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Low levels of renalase, a flavoprotein released by kidneys, has been linked with cytokine release syndrome and disease severity of viral infections. We sought to, 1) identify traditional and novel predictors of mortality for patients hospitalized with COVID-19; and 2) investigate whether renalase independently predicts mortality. In a retrospective cohort study, clinicopathologic data and blood samples were collected from hospitalized COVID-19 patients. Patients were excluded if

IntroductionIncreasingly, older adults are turning to emergency departments (EDs) to address healthcare needs. To achieve these research demands, infrastructure is needed to both generate evidence of intervention impact and advance the development of implementation science, pragmatic trials evaluation and dissemination of findings from studies addressing the emergency care needs of older adults. The Geriatric Emergency Care Applied Research Network (https://gearnetwork.org) has been created in response to these scientific needs—to build a transdisciplinary infrastructure to support the research that will optimise emergency care for older adults and persons living with dementia.Methods and analysisIn this paper, we describe our approach to developing the GEAR Network infrastructure, the scoping reviews to identify research and clinical gaps and its use of consensus-driven research priorities with a transdisciplinary taskforce of stakeholders that includes patients and care partners. We describe how priority topic areas are ascertained, the process of conducting scoping reviews with integrated academic librarians performing standardised searches and providing quality control on reviews, input and support from the taskforce and conducting a large-scale consensus workshop to prioritise future research topics. The GEAR Network approach provides a framework and systematic approach to develop a research agenda and support research in geriatric emergency care.Ethics and disseminationThis is a systematic review of previously conducted research; accordingly, it does not constitute human subjects research needing ethics review. These reviews will be prepared as manuscripts and submitted for publication to peer-reviewed journals, and the results will be presented at conferences.Open Science Framework registered DOI: 10.17605/OSF.IO/6QRYX, 10.17605/OSF.IO/AKVZ8, 10.17605/OSF.IO/EPVR5, 10.17605/OSF.IO/VXPRS.

To identify research and practice gaps to establish future research priorities to advance the detection of cognitive impairment and dementia in the emergency department (ED).Literature review and consensus-based rankings by a transdisciplinary, stakeholder task force of experts, persons living with dementia, and care partners.Scoping reviews focused on adult ED patients.Two systematic scoping reviews of 7 medical research databases focusing on best tools and approaches for detecting cognitive impairment and dementia in the ED in terms of (1) most accurate and (2) most pragmatic to implement. The results were screened, reviewed, and abstracted for relevant information and presented at the stakeholder consensus conference for discussion and ranked prioritization.We identified a total of 1464 publications and included 45 to review for accurate tools and approaches for detecting cognitive impairment and dementia. Twenty-seven different assessments and instruments have been studied in the ED setting to evaluate cognitive impairment and dementia, with many focusing on sensitivity and specificity of instruments to screen for cognitive impairment. For pragmatic tools, we identified a total of 2166 publications and included 66 in the review. Most extensively studied tools included the Ottawa 3DY and Six-Item Screener (SIS). The SIS was the shortest to administer (1 minute). Instruments with the highest negative predictive value were the SIS (vs MMSE) and the 4 A's Test (vs expert diagnosis). The GEAR 2.0 Advancing Dementia Care Consensus conference ranked research priorities that included the need for more approaches to recognize more effectively and efficiently persons who may be at risk for cognitive impairment and dementia, while balancing the importance of equitable screening, purpose, and consequences of differentiating various forms of cognitive impairment.The scoping review and consensus process identified gaps in clinical care that should be prioritized for research efforts to detect cognitive impairment and dementia in the ED setting. These gaps will be addressed as future GEAR 2.0 research funding priorities.

Introduction Coronary microvascular dysfunction (CMD) may be a manifestation of systemic small vessel disease, including the brain. The prevalence of cognitive impairment in CMD patients is poorly understood. Purpose To assess the prevalence of cognitive impairment in patients with CMD. Methods Between April 2018-March 2020, we enrolled patients with chest discomfort who were admitted to a chest pain observation unit and underwent 3D cardiac positron emission tomography/computed tomography (PET/CT). Exclusions included myocardial infarction, hypertensive urgency, and heart failure. Patients were categorized as 1) Normal: coronary flow reserve (CFR) ≥2.5 without perfusion defect or calcification, 2) Possible CMD: CFR 2–2.5 without perfusion defects or calcification, 3) CMD: CFR Results Of 111 patients consented, 109 patients had complete data for analysis. (Table 1) Mean age was 57 years (± 11), 68% were female, and 49% were non-White. All 11 patients with CMD were females, with a mean age of 59 years (±12). The majority (72%) of CMD patients had cognitive impairment on the MoCA compared to 25% of patients with normal flows (unadjusted OR: 8.00 [95% CI 1.70–37.67]), even after adjustment for age, sex, and race (OR: 37.23 (95% CI 2.01–677.05). MoCA scores did not differ significantly between the normal and the CAD/CALC group (unadjusted OR: 0.95 [95% CI 0.30–3.070]), or the possible CMD group (1.44 [95% CI 0.50–4.14]). Additionally, non-White patients were more likely to demonstrate cognitive impairment on MoCA than White patients (OR: 9.47 [95% CI 3.48–25.81]). There was no significant nonparametric correlation between CFR and the MoCA score (r=0.05, p=0.6). Conclusion Patients with CMD are more likely to have cognitive impairment, supporting the need to further investigate the heart-brain connection in systemic small vessel disease. FUNDunding Acknowledgement Type of funding sources: None.

Cardiac rehabilitation (CR) improves major adverse cardiac outcomes in patients recovering from myocardial infarction. CR influences outcomes through attenuation of cardiac risk factors, lifestyle changes, and biological effects on endothelial function. The clinical profile and sex-specific outcomes with CR after coronary artery bypass grafting (CABG) is less well defined.This retrospective cohort study of consecutive patients undergoing elective or urgent CABG was performed between 2014 and 2016 at a single site. Patients requiring concomitant procedures were excluded. Patients received referral to a 12-week, 36-session CR program standardized through the health care system and tracked via electronic health records. Clinical data and complications during hospitalization were abstracted from Society of Thoracic Surgeons (STS) registry and matched with 12-months outcomes from electronic health records. Primary composite outcomes were mortality and STS-defined complications within 12 months after CABG. Kaplan-Meier plots for mortality were generated from conditional 6-month survival data.Of 756 patients undergoing CABG, 420 met the eligibility criteria (mean age, 66 years). Women (18%) had a similar cardiac risk profile to men except for a higher hemoglobin ASex differences exist with CR after CABG. Future studies should confirm these findings in larger cohorts and corroborate the effect on endothelial function and other biological markers.

BACKGROUND: We assessed the utility of EndoPAT, a device that measures reactive hyperemia index (RHI) as a clinical screening tool for identifying low coronary flow reserve (CFR). Distinguishing normal from low CFR aids assessment for coronary microvascular dysfunction (CMD) or large vessel coronary artery disease (CAD). METHODS: From June 2014-May 2019, in a convenience sample, we measured RHI in adults undergoing clinically indicated cardiac Rubidium-82 positron emission tomography/computed tomography (PET/CT) at a single center. Exclusion criteria were inability to consent, lack of English proficiency, and physical limitation. We defined low RHI as 0.05). Conversely, mean augmentation index, a measure of arterial stiffness, was higher with low RHI (p=0.005) but not CFR (p=0.625). RHI was lower in patients we identified as CMD (low CFR, no perfusion defect and calcium score of 0) (1.88 versus 2.21; p=0.35) although we were underpowered (n=12) to meet statistical significance. CONCLUSIONS: Peripheral RHI is insufficient as a clinical screening tool for low CFR as measured by cardiac PET/CT. Differences in vascular pathology assessed by each method may explain this finding.

Although microvascular dysfunction (MVD) has been well characterized in individual organs as different disease entities, clinical evidence is mounting in support of an underlying systemic process. To address this hypothesis, we systematically searched PubMed and Medline for studies in adults published between 2014 and 2019 that measured blood biomarkers of MVD in three vital organs i.e. brain, heart, and the kidney. Of the 9706 unique articles 321 met the criteria, reporting 49 biomarkers of which 16 were common to the three organs. Endothelial dysfunction, inflammation including reactive oxidation, immune activation, and coagulation were the commonly recognized pathways. Triglyceride, C-reactive protein, Cystatin C, homocysteine, uric acid, IL-6, NT-proBNP, thrombomodulin, von Willebrand Factor, and uric acid were increased in MVD of all three organs. In contrast, vitamin D was decreased. Adiponectin, asymmetric dimethylarginine, total cholesterol, high-density and low-density cholesterol were found to be variably increased or decreased in studies. We review the pathways underlying MVD in the three organs and summarize evidence supporting its systemic nature. This scoping review informs clinicians and researchers in the multi-system manifestation of MVD. Future work should focus on longitudinal investigations to evaluate the multi-system involvement of this disease.

Pulmonary hypertension (PH) is a condition associated with high morbidity and mortality. Patients with PH who require critical care usually have severe right ventricular (RV) dysfunction. Although different groups of PH have different etiologies, pulmonary vascular dysfunction is common in these groups. PH can lead to increased pulmonary artery pressure, which can ultimately cause RV failure. Clinicians should be familiar with the presentations of this disease and diagnostic tools. The contributing factors, if present (e.g., sepsis), and coexisting conditions (e.g., arrhythmias) should be identified and addressed accordingly. The preload should be optimized by fluid administration, diuretics, and dialysis, if necessary. On the other hand, the RV afterload should be reduced to improve the RV function with pulmonary vasodilators, such as prostacyclins, inhaled nitric oxide, and phosphodiesterase type 5 inhibitors, especially in group 1 PH. Inotropes are also used to improve RV contractility, and if inadequate, use of ventricular assist devices and extracorporeal life support should be considered in suitable candidates. Moreover, vasopressors should be used to maintain systemic blood pressure, albeit cautiously, as they increase the RV afterload. Measures should be also taken to ensure adequate oxygenation. However, mechanical ventilation is avoided in RV failure. In this study, we reviewed the pathophysiology, manifestations, diagnosis, monitoring, and management strategies of PH, especially in intensive care units.

INTRODUCTION: Coronary microvascular dysfunction (CMD) is a complex disease, difficult to diagnose and often requires advanced imaging. We used mass spectrometry (MS) using discovery approach to search for serum proteins as potential biomarkers in these patients. METHODS: We used serum samples from 10 patients with CMD and 10 with normal coronary flow reserve (CFR) admitted to an observation unit where acute myocardial infarction was excluded. We identified CMD using (82)Rb positron emission tomography/computed tomography as CFR < 2 in response to regadenoson, in the absence of coronary calcification or regional perfusion defects. We used MS to identify potential protein biomarkers that were differentially expressed in cases and controls. RESULTS: Baseline characteristics were not different between cases and controls, except for beta-blocker use and which was higher in cases, and mean (SD) CFR which was lower in cases [1.19 (0.23) and 2.78 (0.78) in cases and controls respectively; p < 0.01]. We identified 5345 peptides corresponding to 209 proteins, and identified 197 proteins by peptides with suitable properties to infer relative quantitation values. While the calculated values for some proteins (e.g. vascular cell adhesion molecule-1, apolipoprotein C and Von Willebrand Factor) indicate fold-differences between groups, these are most likely a result of high values in only 1–2 patients and are not statistically significant. CONCLUSION: Mass spectrometry using discovery approach may not be an adequate method for quantitative assessment of serum proteins in CMD patients. Future MS studies should evaluate other approaches including tissue samples or serial measurements.

Background and Objectives. Cataract is the leading cause of blindness worldwide. Although surgery is now considered the most successful cure, the development of alternative treatments is needed due to postsurgical complications. Oxidative stress in the lens is considered to be the most crucial factor in the formation of cataracts. Therefore, the effects of the hydroalcoholic extract of Asparagus officinalis L, a traditional antioxidative plant, on cataract formation of sodium selenite were evaluated. Materials and Methods. Neonatal rats received a single dose of sodium selenite as an intraperitoneal injection (30 μmol/kg) on day 10 postnatal to induce cataract. Animals were then posttreated with various oral solutions of A. officinalis extract at 200 mg/kg or 400 mg/kg once daily on days 10–16 postnatal. Cataract was evaluated by slit-lamp, and lens opacification was analyzed in each group 24 hours after the last treatment at day seven postadministration of the extracts or vehicle. The total protein concentration of lenses, glutathione reductase activity as the glutathione antioxidant capacity, and malondialdehyde content as a marker of lipid peroxidation were further assessed in removed rat lenses on day 30 postnatal. Results. All lenses in the healthy and control plant groups were clear. Sodium selenite significantly increased cataract grade (2.8 ± 0.2) when compared to the healthy group p = 0.001 . However, cataract grades were decreased considerably as 1.9 ± 0.72 and 1.5 ± 0.85 in groups that received 200 mg/kg and 400 mg/kg oral extract of A. officinalis, respectively. A. officinalis extract also restored all abnormalities of biochemical markers induced by sodium selenite. Conclusion. Our data suggest that A. officinalis could be a promising candidate as a safe alternative treatment in cataracts upon further clinical trials. This effect is probably associated with the antioxidant activity of A. officinalis.

Numerous studies have demonstrated that the pigmentation of iris and around the eyelid is a common side effect of latanoprost, a prostaglandin F2alpha analogue used in the treatment of glaucoma. Hence, the authors decided to study the effectiveness of topical latanoprost on vitiligo patches around the eyelid. In this randomized, double-blind, clinical trial study, 31 patients with vitiligo vulgaris and focal vitiligo involving the eyelids were evaluated. Patients were randomly divided into two groups. First group received topical latanoprost gel twice daily for 12 weeks, whereas the second group received placebo with the same protocol. To evaluate severity of the disease the VIDA rating system was used. Serial photos of the patches were taken to compare and evaluate the repigmentation percentage of the patches. The patients in both groups had almost similar VIDA score (p > .05). First group showed improved pigmentation, whereas participants in the second group did not show any improvement in the pigmentation. The group treated with latanoprost showed significant reduction in the symptoms of the disease, whereas those treated with placebo did not show any alteration (p > .05). No significant complications were observed in either groups. Latanoprost proved effective in treating vitiligo disease involving eyelids.

Introduction: The incidence and details of sudden cardiac arrest (SCA) during exercise in the general population are not well described. We describe a cohort ages 2-85 who experienced an SCA within ≤ 1 hour of moderate to vigorous activity in 4 metropolitan areas of British Columbia, Canada. Methods: We reviewed prehospital records of consecutive out-of-hospital cardiac arrests (OHCAs) in the provincial BC OHCA Registry from June 17 2017 to August 16 2018. We included non-traumatic OHCAs treated by EMS occurring within ≤ 1 hour of exercise. We defined SCA as an OHCA of no obvious cause, witnessed/unwitnessed, survived/died. We assigned an estimated metabolic equivalent (MET) score to each type of physical activity. We defined moderate exercise as a MET score of 3-5.9 and vigorous as ≥6. Results: A total of 2674 OHCAs occurred during the study period of which 56 SCAs (2.1%) occurred within ≤1 hour of participation in 23 types of exercise (Figure 1). The incidence of SCA during exercise was 1.45 (95% CI 1.10-1.88) per 100,000 population. The median age was 56.5 [IQR 45-69] and 87.5% (49/56) were male. Most exercise related SCAs occurred in public (49/56 87.5%), 83.3% (45/54) were bystander witnessed and 85% (46/54) received bystander CPR. Over 70% (40/56) had a shockable rhythm. The survival rate was 55.4% (31/56). Half of the SCAs collapsed during exercise (49.1%; 26/53) while the other half collapsed within ≤1 hour after exercising (51%; 27/53). Symptom data were available in 46% of patients (23/50) with most experiencing chest pain, dizziness, feeling unwell or seizure just prior to collapse. Conclusions: SCAs during exercise are rare and frequently occur in a public location. Survival is high and may be related to witnessed and public location status. Equal numbers of SCAs collapsed during or ≤ 1 hour of exercising and symptoms were present in almost half. Future research is needed to determine what factors could predict those at highest risk for SCA in order to prevent future events.

Beta thalassemia (β-thalassemia) is a hereditary disease caused by defective globin synthesis and can be classified into three categories of minor (β-TMi), intermedia (β-TI), and major (β-TM) thalassemia. The aim of our study is to investigate the effects of β-thalassemia and its treatment methods on different parts of the eye and how early-diagnostic methods of ocular complications in this disorder would prevent further ocular complications in these patients by immediate treatment and diet change. We developed a search strategy using a combination of the words Beta thalassemia, Ocular abnormalities, Iron overload, chelation therapy to identify all articles from PubMed, Web of Science, Scopus, and Google Scholar up to December 2018. To find more articles and to ensure that databases were thoroughly searched, the reference lists of selected articles were also reviewed. Complications such as retinopathy, crystalline lens opacification, color vision deficiency, nyctalopia, depressed visual field, reduced visual acuity, reduced contrast sensitivity, amplitude reduction in a-wave and b-wave in Electroretinography (ERG), and decrease in the Arden ratio in Electrooculography (EOG) have all been reported in β-thalassemia patients undergoing chelation therapy. Ocular problems due to β-thalassemia may be a result of anemia, iron overload in the body tissue, side effects of iron chelators, and the complications of orbital bone marrow expansion.