Publications by authors named "Stephanie Chen"

238 Publications

Treatment-Associated Stroke in Patients Undergoing Endovascular Therapy in the ARUBA Trial.

Stroke 2021 Nov 8;52(11):e710-e714. Epub 2021 Oct 8.

Department of Neurosurgery, University of Miami, FL.

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http://dx.doi.org/10.1161/STROKEAHA.120.033743DOI Listing
November 2021

Assessing the rate, natural history, and treatment trends of intracranial aneurysms in patients with intracranial dural arteriovenous fistulas: a Consortium for Dural Arteriovenous Fistula Outcomes Research (CONDOR) investigation.

J Neurosurg 2021 Sep 10:1-10. Epub 2021 Sep 10.

Departments of18Neurological Surgery.

Objective: There is a reported elevated risk of cerebral aneurysms in patients with intracranial dural arteriovenous fistulas (dAVFs). However, the natural history, rate of spontaneous regression, and ideal treatment regimen are not well characterized. In this study, the authors aimed to describe the characteristics of patients with dAVFs and intracranial aneurysms and propose a classification system.

Methods: The Consortium for Dural Arteriovenous Fistula Outcomes Research (CONDOR) database from 12 centers was retrospectively reviewed. Analysis was performed to compare dAVF patients with (dAVF+ cohort) and without (dAVF-only cohort) concomitant aneurysm. Aneurysms were categorized based on location as a dAVF flow-related aneurysm (FRA) or a dAVF non-flow-related aneurysm (NFRA), with further classification as extra- or intradural. Patients with traumatic pseudoaneurysms or aneurysms with associated arteriovenous malformations were excluded from the analysis. Patient demographics, dAVF anatomical information, aneurysm information, and follow-up data were collected.

Results: Of the 1077 patients, 1043 were eligible for inclusion, comprising 978 (93.8%) and 65 (6.2%) in the dAVF-only and dAVF+ cohorts, respectively. There were 96 aneurysms in the dAVF+ cohort; 10 patients (1%) harbored 12 FRAs, and 55 patients (5.3%) harbored 84 NFRAs. Dural AVF+ patients had higher rates of smoking (59.3% vs 35.2%, p < 0.001) and illicit drug use (5.8% vs 1.5%, p = 0.02). Sixteen dAVF+ patients (24.6%) presented with aneurysm rupture, which represented 16.7% of the total aneurysms. One patient (1.5%) had aneurysm rupture during follow-up. Patients with dAVF+ were more likely to have a dAVF located in nonconventional locations, less likely to have arterial supply to the dAVF from external carotid artery branches, and more likely to have supply from pial branches. Rates of cortical venous drainage and Borden type distributions were comparable between cohorts. A minority (12.5%) of aneurysms were FRAs. The majority of the aneurysms underwent treatment via either endovascular (36.5%) or microsurgical (15.6%) technique. A small proportion of aneurysms managed conservatively either with or without dAVF treatment spontaneously regressed (6.2%).

Conclusions: Patients with dAVF have a similar risk of harboring a concomitant intracranial aneurysm unrelated to the dAVF (5.3%) compared with the general population (approximately 2%-5%) and a rare risk (0.9%) of harboring an FRA. Only 50% of FRAs are intradural. Dural AVF+ patients have differences in dAVF angioarchitecture. A subset of dAVF+ patients harbor FRAs that may regress after dAVF treatment.
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http://dx.doi.org/10.3171/2021.1.JNS202861DOI Listing
September 2021

Consortium for Dural Arteriovenous Fistula Outcomes Research (CONDOR): rationale, design, and initial characterization of patient cohort.

J Neurosurg 2021 Sep 10:1-11. Epub 2021 Sep 10.

6Department of Neurological Surgery, University of Virginia Health System, Charlottesville, Virginia.

Objective: Cranial dural arteriovenous fistulas (dAVFs) are rare lesions, hampering efforts to understand them and improve their care. To address this challenge, investigators with an established record of dAVF investigation formed an international, multicenter consortium aimed at better elucidating dAVF pathophysiology, imaging characteristics, natural history, and patient outcomes. This report describes the design of the Consortium for Dural Arteriovenous Fistula Outcomes Research (CONDOR) and includes characterization of the 1077-patient cohort.

Methods: Potential collaborators with established interest in the field were identified via systematic review of the literature. To ensure uniformity of data collection, a quality control process was instituted. Data were retrospectively obtained.

Results: CONDOR comprises 14 centers in the United States, the United Kingdom, the Netherlands, and Japan that have pooled their data from 1077 dAVF patients seen between 1990 and 2017. The cohort includes 359 patients (33%) with Borden type I dAVFs, 175 (16%) with Borden type II fistulas, and 529 (49%) with Borden type III fistulas. Overall, 852 patients (79%) presented with fistula-related symptoms: 427 (40%) presented with nonaggressive symptoms such as tinnitus or orbital phenomena, 258 (24%) presented with intracranial hemorrhage, and 167 (16%) presented with nonhemorrhagic neurological deficits. A smaller proportion (224 patients, 21%), whose dAVFs were discovered incidentally, were asymptomatic. Many patients (85%, 911/1077) underwent treatment via endovascular embolization (55%, 587/1077), surgery (10%, 103/1077), radiosurgery (3%, 36/1077), or multimodal therapy (17%, 184/1077). The overall angiographic cure rate was 83% (758/911 treated), and treatment-related permanent neurological morbidity was 2% (27/1467 total procedures). The median time from diagnosis to follow-up was 380 days (IQR 120-1038.5 days).

Conclusions: With more than 1000 patients, the CONDOR registry represents the largest registry of cranial dAVF patient data in the world. These unique, well-annotated data will enable multiple future analyses to be performed to better understand dAVFs and their management.
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http://dx.doi.org/10.3171/2021.1.JNS202790DOI Listing
September 2021

Outcomes of Central Hepatectomy for Pediatric Liver Tumors.

J Surg Res 2021 Aug 28;268:570-575. Epub 2021 Aug 28.

Division of Pediatric Surgery, Children's Hospital Los Angeles, Los Angeles, California; Department of Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California. Electronic address:

Background: Central hepatectomy (CH) is an uncommon surgical technique that is an option for resection of centrally located tumors, with the advantage of sparing normal hepatic parenchyma. Few studies have described outcomes in children undergoing CH.

Materials And Methods: An IRB-approved, retrospective chart review of patients who underwent CH at Children's Hospital Los Angeles between 2005 and 2016 was performed. Data included patient demographics, peri-operative factors, and post-operative outcomes. The IRB approved waiver of consent.

Results: Eight patients (4F:4M) with median age of 1.9 Y underwent CH: 7 patients for HB and 1 patient for focal nodular hyperplasia. Two of the seven HB patients had metastatic disease at diagnosis. Six of the seven HB patients received a median of 4 rounds (3-7 rounds) of pre-operative chemotherapy. The median operative time was 197.5 Min (143-394 Min) with median blood loss of 175 mL (100-1200 mL). Complications included a bile fluid collection requiring aspiration. Seven patients had negative margins on pathology. One patient with a positive margin successfully completed therapy, without recurrent disease. All patients survived to follow-up, with a median follow-up duration of 1.1 Y (0.1-12.1 Y). Two patients developed recurrent disease requiring formal hepatic lobectomy and orthotopic liver transplantation. These patients had negative pathologic margins, with tumor within 1 mm of resection margins.

Conclusion: CH is an effective alternative to extended hepatectomy for patients with centrally located liver tumors and is associated with good clinical and pathologic outcomes.
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http://dx.doi.org/10.1016/j.jss.2021.06.077DOI Listing
August 2021

An N-Cadherin 2 expressing epithelial cell subpopulation predicts response to surgery, chemotherapy and immunotherapy in bladder cancer.

Nat Commun 2021 08 12;12(1):4906. Epub 2021 Aug 12.

Department of Surgery (Urology), Cedars-Sinai Medical Center, Los Angeles, CA, USA.

Neoadjuvant chemotherapy (NAC) prior to surgery and immune checkpoint therapy (ICT) have revolutionized bladder cancer management. However, stratification of patients that would benefit most from these modalities remains a major clinical challenge. Here, we combine single nuclei RNA sequencing with spatial transcriptomics and single-cell resolution spatial proteomic analysis of human bladder cancer to identify an epithelial subpopulation with therapeutic response prediction ability. These cells express Cadherin 12 (CDH12, N-Cadherin 2), catenins, and other epithelial markers. CDH12-enriched tumors define patients with poor outcome following surgery with or without NAC. In contrast, CDH12-enriched tumors exhibit superior response to ICT. In all settings, patient stratification by tumor CDH12 enrichment offers better prediction of outcome than currently established bladder cancer subtypes. Molecularly, the CDH12 population resembles an undifferentiated state with inherently aggressive biology including chemoresistance, likely mediated through progenitor-like gene expression and fibroblast activation. CDH12-enriched cells express PD-L1 and PD-L2 and co-localize with exhausted T-cells, possibly mediated through CD49a (ITGA1), providing one explanation for ICT efficacy in these tumors. Altogether, this study describes a cancer cell population with an intriguing diametric response to major bladder cancer therapeutics. Importantly, it also provides a compelling framework for designing biomarker-guided clinical trials.
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http://dx.doi.org/10.1038/s41467-021-25103-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8361097PMC
August 2021

Microsurgical Clipping and Bypass for Fusiform Middle Cerebral Artery Aneurysm: 2-Dimensional Operative Video.

Oper Neurosurg (Hagerstown) 2021 Oct;21(5):E445-E446

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

Fusiform middle cerebral artery (MCA) aneurysms that require treatment can often necessitate complex endovascular or microsurgical treatment. We present a case of a 25-yr-old female with an incidentally discovered left 14-mm fusiform MCA aneurysm incorporating the frontal MCA trunk origin in its dome. The location and anatomy were not favorable for endovascular treatment with flow diversion.  The patient was offered continued observation or microsurgical treatment. Direct clipping of this aneurysm was not possible. After a thorough discussion of the risks, benefits, indications, and natural history of the lesion, the patient desired to have the aneurysm treated given her young age, location, size of the aneurysm, and the significant clinical experience of the treating team in bypass surgery.  The patient underwent superficial temporal artery to frontal M2 (STA-FM2) direct bypass for flow replacement followed by microsurgical trapping and clip ligation. The patient was maintained on antiplatelet therapy preoperatively and postoperatively. The patient had a transient aphasia and mild right upper extremity weakness (4/5) in the immediate postoperative period, which fully recovered by the time of patient discharge. The case presentation, surgical anatomy, technique, and postoperative course and outcome are reviewed. The different strategies for bypass and clip ligation are reviewed with particular focus on the anatomic constraints for each bypass configuration. The outcomes of bypass surgery for MCA aneurysms are reviewed.1-7 The patient gave verbal consent for participating in the procedure, surgical video, and publication of their image.
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http://dx.doi.org/10.1093/ons/opab281DOI Listing
October 2021

Neural fragility as an EEG marker of the seizure onset zone.

Nat Neurosci 2021 10 5;24(10):1465-1474. Epub 2021 Aug 5.

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

Over 15 million patients with epilepsy worldwide do not respond to drugs. Successful surgical treatment requires complete removal or disconnection of the seizure onset zone (SOZ), brain region(s) where seizures originate. Unfortunately, surgical success rates vary between 30 and 70% because no clinically validated biological marker of the SOZ exists. We develop and retrospectively validate a new electroencephalogram (EEG) marker-neural fragility-in a retrospective analysis of 91 patients by using neural fragility of the annotated SOZ as a metric to predict surgical outcomes. Fragility predicts 43 out of 47 surgical failures, with an overall prediction accuracy of 76% compared with the accuracy of clinicians at 48% (successful outcomes). In failed outcomes, we identify fragile regions that were untreated. When compared to 20 EEG features proposed as SOZ markers, fragility outperformed in predictive power and interpretability, which suggests neural fragility as an EEG biomarker of the SOZ.
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http://dx.doi.org/10.1038/s41593-021-00901-wDOI Listing
October 2021

Pleiotropy-guided transcriptome imputation from normal and tumor tissues identifies candidate susceptibility genes for breast and ovarian cancer.

HGG Adv 2021 Jul 16;2(3). Epub 2021 Jun 16.

Department of Virus, Lifestyle, and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark.

Familial, sequencing, and genome-wide association studies (GWASs) and genetic correlation analyses have progressively unraveled the shared or pleiotropic germline genetics of breast and ovarian cancer. In this study, we aimed to leverage this shared germline genetics to improve the power of transcriptome-wide association studies (TWASs) to identify candidate breast cancer and ovarian cancer susceptibility genes. We built gene expression prediction models using the PrediXcan method in 681 breast and 295 ovarian tumors from The Cancer Genome Atlas and 211 breast and 99 ovarian normal tissue samples from the Genotype-Tissue Expression project and integrated these with GWAS meta-analysis data from the Breast Cancer Association Consortium (122,977 cases/105,974 controls) and the Ovarian Cancer Association Consortium (22,406 cases/40,941 controls). The integration was achieved through application of a pleiotropy-guided conditional/conjunction false discovery rate (FDR) approach in the setting of a TWASs. This identified 14 candidate breast cancer susceptibility genes spanning 11 genomic regions and 8 candidate ovarian cancer susceptibility genes spanning 5 genomic regions at conjunction FDR < 0.05 that were >1 Mb away from known breast and/or ovarian cancer susceptibility loci. We also identified 38 candidate breast cancer susceptibility genes and 17 candidate ovarian cancer susceptibility genes at conjunction FDR < 0.05 at known breast and/or ovarian susceptibility loci. The 22 genes identified by our cross-cancer analysis represent promising candidates that further elucidate the role of the transcriptome in mediating germline breast and ovarian cancer risk.
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http://dx.doi.org/10.1016/j.xhgg.2021.100042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8312632PMC
July 2021

Volumetric glutamate imaging (GluCEST) using 7T MRI can lateralize nonlesional temporal lobe epilepsy: A preliminary study.

Brain Behav 2021 08 13;11(8):e02134. Epub 2021 Jul 13.

Penn Epilepsy Center, Department of Neurology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.

Introduction: Drug-resistant epilepsy patients show worse outcomes after resection when standard neuroimaging is nonlesional, which occurs in one-third of patients. In prior work, we employed 2-D glutamate imaging, Glutamate Chemical Exchange Saturation Transfer (GluCEST), to lateralize seizure onset in nonlesional temporal lobe epilepsy (TLE) based on increased ipsilateral GluCEST signal in the total hippocampus and hippocampal head. We present a significant advancement to single-slice GluCEST imaging, allowing for three-dimensional analysis of brain glutamate networks.

Methods: The study population consisted of four MRI-negative, nonlesional TLE patients (two male, two female) with electrographically identified left temporal onset seizures. Imaging was conducted on a Siemens 7T MRI scanner using the CEST method for glutamate, while the advanced normalization tools (ANTs) pipeline and the Automated Segmentation of the Hippocampal Subfields (ASHS) method were employed for image analysis.

Results: Volumetric GluCEST imaging was validated in four nonlesional TLE patients showing increased glutamate lateralized to the hippocampus of seizure onset (p = .048, with a difference among ipsilateral to contralateral GluCEST signal percentage ranging from -0.05 to 1.37), as well as increased GluCEST signal in the ipsilateral subiculum (p = .034, with a difference among ipsilateral to contralateral GluCEST signal ranging from 0.13 to 1.57).

Conclusions: The ability of 3-D, volumetric GluCEST to localize seizure onset down to the hippocampal subfield in nonlesional TLE is an improvement upon our previous 2-D, single-slice GluCEST method. Eventually, we hope to expand volumetric GluCEST to whole-brain glutamate imaging, thus enabling noninvasive analysis of glutamate networks in epilepsy and potentially leading to improved clinical outcomes.
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http://dx.doi.org/10.1002/brb3.2134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8413808PMC
August 2021

Atlanto-Occipital Decompression of Vertebral Artery for a Variant of Bow Hunter's Syndrome: 2-Dimensional Operative Video.

Oper Neurosurg (Hagerstown) 2021 Sep;21(4):E363-E364

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

Rotational vertebral artery (VA) occlusion syndrome, also known as bow hunter's syndrome, is an uncommon variant of vertebrobasilar insufficiency typically occurring with head rotation.1-3 The most common presenting symptom is dizziness (76.8%), followed by visual abnormalities and syncope (50.4% and 40.4%, respectively).2 Osteophytic compression due to spinal spondylosis has been shown to be the most common etiology (46.2%), with other factors, such as a fibrous band, muscular compression, or spinal instability, being documented.1,2 Treatment is dependent on the level and site of VA compression with anterior, anterolateral, or posterior approaches being described.1,4 We present the case of a 72-yr-old male with osteophytic compression of the V3 segment of the vertebral artery at the occipital-cervical junction. The patient underwent a C1 hemilaminectomy and removal of osteophytic compression from the occipital-cervical joint. The patient had complete resolution of compression of his vertebral artery on postoperative imaging and remained neurologically intact following the procedure. We review the literature on this topic, the technical nuances of the procedure performed, and review the different treatment modalities available for this rare condition.1-11  The patient consented to the procedure and to publication of their image.
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http://dx.doi.org/10.1093/ons/opab231DOI Listing
September 2021

The effect of obesity on pain severity and pain interference.

Pain Manag 2021 Sep 9;11(5):571-581. Epub 2021 Jun 9.

Department of Anesthesiology, Weill Cornell Medicine, New York, NY 10065, USA.

Obesity is one of the most prevalent comorbidities associated with chronic pain, which can severely interfere with daily living and increase utilization of clinical resources. We hypothesized that a higher level of obesity, measured by BMI, would be associated with increased pain severity (intensity) and interference (pain related disability). Participant data was pulled from a multisite chronic pain outpatient database and categorized based on BMI. A total of 2509 patients were included in the study. We found significant differences between BMI groups for all pain severity scores (worst, least, average, current) and total pain interference score. Obese patients had significantly higher scores than normal weight patients. We found obesity to be associated with increased pain severity and pain interference.
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http://dx.doi.org/10.2217/pmt-2020-0089DOI Listing
September 2021

Microsurgical Clip Trapping of Dorsal Internal Carotid Artery Blister Ruptured Aneurysm: 2-Dimensional Operative Video.

Oper Neurosurg (Hagerstown) 2021 08;21(3):E244-E245

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

Dorsal internal carotid artery (ICA) blister aneurysms are an uncommon aneurysm variant constituting 0.3% to 1% of intracranial aneurysms and can be due to ulceration, atherosclerosis, or dissection.1-3 Despite its rarity, it carries a high risk of rupture with an estimation of 0.9% to 6.5% among intracranial aneurysms.1,2 Blister aneurysms are small in size, have no distinguishable neck, and have a friable wall that can easily rupture if manipulated, hence the difficulty in its treatment utilizing both microsurgical and endovascular techniques.1,2,4-6 Endovascular coiling of these lesions may not be adequate due to the broad-based size; stenting requires the use of antiplatelet medications, which could lead to rebleeding; flow diversion takes longer to exert its treatment effect.1,4 Conversely, microsurgical management carries a higher intraoperative rupture rate.2 Microsurgical options include clipping, clip reconstruction, trapping with bypass, and wrapping.4,7 We present a case of a 38-yr-old man who presented with a ruptured right dorsal ICA blister aneurysm treated with microsurgical trapping with intraoperative flow measurements. We demonstrate how the use of quantitative intraoperative flow measurements allows confident sacrifice of the supraclinoid ICA. We also demonstrate in contrast another case example of utilizing a clip-graft repair. The patient remained unchanged with an intact neurological exam, and postoperative imaging showed no aneurysm remnant and patent anterior choroidal artery. We review the literature and management of dorsal ICA aneurysms.8-15 We also review the technical nuances and different endovascular and microsurgical treatments that can be used for this condition.  The patient gave informed consent for the procedure and verbal consent to the publication.
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http://dx.doi.org/10.1093/ons/opab196DOI Listing
August 2021

Teaching Pathology in an Integrated Preclinical Medical School Curriculum and Adaptations to COVID-19 Restrictions.

Acad Pathol 2021 Jan-Dec;8:23742895211015337. Epub 2021 May 19.

Department of Pathology, University of Iowa Hospitals and Clinics, Iowa City, IA, USA.

The coronavirus disease 2019 (COVID-19) pandemic has had a major impact on education at all age levels, including professional schools and health professions programs. We describe the experience of adapting preclinical medical school courses within an integrated curriculum to virtual instruction. A major feature of two of the courses were pathology small groups adapted from pathology courses in the previous medical school curriculum. These small groups were designed to use facilitated groups of 8 to 10 students. With a sudden change to virtual learning, these small groups were shifted to large group virtual sessions. In general, the conversion went well, with ongoing optimization of the format of the large group sessions mainly occurring over the first several sessions. End-of-course student evaluations were generally positive, but with a preference toward returning to live sessions in the future. Scores on 5 multiple choice examinations in the spring 2020 course were essentially identical in mean, standard deviation, and distribution to examinations in the previous 2 years of the course that had similar layout and topic organization. We discuss the challenges and successes of the switch to virtual instruction and of teaching pathology content within an integrated medical school curriculum.
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http://dx.doi.org/10.1177/23742895211015337DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138288PMC
May 2021

Brain-Responsive Neurostimulation for the treatment of adults with epilepsy in tuberous sclerosis complex: A case series.

Epilepsia Open 2021 Jun 13;6(2):419-424. Epub 2021 Mar 13.

Baylor College of Medicine, Houston, TX, USA.

Objective: Tuberous sclerosis complex (TSC) is a genetic disorder primarily characterized by the development of multisystem benign tumors. Epilepsy is the most common neurologic manifestation, affecting 80%-90% of TSC patients. The diffuse structural brain abnormalities and the multifocal nature of epilepsy in TSC pose diagnostic challenges when evaluating patients for epilepsy surgery.

Methods: We retrospectively reviewed the safety experience and efficacy outcomes of five adult TSC patients who were treated with direct brain-responsive neurostimulation (RNS System, NeuroPace, Inc).

Results: The average follow-up duration was 20 months. All five patients were responders (≥50% disabling seizure reduction) at last follow-up. The median reduction in disabling seizures was 58% at 1 year and 88% at last follow-up. Three of the five patients experienced some period of seizure freedom ranging from 3 months to over 1 year.

Significance: In this small case series, we report the first safety experience and efficacy outcomes in patients with TSC-associated drug-resistant focal epilepsy treated with direct brain-responsive neurostimulation.
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http://dx.doi.org/10.1002/epi4.12481DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166788PMC
June 2021

Resident-performed immediate sequential bilateral cataract surgery during the COVID-19 pandemic.

Indian J Ophthalmol 2021 06;69(6):1579-1584

Department of Ophthalmology, University of California San Francisco, San Francisco, CA, USA.

Purpose: To assess visual outcomes and patient satisfaction for senior resident-performed immediate sequential bilateral cataract surgery (ISBCS) versus delayed sequential bilateral cataract surgery (DSBCS) during the COVID-19 pandemic, when minimizing healthcare-related exposures for patients and providers are paramount.

Methods: This was a pilot retrospective cohort study of all ISBCS and DSBCS patients who underwent senior resident-performed cataract surgery from May to September 2020 at a single academic institution. Outcome measures were final corrected distance visual acuity (CDVA), final manifest refraction (MRx), intraoperative and postoperative complications rates, total number of visits, and patient satisfaction assessed postoperatively by telephone questionnaire.

Results: Twenty-two eyes of 14 patients and 56 eyes of 28 patients underwent senior resident-performed ISBCS and DSBCS, respectively. Final CDVA was 20/25 or better in 21 (95%) ISBCS and 51 (91%) DSBCS eyes (P = 0.670). Deviation of final MRx from target refraction was within 0.50 D in 17 (77%) ISBCS and 47 (84%) DSBCS eyes (P = 0.522). There was no significant difference in intraoperative (P = 1.000) or postoperative (P = 1.000) complications. ISBCS patients averaged 3.5 fewer visits than DSBCS patients (5.9 vs 9.5, P < 0.001). All ISBCS and 20 DSBCS patients (87%) reported they were "very satisfied" or "satisfied" with their experience (P = 0.701). Five of six senior residents responded that they preferred performing ISBCS over DSBCS.

Conclusion: This early experience suggests that senior resident-performed ISBCS is as safe and effective as DSBCS, with the added benefit of averaging fewer in-person visits. Residency programs should consider offering senior resident-performed ISBCS to select patients during the COVID-19 pandemic.
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http://dx.doi.org/10.4103/ijo.IJO_226_21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8302298PMC
June 2021

Pregnancy-Associated Spontaneous Coronary Artery Dissection: Clinical Characteristics, Outcomes, and Risk During Subsequent Pregnancy.

J Invasive Cardiol 2021 06 14;33(6):E457-E466. Epub 2021 May 14.

Department of Cardiology, Kaiser Permanente San Rafael Medical Center, 99 Montecillo Road, San Rafael, CA 94903 USA.

Objectives: Spontaneous coronary artery dissection (SCAD) is a common cause of pregnancy-associated myocardial infarction.

Methods: This study compares the clinical course and longitudinal follow-up of 22 cases of pregnancy-associated SCAD (P-SCAD) with 285 cases of non-pregnancy SCAD (NP-SCAD) from Kaiser Permanente Northern California between September 2002 through June 2017.

Results: Age in the P-SCAD group was significantly lower than in the NP-SCAD group (37.1 ± 5.7 years vs 50.9 ± 9.9 years, respectively; P<.001). Both cohorts were racially diverse, but the P-SCAD group had fewer whites (27.3% vs 50.7%; P=.03). The P-SCAD group had higher multigravidity (54.6% vs 31.4%; P=.03) and 68.2% were of advanced maternal age. The rates of ST-elevation myocardial infarction, ventricular tachycardia/fibrillation, and left main coronary dissection were similar. Proximal vessel dissection (31.8% vs 7.7%; P<.01), multiple vessel dissection (31.8% vs 9.5%; P<.01), and reduced ejection fraction at presentation (49.6 ± 10.5% vs 55.7 ± 10.4%; P=.01) were more common in the P-SCAD group vs the NP-SCAD group, respectively. More P-SCAD patients had cardiogenic shock and/or required intra-aortic balloon pump support (9.1% vs 1.1%; P=.04). Medical management was the principal coronary treatment strategy in both groups. P-SCAD patients experienced more major adverse cardiovascular events (50.0% vs 26.0%; P=.02), driven by persistent reduced ejection fraction ≤45% at follow-up (18.2% vs 5.3%; P=.04). Recurrent SCAD (18.2% vs 11.2%; P=.31) and cardiovascular death (0% vs 0.4%; P>.99) were similar in the P-SCAD group vs the NP-SCAD group, respectively. Seven patients had successful subsequent pregnancies without cardiac complications.

Conclusion: P-SCAD has a higher-risk presentation, but similar long-term prognosis compared with NP-SCAD. In addition, subsequent pregnancy after SCAD may present acceptable risk.
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June 2021

It Takes a Team to Make It Through: The Role of Social Support for Survival and Self-Care After Allogeneic Hematopoietic Stem Cell Transplant.

Front Psychol 2021 26;12:624906. Epub 2021 Mar 26.

Department of Psychology, Columbia University, New York, NY, United States.

Background: Social support plays an important role for health outcomes. Support for those living with chronic conditions may be particularly important for their health, and even for their survival. The role of support for the survival of cancer patients after receiving an allogeneic hematopoietic cell transplant (alloHCT) is understudied. To better understand the link between survival and support, as well as different sources and functions of support, we conducted two studies in alloHCT patients. First, we examined whether social support is related to survival (Study 1). Second, we examined who provides which support and which specific support-related functions and tasks are fulfilled by lay caregivers and healthcare professionals (Study 2).

Methods: In Study 1, we conducted a retrospective chart review of alloHCT patients ( = 173, 42.8% female, age: = 49.88) and registered availability of a dedicated lay caregiver and survival. In Study 2, we prospectively followed patients after alloHCT ( = 28, 46.4% female, age: = 53.97, 46.4% ethnic minority) from the same hospital, partly overlapping from Study 1, who shared their experiences of support from lay caregivers and healthcare providers in semi-structured in-depth interviews 3 to 6 months after their first hospital discharge.

Results: Patients with a dedicated caregiver had a higher probability of surviving to 100 days (86.7%) than patients without a caregiver (69.6%), OR = 2.84, = 0.042. Study 2 demonstrated the importance of post-transplant support due to patients' emotional needs and complex self-care regimen. The role of lay caregivers extended to many areas of patients' daily lives, including support for attending doctor's appointments, managing medications and financial tasks, physical distancing, and maintaining strict dietary requirements. Healthcare providers mainly fulfilled medical needs and provided informational support, while lay caregivers were the main source of emotional and practical support.

Conclusion: The findings highlight the importance of studying support from lay caregivers as well as healthcare providers, to better understand how they work together to support patients' adherence to recommended self-care and survival.
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http://dx.doi.org/10.3389/fpsyg.2021.624906DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044751PMC
March 2021

Radial Artery Access for Cerebral Angiography: 2-Dimensional Operative Video.

Oper Neurosurg (Hagerstown) 2021 05;20(6):E431-E432

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

A number of studies have demonstrated that the radial artery is a safer access site than the femoral artery for endovascular procedures.1-4 In the prospective randomized studies comparing transradial and transfemoral approaches for cardiac procedures, there was a 60% reduction in access site complications as well as significant decreases in all-cause mortality with the transradial approach as compared to transfemoral, which has led to the adoption of a radial first strategy.5-7 Neurointerventional studies have demonstrated similar safety benefits as well as improved patient preference.8-14 In this video, a patient presented with an unruptured anterior communicating artery aneurysm and consented to a transradial artery diagnostic cerebral angiogram. This technical video demonstrates the key preprocedural preparation, room setup, patient positioning, steps for radial artery, and distal radial artery puncture and sheath placement. Distal transradial artery access is our preferred approach for diagnostic cerebral angiography because of an improved safety profile and procedural ergonomics. In cases in which a larger radial artery is advantageous such as for neurointerventions requiring larger systems, a standard transradial approach may be performed.9 In this video, a full 6-vessel cerebral angiogram is performed, followed by our arteriotomy closure technique using our standard equipment including a 10-cm 5 French Glidesheath Slender (Terumo, Japan), 100-cm hydrophilic coated 5 French Simmons 1 catheter (Merit OEM), 0.035 hydrophilic coated guidewire, and SafeGuard closure device (Merit, Salt Lake City, Utah).
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http://dx.doi.org/10.1093/ons/opab071DOI Listing
May 2021

Frozen Section Quality Assurance.

Am J Clin Pathol 2021 Aug;156(3):461-470

Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.

Objectives: Composite frozen section turnaround time has limited value, precluding assessment of certain processes: slide preparation (technical) and diagnosis (interpretation). We examined whether measuring these elements could identify delays, hypothesizing that longer times were related to (1) inefficient technical processes and (2) case-specific diagnostic challenges.

Methods: Technical and interpretive times were determined for 1,992 specimens submitted for frozen section in 2017; the data were sorted by surgical specialty. Mean and quartile times were determined for each category with all specimens assessed equally, including those with multiple frozen section blocks.

Results: Technical times were significantly longer than interpretive times. Specialty grouping facilitated trend identification and enabled assessment of technical and interpretation challenges. We identified technical issues with certain gross specimens involving overdissection and interpretation delays for specific neoplasms and margins.

Conclusions: Measuring technical and interpretative times and subcategorizing by specialty has aided the assessment of frozen section processing in our laboratory, enabling case isolation for process improvement.
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http://dx.doi.org/10.1093/ajcp/aqaa259DOI Listing
August 2021

Bidirectional Association between Visual Impairment and Dementia Among Older Adults in the United States Over Time.

Ophthalmology 2021 Sep 27;128(9):1276-1283. Epub 2021 Feb 27.

Byers Eye Institute, Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, California; Veterans Affairs Palo Alto Health Care System, Palo Alto, California. Electronic address:

Purpose: Although visual impairment (VI) has been associated with worse cognitive performance among older adults, the temporal relationship between the 2 remains subject to debate. Our objective was to investigate the longitudinal impact of VI on cognitive function and vice versa.

Design: Retrospective, time-to-event study.

Participants: National Health and Aging Trends Study (NHATS) participants from 2011 to 2018 cycles.

Methods: A total of 10 676 participants aged 65 years and older were included. Cox proportional hazards regression models evaluated the impact of baseline VI on subsequent dementia and impact of baseline dementia on subsequent VI. Models were adjusted for potential confounding variables, including demographics, clinical comorbidities, and hearing and physical function limitations.

Main Outcome Measures: Hazard ratio (HR) for incident dementia among participants with baseline self-reported VI and HR for incident VI among participants with baseline dementia.

Results: Of the 10 676 participants included in the analysis, approximately 40% were aged 65-74 years, 40% were aged 75-84 years, and the remaining 20% were aged 85 years and older. The majority were female (59%), and 68% self-identified as non-Hispanic White. Among participants with normal cognitive status at baseline, subsequent dementia was observed in 1753 (16%), and among participants with normal self-reported vision at baseline, subsequent VI was reported in 2371 (22%). In adjusted regression models, participants with baseline VI had higher likelihood of developing dementia over subsequent follow-up (HR, 2.3; 95% confidence interval [CI], 2.0-2.6; P < 0.001). Likewise, participants with baseline dementia had a higher likelihood of developing self-reported VI over time (HR, 2.5; 95% CI, 2.2-2.8; P < 0.001).

Conclusions: Self-reported VI in the US Medicare population is associated with greater dementia likelihood over time, and dementia is similarly associated with greater VI likelihood over time. Associations are likely multifactorial and bidirectional and could be explained by intervening variables in the path from VI to dementia, or vice versa, or by common risk factors for pathological processes in both eyes and brain. These findings suggest the need for early identification of older adults with visual compromise and consideration of visual disability in the cognitively impaired.
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http://dx.doi.org/10.1016/j.ophtha.2021.02.021DOI Listing
September 2021

Recurrent Syncope Caused by a Dural Arteriovenous Fistula: A Case Report and Review of the Literature.

Neurologist 2021 Mar 4;26(2):62-65. Epub 2021 Mar 4.

Department of Neurosurgery, University of Miami, Miami, FL.

Background: Dural arteriovenous fistulas (DAVFs) are pathologic vascular connections that shunt dural arterial flow directly to dural venous drainage. Only a few isolated case reports describe syncope on presentation. We report the first case of DAVF causing recurrent, progressive syncope in an otherwise asymptomatic patient.

Case Report: A female in her late 20s presented with a 9-year history of syncopal episodes and was found to have a DAVF. Syncopal episodes were exacerbated by positional changes, strenuous activity and emotional stressors. Symptoms occurred upon wakening and lasted for 2 to 3 hours before she was able to regain functionality. Physical examination revealed no abnormalities. Magnetic resonance imaging of the brain showed no irregularities. Magnetic resonance angiography revealed abnormal serpiginous structures in the left jugular foramen which communicated with the ascending pharyngeal branch of the left external carotid artery. Cerebral angiogram disclosed a left jugular bulb DAVF supplied by the left ascending pharyngeal and left occipital arteries. The DAVF was successfully managed by progressive endovascular embolization with coils and Onyx 34. On clinical follow-up evaluation, the patient had no further episodes of dizziness or syncope.

Conclusion: We present an atypical case of DAVF in a patient presenting with recurrent syncope. Only 4 cases of DAVF causing syncope have been reported, all in combination with other neurological symptoms. In comparison, we report a unique case of DAVF presenting solely with recurrent syncope, a previously undocumented finding in the literature. Our case adds to other reports of nonspecific DAVF presentations and highlights the importance of considering this etiology.
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http://dx.doi.org/10.1097/NRL.0000000000000322DOI Listing
March 2021

Prolonged activation of carbon dioxide-sensitive neurons in mosquitoes.

Interface Focus 2021 Apr 12;11(2):20200043. Epub 2021 Feb 12.

Department of Molecular, Cell and Systems Biology, University of California, Riverside, CA 92521, USA.

Many insects can detect carbon dioxide (CO) plumes using a conserved receptor made up of members of the gustatory receptor (Gr) family Gr1, Gr2 and Gr3. Mosquitoes are attracted to host animals for blood meals using plumes of CO in the exhaled breath using the receptor expressed in the A neuron of the capitate peg sensilla type on the maxillary palps. The receptor is known to also detect several other classes of odorants, including ones emitted from human skin. Here, we discover that a common skin odorant, butyric acid, can cause a phasic activation followed by an unusually prolonged tonic activity after the stimulus is over in the CO neurons of mosquitoes. The effect is conserved in both and mosquitoes. This raises a question about its role in a mosquito's preference for the skin odour of different individuals. Butyric acid belongs to a small number of odorants known to cause the prolonged activation of the CO receptor. A chemical informatic analysis identifies a specific set of physico-chemical features that can be used in a machine learning predictive model for the prolonged activators. Interestingly, this set is different from physico-chemical features selected for activators or inhibitors, indicating that each has a distinct structural basis. The structural understanding opens up an opportunity to find novel ligands to manipulate the CO receptor and mosquito behaviour.
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http://dx.doi.org/10.1098/rsfs.2020.0043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898149PMC
April 2021

Onyx embolization for dural arteriovenous fistulas: a multi-institutional study.

J Neurointerv Surg 2021 Feb 25. Epub 2021 Feb 25.

Department of Neurosurgery, University of Illinois at Chicago, Chicago, Illinois, USA.

Background: Although the liquid embolic agent, Onyx, is often the preferred embolic treatment for cerebral dural arteriovenous fistulas (DAVFs), there have only been a limited number of single-center studies to evaluate its performance.

Objective: To carry out a multicenter study to determine the predictors of complications, obliteration, and functional outcomes associated with primary Onyx embolization of DAVFs.

Methods: From the Consortium for Dural Arteriovenous Fistula Outcomes Research (CONDOR) database, we identified patients who were treated for DAVF with Onyx-only embolization as the primary treatment between 2000 and 2013. Obliteration rate after initial embolization was determined based on the final angiographic run. Factors predictive of complete obliteration, complications, and functional independence were evaluated with multivariate logistic regression models.

Results: A total 146 patients with DAVFs were primarily embolized with Onyx. Mean follow-up was 29 months (range 0-129 months). Complete obliteration was achieved in 80 (55%) patients after initial embolization. Major cerebral complications occurred in six patients (4.1%). At last follow-up, 84% patients were functionally independent. Presence of flow symptoms, age over 65, presence of an occipital artery feeder, and preprocedural home anticoagulation use were predictive of non-obliteration. The transverse-sigmoid sinus junction location was associated with fewer complications, whereas the tentorial location was predictive of poor functional outcomes.

Conclusions: In this multicenter study, we report satisfactory performance of Onyx as a primary DAVF embolic agent. The tentorium remains a more challenging location for DAVF embolization, whereas DAVFs located at the transverse-sigmoid sinus junction are associated with fewer complications.
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http://dx.doi.org/10.1136/neurintsurg-2020-017109DOI Listing
February 2021

Upper extremity transvenous access for neuroendovascular procedures: an international multicenter case series.

J Neurointerv Surg 2021 Apr 16;13(4):357-362. Epub 2021 Feb 16.

Neurological Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA.

Background: Radial artery access for transarterial procedures has gained recent traction in neurointerventional due to decreased patient morbidity, technical feasibility, and improved patient satisfaction. Upper extremity transvenous access (UETV) has recently emerged as an alternative strategy for the neurointerventionalist, but data are limited. Our objective was to quantify the use of UETV access in neurointerventions and to measure failure and complication rates.

Methods: An international multicenter retrospective review of medical records for patients undergoing UETV neurointerventions or diagnostic procedures was performed. We also present our institutional protocol for obtaining UETV and review the existing literature.

Results: One hundred and thirteen patients underwent a total of 147 attempted UETV procedures at 13 centers. The most common site of entry was the right basilic vein. There were 21 repeat puncture events into the same vein following the primary diagnostic procedure for secondary interventional procedures without difficulty. There were two minor complications (1.4%) and five failures (ie, conversion to femoral vein access) (3.4%).

Conclusions: UETV is safe and technically feasible for diagnostic and neurointerventional procedures. Further studies are needed to determine the benefit over alternative venous access sites and the effect on patient satisfaction.
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http://dx.doi.org/10.1136/neurintsurg-2020-017102DOI Listing
April 2021

Low-risk human papilloma virus positive oropharyngeal cancer with one positive lymph node: Equivalent outcomes in patients treated with surgery and radiation therapy versus surgery alone.

Head Neck 2021 06 15;43(6):1759-1768. Epub 2021 Feb 15.

Department of Otolaryngology - Head and Neck Surgery, Washington University School of Medicine, St Louis, Missouri, USA.

Background: For human papilloma virus positive (HPV+) oropharyngeal squamous cell carcinoma (OPSCC), management recommendations for patients with a single metastatic lymph node <6 cm in diameter remain nebulous, leading to treatment heterogeneity in this common subgroup of patients.

Methods: We utilized the National Cancer Database to perform survival and multivariable analyses of patients with HPV+ OPSCC with one positive lymph node <6 cm and negative surgical margins.

Results: We found that 5-year survival is comparable between patients who receive surgery and adjuvant radiation versus surgery alone. In multivariable analyses, we found no significant difference in the hazard ratio of overall survival after adjusting for various potential confounders.

Conclusions: These data suggest that patients with margin-negative HPV+ OPSCC with a single positive lymph node <6 cm have comparable survival with or without adjuvant radiation. Future studies exploring outcomes for this specific group in randomized-controlled trials will be critical for further evaluating these initial observations.
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http://dx.doi.org/10.1002/hed.26642DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106657PMC
June 2021

Observation Versus Intervention for Low-Grade Intracranial Dural Arteriovenous Fistulas.

Neurosurgery 2021 05;88(6):1111-1120

Department of Neurosurgery, Brigham and Women's Hospital, Boston, Massachusetts, USA.

Background: Low-grade intracranial dural arteriovenous fistulas (dAVF) have a benign natural history in the majority of cases. The benefit from treatment of these lesions is controversial.

Objective: To compare the outcomes of observation versus intervention for low-grade dAVFs.

Methods: We retrospectively reviewed dAVF patients from institutions participating in the CONsortium for Dural arteriovenous fistula Outcomes Research (CONDOR). Patients with low-grade (Borden type I) dAVFs were included and categorized into intervention or observation cohorts. The intervention and observation cohorts were matched in a 1:1 ratio using propensity scores. Primary outcome was modified Rankin Scale (mRS) at final follow-up. Secondary outcomes were excellent (mRS 0-1) and good (mRS 0-2) outcomes, symptomatic improvement, mortality, and obliteration at final follow-up.

Results: The intervention and observation cohorts comprised 230 and 125 patients, respectively. We found no differences in primary or secondary outcomes between the 2 unmatched cohorts at last follow-up (mean duration 36 mo), except obliteration rate was higher in the intervention cohort (78.5% vs 24.1%, P < .001). The matched intervention and observation cohorts each comprised 78 patients. We also found no differences in primary or secondary outcomes between the matched cohorts except obliteration was also more likely in the matched intervention cohort (P < .001). Procedural complication rates in the unmatched and matched intervention cohorts were 15.4% and 19.2%, respectively.

Conclusion: Intervention for low-grade intracranial dAVFs achieves superior obliteration rates compared to conservative management, but it fails to improve neurological or functional outcomes. Our findings do not support the routine treatment of low-grade dAVFs.
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http://dx.doi.org/10.1093/neuros/nyab024DOI Listing
May 2021

Emergence of a Novel SARS-CoV-2 Variant in Southern California.

JAMA 2021 04;325(13):1324-1326

Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, California.

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http://dx.doi.org/10.1001/jama.2021.1612DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7879386PMC
April 2021

Netosis and Inflammasomes in Large Vessel Occlusion Thrombi.

Front Pharmacol 2020 22;11:607287. Epub 2021 Jan 22.

Department of Neurological Surgery and the Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL, United States.

The inflammatory response appears to play a critical role in clotting in which neutrophil extracellular traps (NETs) are the major drivers of thrombosis in acute ischemic stroke (AIS). The inflammasome is an innate immune complex involved in the activation of interleukin (IL)-18 and IL-1β through caspase-1, but whether the inflammasome plays a role in NETosis in AIS remains poorly understood. Here we assessed the levels of inflammasome signaling proteins in NETs and their association with clinical and procedural outcomes of mechanical thrombectomy for AIS. Electron microscopy and immunofluorescence indicate the presence of NETs in thrombi of patients with AIS. Moreover, the inflammasome signaling proteins caspase-1 and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) were also present in clots associated with the marker of NETosis citrullinated histone H (CitH3). Analysis of protein levels by a simple plex assay show that caspase-1, ASC and interleukin (IL)-1β were significantly elevated in clots when compared to plasma of AIS patients and healthy controls, while IL-18 levels were lower. Moreover, multivariate analyses show that IL-1β levels in clots contribute to the number of passes to achieve complete recanalization, and that ASC, caspase-1 and IL-18 are significant contributors to time to recanalization. Thus, inflammasome proteins are elevated in NETs present in thrombi of patients with AIS that contribute to poor outcomes following stroke.
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http://dx.doi.org/10.3389/fphar.2020.607287DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868597PMC
January 2021

Acute Invasive Fungal Sinusitis: A 30-Year Review of Pathology Practice and Possible Utility of the DiffQuik® Stain.

Head Neck Pathol 2021 Sep 5;15(3):852-858. Epub 2021 Feb 5.

Department of Pathology & Immunology, Washington University School of Medicine-Barnes Jewish Hospital, St. Louis, MO, USA.

Acute invasive fungal rhinosinusitis (AIFRS) is a fulminant disease with a high mortality rate. Here, we review the clinical and pathologic features of AIFRS over a 30-year period at a tertiary-care academic center focusing on diagnostic practice, especially the use of intra-operative consultation (IOC). A 1-year trial of intraoperative staining with DiffQuik® (DQ) was also assessed. There were 202 cases from 104 patients with AIFRS. The incidence of AIFRS increased over time (6.8 per year in the past decade versus 1.9 before 2009) as did the number of IOCs per case (2.4 per case in the past decade versus 0.6 before 2009). Disagreement between final diagnosis and IOC was seen in 8.3 % of patients, and the block-by-block error rate was 14.9 %. Fusarium was the most common fungus identified. An attempt to categorize the fungal organism based on histopathology was performed in 85.6 % of patients, with 91 % agreement with microbial cultures or PCR. Fungal hyphae were subjectively easier to identify on DQ stained cryostat sections compared to on routine hematoxylin and eosin stained sections and hyphae were identified in all 5 blocks in which organisms were present. The increasing incidence of AIFRS and expanding use of IOC indicate a need to improve and standardize the diagnostic protocol. The use of DQ as visual aid in IOC for AIFRS may be useful.
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http://dx.doi.org/10.1007/s12105-021-01295-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8385081PMC
September 2021
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