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Daniel Lamoureux,1 David T Wong,2,3 Tina Felfeli2,4 1Northern Ontario School of Medicine University, Thunder Bay, ON, Canada; 2Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, ON, Canada; 3Department of Ophthalmology, St. Michael’s Hospital, Unity Health Toronto, Toronto, ON, Canada; 4The Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, CanadaCorrespondence: Tina Felfeli, University Health Network, Toronto General Hospital, Eaton Building, 10th Floor, Toronto, ON M5G 2C4, Canada, Tel +1 647 678 1634, Fax +1 416 340 3459, Email tina.felfeli@mail.utoronto.caPurpose: Certain factors such as instrumental and sample processing errors may contribute to variability of ocular biofluid samples when they are run as replicates with multiplex assays. There is a paucity of literature on the variability of replicates in multiplex assays. This study aims to evaluate whether there is significant variability in replicate analyses of multiplex assays.Methods: A total of 152 human ocular biofluid samples (51 aqueous humor and 101 vitreous) were collected and assayed for 27 cytokine biomarker concentrations (pg/mL). Samples were evaluated as replicates (duplicate analysis) at four different time points. Statistical methods including paired samples t-test, 3-way ANOVA, intraclass correlation coefficient (ICC; < 0.5– 0.75=poor-moderate, 0.75-> 0.90 =good-excellent reliability), and coefficients of variation (CV) were employed to evaluate for statistical significance, with Bonferroni corrected P=0.002.Results: Among the 4104 biomarker replicate assays for aqueous humor and vitreous, two analytes (PDGF-BB and IL-7) had a statistically significant difference between the sampled concentrations of the replicates in vitreous samples (mean (diff)=2.05, P< 0.001, mean (diff)=1.56, P< 0.001, respectively). Majority of the ICC values fell within the good-excellent range (86% of samples) with a minority falling in the poor-moderate range (14% of samples). More variability was noted in the vitreous humour, with five analytes (IL-2, IL-10, IL-12(p70), IL-13, IL-17) demonstrating an average ICC of less than 0.5. The CV calculated for each set of replicates suggested that 93% of replicates had an acceptable level of quantitative assay variability (CV< 20%).Conclusion: This study demonstrates that the analysis of most biomarkers in ocular fluids may not require the use of replicates. However, certain analytes such as PDGF-BB and IL-7 may require the use of replicates to ensure reliable results. Caution should be taken when applying these findings to other laboratory settings as our study was conducted by an experienced technician using a standardized protocol. In less standardized settings, replicates may be required in order to ensure accuracy of results. These findings may guide researchers with the design of their studies on ophthalmic biomarker analysis.Keywords: cytokines, aqueous, vitreous, biomarkers, assay

Polymer electrolyte membranes with bicontinuous microphases comprising soft hydrated domains and mechanically robust hydrophobic domains are used in a wide range of electrochemical devices including fuel cells and electrolyzers. The self-assembly, water uptake, and proton conductivity of model block copolymer electrolytes with semicrystalline hydrophobic blocks were investigated. A series of sulfonated polystyrene-block-polyethylene (PSS-PE) copolymers were synthesized to probe the interplay between crystallization, morphology, hydration, and proton transport. In block copolymer systems with amorphous hydrophobic blocks, it has been shown that higher water update and proton conductivity are obtained in low molecular weight systems. However, crystallization is known to disrupt the self-assembly of low molecular weight block copolymers. We found that this disruption results in lower water uptake and proton conductivity. Increasing molecular weight results in less morphological disruption and improvement in performance. © 2014 American Chemical Society.

BioMart Central Portal is a first of its kind, community-driven effort to provide unified access to dozens of biological databases spanning genomics, proteomics, model organisms, cancer data, ontology information and more. Anybody can contribute an independently maintained resource to the Central Portal, allowing it to be exposed to and shared with the research community, and linking it with the other resources in the portal. Users can take advantage of the common interface to quickly utilize different sources without learning a new system for each. The system also simplifies cross-database searches that might otherwise require several complicated steps. Several integrated tools streamline common tasks, such as converting between ID formats and retrieving sequences. The combination of a wide variety of databases, an easy-to-use interface, robust programmatic access and the array of tools make Central Portal a one-stop shop for biological data querying. Here, we describe the structure of Central Portal and show example queries to demonstrate its capabilities.

Sinny Delacroix,1,2 Ramesh G Chokka,1,3 Adam J Nelson,1,2 Dennis T Wong,4 Samuel Sidharta,1,2 Stephen M Pederson,5 Adil Rajwani,1,2 Joanne Nimmo,1,2 Karen S Teo,1,2 Stephen G Worthley1,2 1Cardiovascular Research Centre, Royal Adelaide Hospital, 2Department of Medicine, University of Adelaide, Adelaide, SA, 3South Australian Health and Medical Research Institute, University of Adelaide, Adelaide, SA, 4Monash Medical Centre, Clayton, VIC, 5Bioinformatics Hub, School of Biological Sciences, University of Adelaide, Adelaide, SA, Australia Aim: Preclinical studies have demonstrated improvements in renal blood flow after renal sympathetic denervation (RSDN); however, such effects are yet to be confirmed in patients with resistant hypertension. Herein, we assessed the effects of RSDN on renal artery blood flow and diameter at multiple time points post-RSDN. Methods and results: Patients (n=11) with systolic blood pressures ≥160 mmHg despite taking three or more antihypertensive medications at maximum tolerated dose were recruited into this single-center, prospective, non-blinded study. Magnetic resonance imaging indices included renal blood flow and renal artery diameters at baseline, 1 month and 6 months. In addition to significant decreases in blood pressures (p

In this 2-part review series, the current uses of saliva as a diagnostic fluid are reviewed, first with a focus on known measurements of systemic conditions. In Part 2, the role of saliva to measure bone turnover with a special emphasis on osteoporosis will be discussed. [ABSTRACT FROM AUTHOR]

Background: A higher oropharyngeal leak pressure (OLP) is a marker of efficacy and safety when using laryngeal mask airway devices. The new disposable laryngeal mask airway (LMA™) Supreme™ has lower OLP compared with the LMA ProSeal™. Increased intracuff pressure of laryngeal mask airway devices may improve OLP but may result in more postoperative pharyngolaryngeal adverse events. This study was designed to compare the OLP of the LMA Supreme at varying intracuff pressures.Methods: One hundred and twenty-three patients were divided randomly into three groups. General anesthesia was standardized using a propofol-fentanyl induction and desflurane in air-oxygen for maintenance. Intracuff pressures of the LMA Supreme were adjusted to 80 cm H(2)O, 60 cm H(2)O, and 40 cm H(2)O according to group allocation. The primary outcome was OLP. Secondary outcomes included postoperative pharyngolaryngeal adverse events and the satisfaction scores of patients and anesthesiologists. The OLP was compared amongst groups using analysis of variance with Bonferroni correction. All reported P values are two-sided.Results: The OLP with an intracuff pressure of 80 cm H(2)O was significantly higher compared with 60 cm H(2)O and 40 cm H(2)O (26 [6] vs 20 [6] vs 18 [5] cm H(2)O, respectively; P < 0.001). The incidence of postoperative pharyngolaryngeal adverse events (P = 0.6), patient satisfaction scores (P = 0.2), and anesthesiologist satisfaction scores (P = 0.8) were comparable amongst the three groups.Conclusion: An intracuff pressure of 80 cm H(2)O with the LMA Supreme is associated with a higher OLP compared with 60 cm H(2)O or 40 cm H(2)O without a greater incidence of postoperative pharyngolaryngeal adverse events. For a superior glottic seal when using the LMA Supreme, we recommend intracuff pressures up to 80 cm H(2)O. [ABSTRACT FROM AUTHOR]

The protein compositions, or the proteomes, found in human salivary and plasma fluids are compared. From recent experimental work by many laboratories, a catalogue of 2290 proteins found in whole saliva has been compiled. This list of salivary proteins is compared with the 2698 proteins found in plasma. Approximately 27% of the whole-saliva proteins are found in plasma. However, despite this apparent low degree of overlap, the distribution found across Gene Ontological categories, such as molecular function, biological processes, and cellular components, shows significant similarities. Moreover, nearly 40% of the proteins that have been suggested to be candidate markers for diseases such as cancer, cardiovascular disease, and stroke can be found in whole saliva. These comparisons and correlations should encourage researchers to consider the use of saliva to discover new protein markers of disease and as a diagnostic non-proximal fluid to detect early signs of disease throughout the body. [ABSTRACT FROM AUTHOR]

Background and Objective: The Supreme laryngeal mask airway (LMA) is a new single-use polyvinyl chloride supraglottic device that combines the functionality of the ProSeal and Fastrach airways. High oropharyngeal leak pressures are important as they indicate airway protection, feasibility of positive pressure ventilation and likelihood of successful LMA placement. The oropharyngeal leak pressure of the LMA Supreme is not well established versus the LMA ProSeal. This study was designed to compare the safety and efficacy of the LMA Supreme versus the LMA ProSeal in elective ambulatory procedures.Method: Hospital ethics board approval was obtained. One hundred and five patients were consented and randomly allocated to LMA Supreme or ProSeal groups. Anaesthesia was induced with intravenous propofol 2-3 mg kg(-1) and fentanyl 1-2 microg kg(-1) and maintained with desflurane in an air-oxygen mixture. Anaesthesiologists with more than 5 years of experience performed all of the LMA insertions. Manometry was used to standardize intracuff pressure at 60 cmH2O. The primary outcome was the oropharyngeal leak pressure. Secondary outcomes were the time and number of attempts for insertion, ease of insertion and the anaesthesiologist's satisfaction score of the airway device. The success on first attempt insertion was measured. Patients were interviewed postoperatively for any pharyngolaryngeal adverse events.Results: A total of 99 patients were analysed for the primary outcome. The baseline demographic data for both groups were comparable. The mean oropharyngeal leak pressure with the LMA Supreme was 21 +/- 5 cmH2O (95% confidence interval 20-22). This was significantly lower than that of the LMA ProSeal, 25 +/- 6 cmH2O (95% confidence interval 23-27; P<0.001). The success rate of the first attempt insertion was higher for the LMA Supreme than for the LMA ProSeal (98 and 88%, respectively; P=0.04). There was no difference in the median time taken for insertion with the LMA Supreme versus the LMA ProSeal: 26 s (interquartile range 23-45) versus 30 s (interquartile range 20-38), respectively (P=0.16). The ease of insertion, postoperative pharyngolaryngeal adverse events, patient satisfaction scores and anaesthesiologist's satisfaction scores were comparable in both groups. There were no complications of aspiration or nerve injuries.Conclusion: The LMA Supreme has lower oropharyngeal leak pressures than the LMA ProSeal. The success of the first attempt insertion was higher for the LMA Supreme. The LMA Supreme is a safe, efficacious and easy-to-use disposable supraglottic airway device in elective ambulatory procedures. The higher rate of success on first attempt insertion may make it more suitable as an airway rescue device. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To identify key target genes and activated signaling pathways associated with the pathogenesis of Sjögren's syndrome (SS) by conducting a systems analysis of parotid glands manifesting primary SS or primary SS/mucosa-associated lymphoid tissue (MALT) lymphoma phenotypes. METHODS: A systems biology approach was used to analyze parotid gland tissue samples obtained from patients with primary SS, patients with primary SS/MALT lymphoma, and subjects without primary SS (non-primary SS controls). The tissue samples were assessed concurrently by gene-expression microarray profiling and proteomics analysis, followed by weighted gene-coexpression network analysis. RESULTS: Gene-coexpression modules related to primary SS and primary SS/MALT lymphoma were significantly enriched with genes known to be involved in the immune/defense response, apoptosis, cell signaling, gene regulation, and oxidative stress. Detailed functional pathway analyses indicated that primary SS-associated modules were enriched with genes involved in proteasome degradation, apoptosis, signal peptides of the class I major histocompatibility complex (MHC), complement activation, cell growth and death, and integrin-mediated cell adhesion, while primary SS/MALT lymphoma-associated modules were enriched with genes involved in translation, ribosome biogenesis and assembly, proteasome degradation, class I MHC signal peptides, the G13 signaling pathway, complement activation, and integrin-mediated cell adhesion. Combined analyses of gene expression and proteomics data implicated 6 highly connected 'hub' genes for distinguishing primary SS from non-primary SS, and 8 hub genes for distinguishing primary SS/MALT lymphoma from primary SS. CONCLUSION: Systems biology analyses of the parotid glands from patients with primary SS and those with primary SS/MALT lymphoma revealed pathways and molecular targets associated with disease pathogenesis. The identified gene modules/pathways provide further insights into the molecular mechanisms of primary SS and primary SS/MALT lymphoma. The identified disease-hub genes represent promising targets for therapeutic intervention, diagnosis, and prognosis. [ABSTRACT FROM AUTHOR]

Purpose: To summarize the published literature related to two, new supraglottic airways (SGAs): the Cobra Perilaryngeal Airway (CobraPLA) and the Streamlined Liner of Pharyngeal Airway (SLIPA).Source: We identified original articles, through searches on Medline and PubMed, using the keywords 'Cobra', 'CobraPLA', 'Cobra-PLA', 'PLA', and 'SLIPA'.Principal Findings: Searches identified 28 publications evaluating the CobraPLA, six of which were randomized, controlled trials. Five publications evaluated the SLIPA, two of which were randomized, controlled trials. Studies compared the CobraPLA with a number of SGAs, in regards to both efficacy and safety. While the CobraPLA is comparable to the laryngeal mask airway (LMA) Classic, with respect to insertion times and the incidence and severity of sore throat, the CobraPLA is superior, with respect to airway sealing pressure, and has been used successfully in patients with limited mouth opening and limited head extension. Insertion times, first insertion success rates, recovery times, and hemodynamic responses, associated with insertion of the SLIPA, are similar to those of the LMA Proseal. Although the SLIPA has a unique reservoir chamber to contain regurgitated fluid, the extent of its protection against pulmonary aspiration has not been established in the clinical setting.Conclusion: Both the CobraPLA and the SLIPA are intended for use during short procedures under general anesthesia, and have comparable efficacy and complication rates in comparison to the LMA Classic. Both airways may be considered as primary SGA devices, and the CobraPLA may be also be used as a rescue airway device. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To identify a panel of protein and messenger RNA (mRNA) biomarkers in human whole saliva (WS) that may be used in the detection of primary Sjögren's syndrome (SS). METHODS: Mass spectrometry and expression microarray profiling were used to identify candidate protein and mRNA biomarkers of primary SS in WS samples. Validation of the discovered mRNA and protein biomarkers was also demonstrated using real-time quantitative polymerase chain reaction and immunoblotting techniques. RESULTS: Sixteen WS proteins were found to be down-regulated and 25 WS proteins were found to be up-regulated in primary SS patients compared with matched healthy control subjects. These proteins reflected the damage of glandular cells and inflammation of the oral cavity system in patients with primary SS. In addition, 16 WS peptides (10 up-regulated and 6 down-regulated in primary SS) were found at significantly different levels (P < 0.05) in primary SS patients and controls. Using stringent criteria (3-fold change; P < 0.0005), 27 mRNA in saliva samples were found to be significantly up-regulated in the primary SS patients. Strikingly, 19 of 27 genes that were found to be overexpressed were interferon-inducible or were related to lymphocyte filtration and antigen presentation known to be involved in the pathogenesis of primary SS. CONCLUSION: Our preliminary study has indicated that WS from patients with primary SS contains molecular signatures that reflect damaged glandular cells and an activated immune response in this autoimmune disease. These candidate proteomic and genomic biomarkers may improve the clinical detection of primary SS once they have been further validated. We also found that WS contains more informative proteins, peptides, and mRNA, as compared with gland-specific saliva, that can be used in generating candidate biomarkers for the detection of primary SS. [ABSTRACT FROM AUTHOR]

BACKGROUND: Adenosine stress cardiovascular magnetic resonance (CMR) has been proven an effective tool in detection of reversible ischemia. Limited evidence is available regarding its accuracy in the setting of acute coronary syndromes, particularly in evaluating the significance of non-culprit vessel ischaemia. Adenosine stress CMR and recent advances in semi-quantitative image analysis may prove effective in this area. We sought to determine the diagnostic accuracy of semi-quantitative versus visual assessment of adenosine stress CMR in detecting ischemia in non-culprit territory vessels early after primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI). METHODS: Patients were prospectively enrolled in a CMR imaging protocol with rest and adenosine stress perfusion, viability and cardiac functional assessment 3 days after successful primary-PCI for STEMI. Three short axis slices each divided into 6 segments on first pass adenosine perfusion were visually and semi-quantitatively analysed. Diagnostic accuracy of both methods was compared with non-culprit territory vessels utilising quantitative coronary angiography (QCA) with significant stenosis defined as ?70%. RESULTS: Fifty patients (age 59 ± 12 years) admitted with STEMI were evaluated. All subjects tolerated the adenosine stress CMR imaging protocol with no significant complications. The cohort consisted of 41% anterior and 59% non anterior infarctions. There were a total of 100 non-culprit territory vessels, identified on QCA. The diagnostic accuracy of semi-quantitative analysis was 96% with sensitivity of 99%, specificity of 67%, positive predictive value (PPV) of 97% and negative predictive value (NPV) of 86%. Visual analysis had a diagnostic accuracy of 93% with sensitivity of 96%, specificity of 50%, PPV of 97% and NPV of 43%. CONCLUSION: Adenosine stress CMR allows accurate detection of non-culprit territory stenosis in patients successfully treated with primary-PCI post STEMI. Semi-quantitative analysis may be required for improved accuracy. Larger studies are however required to demonstrate that early detection of non-culprit vessel ischemia in the post STEMI setting provides a meaningful test to guide clinical decision making and ultimately improved patient outcomes. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the association between baseline clinical characteristics of patients with diabetic macular edema (DME) and quantitative intravenous fluorescein angiography (IVFA) parameters., Methods: Consecutive patients with DME presenting with a central macular thickness (CMT) >310 μm were recruited from 2017-2023. Ultra-widefield IVFA images were analyzed with the RETICAD algorithm to extract quantitative measures of blood-retinal barrier (BRB) permeability, retinal perfusion, and blood flow. Univariable and multivariable regression models were used to investigate associations between IVFA parameters and baseline best-corrected visual acuity (BCVA), CMT, and macular volume., Results: The study population consisted of 56 eyes with DME, and seven eyes from healthy controls. In our multivariable analysis, BRB permeability measured in the central and peripheral retina was significantly associated with BCVA (p=0.003 and 0.002, respectively) and macular volume (p=0.025 and 0.045, respectively). Both central and peripheral BRB permeability were significantly higher in DME eyes relative to healthy controls (p<0.001)., Conclusion: Increased BRB permeability measured on IVFA in DME eyes was associated with a greater baseline macular volume and worse BCVA, suggesting its potential in providing an objective assessment of disease severity. Future research should explore the clinical utility of quantitative IVFA measurements in diverse patient populations.

Purpose: To assess long-term redetachment rates of the Pneumatic Retinopexy versus Vitrectomy for the Management of Primary Rhegmatogenous Retinal Detachment Outcomes Randomized Trial (PIVOT)., Design: Randomized controlled trial., Subjects: PIVOT trial participants., Methods: This study was performed at St. Michael's Hospital, Unity Health Toronto, Toronto, Canada. PIVOT trial participants who had undergone either pneumatic retinopexy (PnR) or pars plana vitrectomy (PPV) for rhegmatogenous retinal detachment (RRD) repair with a minimum follow-up of 2 years were assessed for long-term redetachment by chart review or telephone interview. The latter was the only accepted method for those with <2 years of follow-up. Patients were only eligible if no reintervention to reattach the retina was performed within the first year of the initial procedure., Main Outcome Measures: Long-term redetachment rates for PnR vs. PPV after RRD repair., Results: Sixty-one participants who underwent PPV and 62 who underwent PnR were analyzed. The long-term redetachment rates were 0% and 1.61% (1/62) in the PPV and PnR groups, respectively (P = 0.32). The mean follow-up duration in years was 5.43 ± 3.60 vs. 5.51 ± 3.03 in the PPV and PnR groups, respectively., Conclusions: There was no statistically significant difference in long-term redetachment rates for PnR vs. PPV. Both procedures are durable treatment options for RRD over an extended period, rarely requiring additional intervention for redetachment., Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Dual inhibition of the angiopoietin (Ang)/Tie and vascular endothelial growth factor (VEGF) signalling pathways in patients with retinal diseases, such as neovascular age-related macular degeneration (nAMD) and diabetic macular oedema (DME), may induce greater vascular stability and contribute to increased treatment efficacy and durability compared with treatments that only target the VEGF pathway. Faricimab, a bispecific intravitreal agent that inhibits both VEGF and Ang-2, is the first injectable ophthalmic drug to achieve treatment intervals of up to 16 weeks in Phase 3 studies for nAMD and DME while exhibiting improvements in visual acuity and retinal thickness. Data from real-world studies have supported the safety, visual and anatomic benefits and durability of faricimab, even in patients who were previously treated with other intravitreal agents. These evidence-based expert recommendations from a panel of retina specialists consolidate current evidence with clinical experience for the optimal use of faricimab in patients with nAMD or DME, with a focus on switching from an anti-VEGF agent to faricimab., Competing Interests: Competing interests: DTW has received consulting fees from AbbVie, Alcon, Apellis, Astellas, Bausch Health, Bayer, Biogen, Hoffmann-La Roche, Novartis, Regeneron, Ripple Therapeutics and Zeiss and has received grants/research support from Bayer, Hoffmann-La Roche and Novartis. SA has been a consultant for Hoffmann-La Roche, Bayer, Novartis and Apobiologix and a speaker for Hoffmann-La Roche. DM has been an advisor for Alcon, Apellis, Bayer, Hoffmann-La Roche, Novartis, Novo Nordisk and Preceyes and has received research support from Alcon, Apellis, Bayer, Ionis, Janssen, Opthea, RegenXBio, Preceyes and Hoffmann-La Roche. SS has been a consultant to Novartis, Bayer, Biogen and Hoffman-La Roche and has received research funding from Novartis and Bayer. DY has received honoraria from Hoffmann-La Roche, Bayer, Novartis and Apellis and has received research grants from Hoffmann-La Roche and Alimera Sciences., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Hallux valgus recurrence after traditional open bunion surgery is a notable concern. New minimally invasive bunion surgery (MIBS) offers a promising new revision option for those with recurrent hallux valgus. This innovative approach signifies a noteworthy departure from traditional open surgical methods by minimizing tissue damage, allowing immediate weight bearing, and providing improved patient satisfaction outcomes. This article provides is insights into this emerging method, case examples, and key surgical treatment pearls for treating the recurrent bunion with MIBS. As more surgeons gain MIBS experience, this approach will likely become the gold standard revision method for revisions., Competing Interests: Disclosure Consultant for Voom Medical Devices, Inc., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To compare the efficacy of brolucizumab and aflibercept treatment in reducing the maximum thickness of pigment epithelial detachments (PEDs) and sub-retinal pigment epithelium (sub-RPE) fluid in patients with neovascular age-related macular degeneration in the HAWK and HARRIER studies., Design: HAWK and HARRIER were 96-week, prospective, randomized, double-masked, controlled, multicenter studies., Participants: A total of 1775 patients across 11 countries were included in the HAWK study, and 1048 patients across 29 countries were included in the HARRIER study., Intervention: After 3 monthly loading doses, brolucizumab-treated eyes received injections every 12 weeks or every 8 weeks if disease activity (DA) was detected. Aflibercept-treated eyes received fixed 8-week dosing., Main Outcome Measures: Maximum thickness of PEDs and sub-RPE fluid across the macula were assessed at baseline through week 96 in the brolucizumab- and aflibercept-treated patients and in the patient subgroups with DA at week 16 (matched in terms of injection number and treatment interval)., Results: At week 96, there were greater mean percentage reductions from baseline in maximum thickness of both PEDs and sub-RPE fluid in brolucizumab-treated patients vs. aflibercept-treated patients (PED: 19.7% [n = 336] vs. 11.9% [n = 335] in HAWK; 29.5% [n = 364] vs. 18.3% [n = 361] in HARRIER. Sub-RPE fluid: 75.4% vs. 57.3% in HAWK; 86.0% vs. 76.3% in HARRIER). A similar trend in mean percentage reductions was observed in patients with DA at week 16., Conclusions: This analysis shows that brolucizumab achieved greater reductions in PEDs and sub-RPE fluid thickness than aflibercept in HAWK and HARRIER., Trial Registration: ClinicalTrials.gov Identifiers: NCT02307682 (HAWK) and NCT02434328 (HARRIER)., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Introduction: Neovascular age-related macular degeneration is a global public-health concern, associated with a considerable burden to individuals, healthcare systems, and society. The objective of this study was to understand different perspectives on the challenges associated with the clinical management of neovascular age-related macular degeneration, which could elucidate measures to comprehensively improve clinical care and outcomes., Methods: A survey was carried out of patients with neovascular age-related macular degeneration, their providers, and clinic staff in 77 clinics across 24 countries on six continents, from a diverse range of healthcare systems, settings, and reimbursement models. Surveys comprised a series of single/multiple-response questions completed anonymously. Data gathered included patient personal characteristics, appointment attendance challenges, treatment experiences, and opportunities to improve support. Provider and clinic staff surveys asked similar questions about their perspectives; clinic characteristics were also captured., Results: There were 6425 responses; 4558 patients with neovascular age-related macular degeneration, 659 providers, and 1208 clinic staff. Challenges identified included concern about patient burden to family/friends, high frequency of treatment, difficulties in traveling to appointments, long waiting times, and insufficient comprehension of neovascular age-related macular degeneration. Participants identified logistical (improved financial assistance with treatment and out-of-pocket costs, and appointment reminders), operational (addressing clinic set up to reduce waiting times and improving the amount of time providers spend with patients), and educational (improving quality and provision of patient information and expectation-setting) opportunities to improve care., Conclusions: The wealth of data generated by this global survey highlights the breadth of challenges associated with clinical management of patients with neovascular age-related macular degeneration. Addressing the opportunities raised could improve patient adherence to treatment and potentially outcomes, reduce appointment burden, and increase clinic capacity., Competing Interests: Declarations. Conflict of Interest: Anat Loewenstein: Consultant: 4DMT, AbbVie, Alkeus, Annexon, Apellis, Astellas, Bayer Health Care, Beyeonics, Eyepoint, Johnson & Johnson, NotalVision, Novartis, Ocular Therapeutics, Oculis, Ocuphire Pharma, Ocuterra, Opthea, Oxurion, Roche, Syneos; Michelle Sylvanowicz: Employee: Bayer; Winfried M. Amoaku: Advisory board membership: AbbVie, Alcon, Alimera, Allergan, Apellis, Bayer, Bausch + Lomb, Bioeq, Novartis, Pfizer; Speaker fees: Alimera, Allergan, Bayer, Novartis, Pfizer; Support for travel: Alimera, Allergan, Bayer, Novartis, Pfizer; Research sponsorship and funding: Allergan, Bayer, Boehringer Ingelheim, CenterVue, Gyroscope, Novartis, Optos; Tariq Aslam: Tariq Aslam is an Editor in Chief of Ophthalmology and Therapy, and was not involved in the selection of peer reviewers for the manuscript nor any subsequent editorial decisions. Consultant: Novartis, Bayer, Laboratoires, Théa Pharmaceuticals, Bausch & Lomb, Oraya; Chui Ming Gemmy Cheung: Financial support (to institution): Allergan, Bayer, Boehringer Ingelheim, Novartis, Roche, Topcon, Zeiss; Stock: Avirmax; Bora Eldem: Consultant: Allergan, Bayer, Novartis, Roche; Robert P. Finger: Research grant: CentreVue, Heidelberg Engineering, Novartis, Zeiss; Consultant: Alimera, Allergan, Bayer, Ellex, Inositec, Novartis, Opthea, Roche/Genentech, Santhera; Support for travel: Novartis; Richard P. Gale: Consultant/advisory boards: Allergan, Alimera, Bayer, Novartis, Santen; Educational travel grants: Allergan, Bayer, Heidelberg, Novartis; Research grants: Allergan, Bayer, Novartis, Roche; Laurent Kodjikian: Consultant: AbbVie, Alcon, Allergan, Bayer, Krystal Biotech, Novartis, Regeneron, Théa; Adrian Koh: Consultant: Allergan, Bayer, Carl Zeiss, Heidelberg, Novartis, Topcon; Jean-François Korobelnik: Consultant: AbbVie, Apellis, Bayer, Eyepoint Pharma, Ocuphire, Roche, Thea, Carl Zeiss Meditec; Member of DSMB for Alexion, Novo Nordisk, Opthea; Xiaofeng Lin: Consultant: Bayer; Paul Mitchell: Consultant: Allergan, Bayer, Novartis; Steering Committee member: Bayer; Moira Murphy: Employee: Exploristics, Ltd.; Mali Okada: Non-financial support and personal fees: Bayer; Ian Pearce: Lecture fees: Allergan, Bayer, Heidelberg, Novartis; Consultant: Allergan, Alimera, Bayer, Novartis; Support for travel: Allergan, Bayer, Novartis; Francisco J. Rodriguez: Consultant: Bayer, Novartis, Roche; Speaker: Bayer, Novartis, Roche; Research funding: Novartis; Jude Stern: Employee: The International Agency for the Prevention of Blindness; S. James Talks: Advisory board member, speaker fees, and research support: Bayer, Novartis; research grants: Boehringer Ingelheim, Roche; Consultant: Bayer; David T. Wong: Grants/research support: Bayer, Novartis, Roche; Consultant: Alcon, Allergan, Bausch Health, Bayer, Novartis, Topcon, Zeiss; Equity: Arctic DX; Tien Yin Wong: Clinical trial grants: Allergan, Bayer, Boehringer Ingelheim, Genentech, Merck, Novartis, Oxurion (formerly ThromboGenics), Roche, Samsung Bioepis, NMRC Singapore, Novartis Singapore; Consulting fees/travel support/review fees: Allergan, Bayer, Boehringer Ingelheim, Genentech, Merck, Novartis, Oxurion (formerly ThromboGenics), Roche, Samsung Bioepis; Stock: EyRIS, Plano; Focke Ziemssen: Travel grants and personal fees: Allergan, Alimera, Bayer Healthcare, Biogen, Boehringer Ingelheim, Clearside, Novartis, Novo Nordisk, MSD Sharp & Dohme, Roche, Optos; Jane Barratt: Consultant: Bayer. Ethical Approval: The survey was designed and developed according to the Declaration of Helsinki and the World Health Organization’s International Ethical Guidelines for Biomedical Research. While the survey is a Primary Market Research Survey (which does not require ethics committee approval), individual institutions and countries assessed local requirements. Furthermore, informed consent was acquired, no personally identifiable information was collected, and treatment decisions were not informed by response to the survey., (© 2024. The Author(s).)

Background: One third of organ donors suffer catastrophic brain injury (CBI). There are no standard guidelines for the management of traumatic CBI prior to brain death, and not all trauma centers have institutional CBI guidelines. In addition, there is high variability in management between institutions with guidelines. Catastrophic brain injury guidelines vary and may include various combinations of hormone therapy, vasopressors, fluid resuscitation, and other practices. We hypothesized that centers with CBI guidelines have higher organ donation rates than those without., Methods: This prospective, observational EAST-sponsored multicenter trial included adult (18+ years old) traumatic-mechanism CBI patients at 33 level I and II trauma centers from January 2022 to May 2023. Catastrophic brain injury was defined as a brain injury causing loss of function above the brain stem and subsequent death. Cluster analysis with linear mixed-effects model including UNOS regions and hospital size by bed count was used to determine whether CBI guidelines are associated with organ donation., Results: A total of 790 CBI patients were included in this analysis. In unadjusted comparison, CBI guideline centers had higher rates of organ donation and use of steroids, whole blood, and hormone therapy. In a linear mixed-effects model, CBI guidelines were not associated with organ donation. Registered organ donor status, steroid hormones, and vasopressin were associated with increased relative risk of donation., Conclusion: There is high variability in management of CBI, even at centers with CBI guidelines in place. While the use of institutional CBI guidelines was not associated with increased organ donation, guidelines in this study were not identical. Hormone replacement with steroids and vasopressin was associated with increased donation. Hormone resuscitation is a common feature of CBI guidelines. Further analysis of individual practices that increase organ donation after CBI may allow for more effective guidelines and an overall increase in donation to decrease the long waiting periods for organ transplant recipients., Level of Evidence: Prognostic and Epidemiological; Level II., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)