Publications by authors named "Nanthiya Sujijantarat"

15 Publications

  • Page 1 of 1

DIAPH1 Variants in Non-East Asian Patients With Sporadic Moyamoya Disease.

JAMA Neurol 2021 Jun 14. Epub 2021 Jun 14.

Yale Center for Genome Analysis, West Haven, Connecticut.

Importance: Moyamoya disease (MMD), a progressive vasculopathy leading to narrowing and ultimate occlusion of the intracranial internal carotid arteries, is a cause of childhood stroke. The cause of MMD is poorly understood, but genetic factors play a role. Several familial forms of MMD have been identified, but the cause of most cases remains elusive, especially among non-East Asian individuals.

Objective: To assess whether ultrarare de novo and rare, damaging transmitted variants with large effect sizes are associated with MMD risk.

Design, Setting, And Participants: A genetic association study was conducted using whole-exome sequencing case-parent MMD trios in a small discovery cohort collected over 3.5 years (2016-2019); data were analyzed in 2020. Medical records from US hospitals spanning a range of 1 month to 1.5 years were reviewed for phenotyping. Exomes from a larger validation cohort were analyzed to identify additional rare, large-effect variants in the top candidate gene. Participants included patients with MMD and, when available, their parents. All participants who met criteria and were presented with the option to join the study agreed to do so; none were excluded. Twenty-four probands (22 trios and 2 singletons) composed the discovery cohort, and 84 probands (29 trios and 55 singletons) composed the validation cohort.

Main Outcomes And Measures: Gene variants were identified and filtered using stringent criteria. Enrichment and case-control tests assessed gene-level variant burden. In silico modeling estimated the probability of variant association with protein structure. Integrative genomics assessed expression patterns of MMD risk genes derived from single-cell RNA sequencing data of human and mouse brain tissue.

Results: Of the 24 patients in the discovery cohort, 14 (58.3%) were men and 18 (75.0%) were of European ancestry. Three of 24 discovery cohort probands contained 2 do novo (1-tailed Poisson P = 1.1 × 10-6) and 1 rare, transmitted damaging variant (12.5% of cases) in DIAPH1 (mammalian diaphanous-1), a key regulator of actin remodeling in vascular cells and platelets. Four additional ultrarare damaging heterozygous DIAPH1 variants (3 unphased) were identified in 3 other patients in an 84-proband validation cohort (73.8% female, 77.4% European). All 6 patients were non-East Asian. Compound heterozygous variants were identified in ena/vasodilator-stimulated phosphoproteinlike protein EVL, a mammalian diaphanous-1 interactor that regulates actin polymerization. DIAPH1 and EVL mutant probands had severe, bilateral MMD associated with transfusion-dependent thrombocytopenia. DIAPH1 and other MMD risk genes are enriched in mural cells of midgestational human brain. The DIAPH1 coexpression network converges in vascular cell actin cytoskeleton regulatory pathways.

Conclusions And Relevance: These findings provide the largest collection to date of non-East Asian individuals with sporadic MMD harboring pathogenic variants in the same gene. The results suggest that DIAPH1 is a novel MMD risk gene and impaired vascular cell actin remodeling in MMD pathogenesis, with diagnostic and therapeutic ramifications.
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http://dx.doi.org/10.1001/jamaneurol.2021.1681DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8204259PMC
June 2021

Vessel wall MRI in ruptured cranial dural arteriovenous fistulas.

Interv Neuroradiol 2021 Jan 11:1591019920988205. Epub 2021 Jan 11.

Department of Neurosurgery, Yale University School of Medicine, New Haven, USA.

Intracranial high-resolution vessel wall MRI (VW-MRI) is an imaging paradigm that is useful in site-of-rupture identification in patients presenting with spontaneous subarachnoid hemorrhage and multiple intracranial aneurysms. Only a handful of case reports describe its potential utility in the evaluation of more complex brain vascular malformations. We report for the first time three patients with ruptured cranial dural arteriovenous fistulas (dAVFs) that were evaluated with high-resolution VW-MRI. The presumed site-of-rupture was identified based on contiguity of a venous ectasia with adjacent blood products and thick, concentric wall enhancement. This preliminary experience suggests a role for high-resolution VW-MRI in the evaluation of ruptured cranial dAVFs, in particular, site-of-rupture identification. It also supports an emerging hypothesis that all spontaneously ruptured, macrovascular lesions demonstrate avid vessel wall enhancement.
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http://dx.doi.org/10.1177/1591019920988205DOI Listing
January 2021

Predictors of Extended Length of Stay Following Treatment of Unruptured Adult Cerebral Aneurysms: A Study of The National Inpatient Sample.

J Stroke Cerebrovasc Dis 2020 Nov 19;29(11):105230. Epub 2020 Aug 19.

Department of Neurosurgery, Yale University School of Medicine, New Haven, CT; Department of Radiology & Biomedical Imaging, Yale University School of Medicine, New Haven, CT. Electronic address:

Background: In an unprecedented era of soaring healthcare costs, payers and providers alike have started to place increased importance on measuring the quality of surgical procedures as a surrogate for operative success. One metric used is the length of hospital stay (LOS) during index admission. For the treatment of unruptured cerebral aneurysms, the determinants of extended length of stay are relatively unknown. The aim of this study was to identify the patient- and hospital-level factors associated with extended LOS following treatment for unruptured cerebral aneurysms.

Methods: The National Inpatient Sample years 2010 - 2014 was queried. Adults (≥18 years) with unruptured aneurysms undergoing either clipping or coiling were selected using the International Classification of Diseases, Ninth Revision, Clinical Modification coding system. Extended LOS was defined as greater than 75 percentile for the entire cohort (>5 days). Weighted patient demographics, comorbidities, complications, LOS, disposition and total cost were recorded. Multivariate logistic regression was used to determine the odds ratio for risk-adjusted extended LOS. The primary outcome was the degree which patient comorbidities or postoperative complications correlated with extended LOS.

Results: A total of 46,880 patients were identified for which 9,774 (20.8%) patients had extended LOS (Normal LOS: 37,106; Extended LOS: 9,774). Patients in the extended LOS cohort presented with a greater number of comorbidities compared to the normal LOS cohort. A greater proportion of the normal LOS cohort was coiled (Normal LOS: 63.0% vs. Extended LOS: 33.5%, P<0.001), while more patients in the extended LOS cohort were clipped (Normal LOS: 37.0% vs. Extended LOS: 66.5%, P<0.001). The overall complication rate was higher in the extended LOS cohort (Normal LOS: 7.3% vs. Extended LOS: 43.8%, P<0.001). On average, the extended LOS cohort incurred a total cost nearly twice as large (Normal LOS: $26,050 ± 13,430 vs. Extended LOS: $52,195 ± 37,252, P<0.001) and had more patients encounter non-routine discharges (Normal LOS: 8.5% vs. Extended LOS: 52.5%, P<0.001) compared to the normal LOS cohort. On weighted multivariate logistic regression, multiple patient-specific factors were associated with extended LOS. These included demographics, preadmission comorbidities, choice of procedure, and inpatient complications. The odds ratio for extended LOS was 5.14 (95% CI, 4.30 - 6.14) for patients with 1 complication and 19.58 (95% CI, 15.75 - 24.34) for patients with > 1 complication.

Conclusions: Our study demonstrates that extended LOS after treatment of unruptured aneurysms is influenced by a number of patient-level factors including demographics, preadmission comorbidities, type of aneurysm treatment (open surgical versus endovascular), and, importantly, inpatient complications. A better understanding of these independent predictors of prolonged length of hospital stay may help to improve patient outcomes and decrease overall healthcare costs.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.105230DOI Listing
November 2020

Posterior Reversible Encephalopathy Syndrome Caused by Induced Hypertension to Treat Cerebral Vasospasm Secondary to Aneurysmal Subarachnoid Hemorrhage.

World Neurosurg 2020 11 25;143:e309-e323. Epub 2020 Jul 25.

Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut, USA. Electronic address:

Objective: The aim of the present study was to describe the case of a patient who had presented to a university hospital with induced-hypertension (IH) posterior reversible encephalopathy syndrome (PRES). We also reviewed all other reports of such patients.

Methods: We have described the clinical course of a patient who had presented to the university hospital neurosurgical department. We also performed a systematic review of studies related to the incidence of PRES caused by the use of IH in the treatment of cerebral vasospasm after aneurysmal subarachnoid hemorrhage.

Results: The patient had presented with an acute-onset headache and found to have a subarachnoid hemorrhage due to anterior communicating artery aneurysm rupture. She underwent coiling the next day. During the subsequent days, she demonstrated fluctuating clinical examination findings, aphasia, and decreased levels of arousal. Digital subtraction angiography was performed, and the findings were concerning for mild vasospasm of the anterior and middle cerebral arteries. The systolic blood pressure goal was increased to 180-220 mm Hg for an IH trial, which had initially resulted in some transient clinical improvements in her level of arousal. However, the improvement was not sustained. During the next 36 hours, the patient worsened, and she developed left middle cerebral artery syndrome. Given the concern for a possible ischemic event, magnetic resonance imaging was performed, which demonstrated interval development of multiple areas of cortical-based fluid-attenuated inversion recovery hyperintensity consistent with PRES. The systolic blood pressure goal was relaxed to normotension, and ~48 hours later, the patient's clinical status had significantly improved.

Conclusion: IH-PRES is a rare complication that should be remembered in the differential diagnosis for at-risk patients.
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http://dx.doi.org/10.1016/j.wneu.2020.07.135DOI Listing
November 2020

Laser interstitial thermal therapy (LITT) vs. bevacizumab for radiation necrosis in previously irradiated brain metastases.

J Neurooncol 2020 Jul 29;148(3):641-649. Epub 2020 Jun 29.

Department of Neurosurgery, Yale University School of Medicine, 333 Cedar St, New Haven, CT, 06520, USA.

Purpose: Both laser interstitial thermal therapy (LITT) and bevacizumab have been used successfully to treat radiation necrosis (RN) after radiation for brain metastases. Our purpose is to compare pre-treatment patient characteristics and outcomes between the two treatment options.

Methods: Single-institution retrospective chart review identified brain metastasis patients who developed RN between 2011 and 2018. Pre-treatment factors and treatment responses were compared between those treated with LITT versus bevacizumab.

Results: Twenty-five patients underwent LITT and 13 patients were treated with bevacizumab. The LITT cohort had a longer overall survival (median 24.8 vs. 15.2 months for bevacizumab, p = 0.003) and trended to have a longer time to local recurrence (median 12.1 months vs. 2.0 for bevacizumab), although the latter failed to achieve statistical significance (p = 0.091). LITT resulted in an initial increase in lesional volume compared to bevacizumab (p < 0.001). However, this trend reversed in the long term follow-up, with LITT resulting in a median volume decrease at 1 year post-treatment of - 64.7% (range - 96.0% to +  > 100%), while bevacizumab patients saw a median volume increase of +  > 100% (range - 63.0% to +  > 100%), p = 0.010.

Conclusions: Our study suggests that patients undergoing LITT for RN have longer overall survival and better long-term lesional volume reduction than those treated with bevacizumab. However, it remains unclear whether our findings are due only to a difference in efficacy of the treatments or the implications of selection bias.
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http://dx.doi.org/10.1007/s11060-020-03570-0DOI Listing
July 2020

Thirty- and 90-Day Readmissions After Treatment of Traumatic Subdural Hematoma: National Trend Analysis.

World Neurosurg 2020 07 6;139:e212-e219. Epub 2020 Apr 6.

Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut, USA; Department of Radiology & Biomedical Imaging, Yale University School of Medicine, New Haven, Connecticut, USA. Electronic address:

Objective: Subdural hematoma (SDH), a form of traumatic brain injury, is a common disease that requires extensive patient management and resource utilization; however, there remains a paucity of national studies examining the likelihood of readmission in this patient population. The aim of this study is to investigate differences in 30- and 90-day readmissions for treatment of traumatic SDH using a nationwide readmission database.

Methods: The Nationwide Readmission Database years 2013-2015 were queried. Patients with a diagnosis of traumatic SDH and a primary procedure code for incision of cerebral meninges for drainage were identified using the International Classification of Diseases, Ninth Revision, Clinical Modification coding system. Patients were grouped by no readmission (Non-R), readmission within 30 days (30-R), and readmission within 31-90 days (90-R).

Results: We identified a total of 14,355 patients, with 3106 (21.6%) patients encountering a readmission (30-R: n = 2193 [15.3%]; 90-R: n = 913 [6.3%]; Non-R: n = 11,249). The most prevalent 30- and 90-day diagnoses seen among the readmitted cohorts were postoperative infection (30-R: 10.5%, 90-R: 13.0%) and epilepsy (30-R: 3.7%, 90-R: 1.1%). On multivariate logistic regression analysis, Medicare, Medicaid, hypertension, diabetes, renal failure, congestive heart failure, and coagulopathy were independently associated with 30-day readmission; Medicare and rheumatoid arthritis/collagen vascular disease were independently associated with 90-day readmission.

Conclusions: In this study, we determine the relationship between readmission rates and complications associated with surgical intervention for traumatic subdural hematoma.
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http://dx.doi.org/10.1016/j.wneu.2020.03.168DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7380544PMC
July 2020

Hemorrhage risk of cerebral dural arteriovenous fistulas following Gamma Knife radiosurgery in a multicenter international consortium.

J Neurosurg 2019 Mar 15;132(4):1209-1217. Epub 2019 Mar 15.

2Department of Neurological Surgery, University of Virginia, Charlottesville, Virginia.

Objective: The authors performed a study to evaluate the hemorrhagic rates of cerebral dural arteriovenous fistulas (dAVFs) and the risk factors of hemorrhage following Gamma Knife radiosurgery (GKRS).

Methods: Data from a cohort of patients undergoing GKRS for cerebral dAVFs were compiled from the International Radiosurgery Research Foundation. The annual posttreatment hemorrhage rate was calculated as the number of hemorrhages divided by the patient-years at risk. Risk factors for dAVF hemorrhage prior to GKRS and during the latency period after radiosurgery were evaluated in a multivariate analysis.

Results: A total of 147 patients with dAVFs were treated with GKRS. Thirty-six patients (24.5%) presented with hemorrhage. dAVFs that had any cortical venous drainage (CVD) (OR = 3.8, p = 0.003) or convexity or torcula location (OR = 3.3, p = 0.017) were more likely to present with hemorrhage in multivariate analysis. Half of the patients had prior treatment (49.7%). Post-GRKS hemorrhage occurred in 4 patients, with an overall annual risk of 0.84% during the latency period. The annual risks of post-GKRS hemorrhage for Borden type 2-3 dAVFs and Borden type 2-3 hemorrhagic dAVFs were 1.45% and 0.93%, respectively. No hemorrhage occurred after radiological confirmation of obliteration. Independent predictors of hemorrhage following GKRS included nonhemorrhagic neural deficit presentation (HR = 21.6, p = 0.027) and increasing number of past endovascular treatments (HR = 1.81, p = 0.036).

Conclusions: Patients have similar rates of hemorrhage before and after radiosurgery until obliteration is achieved. dAVFs that have any CVD or are located in the convexity or torcula were more likely to present with hemorrhage. Patients presenting with nonhemorrhagic neural deficits and a history of endovascular treatments had higher risks of post-GKRS hemorrhage.
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http://dx.doi.org/10.3171/2018.12.JNS182208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6745287PMC
March 2019

Trans-Sulcal Endoport-Assisted Evacuation of Supratentorial Intracerebral Hemorrhage: Initial Single-Institution Experience Compared to Matched Medically Managed Patients and Effect on 30-Day Mortality.

Oper Neurosurg (Hagerstown) 2018 05;14(5):524-531

Department of Neurosurgery, Saint Louis University School of Medicine, St. Louis, Missouri.

Background: The surgical management of supratentorial intracerebral hemorrhages (ICH) remains controversial due to large trials failing to show clear benefits. Several minimally invasive techniques have emerged as an alternative to a conventional craniotomy with promising results.

Objective: To report our experience with endoport-assisted surgery in the evacuation of supratentorial ICH and its effects on outcome compared to matched medical controls.

Methods: Retrospective data were gathered of patients who underwent endoport-assisted evacuation between January 2014 and October 2016 by a single surgeon. Patients who were managed medically during the same period were matched to the surgical cohort. Previously published cohorts investigating the same technique were analyzed against the present cohort.

Results: Sixteen patients were identified and matched to 16 patients treated medically. Location, hemorrhage volume, and initial Glasgow Coma Scale (GCS) score did not differ significantly between the 2 cohorts. The mean volume reduction in the surgical cohort was 92.05% ± 7.05%. The improvement in GCS in the surgical cohort was statistically significant (7-13, P = .006). Compared to the medical cohort, endoport-assisted surgery resulted in a statistically significant difference in in-hospital mortality (6.25% vs 75.0%, P < .001) and 30-d mortality (6.25% vs 81.25%, P < .001). Compared to previously published cohorts, the present cohort had lower median preoperative GCS (7 vs 10, P = .02), but postoperative GCS did not differ significantly (13 vs 14, P = .28).

Conclusion: Endoport-assisted surgery is associated with high clot evacuation and decreases 30-d mortality compared to a similar medical group.
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http://dx.doi.org/10.1093/ons/opx161DOI Listing
May 2018

Staged Trapping of Traumatic Basilar Trunk Pseudoaneurysm: Case Report and Review of Literature.

World Neurosurg 2017 Dec 1;108:991.e7-991.e12. Epub 2017 Sep 1.

Department of Neurosurgery, Saint Louis University, Saint Louis, Missouri, USA. Electronic address:

Background: Traumatic intracranial aneurysms (TICAs) of the posterior circulation in the pediatric populations are rare. Only a few reports in the literature document basilar artery TICA in the pediatric population. These cases were typically associated with a clival fracture and commonly diagnosed weeks to months after trauma. We present a case of a patient with a basilar TICA diagnosed after a motor vehicle collision treated with staged trapping and review of the literature.

Case Description: We present a case of a 14-year-old boy who sustained a high-speed motor vehicle collision and developed a basilar trunk TICA identified on admission. Initially, the patient underwent craniotomy for proximal sacrifice of the basilar artery in hope for spontaneous thrombosis of the aneurysm through flow reversal. Endovascular options were reviewed and felt to be less feasible than surgical trapping. Due to continued filling through the right posterior communicating artery, the second surgery was performed to distally trap the aneurysm. The aneurysm was opened, showing some thrombosis and the absence of flow. Repeat magnetic resonance imaging did not reveal any new infarction, and the patient was discharged with neurologic improvement over time. At 1 year, he was able to ambulate unassisted and had a modified Rankin Scale score of 3.

Conclusion: Development of a TICA may be more acute than literature previously suggested. Treatment consists of a wide range of options and should be considered, especially in the pediatric population, to prevent rupture. Trapping can be performed safely if adequate collateral flow is present in the setting of a large basilar artery aneurysm.
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http://dx.doi.org/10.1016/j.wneu.2017.08.144DOI Listing
December 2017

Characteristics and predictors of oral cancer knowledge in a predominantly African American community.

PLoS One 2017 17;12(5):e0177787. Epub 2017 May 17.

Saint Louis University Cancer Center, Saint Louis, MO, United States of America.

Purpose: To characterize smoking and alcohol use, and to describe predictors of oral cancer knowledge among a predominantly African-American population.

Methods: A cross-sectional study was conducted between September, 2013 among drag racers and fans in East St. Louis. Oral cancer knowledge was derived from combining questionnaire items to form knowledge score. Covariates examined included age, sex, race, marital status, education status, income level, insurance status, tobacco and alcohol use. Adjusted linear regression analysis measured predictors of oral cancer knowledge.

Results: Three hundred and four participants completed questionnaire; 72.7% were African Americans. Smoking rate was 26.7%, alcohol use was 58.3%, and mean knowledge score was 4.60 ± 2.52 out of 17. In final adjusted regression model, oral cancer knowledge was associated with race and education status. Compared with Caucasians, African Americans were 29% less likely to have high oral cancer knowledge (β = -0.71; 95% CI: -1.35, -0.07); and participants with a high school diploma or less were 124% less likely to have high oral cancer knowledge compared with college graduates (β = -1.24; 95% CI: -2.44, -0.41).

Conclusions: There was lower oral cancer knowledge among African Americans and those with low education. The prevalence of smoking was also very high. Understanding predictors of oral cancer knowledge is important in future design of educational interventions specifically targeted towards high-risk group for oral cancer.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0177787PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5435300PMC
September 2017

Awake High-Flow Extracranial to Intracranial Bypass for Complex Cerebral Aneurysms: Institutional Clinical Trial Results.

World Neurosurg 2017 Sep 14;105:557-567. Epub 2017 Apr 14.

Saint Louis University Center for Outcomes Research, St. Louis, Missouri, USA.

Objective: Assess the potential added benefit to patient outcomes of "awake" neurological testing when compared with standard neurophysiologic testing performed under general endotracheal anesthesia.

Methods: Prospective study of 30 consecutive adult patients who underwent awake high flow extracranial to intracranial (HFEC-IC) bypass. Clinical neurological and neurophysiologic findings were recorded. Primary outcome measures were the incidence of stroke/cerebrovascular accident (CVA), length of stay, discharge to rehabilitation, 30-day modified Rankin scale score, and death. An analysis was also performed of a retrospective control cohort (n = 110 patients who underwent HFEC-IC for internal carotid artery (ICA) aneurysms under standard general endotracheal anesthesia).

Results: Five patients (16.6%) developed clinical awake neurological changes (4, contralateral hemiparesis; 1, ipsilateral visual changes) during the 10-minute ICA occlusion test. These patients had 2 kinks in the graft, 1 vasospasm, 1 requiring reconstruction of the distal anastomosis, and 1 developed blurring of vision that reversed after the removal of the distal permanent clip on the ICA. Three of these 5 patients had asynchronous clinical "awake" neurological and neurophysiologic changes. Two patients (7%) developed CVA. Median length of stay was 4 days. Twenty-eight of 30 patients were discharged to home. Median modified Rankin scale score was 1. There were no deaths in this series. Absolute risk reduction in the awake craniotomy group (n = 30) relative to control retrospective group (n = 110) was 7% for CVA, 9% for discharge to rehabilitation, and 10% for graft patency.

Conclusions: Temporary ICA occlusion during HFEC-IC bypass for ICA aneurysms in conjunction with awake intraoperative clinical testing was effective in detecting a subset of patients (n = 3, 10%) in whom neurological deficit was not detected by neurophysiologic monitoring alone.
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http://dx.doi.org/10.1016/j.wneu.2017.04.016DOI Listing
September 2017

Proposed clinical internal carotid artery classification system.

J Craniovertebr Junction Spine 2016 Jul-Sep;7(3):161-70

Department of Neurological Surgery, Saint Louis University, Saint Louis, Missouri, United States of America.

Introduction: Numerical classification systems for the internal carotid artery (ICA) are available, but modifications have added confusion to the numerical systems. Furthermore, previous classifications may not be applicable uniformly to microsurgical and endoscopic procedures. The purpose of this study was to develop a clinically useful classification system.

Materials And Methods: We performed cadaver dissections of the ICA in 5 heads (10 sides) and evaluated 648 internal carotid arteries with computed tomography angiography. We identified specific anatomic landmarks to define the beginning and end of each ICA segment.

Results: The ICA was classified into eight segments based on the cadaver and imaging findings: (1) Cervical segment; (2) cochlear segment (ascending segment of the ICA in the temporal bone) (relation of the start of this segment to the base of the styloid process: Above, 425 sides [80%]; below, 2 sides [0.4%]; at same level, 107 sides [20%]; P < 0.0001) (relation of cochlea to ICA: Posterior, 501 sides [85%]; posteromedial, 84 sides [14%]; P < 0.0001); (3) petrous segment (horizontal segment of ICA in the temporal bone) starting at the crossing of the eustachian tube superolateral to the ICA turn in all 10 samples; (4) Gasserian-Clival segment (ascending segment of ICA in the cavernous sinus) starting at the petrolingual ligament (PLL) (relation to vidian canal on imaging: At same level, 360 sides [63%]; below, 154 sides [27%]; above, 53 sides [9%]; P < 0.0001); in this segment, the ICA projected medially toward the clivus in 275 sides (52%) or parallel to the clivus with no deviation in 256 sides (48%; P < 0.0001); (5) sellar segment (medial loop of ICA in the cavernous sinus) starting at the takeoff of the meningeal hypophyseal trunk (ICA was medial into the sella in 271 cases [46%], lateral without touching the sella in 127 cases [23%], and abutting the sella in 182 cases [31%]; P < 0.0001); (6) sphenoid segment (lateral loop of ICA within the cavernous sinus) starting at the crossing of the fourth cranial nerve on the lateral aspect of the cavernous ICA and located directly lateral to the sphenoid sinus; (7) ring segment (ICA between the 2 dural rings) starting at the crossing of the third cranial nerve on the lateral aspect of the ICA; (8) cisternal segment starting at the distal dural ring.

Conclusions: The classification may be applied uniformly to all skull base surgical approaches including lateral microsurgical and ventral endoscopic approaches, obviating the need for 2 separate classification systems. The classification allows extrapolation of relevant clinical information because each named segment may indicate potential surgical risk to specific structures.
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http://dx.doi.org/10.4103/0974-8237.188412DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4994148PMC
September 2016

Knockdown of Autophagy Inhibits Infectious Hepatitis C Virus Release by the Exosomal Pathway.

J Virol 2016 02 18;90(3):1387-96. Epub 2015 Nov 18.

Department of Pathology, Saint Louis University, Saint Louis, Missouri, USA Department of Internal Medicine, Saint Louis University, Saint Louis, Missouri, USA

Unlabelled: Hepatitis C virus (HCV) is a major cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma in humans. We showed previously that HCV induces autophagy for viral persistence by preventing the innate immune response. Knockdown of autophagy reduces extracellular HCV release, although the precise mechanism remains unknown. In this study, we observed that knockdown of autophagy genes enhances intracellular HCV RNA and accumulates infectious virus particles in cells. Since HCV release is linked with the exosomal pathway, we examined whether autophagy proteins associate with exosomes in HCV-infected cells. We observed an association between HCV and the exosomal marker CD63 in autophagy knockdown cells. Subsequently, we observed that levels of extracellular infectious HCV were significantly lower in exosomes released from autophagy knockdown cells. To understand the mechanism for reduced extracellular infectious HCV in the exosome, we observed that an interferon (IFN)-stimulated BST-2 gene is upregulated in autophagy knockdown cells and associated with the exosome marker CD63, which may inhibit HCV assembly or release. Taken together, our results suggest a novel mechanism involving autophagy and exosome-mediated HCV release from infected hepatocytes.

Importance: Autophagy plays an important role in HCV pathogenesis. Autophagy suppresses the innate immune response and promotes survival of virus-infected hepatocytes. The present study examined the role of autophagy in secretion of infectious HCV from hepatocytes. Autophagy promoted HCV trafficking from late endosomes to lysosomes, thus providing a link with the exosome. Inhibition of HCV-induced autophagy could be used as a strategy to block exosome-mediated virus transmission.
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http://dx.doi.org/10.1128/JVI.02383-15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4719613PMC
February 2016

Luciferase inhibition by a novel naphthoquinone.

J Photochem Photobiol B 2012 Feb 8;107:55-64. Epub 2011 Dec 8.

Department of Chemistry and Biochemistry, The University of Tulsa, Tulsa, OK 74104, USA.

The novel naphthoquinone 12,13-dihydro-N-methyl-6,11,13-trioxo-5H-benzo[4,5]cyclohepta[1,2-b]naphthalen-5,12-imine (hereafter called TU100) was created as a potential chemotherapeutic agent. Previous work showed it is an irreversible inhibitor of type I and II topoisomerases that alkylates specific enzyme thiols. While analyzing the effect of TU100 on cancer cells, we discovered it is a potent inhibitor of luciferase derived from both Photinus pyralis (fireflies) and Renilla reniformis (sea pansy). Pre-incubation experiments showed that TU100 does not irreversibly inactivate luciferase, indicating its mechanism is different from that observed with topoisomerases. Firefly luciferase generates light using ATP and luciferin as substrates (bioluminescence). An examination of TU100 inhibition at varying substrate concentrations revealed the drug is uncompetitive with respect to ATP and competitive with respect to luciferin. The TU100 binding constant (K(I)) is 2.5±0.7 μM as determined by Dixon plot analysis. These data suggest TU100 specifically binds the luciferase-ATP complex and prevents its interaction with luciferin. Given the novel structure of TU100, unique mechanism of action, and ability to target luciferase from different species, these results identify TU100 as an important new reagent for investigating and regulating bioluminescent enzymes.
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http://dx.doi.org/10.1016/j.jphotobiol.2011.11.008DOI Listing
February 2012
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