Early Prediction of Response of Hepatocellular Carcinoma to Yttrium-90 Radiation Segmentectomy Using a Machine Learning MR Imaging Radiomic Approach.

PURPOSE: To assess the accuracy of a machine learning (ML) approach based on magnetic resonance (MR) imaging radiomic quantification obtained before treatment and early after treatment for prediction of early hepatocellular carcinoma (HCC) response to yttrium-90 transarterial radioembolization (TARE). MATERIALS AND METHODS: In this retrospective single-center study of 76 patients with HCC, baseline and early (1-2 months) post-TARE MR images were collected. Semiautomated tumor segmentation facilitated extraction of shape, first-order histogram, and custom signal intensity-based radiomic features, which were then trained (n = 46) using a ML XGBoost model and validated on a separate cohort (n = 30) not used in training to predict treatment response assessed at 4-6 months (based on modified Response and Evaluation Criteria in Solid Tumors criteria). Performance of this ML radiomic model was compared with those of models comprising clinical parameters and standard imaging characteristics using area under the receiver operating curve (AUROC) analysis for prediction of complete response (CR). RESULTS: Seventy-six tumors with a mean (±SD) diameter of 2.6 cm ± 1.6 were included. Sixty, 12, 1, and 3 patients were classified as having CR, partial response, stable disease, and progressive disease, respectively, at 4-6 months posttreatment on the basis of MR images. In the validation cohort, the radiomic model showed good performance (AUROC, 0.89) for prediction of CR, compared with models comprising clinical and standard imaging criteria (AUROC, 0.58 and 0.59, respectively). Baseline imaging features appeared to be more heavily weighted in the radiomic model. CONCLUSIONS: The use of ML modeling of radiomic data combining baseline and early follow-up MR imaging could predict HCC response to TARE. These models need to be investigated further in an independent cohort.

APOE Stabilization by Exercise Prevents Aging Neurovascular Dysfunction and Complement Induction.

Aging is the major risk factor for neurodegenerative diseases such as Alzheimer's disease, but little is known about the processes that lead to age-related decline of brain structures and function. Here we use RNA-seq in combination with high resolution histological analyses to show that aging leads to a significant deterioration of neurovascular structures including basement membrane reduction, pericyte loss, and astrocyte dysfunction. Neurovascular decline was sufficient to cause vascular leakage and correlated strongly with an increase in neuroinflammation including up-regulation of complement component C1QA in microglia/monocytes. Importantly, long-term aerobic exercise from midlife to old age prevented this age-related neurovascular decline, reduced C1QA+ microglia/monocytes, and increased synaptic plasticity and overall behavioral capabilities of aged mice. Concomitant with age-related neurovascular decline and complement activation, astrocytic Apoe dramatically decreased in aged mice, a decrease that was prevented by exercise. Given the role of APOE in maintaining the neurovascular unit and as an anti-inflammatory molecule, this suggests a possible link between astrocytic Apoe, age-related neurovascular dysfunction and microglia/monocyte activation. To test this, Apoe-deficient mice were exercised from midlife to old age and in contrast to wild-type (Apoe-sufficient) mice, exercise had little to no effect on age-related neurovascular decline or microglia/monocyte activation in the absence of APOE. Collectively, our data shows that neurovascular structures decline with age, a process that we propose to be intimately linked to complement activation in microglia/monocytes. Exercise prevents these changes, but not in the absence of APOE, opening up new avenues for understanding the complex interactions between neurovascular and neuroinflammatory responses in aging and neurodegenerative diseases such as Alzheimer's disease.

Medical Student Attitudes Toward the Use of Peer Physical Exam for Learning Fundoscopy.

Background Peer physical examination learning is commonly practiced in medical schools during preclinical curricula and has been shown to improve empathy for patients. While there is literature regarding medical student attitudes toward peer physical exam learning, no studies to date have specifically examined student attitudes toward fundoscopy and dilation of the eyes for the purposes of learning fundoscopy. This study evaluates medical student preferences with regards to learning fundoscopy on peers and explores attitudes toward alternate approaches. Methods First year medical students at the Icahn School of Medicine at Mount Sinai participated in a 2-hour fundoscopy skills workshop in March 2020. Following the session, the authors administered a voluntary survey querying students on attitudes toward peer physical exam learning and its use in learning peer fundoscopy. Primary study endpoints evaluated (1) student attitudes toward the use of peer physical exam learning, (2) learning benefit of the session, including student comfort with conducting the fundoscopy exam, and (3) empathy toward patients experiencing dilation. Secondary endpoints focused on alternative teaching methods and preferences for nonmydriatic fundoscopy. Analysis of survey data was performed using nonparametric Spearman's correlations, chi-square tests, t -tests, and Mann-Whitney U tests. Results A total of 51/138 (37%) students completed the survey, with 78% indicating they felt peer physical exam learning was a helpful instructional method, including for the fundoscopic exam. The session led to improved self-rated fundoscopy skills and empathy for patients. However, when considering learning with dilation versus alternative nonmydriatic techniques, 96% of students indicated a preference for using alternative nonmydriatic techniques. Conclusion This study found that students' attitudes toward fundoscopy generally aligned with their overall peer physical exam preferences. However, they preferred not using dilation and learning with nonmydriatic fundoscopic techniques. Assessing student learning preferences and incorporating novel instructional tools can help facilitate more successful fundoscopy skills acquisition. These considerations are particularly important in the context of COVID-19 and with advances in teleophthalmology.

A multi-scale/multi-physics model for the theoretical study of the vascular configuration of retinal capillary plexuses based on OCTA data.

The retinal tissue is highly metabolically active and is responsible for translating the visual stimuli into electrical signals to be delivered to the brain. A complex vascular structure ensures an adequate supply of blood and oxygen, which is essential for the function and survival of the retinal tissue. To date, a complete understanding of the configuration of the retinal vascular structures is still lacking. Optical coherence tomography angiography has made available a huge amount of imaging data regarding the main retinal capillary plexuses, namely the superficial capillary plexuses (SCP), intermediate capillary plexuses (ICP) and deep capillary plexuses (DCP). However, the interpretation of these data is still controversial. In particular, the question of whether the three capillary plexuses are connected in series or in parallel remains a matter of debate. In this work, we address this question by utilizing a multi-scale/multi-physics mathematical model to quantify the impact of the two hypothesized vascular configurations on retinal hemodynamics and oxygenation. The response to central retinal vein occlusion (CRVO) and intraocular pressure (IOP) elevation is also simulated depending on whether the capillary plexuses are connected in series or in parallel. The simulation results show the following: (i) in the in series configuration, the plexuses exhibit a differential response, with DCP and ICP experiencing larger pressure drops than SCP; and (ii) in the in parallel configuration, the blood flow redistributes uniformly in the three plexuses. The different vascular configurations show different responses also in terms of oxygen profiles: (i) in the in series configuration, the outer nuclear layer, outer plexiform layer and inner nuclear layer (INL) are those most affected by CRVO and IOP elevation; and (ii) in the in parallel configuration the INL and ganglion cell layer are those most affected. The in series results are consistent with studies on paracentral acute middle maculopathy, secondary to CRVO and with studies on IOP elevation, in which DCP and ICP and the retinal tissues surrounding them are those most affected by ischemia. These findings seem to suggest that the in series configuration better describes the physiology of the vascular retinal capillary network in health and disease.

Risks and rewards of increasing patient access to medical records in clinical ophthalmology using OpenNotes.

BACKGROUND: The implementation of OpenNotes and corresponding increase in patient access to medical records requires thorough assessment of the risks and benefits of note-sharing. Ophthalmology notes are unique among medical records in that they extensively utilize non-standardized abbreviations and drawings; they are often indecipherable even to highly-educated clinicians outside of ophthalmology. No studies to date have assessed ophthalmologist perceptions of OpenNotes. METHODS: A cross-sectional study was conducted from 4/28 to 5/12/2016. A survey was distributed to 30 clinicians (25 ophthalmologists, three optometrists, two nurses) in the University of Colorado's Department of Ophthalmology to evaluate provider attitudes towards granting patients access to online medical records. RESULTS: Many clinicians felt patients would have difficulty understanding their records and may be unnecessarily alarmed or offended by them. Some clinicians worried their workload would increase and feared having to change the way they document. Perceived benefits of OpenNotes included improving patient understanding of their medical conditions, strengthening patient-physician trust, and enhancing patient care. Many perceived risks and benefits of note-sharing were associated with conceptions of the ideal clinician-patient relationship. CONCLUSIONS: Clinicians in ophthalmology perceived both benefits and consequences of increasing patient access to ophthalmic records, and there were significant correlations between these perceptions and their conceptions of the clinician-patient relationship. This is the first study to assess potential ophthalmology provider attitudes toward sharing ophthalmic records. Although limited in sample size and power, this study demonstrates some ways patient-accessible ophthalmic records can affect the clinical practice of ophthalmology and emphasizes the unique challenges of OpenNotes in ophthalmology.

Open Conjunctival Approach for Sub-Tenon's Xen Gel Stent Placement and Bleb Morphology by Anterior Segment Optical Coherence Tomography.

PRCIS: Sub-Tenon's implantation of the Xen Gel stent resulted in significant intraocular pressure (IOP) lowering along with a low rate of postoperative bleb needling, and a favorable bleb morphology on anterior segment optical coherence tomography (AS-OCT). PURPOSE: The aim was to assess clinical outcomes and bleb morphology following sub-Tenon's implantation of the Xen Gel Stent. METHODS: The medical records of patients who underwent sub-Tenon's Xen Gel Stent implantation with intraoperative mitomycin-C through an open conjunctival approach were reviewed. Postoperative IOP and number of glaucoma medications at 1, 3, 6, 9, and 12 months were assessed. Bleb morphology was analyzed at various timepoints using AS-OCT (Topcon DRI OCT version 1.1.1). RESULTS: Twenty-six eyes were included in the study. Mean age was 69.4±8.0 years. Mean preoperative IOP was 28.1±7.8 mm Hg on an average of 3.5±0.9 glaucoma medications. Mean IOP at postoperative month 12 (n=23 eyes) was 12.9±4.0 mm Hg (P<0.01) on an average of 0.3±0.6 (P<0.01) glaucoma medications. Three eyes (12%) required postoperative needle revision. Bleb morphology in the early postoperative period (≤3 mo) was characterized by multiple small subconjunctival microcysts on AS-OCT. At the intermediate (6 to 12 mo) and long-term (>12 mo) timepoints, reduction in microcysts with multiple internal parallel layers of aqueous flow and a uniform pattern were more frequently noted. All functional blebs were characterized by the presence of a posterior episcleral fluid lake. Failed blebs showed absence of aqueous humor around the distal end of the microshunt. CONCLUSION: Following an open conjunctival approach, sub-Tenon's placement of the Xen Gel Stent with significant IOP lowering was achieved. In eyes with good shunt function, bleb morphology by AS-OCT showed a posterior episcleral fluid lake similar to findings following trabeculectomy.

The Effect of Phacoemulsification on Intraocular Pressure in Eyes with Preexisting Glaucoma Drainage Implants.

PURPOSE: To study the effect of phacoemulsification on intraocular pressure (IOP) control in patients with preexisting glaucoma drainage implants (GDIs). DESIGN: Retrospective, observational case series. PARTICIPANTS: A total of 45 patients (51 eyes) with previously placed GDIs who underwent phacoemulsification between January 2013 and March 2018. METHODS: The list of patients was obtained from billing records. Clinical data were retrieved from the corresponding electronic medical records. MAIN OUTCOME MEASURES: Intraocular pressure, number of glaucoma medications before and after phacoemulsification (postoperative day 1, week 1, months 1, 3, 6, 12, 18, and 24), rate of failure (failure defined as IOP >18 mmHg and IOP increase >20% at 2 consecutive visits after month 1, need for additional glaucoma surgery, or loss of light perception vision), and postoperative complications. RESULTS: Mean follow-up was 23.0 ± 11.1 months. The average interval between GDI surgery and phacoemulsification was 9.4 ± 6.7 months. An Ahmed glaucoma valve (AGV; New World Medical) was implanted in 12 eyes, a Baerveldt glaucoma implant (BGI; Johnson & Johnson Surgical Vision) was implanted in 36 eyes, and a Molteno (Molteno Ophthalmic Limited) glaucoma implant was implanted in 3 eyes. Before phacoemulsification, the mean IOP was 14.4 ± 4.4 mmHg on 2.1 ± 1.3 glaucoma medications. At postoperative month 24, the mean IOP was 12.6 ± 4.4 mmHg (n = 29, P = 0.519) on 2.0 ± 1.6 (P = 0.457) glaucoma medications. The reduction in IOP was significant only at postoperative week 1 (P = 0.031). The cumulative failure rate was 3.9% at 1 year and 11.8% at 2 years. The AGV group had a significantly higher mean IOP before phacoemulsification than the BGI group (P = 0.016). Analysis of covariance, taking the baseline IOP as a covariate, revealed no differences in postoperative IOP and number of glaucoma medications between groups, except for month 18 (1 patient in the BGI group had uncontrolled IOP requiring surgery). Postoperative complications included cystoid macular edema (10%), corneal decompensation (6%), and choroidal effusion (4%). CONCLUSIONS: Phacoemulsification after GDI surgery resulted in a transient reduction in IOP at postoperative week 1. Patients with previously placed AGVs had similar postoperative outcomes compared with those with BGIs.

Two-Year Experience With Latanoprostene Bunod in Clinical Practice.

PRECIS: We retrospectively reviewed records of patients prescribed latanoprostene bunod 0.024% (LBN) to assess its efficacy and safety in a real-world clinical setting. LBN was efficacious in lowering intraocular pressure (IOP) and had a favorable safety profile. PURPOSE: The aim of this study was to evaluate the usage of LBN, the first topical nitric oxide-donating prostaglandin analog (PGA) for reducing IOP, in clinical practice. PATIENTS AND METHODS: Retrospective review identified patients prescribed LBN by 5 glaucoma specialists at an academic center from January 2018 to November 2019. Fifty-six patients (102 eyes) met inclusion criteria of an IOP measured at the visit LBN was prescribed and at 2 visits ≥7 days after beginning treatment, with no surgeries, lasers or medication changes during follow-up. Main outcome measures were IOP, number of ocular medications, and adverse effects. RESULTS: IOP (mean±SD, mm Hg) at the visit LBN was prescribed was 16.2±4.3 on 3.2±1.5 glaucoma medications. IOP at most recent visit was 13.7±3.8 on 3.2±1.6 medications. Mean IOP reduction was 2.1±3.5 (P<0.0001) at first follow-up, after 38.7±36.5 days, and 2.5±3.3 (P<0.0001) at last follow-up, after 235.9±160.8 days. Pressure decreased ≥2 mm Hg in 60%, ≥3 mm Hg in 46%, and ≥4 mm Hg in 34% of eyes. All patients received LBN as replacement for a PGA or latanoprost/netarsudil fixed-dose combination. Forty-three patients remained on LBN throughout the follow-up period. Seven were discontinued for insufficient pressure control, 4 for adverse effects including pain and itching, and 2 for financial reasons. CONCLUSIONS: In 2 years of clinical use of LBN, patients exhibited IOP reductions that were statistically significant overall and clinically meaningful in 60% of patients. LBN was well-tolerated and may be more efficacious than traditional PGAs.

The Efficacy of the After-visit Summary in Medication Recall Among Glaucoma Patients.

PRéCIS:: To assess the after-visit summary (AVS) as a tool for glaucoma medication recall. Medication recall was associated with level of education and complexity of medication regimen. Receiving an AVS was not associated with better medication recall. PURPOSE: The purpose of this study was to determine whether patients given the AVS have better or worse glaucoma medication recall. MATERIALS AND METHODS: Observational clinical study. Adults on ≥1 glaucoma medications examined between June 30, 2017 and August 2, 2017. DATA COLLECTION: in-person questionnaire and retrospective chart review. Self-reported glaucoma medications compared with prescribed glaucoma medication regimen verified by electronic medical record. Medication recall assessed using 3-point scoring: 1 point each for; (1) name or color of bottle or cap; (2) treatment eye(s); and (3) dosing regimen. DATA ANALYSIS: 2-sample Welch t test, 2-proportion z-test, analysis of variance, univariate, and multivariate regression. RESULTS: A total of 118 patients enrolled: age 69.7±12.9 years (mean±SD), 55.9% of patients had received an AVS at the previous visit. Of these, 33.3% reported receiving an AVS, 51.2% reported not receiving one (15.1% did not recall or respond). Patients who had received AVSs had lower medication recall scores than those who did not (2.4±1.0 vs. 2.7±0.6, P=0.04). Receipt of an AVS was associated with having Nisha Chadha as their provider (P=0.01), fewer days since prior visit (P=0.0001), and medication regimen change at prior visit (P<0.0001). Multivariate analysis revealed completion of associate's degree or higher and fewer prescribed medications to be independent predictors of higher recall score (P=0.0002 and 0.002). CONCLUSIONS: AVSs were conceived to enhance patient care. This study indicates this goal is not achieved consistently. Less education and more complex medication regimens were identified as barriers to medication recall. Additional investigations should explore if modifying this document and enhanced explanation of its use will impact medication recall and health outcomes.

Training in and comfort with diagnosis and management of ophthalmic emergencies among emergency medicine physicians in the United States.

BACKGROUND/OBJECTIVES: Patients with ophthalmic emergencies often present to emergency rooms. Emergency medicine (EM) physicians should feel comfortable encountering these conditions. We assessed EM physicians' comfort working up, diagnosing, and managing ophthalmic emergencies. SUBJECTS/METHODS: 329 EM physicians participated in this cross-sectional multicentre survey. Questions inquired about the amount, type, and self-perceived adequacy of ophthalmic training. Likert scales were used to assess confidence and comfort working up, diagnosing, and managing ophthalmic emergencies. RESULTS: Participants recall receiving a median of 5 and 10 h of ophthalmic training in medical school and residency, respectively. Few feel this prepared them for residency (16.5%) or practice (52.0%). Only 50.6% feel confident with their ophthalmic exam. Most (75.0%) feel confident in their ability to identify an ophthalmic emergency, but 58.8% feel well prepared to work them up. Responders feel more comfortable diagnosing acute retrobulbar hematoma (72.5%), retinal detachment (69.8%), and acute angle closure glaucoma (78.0%) than central retinal artery occlusion (28.9%) or giant cell arteritis (53.2%). Only 60.2% feel comfortable determining if canthotomy and cantholysis is necessary in the setting of acute retrobulbar hematoma, and 40.3% feel comfortable performing the procedure. There was a trend towards attending physicians and providers in urban and academic settings feeling more comfortable diagnosing and managing ophthalmic emergencies compared to trainees, non-urban, and non-academic physicians. CONCLUSIONS: Many participants do not feel comfortable using ophthalmic equipment, performing an eye exam, making vision or potentially life-saving diagnoses, or performing vision-saving procedures, suggesting the need to increase ophthalmic training in EM curricula.

Restrained Dendritic Growth of Adult-Born Granule Cells Innervated by Transplanted Fetal GABAergic Interneurons in Mice with Temporal Lobe Epilepsy.

The dentate gyrus (DG) is a region of the adult rodent brain that undergoes continuous neurogenesis. Seizures and loss or dysfunction of GABAergic synapses onto adult-born dentate granule cells (GCs) alter their dendritic growth and migration, resulting in dysmorphic and hyperexcitable GCs. Additionally, transplants of fetal GABAergic interneurons in the DG of mice with temporal lobe epilepsy (TLE) result in seizure suppression, but it is unknown whether increasing interneurons with these transplants restores GABAergic innervation to adult-born GCs. Here, we address this question by birth-dating GCs with retrovirus at different times up to 12 weeks after pilocarpine-induced TLE in adult mice. Channelrhodopsin 2 (ChR2)-enhanced yellow fluorescent protein (EYFP)-expressing medial-ganglionic eminence (MGE)-derived GABAergic interneurons from embryonic day (E)13.5 mouse embryos were transplanted into the DG of the TLE mice and GCs with transplant-derived inhibitory post-synaptic currents (IPSCs) were identified by patch-clamp electrophysiology and optogenetic interrogation. Putative synaptic sites between GCs and GABAergic transplants were also confirmed by intracellular biocytin staining, immunohistochemistry, and confocal imaging. 3D reconstructions of dendritic arbors and quantitative morphometric analyses were carried out in >150 adult-born GCs. GABAergic inputs from transplanted interneurons correlated with markedly shorter GC dendrites, compared to GCs that were not innervated by the transplants. Moreover, these effects were confined to distal dendritic branches and a short time window of six to eight weeks. The effects were independent of seizures as they were also observed in naïve mice with MGE transplants. These findings are consistent with the hypothesis that increased inhibitory currents over a smaller dendritic arbor in adult-born GCs may reduce their excitability and lead to seizure suppression.