body response to biomaterials and have been studied extensively in various culture conditions in vitro, such as medium supplemented with fetal bovine serum (FBS) or autologous human serum (AHS). Since monocyte maturation into macrophages is highly plastic and may vary considerably depending on the surface, isolation procedures and in vitro culture conditions, we hypothesize that variations in protein adsorption and serum type will greatly impact monocyte behavior in a surface-dependent manner. The impact of xenoproteins on monocyte-surface interactions has not been well studied methodically and the use of AHS rather than FBS for macrophage-biomaterials studies in vitro is far from universal. The commonly used reference materials - tissue culture polystyrene (TCPS), polyethylene glycol (PEG) and polydimethylsiloxane (PDMS) - were employed in this study and we found a 3-fold higher adherent monocyte density on TCPS when AHS was used vs. FBS-supplemented medium. On PEG hydrogels, an 8- to 10-fold higher adhesion density was observed when AHS was employed vs. FBS, while on PDMS no difference in adhesion density was observed between the two sera conditions. Additionally, the presence of lipopolysaccharide abrogated the serum-dependent effect on cell adhesion on TCPS. Significantly different variations in protein release were observed between the serum conditions on these surfaces; in particular, there was a 100-fold higher concentration of growth-related oncogene for the AHS condition on PDMS even though the adhesion levels were comparable between the two serum conditions. These results emphasize the combined impact of the surface type and FBS xenoproteins in mediating the observed monocyte response to biomaterials in vitro.
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http://dx.doi.org/10.1016/j.actbio.2010.08.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3014429PMC
February 2011

Application of MS-based proteomics to study serum protein adsorption/absorption and complement C3 activation on poly(ethylene glycol) hydrogels.

J Biomater Sci Polym Ed 2011 ;22(10):1343-62

a School of Pharmacy, University of Wisconsin-Madison, 777 Highland Avenue, Madison, WI 53705, USA.

Although the interaction between cells and poly(ethylene glycol) (PEG) hydrogels is well documented, there lacks a thorough investigation into the adsorption of blood proteins on these surfaces which dictates the observed cellular and in vivo host response. Thus, a clear understanding of how surface-bound proteins mediate the unique biological property of PEG hydrogels is fundamentally important. The information obtained will also provide insights into future biomaterial design. In this study, several mass-spectrometrybased proteomic tools coupled with complementary immunoassays were employed to survey the complex surface-bound serum proteome. The adsorption of vitronectin, thrombin, fibrinogen and complement component C3 was significantly lower on PEG hydrogels than on tissue culture polystyrene (TCPS). Although PEG hydrogels mediated lower C3 adsorption than TCPS, the extent of C3 activation between the two surfaces was comparable. Adherent monocyte density was also significantly lower on PEG hydrogels as compared to TCPS. Taken together, these results support the critical role of the complement C3 in mediating monocyte adhesion on biomaterials. Thus we conclude that the biocompatibility of PEG hydrogels both in vitro and in vivo can be partly contributed to their limited C3 interaction and monocyte activity.
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http://dx.doi.org/10.1163/092050610X508400DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3855078PMC
June 2016
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