UW Neurological Surgery Recent PubMed Publications

Lemierre's syndrome treated operatively.

Proc (Bayl Univ Med Cent). 2020 Jun 23;33(4):671-673

Authors: Lanfear AT, Hamandi M, Fan J, Bolin ML, Williams M, DiMaio JM, Waters J

Abstract
Lemierre's syndrome (LS) is a pharyngeal infection complicated by infectious jugular vein thrombosis and septic emboli. Most commonly caused by Fusobacterium necrophorum, it may result in metastatic infection, especially when antibiotic treatment is delayed. Patients with LS are often healthy adults between 16 and 30 years who present with prolonged symptoms of pharyngitis, lateral neck pain, and fever. Other symptoms may include shortness of breath, tachycardia, and hypotension. When administered promptly, antibiotics can act as an effective treatment. However, complications may arise that require additional intervention. Herein, we report a case of LS in a young adult, complicated by severe pleural effusions that required surgical decortication.

PMID: 33100566 [PubMed]

Sutureless valve and rapid deployment valves: a systematic review and meta-analysis of comparative studies.

Ann Cardiothorac Surg. 2020 Sep;9(5):364-374

Authors: Flynn CD, Williams ML, Chakos A, Hirst L, Muston B, Tian DH

Abstract
Background: The treatment of aortic valve disease is the most common valvular surgery in industrialized nations, with 3-9% of the population over the age of eighty having at least moderate aortic stenosis. As transcatheter aortic valve replacement (TAVR) has become more established, newer surgical prostheses have been developed with a variety of anchoring systems that do not rely solely on sutures to hold the valve in an appropriate position. The Edwards Intuity valve is a bovine pericardial prosthesis that is modelled on the widely implanted Perimount MagnaEase aortic prosthesis. The Perceval valve is a bovine pericardial valve attached to a self-expanding nitinol stent, which uses the radial force exerted on the patient's aortic annulus and aortic root by the stent portion to hold the valve in position. This meta-analysis compares the outcomes of comparative studies of these two valve systems.
Methods: This systematic review and meta-analysis compares the outcomes of rapid deployment valves (RDV) and sutureless valves (SURD) and was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations and guidance. The search strategy interrogated six electronic databases. Outcomes measured included all-cause mortality at latest follow up, stroke, cross-clamp and cardiopulmonary bypass (CPB) times, pacemaker implantation rates, paravalvular leak and post-operative transvalvular gradient.
Results: The search strategy identified 407 unique papers for initial assessment with seven studies qualifying for inclusion in the analysis. The outcomes of 4,076 patients (1,650 RDV, 2,426 SURD) were included. There was no difference in mortality, stroke or moderate or worse paravalvular regurgitation between the two groups. SURD had significantly shorter CPB time by 15.7 minutes [95% confidence interval (CI): 4.2-27.1; P=0.007] and a shorter cross-clamp time by 11.3 minutes (95% CI: 6.3-16.3; P<0.001) compared to RDV. RDV had a lower post-operative transvalvular gradient by 2.5 mmHg (95% CI: 1.2-3.8; P<0.001) and a lower rate of mild paravalvular regurgitation (OR 2.51; 95% CI: 1.435-4.768; P=0.004).
Conclusions: Both valve types have an adequate safety profile and are comparable to conventional sutured prostheses. There was a significant reduction in cross-clamp and CPB times associated with SURD. This may be of benefit for patients requiring multiple concomitant procedures and increases the utility of minimally invasive valve replacement. However, SURD was associated with higher post-operative transvalvular gradients and a higher incidence of paravalvular regurgitation.

PMID: 33102175 [PubMed]

Estimating minimal clinically important differences for two scales in patients with chronic traumatic brain injury.

Curr Med Res Opin. 2020 Oct 23;:1

Authors: Mattke S, Cramer SC, Wang M, Bettger JP, Cockroft KM, Feng W, Jaffee M, Oyesanya TO, Puccio AM, Temkin N, Winstein C, Wolf SL, Yochelson MR

Abstract
Background: This study aimed to establish the minimal clinically important difference (MCID) for the Fugl-Meyer Motor Scale (FMMS) and the Disability Rating Scale (DRS) to evaluate interventions in patients with motor deficits in the chronic phase after traumatic brain injury (TBI). Methods: MCIDs were established with a structured expert consultation process, the RAND/UCLA modified Delphi method. This process consisted of a literature review and input from a 10-person, multidisciplinary expert panel. The experts were asked to rate meaningfulness of improvements in hypothetical patients and numeric changes via two rounds of ratings and an in-person meeting. Results: The estimated MCIDs were six and five points on the FMMS Upper and Lower Extremity Scale, respectively, and one point on the DRS. The experts argued against establishing an MCID for the combined FMMS because the same change was more likely to be meaningful if concentrated in one extremity and because a meaningful improvement in one extremity implies meaningfulness irrespective of the changes in the other. Conclusions: This study is the first to establish MCIDs for the FMMS and the DRS in the chronic phase after TBI. The results may be helpful for the design and interpretation of clinical trials of interventions.

PMID: 33095678 [PubMed - as supplied by publisher]

Meta-analysis investigating the role of interleukin-6 mediated inflammation in type 2 diabetes.

EBioMedicine. 2020 Oct 20;61:103062

Authors: Bowker N, Shah RL, Sharp SJ, Luan J, Stewart ID, Wheeler E, Ferreira MAR, Baras A, Wareham NJ, Langenberg C, Lotta LA

Abstract
BACKGROUND: Evidence from animal models and observational epidemiology points to a role for chronic inflammation, in which interleukin 6 (IL-6) is a key player, in the pathophysiology of type 2 diabetes (T2D). However, it is unknown whether IL-6 mediated inflammation is implicated in the pathophysiology of T2D.
METHODS: We performed a meta-analysis of 15 prospective studies to investigate associations between IL-6 levels and incident T2D including 5,421 cases and 31,562 non-cases. We also estimated the association of a loss-of-function missense variant (Asp358Ala) in the IL-6 receptor gene (IL6R), previously shown to mimic the effects of IL-6R inhibition, in a large trans-ethnic meta-analysis of six T2D case-control studies including 260,614 cases and 1,350,640 controls.
FINDINGS: In a meta-analysis of 15 prospective studies, higher levels of IL-6 (per log pg/mL) were significantly associated with a higher risk of incident T2D (1·24 95% CI, 1·17, 1·32; P = 1 × 10-12). In a trans-ethnic meta-analysis of 260,614 cases and 1,350,640 controls, the IL6R Asp358Ala missense variant was associated with lower odds of T2D (OR, 0·98; 95% CI, 0·97, 0·99; P = 2 × 10-7). This association was not due to diagnostic misclassification and was consistent across ethnic groups. IL-6 levels mediated up to 5% of the association between higher body mass index and T2D.
INTERPRETATION: Large-scale human prospective and genetic data provide evidence that IL-6 mediated inflammation is implicated in the etiology of T2D but suggest that the impact of this pathway on disease risk in the general population is likely to be small.
FUNDING: The EPICNorfolk study has received funding from the Medical Research Council (MRC) (MR/N003284/1, MC-UU_12015/1 and MC_PC_13048) and Cancer Research UK (C864/A14136). The Fenland Study is funded by the MRC (MC_UU_12015/1 and MC_PC_13046).

PMID: 33096487 [PubMed - as supplied by publisher]

The Pathophysiology of Rett Syndrome With a Focus on Breathing Dysfunctions.

Physiology (Bethesda). 2020 Nov 01;35(6):375-390

Authors: Ramirez JM, Karlen-Amarante M, Wang JJ, Bush NE, Carroll MS, Weese-Mayer DE, Huff A

Abstract
Rett syndrome (RTT), an X-chromosome-linked neurological disorder, is characterized by serious pathophysiology, including breathing and feeding dysfunctions, and alteration of cardiorespiratory coupling, a consequence of multiple interrelated disturbances in the genetic and homeostatic regulation of central and peripheral neuronal networks, redox state, and control of inflammation. Characteristic breath-holds, obstructive sleep apnea, and aerophagia result in intermittent hypoxia, which, combined with mitochondrial dysfunction, causes oxidative stress-an important driver of the clinical presentation of RTT.

PMID: 33052774 [PubMed - in process]

Republished: Successful treatment of direct carotid-cavernous fistula in a patient with Ehlers-Danlos syndrome type IV without arterial puncture: the transvenous triple-overlay embolization (TAILOREd) technique.

J Neurointerv Surg. 2020 Nov;12(11):e8

Authors: Huynh TJ, Morton RP, Levitt MR, Ghodke BV, Wink O, Hallam DK

Abstract
We report successful transvenous treatment of direct carotid-cavernous fistula in a patient with Ehlers-Danlos syndrome type IV using a novel triple-overlay embolization (TAILOREd) technique without the need for arterial puncture, which is known to be highly risky in this patient group. The TAILOREd technique allowed for successful treatment using preoperative MR angiography as a three-dimensional overlay roadmap combined with cone beam CT and live fluoroscopy, precluding the need for an arterial puncture.

PMID: 33060177 [PubMed - indexed for MEDLINE]

Weekly dengue forecasts in Iquitos, Peru; San Juan, Puerto Rico; and Singapore.

PLoS Negl Trop Dis. 2020 10;14(10):e0008710

Authors: Benedum CM, Shea KM, Jenkins HE, Kim LY, Markuzon N

Abstract
BACKGROUND: Predictive models can serve as early warning systems and can be used to forecast future risk of various infectious diseases. Conventionally, regression and time series models are used to forecast dengue incidence, using dengue surveillance (e.g., case counts) and weather data. However, these models may be limited in terms of model assumptions and the number of predictors that can be included. Machine learning (ML) methods are designed to work with a large number of predictors and thus offer an appealing alternative. Here, we compared the performance of ML algorithms with that of regression models in predicting dengue cases and outbreaks from 4 to up to 12 weeks in advance. Many countries lack sufficient health surveillance infrastructure, as such we evaluated the contribution of dengue surveillance and weather data on the predictive power of these models.
METHODS: We developed ML, regression, and time series models to forecast weekly dengue case counts and outbreaks in Iquitos, Peru; San Juan, Puerto Rico; and Singapore from 1990-2016. Forecasts were generated using available weekly dengue surveillance, and weather data. We evaluated the agreement between model forecasts and actual dengue observations using Mean Absolute Error and Matthew's Correlation Coefficient (MCC).
RESULTS: For near term predictions of weekly case counts and when using surveillance data, ML models had 21% and 33% less error than regression and time series models respectively. However, using weather data only, ML models did not demonstrate a practical advantage. When forecasting weekly dengue outbreaks 12 weeks in advance, ML models achieved a maximum MCC of 0.61.
CONCLUSIONS: Our results identified 2 scenarios when ML models are advantageous over regression model: 1) predicting dengue weekly case counts 4 weeks ahead when dengue surveillance data are available and 2) predicting weekly dengue outbreaks 12 weeks ahead when dengue surveillance data are unavailable. Given the advantages of ML models, dengue early warning systems may be improved by the inclusion of these models.

PMID: 33064770 [PubMed - indexed for MEDLINE]

Early Effects of COVID-19 Pandemic on Neurosurgical Training in the United States: A Case Volume Analysis of 8 Programs.

World Neurosurg. 2021 01;145:e202-e208

Authors: Aljuboori ZS, Young CC, Srinivasan VM, Kellogg RT, Quon JL, Alshareef MA, Chen SH, Ivan M, Grant GA, McEvoy SD, Davanzo JR, Majid S, Durfy S, Levitt MR, Sieg EP, Ellenbogen RG, Nauta HJ

Abstract
OBJECTIVE: To determine the impact of the 2019 novel coronavirus disease (COVID-19) pandemic on operative case volume in 8 U.S. neurosurgical residency training programs in early 2020 and to survey these programs regarding training activities during this period.
METHODS: A retrospective review was conducted of monthly operative case volumes and types for 8 residency programs for 2019 and January through April 2020. Cases were grouped as elective cranial, elective spine, and nonelective emergent cases. Programs were surveyed regarding residents' perceptions of the impact of COVID-19 on surgical training, didactics, and research participation. Data were analyzed for individual programs and pooled across programs.
RESULTS: Across programs, the 2019 monthly mean ± SD case volume was 211 ± 82; 2020 mean ± SD case volumes for January, February, March, and April were 228 ± 93, 214 ± 84, 180 ± 73, and 107 ± 45. Compared with 2019, March and April 2020 mean cases declined 15% (P = 0.003) and 49% (P = 0.002), respectively. COVID-19 affected surgical case volume for all programs; 75% reported didactics negatively affected, and 90% reported COVID-19 resulted in increased research time. Several neurosurgery residents required COVID-19 testing; however, to our knowledge, only 1 resident from the participating programs tested positive.
CONCLUSIONS: This study documents a significant reduction in operative volume in 8 neurosurgery residency training programs in early 2020. During this time, neurosurgery residents engaged in online didactics and research-related activities, reporting increased research productivity. Residency programs should collect data to determine the educational impact of the COVID-19 pandemic on residents' operative case volumes, identify deficiencies, and develop plans to mitigate any effects.

PMID: 33065350 [PubMed - in process]

Continuous improvement in patient safety and quality in neurological surgery: the American Board of Neurological Surgery in the past, present, and future.

J Neurosurg. 2020 Oct 16;:1-7

Authors: Wang MC, Boop FA, Kondziolka D, Resnick DK, Kalkanis SN, Koehnen E, Selden NR, Heilman CB, Valadka AB, Cockroft KM, Wilson JA, Ellenbogen RG, Asher AL, Byrne RW, Camarata PJ, Huang J, Knightly JJ, Levy EI, Lonser RR, Connolly ES, Meyer FB, Liau LM

Abstract
The American Board of Neurological Surgery (ABNS) was incorporated in 1940 in recognition of the need for detailed training in and special qualifications for the practice of neurological surgery and for self-regulation of quality and safety in the field. The ABNS believes it is the duty of neurosurgeons to place a patient's welfare and rights above all other considerations and to provide care with compassion, respect for human dignity, honesty, and integrity. At its inception, the ABNS was the 13th member board of the American Board of Medical Specialties (ABMS), which itself was founded in 1933. Today, the ABNS is one of the 24 member boards of the ABMS.To better serve public health and safety in a rapidly changing healthcare environment, the ABNS continues to evolve in order to elevate standards for the practice of neurological surgery. In connection with its activities, including initial certification, recognition of focused practice, and continuous certification, the ABNS actively seeks and incorporates input from the public and the physicians it serves. The ABNS board certification processes are designed to evaluate both real-life subspecialty neurosurgical practice and overall neurosurgical knowledge, since most neurosurgeons provide call coverage for hospitals and thus must be competent to care for the full spectrum of neurosurgery.The purpose of this report is to describe the history, current state, and anticipated future direction of ABNS certification in the US.

PMID: 33065539 [PubMed - as supplied by publisher]

Issues of consent and assent in pediatric neurosurgery.

Childs Nerv Syst. 2020 Oct 17;:

Authors: Sen RD, Lee A, Browd SR, Ellenbogen RG, Hauptman JS

Abstract
BACKGROUND: Consent and assent are important concepts to understand in the care of pediatric neurosurgery patients. Recently it has been recommended that although pediatric patients generally do not have the legal capacity to make medical decisions, they be encouraged to be involved in their own care. Given the paucity of information on this topic in the neurosurgery community, the objective is to provide pediatric neurosurgeons with recommendations on how to involve their patients in medical decision-making.
METHODS: We review the essential elements and current guidelines of consent and assent for pediatric patients using illustrative neurosurgical case vignettes.
RESULTS: The pediatric population ranges widely in cognitive and psychological development making the process of consent and assent quite complex. The role of the child or adolescent in medical decision-making, issues associated with obtaining assent or dissent, and informed refusal of treatment are considered.
CONCLUSION: The process of obtaining consent and assent represents a critical yet often overlooked aspect to care of pediatric neurosurgical patients. The pediatric neurosurgeon must be able to distill immensely complex and high-risk procedures into simple, understandable terms. Furthermore, they must recognize when the child's dissent or refusal to treatment is acceptable. In general, allowing children to be involved in their neurosurgical care is empowering and gives them both identity and agency, which is the vital first step to a successful neurosurgical intervention.

PMID: 33068156 [PubMed - as supplied by publisher]

Invasive Pulmonary Aspergillosis in an (Apparently) Immunocompetent Patient.

Cureus. 2020 Sep 04;12(9):e10238

Authors: Teixeira da Silva F, Romano M, Esteves A, Carvalho J, Ferreira M

Abstract
Invasive pulmonary aspergillosis (IPA) is an opportunistic infection that usually threatens immunocompromised patients. However, there are some reports of IPA in immunocompetent patients without the obvious classic risk factors. We present the case of an 82-year-old woman with a prior medical history of chronic obstructive pulmonary disease (COPD) and a recent short-term corticosteroid regimen for an acute exacerbation. She was admitted with dyspnoea, cough, and pleuritic pain and was diagnosed with pneumonia. Clinical deterioration occurred, and a diagnosis of IPA was made. She received treatment with voriconazole but died 14 days after admission. This case highlights the importance of considering IPA among the possible causes of infection in this population. Prompt institution of appropriate antifungal therapy is paramount for the management of this condition.

PMID: 33042679 [PubMed]

Functional impact of a congenital stationary night blindness type 2 mutation depends on subunit composition of Cav1.4 Ca2+ channels.

J Biol Chem. 2020 Oct 08;:

Authors: Williams B, Lopez JA, Maddox JW, Lee A

Abstract
Voltage-gated Cav1 and Cav2 Ca2+ channels are comprised of a pore-forming a1 subunit (Cav1.1-1.4, Cav2.1-2.3) and auxiliary β (β1-4) and α2δ (α2δ-1-4) subunits. The properties of these channels vary with distinct combinations of Cav subunits and alternative splicing of the encoding transcripts. Therefore, the impact of disease-causing mutations affecting these channels may depend on the identities of Cav subunits and splice variants. Here, we analyzed the effects of a congenital stationary night blindness type 2 (CSNB2)-causing mutation, I745T (IT), in Cav1.4 channels typical of those in human retina: Cav1.4 splice variants with or without exon 47 (Cav1.4+ex47, Cav1.4Δex47, respectively), and the auxiliary subunits, β2x13 and α2δ-4. We find that IT caused both Cav1.4 splice variants to activate at significantly more negative voltages and with slower deactivation kinetics than the corresponding WT channels. These effects of the IT mutation, along with unexpected alterations in ion selectivity, were generally larger in channels lacking exon 47. The weaker ion selectivity caused by IT led to hyperpolarizing shifts in the reversal potential and large outward currents that were evident in channels containing the auxiliary subunits β2x13 and α2δ-4 but not in those with β2A and α2δ-1. We conclude that the IT mutation stabilizes channel opening and alters ion selectivity of Cav1.4 in a manner that is strengthened by exclusion of exon 47 and inclusion of β2x13 and α2δ-4. Our results reveal complex actions of IT in modifying the properties of Cav1.4 channels, which may influence the pathological consequences of this mutation in retinal photoreceptors.

PMID: 33037074 [PubMed - as supplied by publisher]

Middle Meningeal Artery Embolization for Chronic Subdural Hematoma: A Multi-Center Experience of 154 Consecutive Embolizations.

Neurosurgery. 2020 Oct 07;:

Authors: Kan P, Maragkos GA, Srivatsan A, Srinivasan V, Johnson J, Burkhardt JK, Robinson TM, Salem MM, Chen S, Riina HA, Tanweer O, Levy EI, Spiotta AM, Kasab SA, Lena J, Gross BA, Cherian J, Cawley CM, Howard BM, Khalessi AA, Pandey AS, Ringer AJ, Hanel R, Ortiz RA, Langer D, Kelly CM, Jankowitz BT, Ogilvy CS, Moore JM, Levitt MR, Binning M, Grandhi R, Siddiq F, Thomas AJ

Abstract
BACKGROUND: Middle meningeal artery (MMA) embolization has emerged as a promising treatment for chronic subdural hematoma (cSDH).
OBJECTIVE: To determine the safety and efficacy of MMA embolization.
METHODS: Consecutive patients who underwent MMA embolization for cSDH (primary treatment or recurrence after conventional surgery) at 15 centers were included. Clinical details and follow-up were collected prospectively. Primary clinical and radiographic outcomes were the proportion of patients requiring additional surgical treatment within 90 d after index treatment and proportion with > 50% cSDH thickness reduction on follow-up computed tomography imaging within 90 d. National Institute of Health Stroke Scale and modified Rankin Scale were also clinical outcomes.
RESULTS: A total of 138 patients were included (mean age: 69.8, 29% female). A total of 15 patients underwent bilateral interventions for 154 total embolizations (66.7% primary treatment). At presentation, 30.4% and 23.9% of patients were on antiplatelet and anticoagulation therapy, respectively. Median admission cSDH thickness was 14 mm. A total of 46.1% of embolizations were performed under general anesthesia, and 97.4% of procedures were successfully completed. A total of 70.2% of embolizations used particles, and 25.3% used liquid embolics with no significant outcome difference between embolization materials (P > .05). On last follow-up (mean 94.9 d), median cSDH thickness was 4 mm (71% median thickness reduction). A total of 70.8% of patients had >50% improvement on imaging (31.9% improved clinically), and 9 patients (6.5%) required further cSDH treatment. There were 16 complications with 9 (6.5%) because of continued hematoma expansion. Mortality rate was 4.4%, mostly unrelated to the index procedure but because of underlying comorbidities.
CONCLUSION: MMA embolization may provide a safe and efficacious minimally invasive alternative to conventional surgical techniques.

PMID: 33026434 [PubMed - as supplied by publisher]

Unsupervised Sleep and Wake State Identification in Long-Term Electrocorticography Recordings.

Annu Int Conf IEEE Eng Med Biol Soc. 2020 07;2020:629-632

Authors: Sun S, Jiang LP, Peterson SM, Herron J, Weaver K, Ko A, Ojemann J, Rao RPN

Abstract
Studying the neural correlates of sleep can lead to revelations in our understanding of sleep and its interplay with different neurological disorders. Sleep research relies on manual annotation of sleep stages based on rules developed for healthy adults. Automating sleep stage annotation can expedite sleep research and enable us to better understand atypical sleep patterns. Our goal was to create a fully unsupervised approach to label sleep and wake states in human electro-corticography (ECoG) data from epilepsy patients. Here, we demonstrate that with continuous data from a single ECoG electrode, hidden semi-Markov models (HSMM) perform best in classifying sleep/wake states without excessive transitions, with a mean accuracy (n=4) of 85.2% compared to using K-means clustering (72.2%) and hidden Markov models (81.5%). Our results confirm that HSMMs produce meaningful labels for ECoG data and establish the groundwork to apply this model to cluster sleep stages and potentially other behavioral states.

PMID: 33018066 [PubMed - indexed for MEDLINE]

Rebound effect in deep brain stimulation for essential tremor and symptom severity estimation from neural data.

Annu Int Conf IEEE Eng Med Biol Soc. 2020 07;2020:3621-3624

Authors: Cooper SS, Ferleger BI, Ko AL, Herron JA, Chizeck HJ

Abstract
Deep brain stimulation (DBS) is a safe and established treatment for essential tremor (ET). However, there remains considerable room for improvement due to concerns associated with the initial implant surgery, semi-regular revision surgeries for battery replacements, and side effects including paresthesia, gait ataxia, and emotional disinhibition that have been associated with continuous, or conventional, DBS (cDBS) treatment. Adaptive DBS (aDBS) seeks to ameliorate some of these concerns by using feedback from either an external wearable or implanted sensor to modulate stimulation parameters as needed. aDBS has been demonstrated to be as or more effective than cDBS, but the purely binary control system most commonly deployed by aDBS systems likely still provides sub-optimal treatment and may introduce new issues. One example of these issues is rebound effect, in which the tremor symptoms of an ET patient receiving DBS therapy temporarily worsen after cessation of stimulation before leveling out to a steady state. Here is presented a quantitative analysis of rebound effect in 3 patients receiving DBS for ET. Rebound was evident in all 3 patients by both clinical assessment and inertial measurement unit data, peaking by the latter at Tp = 6.65 minutes after cessation of stimulation. Using features extracted from neural data, linear regression was applied to predict tremor severity, with $R_{avg{\text{ }}}^2 = 0.82$. These results strongly suggest that rebound effect and the additional information made available by rebound effect should be considered and exploited when designing novel aDBS systems.

PMID: 33018786 [PubMed - indexed for MEDLINE]

A tablet- and mobile-based application for remote diagnosis and analysis of movement disorder symptoms.

Annu Int Conf IEEE Eng Med Biol Soc. 2020 07;2020:5588-5591

Authors: Ferleger BI, Sonnet KS, Morriss TH, Ko AL, Chizeck HJ, Herron JA

Abstract
One significant hindrance to effective diagnosis of movement disorders (MDs) and analysis of their progression is the requirement for patients to conduct tests in the presence of a clinician. Here is presented a pilot study for diagnosis of essential tremor (ET), the world's most common MD, through analysis of a tablet- or mobile-based drawing task that may be selected at will, with the spiral- and line-drawing tasks of the Fahn-Tolosa-Marin tremor rating scale serving as our task in this work. This system replaces the need for pen-and-paper drawing tests while permitting advanced quantitative analysis of drawing smoothness, pressure applied, and other measures. Data is securely recorded and stored in the cloud, from which all analysis was conducted remotely. This will enable longitudinal analysis of patient disease progression without the need for excessive clinical visits. Several features were extracted and recursive feature elimination applied to rank the features' individual contribution to our classifier. Maximum cross-validated classification accuracy on a preliminary sample set was 98.3%. Future work will involve collecting healthy subject data from an age-controlled population and extending this diagnostic application to additional conditions, as well as incorporating regression-based symptom severity analysis. This highly promising new technology has the potential to substantially alleviate the demands placed on both clinicians and patients by bringing MD treatment more into line with the era of personalized medicine.

PMID: 33019244 [PubMed - indexed for MEDLINE]

Glioma-derived IL-33 orchestrates an inflammatory brain tumor microenvironment that accelerates glioma progression.

Nat Commun. 2020 10 05;11(1):4997

Authors: De Boeck A, Ahn BY, D'Mello C, Lun X, Menon SV, Alshehri MM, Szulzewsky F, Shen Y, Khan L, Dang NH, Reichardt E, Goring KA, King J, Grisdale CJ, Grinshtein N, Hambardzumyan D, Reilly KM, Blough MD, Cairncross JG, Yong VW, Marra MA, Jones SJM, Kaplan DR, McCoy KD, Holland EC, Bose P, Chan JA, Robbins SM, Senger DL

Abstract
Despite a deeper molecular understanding, human glioblastoma remains one of the most treatment refractory and fatal cancers. It is known that the presence of macrophages and microglia impact glioblastoma tumorigenesis and prevent durable response. Herein we identify the dual function cytokine IL-33 as an orchestrator of the glioblastoma microenvironment that contributes to tumorigenesis. We find that IL-33 expression in a large subset of human glioma specimens and murine models correlates with increased tumor-associated macrophages/monocytes/microglia. In addition, nuclear and secreted functions of IL-33 regulate chemokines that collectively recruit and activate circulating and resident innate immune cells creating a pro-tumorigenic environment. Conversely, loss of nuclear IL-33 cripples recruitment, dramatically suppresses glioma growth, and increases survival. Our data supports the paradigm that recruitment and activation of immune cells, when instructed appropriately, offer a therapeutic strategy that switches the focus from the cancer cell alone to one that includes the normal host environment.

PMID: 33020472 [PubMed - indexed for MEDLINE]

Idiopathic Intracranial Hypertension in the United States: Demographic and Socioeconomic Disparities.

Front Neurol. 2020;11:869

Authors: Ghaffari-Rafi A, Mehdizadeh R, Ko AWK, Ghaffari-Rafi S, Leon-Rojas J

Abstract
Background: Obesity's risk increases for low-income, female, young, and Black patients. By extrapolation, idiopathic intracranial hypertension (IIH)-a disease associated with body mass index-would potentially display socioeconomic and demographic disparities. Methods: IIH incidence (per 100,000) was investigated with respect to sex, age, income, residence, and race/ethnicity, by querying the largest United States (US) healthcare administrative dataset (1997-2016), the National (Nationwide) Inpatient Sample. Results: Annual national incidence (with 25th and 75th quartiles) for IIH was 1.15 (0.91, 1.44). Females had an incidence of 1.97 (1.48, 2.48), larger (p = 0.0000038) than males at 0.36 (0.26, 0.38). Regarding age, largest incidence was among those 18-44 years old at 2.47 (1.84, 2.73). Low-income patients had an incidence of 1.56 (1.47, 1.82), larger (p = 0.00024) than the 1.21 (1.01, 1.36) of the middle/high. No differences (χ2 = 4.67, p = 0.097) were appreciated between urban (1.44; 1.40, 1.61), suburban (1.30; 1.09, 1.40), or rural (1.46; 1.40, 1.48) communities. For race/ethnicity (χ2 = 57, p = 2.57 × 10-12), incidence was largest for Blacks (2.05; 1.76, 2.74), followed by Whites (1.04; 0.79, 1.41), Hispanics (0.67; 0.57, 0.94), and Asian/Pacific Islanders (0.16; 0.11, 0.19). Year-to-year, incidence rose for all strata subsets except Asian/Pacific Islanders (τ = -0.84, p = 0.00000068). Conclusion: IIH demonstrates several sociodemographic disparities. Specifically, incidences are larger for those low-income, Black, 18-44 years old, or female, while annually increasing for all subsets, except Asian/Pacific Islanders. Hence, IIH differentially afflicts the US population, yielding in healthcare inequalities.

PMID: 33013623 [PubMed]

Association Between Immune Checkpoint Inhibitors with Cardiovascular Events and Atherosclerotic Plaque.

Circulation. 2020 Oct 02;:

Authors: Drobni ZD, Alvi RM, Taron J, Zafar A, Murphy SP, Rambarat PK, Mosarla RC, Lee C, Zlotoff DA, Raghu VK, Hartmann SE, Gilman HK, Gong J, Zubiri L, Sullivan RJ, Reynolds KL, Mayrhofer T, Zhang L, Hoffmann U, Neilan TG

Abstract
Background: Immune checkpoint inhibitors (ICI) treat an expanding range of cancers. Consistent basic data suggest that these same checkpoints are critical negative regulators of atherosclerosis. Therefore, our objectives were to test whether ICIs were associated with accelerated atherosclerosis and a higher risk of atherosclerosis-related cardiovascular events. Methods: The study was situated in a single academic medical center. The primary analysis evaluated whether exposure to an ICI was associated with atherosclerotic cardiovascular events in 2842 patients and 2842 controls, matched by age, a history of cardiovascular events and cancer type. In a second design, a case-crossover analysis was performed with an "at-risk period" defined as the two-year period after and the "control period" as the two-year prior to treatment. The primary outcome was a composite of atherosclerotic cardiovascular events (myocardial infarction, coronary revascularization and ischemic stroke). Secondary outcomes included the individual components of the primary outcome. Additionally, in an imaging sub-study (n=40), the rate of atherosclerotic plaque progression was compared from before and after starting an ICI. All study measures and outcomes were blindly adjudicated. Results: In the matched cohort study, there was a 3-fold higher risk for cardiovascular events after starting an ICI (HR, 3.3 [95% CI, 2.0-5.5]; P<0.001). There was a similar increase in each of the individual components of the primary outcome. In the case-crossover, there was also an increase in cardiovascular events from 1.37 to 6.55 per 100 person-years at two years (adjusted HR, 4.8 [95% CI, 3.5-6.5]; P<0.001). In the imaging study, the rate of progression of total aortic plaque volume was >3-fold higher with ICIs (from 2.1%/year pre-to 6.7%/year post). This association between ICI use and increased atherosclerotic plaque progression was attenuated with concomitant use of statins or corticosteroids. Conclusions: Cardiovascular events were higher after initiation of ICIs, potentially mediated by accelerated progression of atherosclerosis. Optimization of cardiovascular risk factors and increased awareness of cardiovascular risk, prior to, during and after treatment, should be considered among patients on an ICI.

PMID: 33003973 [PubMed - as supplied by publisher]

Validation of an mRNA-based Urine Test for the Detection of Bladder Cancer in Patients with Haematuria.

Eur Urol Oncol. 2020 Sep 28;:

Authors: Valenberg FJPV, Hiar AM, Wallace E, Bridge JA, Mayne DJ, Beqaj S, Sexton WJ, Lotan Y, Weizer AZ, Jansz GK, Stenzl A, Danella JF, Cline KJ, Williams MB, Montgomery S, David RD, Harris R, Klein EW, Bradford TJ, Wolk FN, Westenfelder KR, Trainer AF, Richardson TA, Egerdie RB, Goldfarb B, Zadra JA, Lu X, Simon IM, Campbell SA, Bates MP, Higuchi RG, Witjes JA

Abstract
BACKGROUND: In patients with haematuria, a fast, noninvasive test with high sensitivity (SN) and negative predictive value (NPV), which is able to detect or exclude bladder cancer (BC), is needed. A newly developed urine assay, Xpert Bladder Cancer Detection (Xpert), measures five mRNA targets (ABL1, CRH, IGF2, UPK1B, and ANXA10) that are frequently overexpressed in BC.
OBJECTIVE: To validate the performance of Xpert in patients with haematuria.
DESIGN, SETTING, AND PARTICIPANTS: Voided precystoscopy urine specimens were prospectively collected at 22 sites from patients without prior BC undergoing cystoscopy for haematuria. Xpert, cytology, and UroVysion procedures were performed. Technical validation was performed and specificity (SP) was determined in patients without BC.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Test characteristics were calculated based on cystoscopy and histology results, and compared between Xpert, cytology, and UroVysion.
RESULTS AND LIMITATIONS: We included 828 patients (mean age 64.5 yr, 467 males, 401 never smoked). Xpert had an SN of 78% (95% confidence interval [CI]: 66-87) overall and 90% (95% CI: 76-96) for high-grade (HG) tumours. The NPV was 98% (95% CI: 97-99) overall. The SP was 84% (95% CI: 81-86). In patients with microhaematuria, only one HG patient was missed (NPV 99%). Xpert had higher SN and NPV than cytology and UroVysion. Cytology had the highest SP (97%). In a separate SP study, Xpert had an SP of 89% in patients with benign prostate hypertrophy and 92% in prostate cancer patients.
CONCLUSIONS: Xpert is an easy-to-use, noninvasive test with improved SN and NPV compared with cytology and UroVysion, representing a promising tool for identifying haematuric patients with a low likelihood of BC who might not need to undergo cystoscopy.
PATIENT SUMMARY: Xpert is an easy-to-perform urine test with good performance compared with standard urine tests. It should help identify (micro)haematuria patients with a very low likelihood to have bladder cancer.

PMID: 33004290 [PubMed - as supplied by publisher]