A Comparative Study of Large Language Models, Human Experts, and Expert-Edited Large Language Models to Neuro-Ophthalmology Questions.

BACKGROUND: While large language models (LLMs) are increasingly used in medicine, their effectiveness compared with human experts remains unclear. This study evaluates the quality and empathy of Expert + AI, human experts, and LLM responses in neuro-ophthalmology. METHODS: This randomized, masked, multicenter cross-sectional study was conducted from June to July 2023. We randomly assigned 21 neuro-ophthalmology questions to 13 experts. Each expert provided an answer and then edited a ChatGPT-4-generated response, timing both tasks. In addition, 5 LLMs (ChatGPT-3.5, ChatGPT-4, Claude 2, Bing, Bard) generated responses. Anonymized and randomized responses from Expert + AI, human experts, and LLMs were evaluated by the remaining 12 experts. The main outcome was the mean score for quality and empathy, rated on a 1-5 scale. RESULTS: Significant differences existed between response types for both quality and empathy (P < 0.0001, P < 0.0001). For quality, Expert + AI (4.16 ± 0.81) performed the best, followed by GPT-4 (4.04 ± 0.92), GPT-3.5 (3.99 ± 0.87), Claude (3.6 ± 1.09), Expert (3.56 ± 1.01), Bard (3.5 ± 1.15), and Bing (3.04 ± 1.12). For empathy, Expert + AI (3.63 ± 0.87) had the highest score, followed by GPT-4 (3.6 ± 0.88), Bard (3.54 ± 0.89), GPT-3.5 (3.5 ± 0.83), Bing (3.27 ± 1.03), Expert (3.26 ± 1.08), and Claude (3.11 ± 0.78). For quality (P < 0.0001) and empathy (P = 0.002), Expert + AI performed better than Expert. Time taken for expert-created and expert-edited LLM responses was similar (P = 0.75). CONCLUSIONS: Expert-edited LLM responses had the highest expert-determined ratings of quality and empathy warranting further exploration of their potential benefits in clinical settings.

Pulmonary embolism response teams. A description of the first 36-month Australian experience.

BACKGROUND: High/intermediate-risk pulmonary embolism (PE) confers increased risk of cardiovascular morbidity and mortality. International guidelines recommend the formation of a PE response team (PERT) for PE management because of the complexity of risk stratification and emerging treatment options. However, there are currently no available Australian data regarding outcomes of PE managed through a PERT. AIMS: To analyse the clinical and outcome data of patients from an Australian centre with high/intermediate-risk PE requiring PERT-guided management. METHODS: We performed a retrospective observational study of 75 consecutive patients with high/intermediate-risk PE who had PERT involvement, between August 2018 and July 2021. We recorded clinical and interventional data at the time of PERT and assessed patient outcomes up to 30 days from PERT initiation. We used unpaired t tests to compare right to left ventricular (RV/LV) ratios by computed tomography criteria or transthoracic echocardiogram (TTE) at baseline and after interventions. RESULTS: Data were available for 74 patients. Initial computed tomography pulmonary angiography RV/LV ratio was increased at 1.65 ± 0.5 and decreased to 1.30 ± 0.29 following PERT-guided interventions (P < 0.001). TTE RV/LV ratio also decreased following PERT-guided management (1.09 ± 0.19 vs 0.93 ± 0.17; P < 0.001). 20% of patients had any bleeding complication, but two-thirds were mild, not requiring intervention. All-cause mortality was 6.8%, and all occurred within the first 7 days of admission. CONCLUSION: The PERT model is feasible in a large Australian centre in managing complex and time-critical PE. Our data demonstrate outcomes comparable with existing published international PERT data. However, successful implementation at other Australian institutions may require adequate centre-specific resource availability and the presence of multispeciality input.

The therapeutically actionable long non-coding RNA 'T-RECS' is essential to cancer cells' survival in NRAS/MAPK-driven melanoma.

Finding effective therapeutic targets to treat NRAS-mutated melanoma remains a challenge. Long non-coding RNAs (lncRNAs) recently emerged as essential regulators of tumorigenesis. Using a discovery approach combining experimental models and unbiased computational analysis complemented by validation in patient biospecimens, we identified a nuclear-enriched lncRNA (AC004540.4) that is upregulated in NRAS/MAPK-dependent melanoma, and that we named T-RECS. Considering potential innovative treatment strategies, we designed antisense oligonucleotides (ASOs) to target T-RECS. T-RECS ASOs reduced the growth of melanoma cells and induced apoptotic cell death, while having minimal impact on normal primary melanocytes. Mechanistically, treatment with T-RECS ASOs downregulated the activity of pro-survival kinases and reduced the protein stability of hnRNPA2/B1, a pro-oncogenic regulator of MAPK signaling. Using patient- and cell line- derived tumor xenograft mouse models, we demonstrated that systemic treatment with T-RECS ASOs significantly suppressed the growth of melanoma tumors, with no noticeable toxicity. ASO-mediated T-RECS inhibition represents a promising RNA-targeting approach to improve the outcome of MAPK pathway-activated melanoma.

Eugenol Suppresses Platelet Activation and Mitigates Pulmonary Thromboembolism in Humans and Murine Models.

Platelets assume a pivotal role in the pathogenesis of cardiovascular diseases (CVDs), emphasizing their significance in disease progression. Consequently, addressing CVDs necessitates a targeted approach focused on mitigating platelet activation. Eugenol, predominantly derived from clove oil, is recognized for its antibacterial, anticancer, and anti-inflammatory properties, rendering it a valuable medicinal agent. This investigation delves into the intricate mechanisms through which eugenol influences human platelets. At a low concentration of 2 µM, eugenol demonstrates inhibition of collagen and arachidonic acid (AA)-induced platelet aggregation. Notably, thrombin and U46619 remain unaffected by eugenol. Its modulatory effects extend to ATP release, P-selectin expression, and intracellular calcium levels ([Ca2+]i). Eugenol significantly inhibits various signaling cascades, including phospholipase Cγ2 (PLCγ2)/protein kinase C (PKC), phosphoinositide 3-kinase/Akt/glycogen synthase kinase-3ß, mitogen-activated protein kinases, and cytosolic phospholipase A2 (cPLA2)/thromboxane A2 (TxA2) formation induced by collagen. Eugenol selectively inhibited cPLA2/TxA2 phosphorylation induced by AA, not affecting p38 MAPK. In ADP-treated mice, eugenol reduced occluded lung vessels by platelet thrombi without extending bleeding time. In conclusion, eugenol exerts a potent inhibitory effect on platelet activation, achieved through the inhibition of the PLCγ2-PKC and cPLA2-TxA2 cascade, consequently suppressing platelet aggregation. These findings underscore the potential therapeutic applications of eugenol in CVDs.

Spiced RCT: Success and Pain Associated with Intravenous Cannulation in the Emergency Department Randomized Controlled Trial.

BACKGROUND: Peripheral venous cannulation is one of the most common procedures in medicine. A larger cannula allows higher rates of fluid to be provided if needed in a deteriorating patient; however, it is also perceived that larger-gauge cannula placement is associated with increased pain and procedural difficulty. OBJECTIVE: This study aimed to compare the pain and procedural difficulty experienced during insertion between 18-gauge (18G) and 20-gauge (20G) cannulas. METHODS: We conducted a single-blinded, randomized controlled trial on adult patients who required peripheral IV cannulation within a tertiary hospital emergency department between April and October 2018. Patients were randomized to either the 18G or 20G cannula group. The primary outcomes of the study-pain experienced by patients and procedural difficulties experienced by clinical staff-were recorded on two separate 10-cm visual analog scales. Other outcomes include first-attempt success rate, operator designation, complications, and the intent and actual use of the IV cannula were documented on preformatted questionnaires. RESULTS: Data from 178 patients were included in the analysis. Eighty-nine patients were allocated to each cannula group. There were no statistically or clinically significant differences between mean pain score (0.23; 95% CI 0.56-1.02; p = 0.5662) and mean procedural difficulty score (0.12; 95% CI 0.66-0.93; p = 0.7396). between the two groups. There was no difference in first-attempt success rate (73 of 89 vs. 75 of 89; p = 0.1288), complications (2 of 89 vs. 1 of 89) between the 20G group and 18G group, respectively. CONCLUSIONS: There was no significant difference between the 18G or 20G cannula for either pain experienced by patients or procedural difficulty experienced by clinicians.

The therapeutically actionable long non-coding RNA 'T-RECS' is essential to cancer cells' survival in NRAS/MAPK-driven melanoma.

Finding effective therapeutic targets to treat NRAS-mutated melanoma remains a challenge. Long non-coding RNAs (lncRNAs) recently emerged as essential regulators of tumorigenesis. Using a discovery approach combining experimental models and unbiased computational analysis complemented by validation in patient biospecimens, we identified a nuclear-enriched lncRNA (AC004540.4) that is upregulated in NRAS/MAPK-dependent melanoma, and that we named T-RECS. Considering potential innovative treatment strategies, we designed antisense oligonucleotides (ASOs) to target T-RECS. T-RECS ASOs reduced the growth of melanoma cells and induced apoptotic cell death, while having minimal impacton normal primary melanocytes. Mechanistically, treatment with T-RECS ASOs downregulated the activity of pro-survival kinases and reduced the protein stability of hnRNPA2/B1, a pro-oncogenic regulator of MAPK signaling. Using patient- and cell line- derived tumor xenograft mouse models, we demonstrated that systemic treatment with T-RECS ASOs significantly suppressed the growth of melanoma tumors, with no noticeable toxicity. ASO-mediated T-RECS inhibition represents a promising RNA-targeting approach to improve the outcome of MAPK pathway-activated melanoma.

Thromboembolic Presentations among Patients Hospitalized to the Intensive Care Unit for Coronavirus Disease 2019 (COVID-19) - A Northern Taiwan Single Center Experience.

Coronavirus Disease 2019 (COVID-19) has been associated with a high thromboembolic risk among patients in intensive care units. Asian populations may share a similar thromboembolic risk, but with a higher prevalence of arterial thromboembolism than venous thromboembolism. To clarify this risk in Taiwan, this single-center retrospective study collected 27 consecutive intensive care unit patients with COVID-19 confirmed by polymerase chain reaction, with a median age of 67.6 years (male 81.5%). Twenty-three patients received prophylactic anticoagulation (85.2%), and there were four bleeding events (14.8%). Nine patients had thromboembolism (33.3%), including three with deep vein thrombosis, two with peripheral artery thromboembolism, and four with ischemic stroke. There were no significant clinical differences between the patients with or without thromboembolism. Initial serum ferritin [adjusted odds ratio (OR): 13.19, 95% confidence interval (CI): 1.01-172.07] and peak serum procalcitonin (adjusted OR: 18.93, 95% CI: 1.08-330.91) were associated with a higher risk of thromboembolism. Furthermore, prophylactic anticoagulation (adjusted OR: 0.01, 95% CI: < 0.001-0.55) was associated with a lower risk of thromboembolism. All cases of deep vein thrombosis and one peripheral artery thromboembolism occurred at intravascular catheter locations. No association between thromboembolism and survival was found (age-adjusted hazard ratio: 0.55, 95% CI: 0.10-2.95). In conclusion, the prevalence of COVID-19 thromboembolism among Taiwanese patients in intensive care units was high, even with prophylactic anticoagulation. Serum ferritin and procalcitonin may identify high-risk populations. Prophylactic anticoagulation may reduce the risk of thromboembolism with a manageable bleeding risk. Larger prospective studies are needed to clarify the risk of COVID-19 thromboembolism and its risk factors in the post-Omicron era.

Comparison of Humoral Antibody Responses and Seroconversion Rates between Two Homologous ChAdOx1 nCoV-19 and mRNA-1273 Vaccination in Patients Undergoing Maintenance Hemodialysis.

BACKGROUND: Hemodialysis patients are at an increased risk of SARS-CoV-2 infection and are excluded from preauthorization COVID-19 vaccine trials; therefore, their immunogenicity is uncertain. METHODS: To compare the antibody responses to homologous ChAdOx1 and mRNA-1273 SARS-CoV-2 vaccination in hemodialysis patients, 103 age- and sex-matched hemodialysis patients with two homologous prime-boost vaccinations were recruited to detect anti-receptor-binding domain (RBD) IgG levels and seroconversion rates (SCRs) 14 days after a prime dose (PD14), before and 28 days after a boost dose (pre-BD0 and BD28). RESULTS: Both mRNA-1273 and ChAdOx1 vaccinations elicited immunogenicity in study subjects, and the former induced higher anti-RBD IgG levels than the latter. The SCRs of both groups increased over time and varied widely from 1.82% to 97.92%, and were significantly different at PD14 and pre-BD0 regardless of different thresholds. At BD28, the SCRs of the ChAdOx1 group and the mRNA-1273 group were comparable using a threshold ≥ 7.1 BAU/mL (93.96% vs. 97.92%) and a threshold ≥ 17 BAU/mL (92.73% vs. 97.92%), respectively, but they were significantly different using a threshold ≥ 20.2% of convalescent serum anti-RBD levels (52.73% vs. 95.83%). The seroconversion (≥20.2% of convalescent level) at BD28 was associated with mRNA-1273 vaccination after being adjusted for age, sex, body mass index, and the presence of solicited reactogenicity after a prime vaccination. CONCLUSION: Our prospective, observational cohort indicates that a full prime-boost mRNA-1273 vaccination is likely to provide higher immune protection in hemodialysis patients compared to ChAdOx1, and this population with a prime-boost ChAdOx1 vaccination should be prioritized for a third dose.

Social Media in Neuro-Ophthalmology: Paradigms, Opportunities, and Strategies.

BACKGROUND: Social media (SoMe) is an integral part of life in the 21st century. Its potential for rapid dissemination and amplification of information offers opportunities for neuro-ophthalmologists to have an outsized voice to share expert-level knowledge with the public, other medical professionals, policymakers, and trainees. However, there are also potential pitfalls, because SoMe may spread incorrect or misleading information. Understanding and using SoMe enables neuro-ophthalmologists to influence and educate that would otherwise be limited by workforce shortages. EVIDENCE ACQUISITION: A PubMed search for the terms "social media" AND "neuro-ophthalmology," "social media" AND "ophthalmology," and "social media" AND "neurology" was performed. RESULTS: Seventy-two neurology articles, 70 ophthalmology articles, and 3 neuro-ophthalmology articles were analyzed. A large proportion of the articles were published in the last 3 years (2020, 2021, 2022). Most articles were analyses of SoMe content; other domains included engagement analysis such as Altmetric analysis, utilization survey, advisory opinion/commentary, literature review, and other. SoMe has been used in medicine to share and recruit for scientific research, medical education, advocacy, mentorship and medical professional networking, and branding, marketing, practice building, and influencing. The American Academy of Neurology, American Academy of Ophthalmology, and North American Neuro-Ophthalmology Society have developed guidelines on the use of SoMe. CONCLUSIONS: Neuro-ophthalmologists may benefit greatly from harnessing SoMe for the purposes of academics, advocacy, networking, and marketing. Regularly creating appropriate professional SoMe content can enable the neuro-ophthalmologist to make a global impact.

Prevalence and correlates of destructive behaviors in the US Naval Surface Forces from 2010-2020.

PURPOSE: To estimate the prevalence of domestic violence, sexual assault, and suicide for United States Navy (USN) personnel between 2010 and 2020 and identify potential associated factors. METHODS: Official report data were used to calculate prevalence rates and odds ratios, accounting for sample and general USN population demographic data to assess differences in over- or underrepresentation of destructive behaviors. RESULTS: Domestic violence and sexual assault offenders tended to be younger lower-ranked males. For sexual assaults, offenders were three times more likely to be senior to the victim, which was not the case for domestic violence. Females were overrepresented in terms of suicidal ideation and attempts relative to the USN population, while males accounted for more actual suicides. The relative rates of suicidal ideation and attempts for females exceeded those for males (i.e., comparing the sample rate against the USN male and female populations), but the sample proportion for completed suicides (compared to the USN population) were greater for males than for females. Those in the junior enlisted (E1-E3) paygrades exhibited greater odds of suicide attempts versus suicidal ideations relative to those in the Petty Officers (E4-E6) paygrades, although E4-E6s completed more suicides. CONCLUSION: The descriptive profile of destructive behaviors in a representative sample of USN personnel provides an overview of the possible factors associated with destructive behaviors and includes an exploration of the relational dynamics and nature of the incidents. The results suggest that sexual assault and domestic violence are characterized by unique relational dynamics and that these destructive behaviors should not necessarily be classified together as male-oriented aggressions (i.e., mainly perpetrated by males against female victims). Those in the E1-E3 and E4-E6 paygrades displayed different patterns in suicidal ideation, attempts, and actual suicides. The results highlight individual characteristics to help inform the development of targeted policies, practices, and interventions for military and other hierarchical organizations (e.g., police).

Toll-like Receptor 2 Mediates VEGF Overexpression and Mesothelial Hyperpermeability in Tuberculous Pleural Effusion.

Toll-like receptor (TLR) is essential for the immune response to Mycobacterium tuberculosis (MTB) infection. However, the mechanism whereby TLR mediates the MTB-induced pleural mesothelial hyperpermeability in tuberculous pleural effusion (TBPE) remains unclear. Pleural effusion size and pleural fluid levels of vascular endothelial growth factor (VEGF) and soluble TLR2 (sTLR2) in patients with TBPE (n = 36) or transudative pleural effusion (TPE, n = 16) were measured. The effects of MTB H37Ra (MTBRa) on pleural mesothelial permeability and the expression of VEGF and zonula occludens (ZO)-1 in human pleural mesothelial cells (PMCs) were assessed. Levels of VEGF and sTLR2 were significantly elevated in TBPE compared to TPE. Moreover, effusion VEGF levels correlated positively, while sTLR2 values correlated negatively, with pleural effusion size in TBPE. In human PMCs, MTBRa substantially activated JNK/AP-1 signaling and upregulated VEGF expression, whereas knockdown of TLR2 remarkably inhibited MTBRa-induced JNK phosphorylation and VEGF overexpression. Additionally, both MTBRa and VEGF markedly reduced ZO-1 expression and induced pleural mesothelial permeability, while TLR2 silencing or pretreatment with anti-VEGF antibody significantly attenuated the MTBRa-triggered effects. Collectively, TLR2 mediates VEGF overproduction and downregulates ZO-1 expression in human PMCs, leading to mesothelial hyperpermeability in TBPE. Targeting TLR2/VEGF pathway may confer a potential treatment strategy for TBPE.

Can Tele-Neuro-Ophthalmology Be Useful Beyond the Pandemic?

PURPOSE OF THE REVIEW: Neuro-ophthalmologists rapidly adopted telehealth during the COVID-19 pandemic to minimize disruption to patient care. This article reviews recent research on tele-neuro-ophthalmology adoption, current limitations, and potential use beyond the pandemic. The review considers how digital transformation, including machine learning and augmented reality, may be applied to future iterations of tele-neuro-ophthalmology. RECENT FINDINGS: Telehealth utilization has been sustained among neuro-ophthalmologists throughout the pandemic. Adoption of tele-neuro-ophthalmology may provide solutions to subspecialty workforce shortage, patient access, physician wellness, and trainee educational needs within the field of neuro-ophthalmology. Digital transformation technologies have the potential to augment tele-neuro-ophthalmology care delivery by providing automated workflow solutions, home-based visual testing and therapies, and trainee education via simulators. Tele-neuro-ophthalmology use has and will continue beyond the COVID-19 pandemic. Digital transformation technologies, when applied to telehealth, will drive and revolutionize the next phase of tele-neuro-ophthalmology adoption and use in the years to come.

Sleep deficiency, operational fatigue and the interplay of compromising factors: Analysis to aid in fatigue management.

The United States Navy is a high-reliability organization that must maintain optimum performance under challenging conditions. One key challenge for sailors is obtaining sufficient sleep, which can lead to fatigue and other outcomes that compromise operational readiness. Identifying sleep issues and their causes is critical for military leaders to care for their personnel, and to make informed, risk-based operational decisions. Though previous studies in shipboard environments have implicated factors responsible for insufficient sleep (e.g. poor sleep environment and work demands), there has been less research into characterizing the complex interplay among such factors in relation to sleep and work-related fatigue outcomes. This study seeks to address this gap. Data were drawn from the Afloat Safety Climate Assessment Survey of 7617 sailors from 73 ships. The survey included demographic characteristics and measures of crew endurance (e.g. sleep, occupational impairment due to fatigue). Descriptive analyses characterized the presence and severity of sleep issues across subpopulations and operational settings (e.g. the type of ship); structural equation modelling techniques characterized and quantified the statistical associations among factors. The results indicate that sleep deficits are widespread, holding across subpopulations and operational settings. Though sleep deficits varied across subpopulations, no group obtained an average of more than 7 hr of sleep per night. Fatigue-induced occupational functional impairment was directly related to sleep deficiency, and sleep environment and job-related factors were contributors to sleep deficiency. Moreover, job-related factors emerged as potentially more consequential. Lastly, factors may exist aboard a ship that could help promote better sleep.

Tele-Neuro-Ophthalmology Utilization, Availability, and Attitudes: Update 1 Year Into the COVID-19 Public Health Emergency.

BACKGROUND: Telehealth was rapidly adopted early in the COVID-19 pandemic as a way to provide medical care while reducing risk of SARS-CoV2 transmission. Since then, telehealth utilization has evolved differentially according to subspecialty. This study assessed changes in neuro-ophthalmology during the first year of the COVID-19 pandemic. METHODS: Telehealth utilization and opinions pre-COVID-19, early pandemic (spring 2020), and 1 year later (spring 2021) were surveyed among practicing neuro-ophthalmologists in and outside the United States using an online platform. Demographics, self-reported utilization, perceived benefits, barriers, and examination suitability were collected over a 2-week period in May 2021. RESULTS: A total of 135 practicing neuro-ophthalmologists (81.5% United States, 47.4% females, median age 45-54 years) completed the survey. The proportion of participants using video visits remained elevated during COVID + 1 year (50.8%) compared with pre-COVID (6%, P < 0.0005, McNemar), although decreased compared with early COVID (67%, P < 0.0005). Video visits were the most commonly used methodology. The proportion of participants using remote testing (42.2% vs 46.2%), virtual second opinions (14.5% vs 11.9%, P = 0.45), and eConsults (13.5% vs 16.2%, P = 0.38) remained similar between early and COVID + 1 year ( P = 0.25). The majority selected increased access to care, better continuity of care, and enhanced patient appointment efficiency as benefits, whereas reimbursement, liability, disruption of in-person clinic flow, limitations of video examinations, and patient technology use were barriers. Many participants deemed many neuro-ophthalmic examination elements unsuitable when collected during a live video session, although participants believed some examination components could be evaluated adequately through a review of ancillary testing or outside records. CONCLUSIONS: One year into the COVID-19 pandemic, neuro-ophthalmologists maintained telemedicine utilization at rates higher than prepandemic levels. Tele-neuro-ophthalmology remains a valuable tool in augmenting patient care.

Interprofessional Electronic Consultations for the Diagnosis and Management of Neuro-Ophthalmic Conditions.

BACKGROUND: Interprofessional electronic consultation (eConsult) is a telemedicine modality in which consulting providers review outside records and provide recommendations without in-person consultation. The purpose of this study was to describe the utilization of eConsults in the management of neuro-ophthalmic conditions. METHODS: Retrospective cohort study of all patients who received an eConsult for a neuro-ophthalmic condition at a single quaternary referral center from 2018 to 2020. Main outcome measures included proportion of eConsults in which sufficient data were provided to the neuro-ophthalmologist to generate a definitive management decision, proportion of patients for whom an in-person neuro-ophthalmology evaluation was recommended, and the eConsult's impact on patient care. RESULTS: Eighty eConsults were conducted on 78 patients during the 3-year study period. Forty-eight (60.0%) subjects were female, mean age was 54 years, and 65 (81.3%) were White. The median time from eConsult request to completion was 4 days (range: 0-34 days). The most frequent eConsult questions were vision/visual field disturbances in 28 (35.0%) cases, optic neuropathies in 22 (27.5%), and optic disc edema in 17 (21.3%). At the time of eConsult, sufficient prior information was provided in 35 (43.8%) cases for the neuro-ophthalmologist to provide a definitive management decision. In 45 (56.3%) eConsults, further diagnostic testing was recommended. In-person neuro-ophthalmology consultation was recommended in 24 (30.0%) cases. Sixty-one (76.3%) eConsults provided diagnostic and/or treatment direction, and 12 (15.0%) provided reassurance. CONCLUSION: eConsults increase access to timely neuro-ophthalmic care and provide diagnostic and treatment direction to non-neuro-ophthalmology providers when sufficient information is provided at the time of eConsult.

Improving community-based first response to out of hospital cardiac arrest (FirstCPR): protocol for a cluster randomised controlled trial.

INTRODUCTION: Out-of-hospital cardiac arrest (OHCA) is associated with poor survival outcomes, but prompt bystander action can more than double survival rates. Being trained, confident and willing-to-perform cardiopulmonary resuscitation (CPR) are known predictors of bystander action. This study aims to assess the effectiveness of a community organisation targeted multicomponent education and training initiative on being willing to respond to OHCAs. The study employs a novel approach to reaching community members via social and cultural groups, and the intervention aims to address commonly cited barriers to training including lack of availability, time and costs. METHODS AND ANALYSIS: FirstCPR is a cluster randomised trial that will be conducted across 200 community groups in urban and regional Australia. It will target community groups where CPR training is not usual. Community groups (clusters) will be stratified by region, size and organisation type, and then randomly assigned to either immediately receive the intervention programme, comprising digital and in-person education and training opportunities about CPR and OHCA over 12 months, or a delayed programme implementation. The primary outcome is self-reported 'training and willingness-to-perform CPR' at 12 months. It will be assessed through surveys of group members that consent in intervention versus control groups and administered prior to control groups receiving the intervention. The primary analysis will follow intention-to-treat principles, use log binomial regression accounting for baseline covariates and be conducted at the individual level, while accounting for clustering within communities. Focus groups and interviews will be conducted to examine barriers and enablers to implementation and costs will also be examined. ETHICS AND DISSEMINATION: Ethical approval was obtained from The University of Sydney. Findings from this study will be disseminated via presentations at scientific conferences, publications in peer-reviewed journals, scientific and lay reports. TRIAL REGISTRATION NUMBER: ACTRN12621000367842.

pcMSC Modulates Immune Dysregulation in Patients With COVID-19-Induced Refractory Acute Lung Injury.

Background and Objectives: The novel coronavirus disease 2019 (COVID-19) has been a pandemic health issue in 30 January 2020. The mortality rate is as high as 50% in critically ill patients. Stem cell therapy is effective for those who are refractory to standard treatments. However, the immune responses that underlie stem cell therapy have not been well reported, particularly, in patients associated with moderate to severe acute respiratory distress syndrome (ARDS). Methods: On Days 0 and 4, an intravenous infusion of 2 × 107 placenta-derived mesenchymal stem cells (pcMSCs) (MatriPlax) were administered to five severe COVID-19 patients refractory to current standard therapies. Peripheral blood inflammatory markers and immune profiles were determined by multi-parameter flow cytometry and studied at Days 0, 4, and 8. Clinical outcomes were also observed. Results: None of the pc-MSC treated patients experienced 28-day mortality compared with the control group and showed a significant improvement in the PaO2/FiO2 ratio, Murray's lung injury scores, reduction in serum ferritin, lactate dehydrogenase (LDH), and C-reactive protein (CRP) levels. The cytokine profiles also showed a reduction in IL-1ß, IFN-γ, IL-2, and IL-6, and an increase in IL-13 and IL-5 type 2 cytokines within 7 days of therapy. Lymphopenia was also significantly improved after 7 days of treatment. Immune cell profiles showed an increase in the proportions of CD4+ T cells (namely, CD4+ naïve T cells and CD4+ memory T cell subtypes), Treg cells, CD19+ B cells (namely, CD19+ naïve B cells, CD27+ switched B cell subtypes) and dendritic cells, and a significant decrease in the proportion of CD14+ monocytes (namely, CD16- classical and CD16+ non-classical subtypes), and plasma/plasmablast cells. No adverse effects were seen at the serial follow-up visits for 2 months after initial therapy. Conclusion: pc-MSCs therapy suppressed hyper-inflammatory states of the innate immune response to COVID-19 infection by increasing Treg cells, decreasing monocytes and plasma/plasmablast cells, and promoting CD4+ T cells and CD19+ B cells toward adaptive immune responses in severely critically ill COVID-19 patients with moderate to severe ARDS, especially those who were refractory to current standard care and immunosuppressive therapies.

Osteogenic Circulating Endothelial Progenitor Cells are Associated with Vascular Aging of the Large Arteries in Rheumatoid Arthritis.

Background and Aim: Rheumatoid arthritis is associated with both abnormal bone metabolism and accelerated vascular aging but a mechanistic link was lacking. This study aims to investigate the role of osteocalcin (OCN)-expressing circulating endothelial progenitor cells (EPCs) in vascular aging, as determined by arterial calcifications in rheumatoid arthritis. Methods: We performed flow cytometry studies in 145 consecutive patients with rheumatoid arthritis to determine osteogenic circulating levels of OCN-positive (OCN+) CD34+KDR+ and OCN+CD34+ versus conventional early EPC CD34+CD133+KDR+. Total calcium load of the thoracic aorta (ascending plus descending) and the carotid arteries were assessed by non-contrast computed tomography (CT) and contrast CT angiography. Results: Osteogenic EPCs OCN+CD34+KDR+ (P = 0.002) and OCN+CD34+ (P = 0.001), together with clinical parameters of age, history of hypertension, systolic blood pressure, serum levels of triglycerides, HbA1c and creatinine, use of leflunomide and brachial-ankle pulse-wave velocity (all P < 0.05), were associated with the clustered presence of aortic and carotid calcification. Multivariable analyses revealed that circulating OCN+CD34+KDR+ (B = 14.4 [95% CI 4.0 to 24.8], P = 0.007) and OCN+CD34+ (B = 9.6 [95% CI 4.9 to 14.3], P < 0.001) remained independently associated with increased aortic calcium load. OCN+CD34+ EPC (B = 0.8 [95% CI 0.1 to 1.5], P = 0.023), but not OCN+CD34+KDR+ EPC (B = 1.2 [95% CI -0.2 to 2.6], P = 0.09), was further independently associated with carotid calcium load. In comparison, conventional early EPC CD34+CD133+KDR+ had no significant association with aortic or carotid calcium load (P = 0.46 and 0.88, respectively). Conclusion: Circulating level of osteogenic EPC is associated with increased vascular aging in terms of calcification of the large arteries in patients with rheumatoid arthritis. The findings may suggest a role of the bone-vascular axis underlying vascular aging in rheumatic diseases. Further research is needed to characterize the mechanistic links and basis of these observations.

Humoral Immunogenicity and Reactogenicity of the Standard ChAdOx1 nCoV-19 Vaccination in Taiwan.

BACKGROUND: The ChAdOx1 nCoV-19 vaccine has been widely administered against SARS-CoV-2 infection; however, data regarding its immunogenicity, reactogenicity, and potential differences in responses among Asian populations remain scarce. METHODS: 270 participants without prior COVID-19 were enrolled to receive ChAdOx1 nCoV-19 vaccination with a prime-boost interval of 8-9 weeks. Their specific SARS-CoV-2 antibodies, neutralizing antibody titers (NT50), platelet counts, and D-dimer levels were analyzed before and after vaccination. RESULTS: The seroconversion rates of anti-RBD and anti-spike IgG at day 28 after a boost vaccination (BD28) were 100% and 95.19%, respectively. Anti-RBD and anti-spike IgG levels were highly correlated (r = 0.7891), which were 172.9 ± 170.4 and 179.3 ± 76.88 BAU/mL at BD28, respectively. The geometric mean concentrations (GMCs) of NT50 for all participants increased to 132.9 IU/mL (95% CI 120.0-147.1) at BD28 and were highly correlated with anti-RBD and anti-spike IgG levels (r = 0.8248 and 0.7474, respectively). Body weight index was statistically significantly associated with anti-RBD IgG levels (p = 0.035), while female recipients had higher anti-spike IgG levels (p = 0.038). The GMCs of NT50 declined with age (p = 0.0163) and were significantly different across age groups (159.7 IU/mL for 20-29 years, 99.4 IU/mL for ≥50 years, p = 0.0026). Injection-site pain, fever, and fatigue were the major reactogenicity, which were more pronounced after prime vaccination and in younger participants (<50 years). Platelet counts decreased and D-dimer levels increased after vaccination but were not clinically relevant. No serious adverse events or deaths were observed. CONCLUSION: The vaccine is well-tolerated and elicited robust humoral immunity against SARS-CoV-2 after standard prime-boost vaccination in Taiwanese recipients.

Characterization and Utility of Remote Interpretation of Visual Field Diagnostic Testing in an Academic Center.

BACKGROUND: The use of remote interpretation of data has risen in neuro-ophthalmology to increase efficiency and maintain social distancing due to the coronavirus disease-19 pandemic. The purpose of this study is to characterize the use and efficiency of remote interpretation of visual fields (VFs) in an academic center and to determine how often the VF interpretation was consistent with the patient's clinical history and imaging at the time of the consult. METHODS: This is a retrospective study at a single academic center that enrolled all patients receiving a remote interpretation of VF from January 1, 2012, through December 31, 2012. Data were collected regarding the referring department, indication for the VF, interpretation of the VF and comparison with any prior VFs, any associated interventions with the VF, and available follow-up VFs. The main outcome measures included 1) characterizing the use of remote VF interpretations and 2) how many remote VF interpretation results were consistent with the referring diagnosis based on the patient's clinical history and imaging. RESULTS: One hundred eighty patients received remote interpretation of VFs. The most frequent referring departments were endocrinology (79; 44%), neurology (51; 28%), and neurosurgery (43; 24%). The VF indications included parasellar lesion (107; 59%), seizure disorder (26; 14%), meningioma (19; 11%), vascular lesion (11; 6%), and others (17; 9%). There were 78 patients (43%) that had an intervention before the VF, whereas 49 (27%) were preoperative VFs. Eighty-seven (48%) of the VFs were interpreted as abnormal. Of all the 180 remote interpretation of VFs, 156 (87%) had VF interpretations that were consistent with the clinical question posed by the referring provider based on clinical history and imaging. Among the other 24 remote VF interpretations (13% of total remote VF interpretations), there was no clear interpretation because of either additional unexpected VF defects (n = 5, 21%), VF defect mismatch (n = 6, 25%), or unreliable VFs (n = 13, 54%). The median wait time for patients receiving remote VF interpretations was 1 day. CONCLUSIONS: Remote interpretation of VFs was most often requested by endocrinology, neurology, and neurosurgery and could be performed very quickly. The most common indications were parasellar lesions, and just less than half of patients receiving remote VF interpretations had a prior intervention. A majority of remote VF interpretations were able to answer the clinical question, given the patient's clinical history and imaging. Remote interpretation of VFs may thus offer referring departments a more efficient method of obtaining VF interpretations than in-office neuro-ophthalmology examinations.