Characterization of Microwave Generator Energy and Ablation Volumes Following Transarterial Embolization in an In Vivo Porcine Liver Model.

PURPOSE: This study aims to characterize the relationship between ablation zone volume (AZV) and microwave ablation (MWA) energy in an in vivo porcine liver model following arterial embolization. MATERIALS AND METHODS: With animal IRB approval, eleven female swine underwent either right (n= 5) or left (n= 6) hepatic artery embolization under fluoroscopic guidance. Subsequently, ultrasound guided MWA was performed in each liver segment (left lateral, left medial, right medial, right lateral) at either 30 Watts (W) (n=4 lobes), 60W (n=4), 65W (n=20), 90W (n=8), 120W (n=4), or 140W (n=4) continuously for 5 minutes. Post-procedural volumetric segmentation was performed on standardized multiphase T1 MRI sequences. RESULTS: AZVs in embolized lobes (15.8 ± 10.6 mL) were significantly larger than non-embolized lobes (11.2 ± 6.5 mL, P <0.01). MWA energy demonstrated significant positive linear correlation with both embolized (R2=0.66, P <0.01) and non-embolized lobes (R2=0.64, P < 0.01). The slope of the linear models corresponded to a 0.95 ± 0.16 and 0.54 ± 0.09 mL/kJ increase in ablation volume per applied kJ of energy (E) in embolized and non-embolized lobes, respectively. In the multivariate model, embolization status significantly modified the relationship between E and AZV as described by the interaction term: 0.42*E*(Embolization Status), (P = 0.031). CONCLUSION: Linear models demonstrate a near 1.8 fold increase in ratio of AZV per unit E, R(AZV:E), when applied to embolized lobes relative to non-embolized lobes. Absolute AZV differences between embolized and non-embolized lobes were greater at higher power MWA.

The SATB1-MIR22-GBA axis mediates glucocerebroside accumulation inducing a cellular senescence-like phenotype in dopaminergic neurons.

Idiopathic Parkinson's disease (PD) is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta, which is associated with neuroinflammation and reactive gliosis. The underlying cause of PD and the concurrent neuroinflammation are not well understood. In this study, we utilize human and murine neuronal lines, stem cell-derived dopaminergic neurons, and mice to demonstrate that three previously identified genetic risk factors for PD, namely SATB1, MIR22HG, and GBA, are components of a single gene regulatory pathway. Our findings indicate that dysregulation of this pathway leads to the upregulation of glucocerebrosides (GluCer), which triggers a cellular senescence-like phenotype in dopaminergic neurons. Specifically, we discovered that downregulation of the transcriptional repressor SATB1 results in the derepression of the microRNA miR-22-3p, leading to decreased GBA expression and subsequent accumulation of GluCer. Furthermore, our results demonstrate that an increase in GluCer alone is sufficient to impair lysosomal and mitochondrial function, thereby inducing cellular senescence. Dysregulation of the SATB1-MIR22-GBA pathway, observed in both PD patients and normal aging, leads to lysosomal and mitochondrial dysfunction due to the GluCer accumulation, ultimately resulting in a cellular senescence-like phenotype in dopaminergic neurons. Therefore, our study highlights a novel pathway involving three genetic risk factors for PD and provides a potential mechanism for the senescence-induced neuroinflammation and reactive gliosis observed in both PD and normal aging.

The SATB1-MIR22-GBA axis mediates glucocerebroside accumulation inducing a cellular senescence-like phenotype in dopaminergic neurons.

Idiopathic Parkinson's Disease (PD) is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta, which is associated with neuroinflammation and reactive gliosis. The underlying cause of PD and the concurrent neuroinflammation are not well understood. In this study, we utilized human and murine neuronal lines, stem cell-derived dopaminergic neurons, and mice to demonstrate that three previously identified genetic risk factors for PD, namely SATB1, MIR22HG, and GBA, are components of a single gene regulatory pathway. Our findings indicate that dysregulation of this pathway leads to the upregulation of glucocerebrosides (GluCer), which triggers a cellular senescence-like phenotype in dopaminergic neurons. Specifically, we discovered that downregulation of the transcriptional repressor SATB1 results in the derepression of the microRNA miR-22-3p, leading to decreased GBA expression and subsequent accumulation of GluCer. Furthermore, our results demonstrate that an increase in GluCer alone is sufficient to impair lysosomal and mitochondrial function, thereby inducing cellular senescence dependent on S100A9 and stress factors. Dysregulation of the SATB1-MIR22-GBA pathway, observed in both PD patients and normal aging, leads to lysosomal and mitochondrial dysfunction due to the GluCer accumulation, ultimately resulting in a cellular senescence-like phenotype in dopaminergic neurons. Therefore, our study highlights a novel pathway involving three genetic risk factors for PD and provides a potential mechanism for the senescence-induced neuroinflammation and reactive gliosis observed in both PD and normal aging.

Physician Electronic Health Record Usage as Affected by the COVID-19 Pandemic.

OBJECTIVES: To utilize metrics from physician action logs to analyze volume, physician efficiency and burden as impacted by telemedicine implementation during the COVID-19 (coronavirus disease 2019) pandemic, and physician characteristics such as gender, years since graduation, and specialty category. METHODS: We selected 11 metrics from Epic Signal, a functionality of the Epic electronic health record (EHR). Metrics measuring time spent in the EHR outside working hours were used as a correlate for burden. We performed an analysis of these metrics among active physicians at our institution across three time periods-prepandemic and telehealth implementation (August 2019), postimplementation of telehealth (May 2020), and follow-up (July 2020)-and correlated them with physician characteristics. RESULTS: Analysis of 495 physicians showed that after the start of the pandemic, physicians overall had fewer appointments per day, higher same day visit closure rates, and spent less time writing notes in the EHR outside 7 a.m. to 7 p.m. on patient scheduled days. Across all three time periods, male physicians had better EHR-defined "efficiency" measures and spent less time in the EHR outside working hours. Years since graduation only had modest associations with higher same day visit closure rates and appointments per day in May 2020. Specialty category was significantly associated with appointments per day and same day closure visit rates and also was a significant factor in the observed changes seen across the three time periods. CONCLUSION: Utilizing EHR-generated reports may provide a scalable and nonintrusive way to monitor trends in physician usage and experience to help guide health systems in increasing productivity and reducing burnout.

Electronic Health Record Usage Patterns: Assessing Telemedicine's Impact on the Provider Experience During the COVID-19 Pandemic.

Telemedicine has been widely implemented during the coronavirus disease 2019 (COVID-19) pandemic; however, its impact on those providing care remains largely understudied. Provider documentation data collected by the electronic health record (EHR) represents an underutilized tool for assessing the provider experience. Through Epic Signal, we collected data regarding the actions logged in the EHR by health care providers of the Montefiore Health System (Bronx, NY) before and after the implementation of telemedicine during the pandemic. Focusing on five metrics (appointments per day, visits closed same day, time spent outside 7 AM-7 PM, time spent on unscheduled days, and pajama time), we performed a preliminary analysis of providers across the institution, by specialty, and according to demographic characteristics such as gender and years since graduation. We observed that after telemedicine implementation, a greater proportion of providers had fewer appointments per day, closed more notes same day, and spent less time in the EHR outside of normal working hours for each of the time-related metrics. We additionally found that providers who graduated longer ago as well as female providers spent more time documenting in the EHR after hours. This brief analysis highlights the potential of using EHR data to inform decisions based on provider well-being, specifically in the setting of telemedicine implementation.

Topical intranasal fluorescein to localize a cerebrospinal fluid leak: a demonstration.

BACKGROUND: Intrathecal fluorescein is commonly used to localize cerebrospinal fluid leaks. This technique is invasive and associated with several potential adverse effects. The purpose of this video presentation is to demonstrate an alternative technique, the intranasal use of dilute topical fluorescein, to localize a cerebrospinal fluid leak intraoperatively. METHODS: A 45-year-old male with a history of benign intracranial hypertension and 2 months of right-sided rhinorrhea underwent surgical repair of a cerebrospinal fluid leak. Topical fluorescein was applied intraoperatively to localize the defect. RESULTS: At 1- and 3-month follow-ups the patient was without cerebrospinal fluid rhinorrhea and the middle turbinate flap was intact. CONCLUSION: Topical application of dilute intranasal fluorescein is a feasible and efficient tool for localizing cerebrospinal fluid leaks.

Deep Learning for Automated Classification of Inferior Vena Cava Filter Types on Radiographs.

PURPOSE: To demonstrate the feasibility and evaluate the performance of a deep-learning convolutional neural network (CNN) classification model for automated identification of different types of inferior vena cava (IVC) filters on radiographs. MATERIALS AND METHODS: In total, 1,375 cropped radiographic images of 14 types of IVC filters were collected from patients enrolled in a single-center IVC filter registry, with 139 images withheld as a test set and the remainder used to train and validate the classification model. Image brightness, contrast, intensity, and rotation were varied to augment the training set. A 50-layer ResNet architecture with fixed pre-trained weights was trained using a soft margin loss over 50 epochs. The final model was evaluated on the test set. RESULTS: The CNN classification model achieved a F1 score of 0.97 (0.92-0.99) for the test set overall and of 1.00 for 10 of 14 individual filter types. Of the 139 test set images, 4 (2.9%) were misidentified, all mistaken for other filter types that appear highly similar. Heat maps elucidated salient features for each filter type that the model used for class prediction. CONCLUSIONS: A CNN classification model was successfully developed to identify 14 types of IVC filters on radiographs and demonstrated high performance. Further refinement and testing of the model is necessary before potential real-world application.

Loss of SATB1 Induces p21-Dependent Cellular Senescence in Post-mitotic Dopaminergic Neurons.

Cellular senescence is a mechanism used by mitotic cells to prevent uncontrolled cell division. As senescent cells persist in tissues, they cause local inflammation and are harmful to surrounding cells, contributing to aging. Generally, neurodegenerative diseases, such as Parkinson's, are disorders of aging. The contribution of cellular senescence to neurodegeneration is still unclear. SATB1 is a DNA binding protein associated with Parkinson's disease. We report that SATB1 prevents cellular senescence in post-mitotic dopaminergic neurons. Loss of SATB1 causes activation of a cellular senescence transcriptional program in dopamine neurons both in human stem cell-derived dopaminergic neurons and in mice. We observed phenotypes that are central to cellular senescence in SATB1 knockout dopamine neurons in vitro and in vivo. Moreover, we found that SATB1 directly represses expression of the pro-senescence factor p21 in dopaminergic neurons. Our data implicate senescence of dopamine neurons as a contributing factor in the pathology of Parkinson's disease.

Deep Learning-Assisted Diagnosis of Cerebral Aneurysms Using the HeadXNet Model.

Importance: Deep learning has the potential to augment clinician performance in medical imaging interpretation and reduce time to diagnosis through automated segmentation. Few studies to date have explored this topic. Objective: To develop and apply a neural network segmentation model (the HeadXNet model) capable of generating precise voxel-by-voxel predictions of intracranial aneurysms on head computed tomographic angiography (CTA) imaging to augment clinicians' intracranial aneurysm diagnostic performance. Design, Setting, and Participants: In this diagnostic study, a 3-dimensional convolutional neural network architecture was developed using a training set of 611 head CTA examinations to generate aneurysm segmentations. Segmentation outputs from this support model on a test set of 115 examinations were provided to clinicians. Between August 13, 2018, and October 4, 2018, 8 clinicians diagnosed the presence of aneurysm on the test set, both with and without model augmentation, in a crossover design using randomized order and a 14-day washout period. Head and neck examinations performed between January 3, 2003, and May 31, 2017, at a single academic medical center were used to train, validate, and test the model. Examinations positive for aneurysm had at least 1 clinically significant, nonruptured intracranial aneurysm. Examinations with hemorrhage, ruptured aneurysm, posttraumatic or infectious pseudoaneurysm, arteriovenous malformation, surgical clips, coils, catheters, or other surgical hardware were excluded. All other CTA examinations were considered controls. Main Outcomes and Measures: Sensitivity, specificity, accuracy, time, and interrater agreement were measured. Metrics for clinician performance with and without model augmentation were compared. Results: The data set contained 818 examinations from 662 unique patients with 328 CTA examinations (40.1%) containing at least 1 intracranial aneurysm and 490 examinations (59.9%) without intracranial aneurysms. The 8 clinicians reading the test set ranged in experience from 2 to 12 years. Augmenting clinicians with artificial intelligence-produced segmentation predictions resulted in clinicians achieving statistically significant improvements in sensitivity, accuracy, and interrater agreement when compared with no augmentation. The clinicians' mean sensitivity increased by 0.059 (95% CI, 0.028-0.091; adjusted P = .01), mean accuracy increased by 0.038 (95% CI, 0.014-0.062; adjusted P = .02), and mean interrater agreement (Fleiss κ) increased by 0.060, from 0.799 to 0.859 (adjusted P = .05). There was no statistically significant change in mean specificity (0.016; 95% CI, -0.010 to 0.041; adjusted P = .16) and time to diagnosis (5.71 seconds; 95% CI, 7.22-18.63 seconds; adjusted P = .19). Conclusions and Relevance: The deep learning model developed successfully detected clinically significant intracranial aneurysms on CTA. This suggests that integration of an artificial intelligence-assisted diagnostic model may augment clinician performance with dependable and accurate predictions and thereby optimize patient care.

Role of the Astroglial Glutamate Exchanger xCT in Ventral Hippocampus in Resilience to Stress.

We demonstrate that stress differentially regulates glutamate homeostasis in the dorsal and ventral hippocampus and identify a role for the astroglial xCT in ventral dentate gyrus (vDG) in stress and antidepressant responses. We provide an RNA-seq roadmap for the stress-sensitive vDG. The transcription factor REST binds to xCT promoter in co-occupancy with the epigenetic marker H3K27ac to regulate expression of xCT, which is also reduced in a genetic mouse model of inherent susceptibility to depressive-like behavior. Pharmacologically, modulating histone acetylation with acetyl-L-carnitine (LAC) or acetyl-N-cysteine (NAC) rapidly increases xCT and activates a network with mGlu2 receptors to prime an enhanced glutamate homeostasis that promotes both pro-resilient and antidepressant-like responses. Pharmacological xCT blockage counteracts NAC prophylactic effects. GFAP+-Cre-dependent overexpression of xCT in vDG mimics pharmacological actions in promoting resilience. This work establishes a mechanism by which vDG protection leads to stress resilience and antidepressant responses via epigenetic programming of an xCT-mGlu2 network.

Upper extremity tumor embolization using a transradial artery approach: technical note.

Transradial access is being used with increasing frequency for interventional radiology procedures and offers several key advantages, including decreased access site complications and increased patient comfort. We report the technique of using transradial access to perform preoperative embolization of a humeral renal cell carcinoma metastasis and pathologic fracture. A transradial approach for performing humeral preoperative tumor embolization has not been previously reported, to our knowledge. In the appropriately selected patient, this approach may be safely used to perform upper extremity embolization.

Brain 5-HT deficiency increases stress vulnerability and impairs antidepressant responses following psychosocial stress.

Brain serotonin (5-HT) deficiency and exposure to psychosocial stress have both been implicated in the etiology of depression and anxiety disorders, but whether 5-HT deficiency influences susceptibility to depression- and anxiety-like phenotypes induced by psychosocial stress has not been formally established. Most clinically effective antidepressants increase the extracellular levels of 5-HT, and thus it has been hypothesized that antidepressant responses result from the reversal of endogenous 5-HT deficiency, but this hypothesis remains highly controversial. Here we evaluated the impact of brain 5-HT deficiency on stress susceptibility and antidepressant-like responses using tryptophan hydroxylase 2 knockin (Tph2KI) mice, which display 60-80% reductions in brain 5-HT. Our results demonstrate that 5-HT deficiency leads to increased susceptibility to social defeat stress (SDS), a model of psychosocial stress, and prevents the fluoxetine (FLX)-induced reversal of SDS-induced social avoidance, suggesting that 5-HT deficiency may impair antidepressant responses. In light of recent clinical and preclinical studies highlighting the potential of inhibiting the lateral habenula (LHb) to achieve antidepressant and antidepressant-like responses, we also examined whether LHb inhibition could achieve antidepressant-like responses in FLX-insensitive Tph2KI mice subjected to SDS. Our data reveal that using designer receptors exclusively activated by designer drugs (DREADDs) to inhibit LHb activity leads to reduced SDS-induced social avoidance behavior in both WT and Tph2KI mice. This observation provides additional preclinical evidence that inhibiting the LHb might represent a promising alternative therapeutic approach under conditions in which selective 5-HT reuptake inhibitors are ineffective.

Sex differences in response to chronic mild stress and congenital serotonin deficiency.

Women exhibit a nearly twofold increased risk of developing depression and anxiety disorders when compared to men, a fact that has been hypothesized to result in part from increased stress susceptibility. Here, we used the tryptophan hydroxylase-2 R439H knock-in mouse (Tph2KI) and the chronic unpredictable mild stress (CMS) model to examine sex differences in response to congenital 5-HT deficiency and chronic stress. Our results demonstrate that female mice, but not 5-HT-deficient animals, exhibit significantly increased susceptibility to CMS-induced despair-like behavior in the forced swim test. In addition, female 5-HT-deficient mice exhibit anhedonia-like behavior in the sucrose preference test, whereas male 5-HT-deficient animals do not, suggesting that females exhibit increased sensitivity to at least some of the effects of congenital 5-HT deficiency. Although CMS did not reduce cell proliferation in the hippocampus, low levels of brain 5-HT were associated with increased hippocampal cell proliferation, an effect that was predominantly observed in females. Overall, these results highlight the importance of interactions between psychiatric disease risk factors such as sex, chronic stress and congenital 5-HT deficiency in the development of aberrant emotional behavior.

System architecture for a magnetically guided endovascular microcatheter.

Magnetic resonance imaging (MRI) guided minimally invasive interventions are an emerging technology. We developed a microcatheter that utilizes micro-electromagnets manufactured on the distal tip, in combination with the magnetic field of a MRI scanner, to perform microcatheter steering during endovascular surgery. The aim of this study was to evaluate a user control system for operating, steering and monitoring this magnetically guided microcatheter. The magnetically-assisted remote control (MARC) microcatheter was magnetically steered within a phantom in the bore of a 1.5 T MRI scanner. Controls mounted in an interventional MRI suite, along with a graphical user interface at the MRI console, were developed with communication enabled via MRI compatible hardware modules. Microcatheter tip deflection measurements were performed by evaluating MRI steady-state free precession (SSFP) images and compared to models derived from magnetic moment interactions and composite beam mechanics. The magnitude and direction of microcatheter deflections were controlled with user hand, foot, and software controls. Data from two different techniques for measuring the microcatheter tip location within a 1.5 T MRI scanner showed correlation of magnetic deflections to our model (R(2): 0.88) with a region of linear response (R(2): 0.98). Image processing tools were successful in autolocating the in vivo microcatheter tip within MRI SSFP images. Our system showed good correlation to response curves and introduced low amounts of MRI noise artifact. The center of the artifact created by the energized microcatheter solenoid was a reliable marker for determining the degree of microcatheter deflection and auto-locating the in vivo microcatheter tip.