A Remote Consult Retinal Artery Occlusion Diagnostic Protocol.

PURPOSE: To report a novel protocol for diagnosis of retinal artery occlusions at the point of care using OCT and a remote consult model. DESIGN: Retrospective case series and evaluation of a diagnostic test or technology. PARTICIPANTS: Adult patients who presented with painless monocular vision loss and were diagnosed with a nonarteritic retinal artery occlusion. METHODS: OCT machines were placed in the stroke center or emergency department at 3 hospitals within our health system. Patients who presented with painless monocular vision loss were evaluated by the stroke neurology service and an OCT was acquired. The images were interpreted remotely by the retina service. An in-house ophthalmology consult was not required to make the final treatment decision. Eligible patients were treated with intra-arterial tissue plasminogen activator (IA-tPA). Patients were followed by ophthalmology during their admission when an in-house consultation service was available or otherwise evaluated immediately after discharge. MAIN OUTCOME MEASURES: Visual acuity (VA) before and after treatment with IA-tPA; time from last known well (LKW) to treatment; and time from presentation to treatment. RESULTS: In the first 18 months since the protocol went live, 59 patients were evaluated. Twenty-five patients (42%) had a confirmed retinal artery occlusion based on OCT and follow-up examination. Ten patients were eligible for treatment, and 9 patients received treatment with IA-tPA. There was a statistically significant improvement in mean VA from logarithm of the minimum angle of resolution (logMAR) 2.14 to logMAR 0.7 within 24 hours after treatment (P = 0.0001) and logMAR 1.04 after 4 weeks (P = 0.01). Clinically significant improvement was noted in 66% of patients within 24 hours and maintained through 1 month in 56% of all treated patients. The mean time to treatment from LKW was 543 minutes and from presentation at the stroke center was 146 minutes. CONCLUSIONS: We report the successful implementation of a remote consult protocol using point-of-care automated OCT. This novel paradigm demonstrates the potential utility of remote consult services for the diagnosis of time-sensitive ophthalmic emergencies. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Creating ophthalmology experiences in undergraduate medical education: pilot of a cased-based learning ophthalmology tool.

PURPOSE: To evaluate medical student perceptions of a novel ophthalmology resource delivered through facilitated workshops in the core clerkship curriculum. METHODS: We created www.2020sim.com, a free case-based learning (CBL) ophthalmology tool, adapted from NephSIM (www.nephsim.com). The tool was first piloted with the internal medicine (IM) residents. After confirming a need, we focused on undergraduate medical education (UME) by expanding the 20/20 SIM content and partnering with the neurology (pilot academic year [AY] 2020-2021) and pediatric clerkships (pilot AY 2021-2022) to deliver a facilitated one-hour ophthalmology workshop within each clerkship's didactic curriculum. We evaluated the tool using pre- and post-surveys and knowledge assessments. RESULTS: Of 80 IM residents, 33 (41.3%) completed the needs assessment. Of the 25 residents who attended the workshop, 23 (92.0%) completed the exit survey. IM residents reported discomfort in several ophthalmology domains (9 of 14 rated mean score < 3.0), confirming a need. Most (n = 21/23, 91.3%) rated the tool as good/excellent. Of 145 neurology clerkship students, 125 (86.2%) and at least 88 (60.7%) students completed the pre- and post-test/exit surveys, respectively. On average, participants highly rated the tool, perceiving 20/20 SIM to be relevant to their education [4.1 (0.8)]. Mean pre- to post-test knowledge scores increased from 7.5 to 8.5/10.0 points (p < 0.001). Of the 136 pediatric clerkship students, 67 (49.3%) and 51 (37.5%) completed the pre- and post-surveys, respectively. Respondents perceived increased comfort with ophthalmology topics after the facilitated workshop [3.8 (0.8)]. Mean pre- to post-test knowledge scores trended from 1.8 to 2.0/5.0 points (p = 0.30). Collectively, 20/139 (14.4%) of exit survey respondents visited www.2020sim.com within 1 month after the workshop. CONCLUSION: After identifying areas of greatest need with residents, we partnered with core clerkships to deliver cross-disciplinary ophthalmology content in UME. We found high engagement with 20/20 SIM, with trends toward increased knowledge.

Mobile Interventional Stroke Teams Improve Outcomes in the Early Time Window for Large Vessel Occlusion Stroke.

BACKGROUND AND PURPOSE: Endovascular thrombectomy for large vessel occlusion stroke is a time-sensitive intervention. The use of a Mobile Interventional Stroke Team (MIST) traveling to Thrombectomy Capable Stroke Centers to perform endovascular thrombectomy has been shown to be significantly faster with improved discharge outcomes, as compared with the drip-and-ship (DS) model. The effect of the MIST model stratified by time of presentation has yet to be studied. We hypothesize that patients who present in the early window (last known well of ≤6 hours) will have better clinical outcomes in the MIST model. METHODS: The NYC MIST Trial and a prospectively collected stroke database were assessed for patients undergoing endovascular thrombectomy from January 2017 to February 2020. Patients presenting in early and late time windows were analyzed separately. The primary end point was the proportion with a good outcome (modified Rankin Scale score of 0-2) at 90 days. Secondary end points included discharge National Institutes of Health Stroke Scale and modified Rankin Scale. RESULTS: Among 561 cases, 226 patients fit inclusion criteria and were categorized into MIST and DS cohorts. Exclusion criteria included a baseline modified Rankin Scale score of >2, inpatient status, or fluctuating exams. In the early window, 54% (40/74) had a good 90-day outcome in the MIST model, as compared with 28% (24/86) in the DS model (P<0.01). In the late window, outcomes were similar (35% versus 41%; P=0.77). The median National Institutes of Health Stroke Scale at discharge was 5.0 and 12.0 in the early window (P<0.01) and 5.0 and 11.0 in the late window (P=0.11) in the MIST and DS models, respectively. The early window discharge modified Rankin Scale was significantly better in the MIST model (P<0.01) and similar in the late window (P=0.41). CONCLUSIONS: The MIST model in the early time window results in better 90-day outcomes compared with the DS model. This may be due to the MIST capturing high-risk fast progressors at an earlier time point. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03048292.

Intra-Arterial Tissue Plasminogen Activator for Central Retinal Artery Occlusion.

PURPOSE: To investigate the benefit of early intra-arterial tissue plasminogen activator (IAT) for treatment of central retinal artery occlusion (CRAO). PATIENTS AND METHODS: Fifteen eyes of 15 patients presenting with acute CRAO were included in this retrospective consecutive interventional case series. Patients were excluded if treatment with IAT was not initiated within 12 hours. The diagnosis was confirmed by an ophthalmologist. IAT was performed via a transfemoral arterial approach. Tissue plasminogen activator (tPA) was infused into the ophthalmic artery in aliquots up to 3mg to a maximum of 22mg. Paracentesis was done at the ophthalmologist's discretion. The primary outcome measure was visual acuity after three weeks. Adverse events were recorded during treatment and follow-up visits. RESULTS: After treatment with IAT, there was a statistically significant improvement in visual acuity, with a mean change of -0.76 (SD 0.91; range -2.4 to 0.85) logMAR (p=0.006). Vision improved by 3 or more lines in 53%, and of these, the mean Snellen visual acuity improvement was >6 lines. Notably, 4 patients (27%) improved from CF or worse to 20/80 or better. The mean dose of tPA used was 17mg and the mean time to treatment was 8.83 hours (range: 5.5 to 12 hours). There were no statistically significant differences based on time to treatment, dose of tPA, or use of a paracentesis. No major adverse events were recorded. CONCLUSION: IAT was safe and showed significant visual improvement in this small uncontrolled study. Larger studies and efforts to decrease time to treatment should be initiated to optimize outcomes.

Acute Cerebrovascular Events With COVID-19 Infection.

BACKGROUND AND PURPOSE: Coronavirus disease 2019 (COVID-19) has been associated with an increased incidence of thrombotic events, including stroke. However, characteristics and outcomes of COVID-19 patients with stroke are not well known. METHODS: We conducted a retrospective observational study of risk factors, stroke characteristics, and short-term outcomes in a large health system in New York City. We included consecutively admitted patients with acute cerebrovascular events from March 1, 2020 through April 30, 2020. Data were stratified by COVID-19 status, and demographic variables, medical comorbidities, stroke characteristics, imaging results, and in-hospital outcomes were examined. Among COVID-19-positive patients, we also summarized laboratory test results. RESULTS: Of 277 patients with stroke, 105 (38.0%) were COVID-19-positive. Compared with COVID-19-negative patients, COVID-19-positive patients were more likely to have a cryptogenic (51.8% versus 22.3%, P<0.0001) stroke cause and were more likely to suffer ischemic stroke in the temporal (P=0.02), parietal (P=0.002), occipital (P=0.002), and cerebellar (P=0.028) regions. In COVID-19-positive patients, mean coagulation markers were slightly elevated (prothrombin time 15.4±3.6 seconds, partial thromboplastin time 38.6±24.5 seconds, and international normalized ratio 1.4±1.3). Outcomes were worse among COVID-19-positive patients, including longer length of stay (P<0.0001), greater percentage requiring intensive care unit care (P=0.017), and greater rate of neurological worsening during admission (P<0.0001); additionally, more COVID-19-positive patients suffered in-hospital death (33% versus 12.9%, P<0.0001). CONCLUSIONS: Baseline characteristics in patients with stroke were similar comparing those with and without COVID-19. However, COVID-19-positive patients were more likely to experience stroke in a lobar location, more commonly had a cryptogenic cause, and had worse outcomes.

Emergent Large Vessel Occlusion Stroke During New York City's COVID-19 Outbreak: Clinical Characteristics and Paraclinical Findings.

BACKGROUND AND PURPOSE: The 2019 novel coronavirus outbreak and its associated disease (coronavirus disease 2019 [COVID-19]) have created a worldwide pandemic. Early data suggest higher rate of ischemic stroke in severe COVID-19 infection. We evaluated whether a relationship exists between emergent large vessel occlusion (ELVO) and the ongoing COVID-19 outbreak. METHODS: This is a retrospective, observational case series. Data were collected from all patients who presented with ELVO to the Mount Sinai Health System Hospitals across New York City during the peak 3 weeks of hospitalization and death from COVID-19. Patients' demographic, comorbid conditions, cardiovascular risk factors, COVID-19 disease status, and clinical presentation were extracted from the electronic medical record. Comparison was made between COVID-19 positive and negative cohorts. The incidence of ELVO stroke was compared with the pre-COVID period. RESULTS: Forty-five consecutive ELVO patients presented during the observation period. Fifty-three percent of patients tested positive for COVID-19. Total patients' mean (±SD) age was 66 (±17). Patients with COVID-19 were significantly younger than patients without COVID-19, 59±13 versus 74±17 (odds ratio [95% CI], 0.94 [0.81-0.98]; P=0.004). Seventy-five percent of patients with COVID-19 were male compared with 43% of patients without COVID-19 (odds ratio [95% CI], 3.99 [1.12-14.17]; P=0.032). Patients with COVID-19 were less likely to be White (8% versus 38% [odds ratio (95% CI), 0.15 (0.04-0.81); P=0.027]). In comparison to a similar time duration before the COVID-19 outbreak, a 2-fold increase in the total number of ELVO was observed (estimate: 0.78 [95% CI, 0.47-1.08], P≤0.0001). CONCLUSIONS: More than half of the ELVO stroke patients during the peak time of the New York City's COVID-19 outbreak were COVID-19 positive, and those patients with COVID-19 were younger, more likely to be male, and less likely to be White. Our findings also suggest an increase in the incidence of ELVO stroke during the peak of the COVID-19 outbreak.

Macrothrombosis and stroke in patients with mild Covid-19 infection.

Coronavirus disease 2019 (COVID-19) is a pandemic disease currently affecting millions of people worldwide. Its neurological implications are poorly understood, and further study is urgently required. A hypercoagulable state has been reported in patients with severe COVID-19, but nothing is known about coagulopathy in patients with milder disease. We describe cases of patients in New York City presenting with stroke secondary to large vessel thrombosis without occlusion, incidentally found to have COVID-19 with only mild respiratory symptoms. This is in contrast to the venous thrombosis and microangiopathy that has been reported in patients with severe COVID-19. Our cases suggest that even in the absence of severe disease, patients with COVID-19 may be at increased risk of thrombus formation leading to stroke, perhaps resulting from viral involvement of the endothelium. Further systematic study is needed because this may have implications for primary and secondary stroke prevention in patients with COVID-19.

Multiple Administrations of Intravenous Thrombolytic Therapy to a Stroke Mimic.

BACKGROUND: Patients who present emergently with focal neurological deficits concerning for acute ischemic stroke can be extremely challenging to diagnose and treat. Unnecessary administration of thrombolytics to potential stroke patients whose symptoms are not caused by an acute ischemic stroke-stroke mimics-may result in patient harm, although the overall risk of hemorrhagic complications among stroke mimics is low. CASE REPORT: We present a case of a stroke mimic patient with underlying psychiatric disease who was treated with intravenous alteplase on four separate occasions in four different emergency departments in the same city. Although he did not suffer hemorrhagic complications, this case highlights the importance of rapid exchange of health information across institutions to improve diagnostic quality and safety. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Increased awareness of stroke mimics by emergency physicians may improve diagnostic safety for a subset of high-risk patients. Establishing rapid cross-institutional communication pathways that are integrated into provider's workflows to convey essential patient health information has potential to improve stroke diagnostic decision-making and thus represents an important topic for health systems research in emergency medicine.

Ethical Challenges in Acute Evaluation of Suspected Psychogenic Stroke Mimics.

Tissue plasminogen activator (tPA) is administered to patients with suspected ischemic stroke to improve blood flow to the brain In rare cases, patients present with complaints of stroke symptoms that appear to be non-organic due to malingering, factitious disorder, or conversion disorder (psychogenic stroke mimics). Deciding whether or not to administer tPA to these patients can be challenging. The risk of hemorrhage after administration of tPA is low, but not zero. The ethical principles of beneficence and nonmaleficence need to be weighed carefully in these situations. We present two cases of patients with suspected psychogenic stroke mimics to illustrate the ethical challenges faced in identifying and managing psychogenic stroke mimics. Further research is needed to demonstrate effective treatment strategies for patients with acute stroke symptoms of psychogenic etiology.

Controversies in Cardiopulmonary Death.

We describe two unusual cases of cardiopulmonary death in mechanically ventilated patients in the neurological intensive care unit. After cardiac arrest, both patients were pulseless for a protracted period. Upon extubation, both developed agonal movements (gasping respiration) resembling life. We discuss these cases and the literature on the ethical and medical controversies associated with determining time of cardiopulmonary death. We conclude that there is rarely a single moment when all of a patient's physiological functions stop working at once. This can pose a challenge for determining the exact moment of death.

The prognostic significance of CXCL1 hypersecretion by human colorectal cancer epithelia and myofibroblasts.

BACKGROUND: Clinical therapy for metastatic colorectal cancer (CRC) remains limited, especially when the tumor harbors a KRAS mutation. This study aimed to identify prognostic biomarkers in CRC that are accessible for therapeutic inhibition. METHODS: Conditioned media from human CRC epithelial cells and myofibroblasts were screened by cytokine arrays for tumorigenic factors. The protein and mRNA expressions of these factors were determined by immunohistochemistry and gene microarrays in human CRC tissues. Prognostic biomarkers were determined by correlation of mRNA expression to overall survival in stage IV CRC patients. Inhibition of CXCL1 was performed with specific neutralizing antibody and lentiviral shRNAs. Malignant growth was assessed by soft agar growth assays and xenograft tumor growth in immunocompromised mice. RESULTS: CXCL1 was highly secreted by KRAS mutant human CRC cells and myofibroblasts in a complementary adaptive response to serum deprivation. Elevated CXCL1 level promoted anchorage-independent growth of murine fibroblasts and human CRC cells. Inhibition of CXCL1 by neutralizing antibody and specific shRNAs decreased CRC tumor growth. Highly elevated CXCL1 expression significantly correlated with decreased overall survival in stage IV CRC patients (hazard ratio 0.28; 95% CI 0.11-0.72). CONCLUSIONS: High CXCL1 expression is a poor prognostic biomarker in metastatic CRC. CXCL1 inhibition suppressed tumorigenic growth of KRAS mutant CRC cells.

Clinical characteristics of patients with lung adenocarcinomas harboring BRAF mutations.

PURPOSE: BRAF mutations occur in non-small-cell lung cancer. Therapies targeting BRAF mutant tumors have recently been identified. We undertook this study to determine the clinical characteristics of patients with lung adenocarcinomas harboring BRAF mutations. PATIENTS AND METHODS: We reviewed data from consecutive patients with lung adenocarcinoma whose tumors underwent BRAF, EGFR, and KRAS mutation testing as well as fluorescence in situ hybridization for ALK rearrangements. Patient characteristics including age, sex, race, performance status, smoking history, stage, treatment history, and overall survival were collected. RESULTS: Among 697 patients with lung adenocarcinoma, BRAF mutations were present in 18 patients (3%; 95% CI, 2% to 4%). The BRAF mutations identified were V600E (50%), G469A (39%), and D594G (11%). Mutations in EGFR were present in 24%, KRAS in 25%, and ALK translocations in 6%. In contrast to patients with EGFR mutations and ALK rearrangements who were mostly never smokers, all patients with BRAF mutations were current or former smokers (P < .001). The median overall survival of advanced-stage patients with BRAF mutations was not reached. In comparison, the median overall survival of patients with EGFR mutations was 37 months (P = .73), with KRAS mutations was 18 months (P = .12), and with ALK rearrangements was not reached (P = .64). CONCLUSION: BRAF mutations occur in 3% of patients with lung adenocarcinoma and occur more commonly in current and former smokers. The incidence of BRAF mutations other than V600E is significantly higher in lung cancer than in melanoma.