Accuracy of Radiomics in Predicting IDH Mutation Status in Diffuse Gliomas: A Bivariate Meta-Analysis.

Purpose To perform a systematic review and meta-analysis assessing the predictive accuracy of radiomics in the noninvasive determination of isocitrate dehydrogenase (IDH) status in grade 4 and lower-grade diffuse gliomas. Materials and Methods A systematic search was performed in the PubMed, Scopus, Embase, Web of Science, and Cochrane Library databases for relevant articles published between January 1, 2010, and July 7, 2021. Pooled sensitivity and specificity across studies were estimated. Risk of bias was evaluated using Quality Assessment of Diagnostic Accuracy Studies-2, and methods were evaluated using the radiomics quality score (RQS). Additional subgroup analyses were performed according to tumor grade, RQS, and number of sequences used (PROSPERO ID: CRD42021268958). Results Twenty-six studies that included 3280 patients were included for analysis. The pooled sensitivity and specificity of radiomics for the detection of IDH mutation were 79% (95% CI: 76, 83) and 80% (95% CI: 76, 83), respectively. Low RQS scores were found overall for the included works. Subgroup analyses showed lower false-positive rates in very low RQS studies (RQS < 6) (meta-regression, z = -1.9; P = .02) compared with adequate RQS studies. No substantial differences were found in pooled sensitivity and specificity for the pure grade 4 gliomas group compared with the all-grade gliomas group (81% and 86% vs 79% and 79%, respectively) and for studies using single versus multiple sequences (80% and 77% vs 79% and 82%, respectively). Conclusion The pooled data showed that radiomics achieved good accuracy performance in distinguishing IDH mutation status in patients with grade 4 and lower-grade diffuse gliomas. The overall methodologic quality (RQS) was low and introduced potential bias. Keywords: Neuro-Oncology, Radiomics, Integration, Application Domain, Glioblastoma, IDH Mutation, Radiomics Quality Scoring Supplemental material is available for this article. Published under a CC BY 4.0 license.

The Applications of Artificial Intelligence in Chest Imaging of COVID-19 Patients: A Literature Review.

Diagnostic imaging is regarded as fundamental in the clinical work-up of patients with a suspected or confirmed COVID-19 infection. Recent progress has been made in diagnostic imaging with the integration of artificial intelligence (AI) and machine learning (ML) algorisms leading to an increase in the accuracy of exam interpretation and to the extraction of prognostic information useful in the decision-making process. Considering the ever expanding imaging data generated amid this pandemic, COVID-19 has catalyzed the rapid expansion in the application of AI to combat disease. In this context, many recent studies have explored the role of AI in each of the presumed applications for COVID-19 infection chest imaging, suggesting that implementing AI applications for chest imaging can be a great asset for fast and precise disease screening, identification and characterization. However, various biases should be overcome in the development of further ML-based algorithms to give them sufficient robustness and reproducibility for their integration into clinical practice. As a result, in this literature review, we will focus on the application of AI in chest imaging, in particular, deep learning, radiomics and advanced imaging as quantitative CT.

Outcomes after Lower Extremity Revascularization for Treatment of Critical Limb Ischemia with Tissue Loss in Patients with Chronic Immune-Mediated Inflammatory Disease.

BACKGROUND: To evaluate outcomes after lower extremity revascularization for critical limb ischemia with tissue loss in patients with chronic immune-mediated inflammatory disease. METHODS: A retrospective medical record review of all lower extremity revascularization for critical limb ischemia with tissue loss at a university-affiliated hospital over a 3-year period was completed for demographics, comorbidities, lower extremity revascularization indication, angiogram results, complications, mortality, limb salvage, and reintervention. Chronic immune-mediated inflammatory disease (CIID) and control (no autoimmune disease) were compared by chi-squared test, Student's t-test, Kaplan-Meier, and Cox Regression. RESULTS: There were 349 procedures performed (297 patients): (1) 44 (13%) primary amputations and (2) 305 (87%) lower extremity revascularizations, in which 83% were endovascular interventions; 12% was bypass; and 5% was hybrid, in which 40% was infrainguinal and 60% was infrageniculate, 72% Wounds Ischemia Infection Score System (WIFi) tissue loss class 2-3, 35% CIID. No differences were noted between CIID and control for primary amputation (P = 0.11), lower extremity revascularization type (P = 0.50), or lower extremity revascularization anatomic level (P = 0.43). Mean age was 71 + 13 years, and 56% of the patients were of male gender. Those with CIID were of similar age as controls (71 ± 14 vs. 71 ± 13; P = 0.87) and presented with comparable runoff: (1) ≤1 vessel (52% vs. 47%; P = 0.67), (2) WIFi tissue loss classification class 2-3 (66% vs. 76%; P = 0.09), and (3) WIFi infection classification class 2-3 (29% vs. 30%; P = 0.9). They were also less likely to be male (47% vs. 61%; P = 0.022) or current smokers (13% vs. 27%; P = 0.008). Postoperative mortality (P = 0.70) morbidity and reoperation (0.31) were comparable. Twenty-four-month survival was similar for CIID and control (83% ± 5% vs. 86% + 3%; P = 0.78), as was the amputation-free interval (69% ± 5% vs. 61% ± 4%; P = 0.18) and need for target extremity revascularization (40% vs. 53%; P = 0.04). Use of steroids and other anti-inflammatory medications was associated with improved 24-month amputation-free interval (87% ± 9% vs. 63% ± 3%; P = 0. 05). Dialysis (odds ratio: 2.6; 1.5-4.7; P = 0.001), WIFi infection class 2-3 (odds ratio: 2.8; 1.6-4.9; P < 0.001), prerunoff vessel (0-1 vs. 2-3) to the foot (odds ratio: 0.52; 0.37-0.73; P < 0.001), steroids/other anti-inflammatory agents (0.29; 0.06-0.96; P = 0.04), and statins (0.44; 0.25-0.77; P = 0.005) were independent predictors of 24-month amputation-free interval (Cox proportional hazard ratio). CONCLUSIONS: Patients with critical limb ischemia, tissue loss, and concomitant CIID can be successfully treated with lower extremity revascularization with similar limb salvage and need for reintervention. Steroid/anti-inflammatory use appears beneficial.

Regulation of Yes-Associated Protein by Laminar Flow.

BACKGROUND: The cells lining the endothelium of blood vessels are recognized as playing critical roles in vascular health and disease. The mechanisms that regulate endothelial cells (ECs) proliferation and release of mediators remain poorly understood but represent a potential source of disease modulation. Actin-cytoskeleton remodeling and cell shape have been suggested as key regulators of phosphorylation of yes-associated protein (YAP) which controls cellular growth and proliferation. Because different types of flow have been shown to affect cell shape and cytoskeleton differently, we hypothesized that the level of phosphorylated yes-associated protein (pYAP; serine 127) decreases in EC exposed to pulsatile uniform flow or steady laminar flow, whereas exposure to pulsatile disturbed flow causes an increase or no change. METHODS: Human umbilical vein endothelial cells (HUVECs) were exposed to pulsatile uniform flow, pulsatile disturbed flow, or steady laminar flow and analyzed by immunoblotting. RESULTS: Exposure of HUVECs to steady laminar flow caused a significant decrease in the levels of pYAP (69.7 + 2.6%, P < 0.05), whereas total YAP levels remained nearly unchanged. Conversely, exposure to either pulsatile uniform or disturbed flow caused a significant decrease in the levels of both pYAP (63.2 + 10.9% and 69.8 + 11.9%, respectively; P < 0.05) and total YAP (57.1 + 17.8% and 58.4 + 16.3%, respectively; P < 0.05). Addition of MG132, a ubiquitin-proteasome system inhibitor, failed to significantly inhibit the decrease in the levels of total YAP in HUVECs exposed to either pulsatile uniform or disturbed flow. CONCLUSIONS: Flow causes a decrease in pYAP. The observed decrease in total YAP levels with pulsatile flow is due to degradation via a proteasome-independent mechanism. This may be a potential target for intervention for disease states such as atherosclerosis and intimal hyperplasia.

Statin Use and Its Association with Essential Tremor and Parkinson's Disease.

BACKGROUND: Statins have potent anti-inflammatory and immunomodulating effects, and may have neuroprotective properties in patients with Parkinson's disease (PD). There are no studies about the use of statins in the related tremor disorder, essential tremor (ET). We determined whether statin use differed in ET cases vs. controls and PD cases vs. METHODS: One hundred and thirty nine ET cases, 108 PD cases, and 124 controls participated in a research study of the epidemiology of movement disorders. They were frequency matched based on age and gender. Statin use was assessed by self-report. RESULTS: In adjusted logistic regression analyses, statin use (current or ever) was inversely associated with PD (ORs 0.56-0.63), with marginal values (p values = 0.07-0.187). In similar adjusted models, ET was not associated with statin use (p values = 0.45-0.50). However, ET was inversely associated with longer-term statin use (adjusted OR 0.27, p values = 0.04-0.048). CONCLUSIONS: We observed a marginally significant inverse association between PD and statin use. Although in primary analyses we found no evidence that statin use was protective in ET, there was an inverse association in analyses that assessed longer term use of statins. Further observational studies are warranted.

Public Knowledge and Attitude toward Essential Tremor: A Questionnaire Survey.

BACKGROUND: Public awareness of and attitude toward disease is an important issue for patients. Public awareness of essential tremor (ET) has never been studied. METHODS: We administered a 10-min, 31-item questionnaire to 250 consecutive enrollees. These included three samples carefully chosen to have a potential range of awareness of ET: 100 individuals ascertained from a vascular disease clinic, 100 individuals from a general neurology clinic, and 50 Parkinson's disease (PD) patients. RESULTS: Leaving aside PD patients, only 10-15% of enrollees had ever heard of or read about "ET." Even among PD patients, only 32.7% had ever heard of or read about ET. After providing enrollees with three synonymous terms for ET ("benign tremor," "kinetic tremor," "familial tremor"), ~40% of non-PD enrollees and 51.0% with PD had ever heard or read about the condition. Even among participants who had heard of ET, ~10% did not know what the main symptom was, 1/3 were either unsure or thought ET was the same disease as PD, 1/4 thought that ET was the same condition as frailty- or aging-associated tremor, 2/3 attributed it to odd causes (e.g., trauma or alcohol abuse), only 1/3 knew of the existence of therapeutic brain surgery, fewer than 1/2 knew that children could have ET, and 3/4 did not know of a celebrity or historical figure with ET. Hence, lack of knowledge and misconceptions were common. CONCLUSION: Public knowledge of the existence and features of ET is overall poor. Greater awareness is important for the ET community.

Increased Odds of Melanoma: Parkinson's Disease, Essential Tremor, Dystonia versus Controls.

OBJECTIVE: Patients with Parkinson's disease (PD) have an increased risk of melanoma, although the mechanisms are unclear. We are unaware of studies that have assessed the association between other movement disorders, such as essential tremor (ET) and dystonia, and melanoma. In this study, we assessed the association between ET, PD, dystonia and cancer (esp. melanoma). METHODS: One hundred and eight PD cases, 139 ET cases, and 54 dystonia cases, and 124 controls were enrolled in a research study of the epidemiology of movement disorders (total n = 425). The groups were frequency matched on age and gender. Cancer diagnoses were made based on self-reports. Melanoma diagnoses were further validated. RESULTS: The prevalence of melanoma was higher in PD cases than controls (13.9 vs. 1.6%, p < 0.001), and was marginally higher in ET cases (5.8%, p = 0.08) and dystonia cases (7.4%, p = 0.06) than controls. In adjusted logistic regression models, the odds of melanoma was 7.09-9.84 times higher in PD cases than controls (p values 0.01-0.003), 3.73-4.10 times higher in ET cases than controls (p values 0.08-0.10), and 4.88-5.27 times higher in dystonia cases than controls (p values 0.06-0.07). CONCLUSION: The links between neurological disorders and melanoma, long-known, may not be specific to PD and may extend to other movement disorders.

Systemic Inflammatory Disease and Its Association With Type II Endoleak and Late Interventions After Endovascular Aneurysm Repair.

IMPORTANCE: Abdominal aortic aneurysms are associated with chronic inflammation within the aortic wall, and previous studies have suggested that chronic inflammation may be a consequence of a dysregulated and persistent autoimmune response. Persistent aortic remodeling after aneurysm repair could place the patient at risk for endoleak or sac rupture. OBJECTIVE: To determine whether patients with systemic inflammatory disease and large aneurysms have persistent aortic remodeling after endovascular aneurysm repair (EVAR). DESIGN, SETTING, AND PARTICIPANTS: The records of all patients who underwent EVAR between July 2002 and June 2011 at the Veterans Affairs Connecticut Healthcare System were included in this retrospective review. Patients were considered to have a systemic inflammatory disease when confirmed by a referring specialist. Post-EVAR surveillance was performed by yearly imaging. INTERVENTION: Endovascular aneurysm repair. MAIN OUTCOMES AND MEASURES: Significant endoleak, defined as endoleak and sac diameter increase of 0.5 cm or greater. RESULTS: A total of 51 of 79 patients (65%) had a systemic inflammatory disease. These patients had similar comorbid conditions compared with patients without inflammation but significantly greater numbers of major postoperative complications after EVAR (23.5% vs 3.6%; P = .02) and overall postoperative complications after EVAR (27.5% vs 7.1%; P = .03). Patients with a history of systemic inflammatory disease developed more endoleaks (45.1% vs 17.9%; P = .02) and late sac expansion (51.0% vs 21.4%; P = .01) and required more interventions (21.6% vs 3.6%; P = .03) during long-term follow-up. Systemic inflammatory disease was significantly associated with significant endoleak (odds ratio, 5.18; 95% CI, 1.56-17.16; P = .007). CONCLUSIONS AND RELEVANCE: Patients with systemic inflammatory disease are at high risk for postoperative complications, type II endoleak, sac expansion, and additional interventions after EVAR. Additional strategies for improving the efficacy of EVAR in these patients may be warranted.

African Trypanosome-Induced Blood-Brain Barrier Dysfunction under Shear Stress May Not Require ERK Activation.

African trypanosomes are tsetse fly transmitted protozoan parasites responsible for human African trypanosomiasis, a disease characterized by a plethora of neurological symptoms and death. How the parasites under microvascular shear stress (SS) flow conditions in the brain cross the blood-brain barrier (BBB) is not known. In vitro studies using static models comprised of human brain microvascular endothelial cells (BMEC) show that BBB activation and crossing by trypanosomes requires the orchestration of parasite cysteine proteases and host calcium-mediated cell signaling. Here, we examine BMEC barrier function and the activation of extracellular signal-regulated kinase (ERK)1/2 and ERK5, mitogen-activated protein kinase family regulators of microvascular permeability, under static and laminar SS flow and in the context of trypanosome infection. Confluent human BMEC were cultured in electric cell-substrate impedance sensing (ECIS) and parallel-plate glass slide chambers. The human BMEC were exposed to 2 or 14 dyn/cm(2) SS in the presence or absence of trypanosomes. Real-time changes in transendothelial electrical resistance (TEER) were monitored and phosphorylation of ERK1/2 and ERK5 analyzed by immunoblot assay. After reaching confluence under static conditions human BMEC TEER was found to rapidly increase when exposed to 2 dyn/cm(2) SS, a condition that mimics SS in brain postcapillary venules. Addition of African trypanosomes caused a rapid drop in human BMEC TEER. Increasing SS to 14 dyn/cm(2), a condition mimicking SS in brain capillaries, led to a transient increase in TEER in both control and infected human BMEC. However, no differences in ERK1/2 and ERK5 activation were found under any condition tested. African trypanosomiasis alters BBB permeability under low shear conditions through an ERK1/2 and ERK5 independent pathway.

Effect of pulsatile and continuous flow on yes-associated protein.

Yes-associated protein (YAP) is a mechanosignaling protein that relays mechanical information to the nucleus by changing its level of phosphorylation. We hypothesize that different flow patterns show differential effect on phosphorylated YAP (pYAP) (S127) and total YAP and could be responsible for flow dependent localization of atherosclerosis. Confluent human umbilical vein endothelial cells (HUVECs) seeded on fibronectin-coated glass slides were exposed to continuous forward flow (CFF) and pulsatile forward flow (PFF) using a parallel plate flow chamber system for 30 minutes. Cell lysates were prepared and immunoblotted to detect the levels of phosphorylated YAP and total YAP. HUVECs exposed to both PFF and CFF showed a mild decrease in the levels of both pYAP (S127) and total YAP. While the levels of pYAP (S127) decreased to 87.85 and 85.21% of static control with PFF and CFF, respectively, the levels of total YAP significantly decreased to 91.31 and 92.27% of static control. No significant difference was seen between CFF and PFF on their effect on pYAP (S127), but both conditions resulted in a significant decrease in total YAP at 30 minutes. The results of this experiment show that the possible effect of different types of flow on YAP is not induced before 30 minutes. Experiments exposing endothelial cells to various types of flow for longer duration of time could help to elucidate the role of YAP in the pathogenesis of atherosclerosis.

Characterization of extracellular signal-regulated kinase 5 levels in human umbilical vein endothelial cells exposed to disturbed and uniform flow.

Extracellular signal-regulated kinase 5 (ERK5) has been reported to regulate endothelial cell integrity and protect from vascular dysfunction under continuous laminar flow. However, the effect of flow on ERK5 levels has not been determined. Confluent human umbilical vein endothelial cells (HUVECs) were seeded on fibronectin coated glass slides and serum starved for 2 hours with 1% fetal bovine serum (FBS). HUVECs were then exposed to to and fro flow (TFF), pulsatile forward flow (PFF), or continuous laminar flow (CLF) in a parallel plate flow chamber for up to 2 hours. At the end of experiment, cell lysates were prepared and immunoblotted with antibodies to total ERK5. Both CLF and TFF exhibited a decrease in ERK5 after levels after 2-hour exposure. However, the level of ERK5 for PFF remained the same. Disturbed, but not uniform pulsatile, flow decreases ERK5 levels in HUVECs.

New modalities in the chronic ischemic diabetic foot management.

The diabetic population is increasing worldwide at a staggering rate. Diabetic foot ulcers are a major contributor to nontraumatic lower limb amputations and peripheral arterial disease is one of main contributing pathophysiologic causes of diabetic ulcers. The dire need to reduce complication and wound healing recovery period of the chronic ischemic diabetic foot (CIDF) is indispensable to limb salvage and improvement of quality of life of patients with CIDF. This article discusses newer modalities that have been proposed to improve CIDF efficiently, safely, and effectively either alone or as adjuvants to conventional therapy.