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Vocal fold immobility was observed in five patients, but no pharyngeal stenosis was noted. Adverse effects, such as postoperative laryngeal chondritis or cervical spondylitis, were seen in three patients who had previously been treated with resection to the muscularis propria or definitive irradiation. CONCLUSION Local steroid injection during TOVS significantly reduced the degree of postoperative scar contracture. However, caution should be used when treating with local steroid injection during TOVS, as this may complicate wound healing in patients who have already received treatment. V.PURPOSE To describe the diagnostic accuracy of 3-dimensional (3D) endothelium-Descemet's membrane complex thickness (En-DMT) in Fuchs' endothelial corneal dystrophy (FECD) and determine its potential role as an objective index of disease severity. DESIGN Observational case-control study. PARTICIPANTS One hundred four eyes of 79 participants (64 eyes of 41 FECD patients and 40 eyes of 38 healthy controls). METHODS All participants received high-definition OCT imaging (Envisu R2210; Bioptigen, Buffalo Grove, IL). Fuchs' endothelial corneal dystrophy was classified clinically into early-stage (without edema) and late-stage (with edema) disease. Automatic and manual segmentation of corneal layers was performed using a custom-built segmental tomography algorithm to generate 3D maps of total corneal thickness (TCT) and En-DMT of the central 6-mm cornea. Regional En-DMT, regional TCT, and central-to-peripheral total corneal thickness ratio (CPTR) were evaluated and correlated to the clinical severity of FECD. Intrac 0.001), compared with CPTR and mean TCT of paracentral zones (0.672 and 0.481, respectively; P less then 0.001). The ICC values ranged from 0.98 (En-DMT) to 0.99 (TCT) with a good agreement between the automatic and manual measurements. CONCLUSIONS Regional 3D En-DMT is a novel diagnostic tool of FECD that can be used to quantify the disease severity with excellent reliability. Improving or maintaining visual acuity is the main goal for the treatment of neovascular age-related macular degeneration (nAMD). Current nAMD standard of care dictates frequent intravitreal (IVT) anti-vascular endothelial growth factor (VEGF) injections, which places a substantial burden on patients, caregivers, and physicians. Brolucizumab, a newly developed anti-VEGF molecule for nAMD treatment, has demonstrated longer durability and improvement in visual and anatomic outcomes in clinical studies in a q12-week regimen, indicating its potential to reduce treatment burden as an important therapeutic tool in nAMD management. This review focuses on the development of brolucizumab and the preclinical and clinical studies evaluating its efficacy, tolerability, and safety. Brolucizumab (also known as "RTH258" and "ESBA1008") is a humanized, single-chain variable fragment (scFv) antibody with a molecular mass of approximately 26 kDa that inhibits VEGF-A. Preclinical studies show that brolucizumab readily penetratelibercept (q8-week). Fewer brolucizumab 6-mg treated eyes had disease activity versus aflibercept, and anatomic outcome results at weeks 16 and 48 demonstrate brolucizumab as a potent drying agent. Moreover, of patients treated with 6 mg brolucizumab, 55.6% and 51.0% maintained a q12-week dosing interval immediately after the loading phase until week 48 in HAWK and HARRIER, respectively. These Phase 3 studies demonstrated that the brolucizumab q12-week regimen maintains efficacy and safety while reducing treatment burden associated with regular IVT injections for patients with nAMD. BACKGROUND In the intensive care unit (ICU), inactivity is common, contributing to ICU-acquired weakness and poor outcomes. Actigraphy may be useful for measuring activity in the ICU. OBJECTIVES To use actigraphy to characterize inactivity and activity in critically ill patients. METHODS This prospective observational study involved 48-h wrist actigraphy in medical ICU (MICU) patients, with activity data captured across 30-s epochs. Inactivity (zero-activity epochs) and activity (levels of non-zero activity) were summarized across key patient (e.g., age) and clinical (e.g., mechanical ventilation status) variables, and compared using multivariable regression. RESULTS Overall, 189,595 30-s epochs were collected in 34 MICU patients. Zero-activity (inactivity) comprised 122,865 (65%) of epochs; these epochs were 24% and 13% more prevalent, respectively, in patients receiving mechanical ventilation (versus none, p  less then  0.001) and in the highest (versus lowest) organ failure score tertile (p = 0.03). Ambulatory (versus non-ambulatory) patients exhibited more non-zero activity (35 more movements per epoch, p  less then  0.001), while those in the highest (versus lowest) organ failure score tertile exhibited less activity (22 fewer movements per epoch, p = 0.03). Significant inactivity/activity differences were not observed when evaluated based on age, sedation, or restraint status. CONCLUSIONS Actigraphy demonstrated that MICU patients are profoundly inactive, including those who are young, non-sedated and non-restrained. Hence, ICU-specific, non-patient-related factors may contribute to inactivity, an issue requiring further investigation. Published by Elsevier Inc.The choroid plexus (ChP) is a major source of cerebrospinal fluid (CSF) production, with a direct and indirect role in protein clearance, and pathogenesis of Alzheimer's disease (AD). Here, we tested the link between the ChP volume and levels of CSF proteins in 2 data sets of (i) healthy controls, mild cognitive impairment (MCI), and AD patients from the Alzheimer's Disease Neuroimaging Initiative (ADNI) (N = 509), and (ii) healthy controls and Parkinson's disease (PD) patients from the Parkinson's Progression Markers Initiative (N = 302). All patients had baseline CSF proteins (amyloid-β, total and phosphorylated-tau and α-synuclein (only in Parkinson's Progression Markers Initiative)). ChP was automatically segmented on 3T structural T1-weighted MRIs. We found negative associations between ChP volume and CSF proteins, which were stronger in healthy controls, early-MCI patients, and PD patients compared with late-MCI and AD patients. Further grouping of patients of ADNI dataset into amyloid-positive and amyloid-negative based on their florbetapir (AV45) PET imaging showed that the association between ChP volume and CSF proteins (t/p-tau) was lower in amyloid-positive group. Our findings support the possible role of ChP in the clearance of CSF proteins, provide evidence for ChP dysfunction in AD, and suggest the need to account for the ChP volume in future studies of CSF-based biomarkers. Several studies have investigated the differential vulnerability of hippocampal subfields during aging and Alzheimer's disease (AD). Results were often contradictory, mainly because these works were based on concatenations of cross-sectional measures in cohorts with different ages or stages of AD, in the absence of a longitudinal design. Here, we investigated 327 participants from a population-based cohort of nondemented older adults with a 14-year clinical follow-up. MRI at baseline and 4 years later were assessed to measure the annualized rates of hippocampal subfields atrophy in each participant using an automatic segmentation pipeline with subsequent quality control. On the one hand, CA4 dentate gyrus was significantly more affected than the other subfields in the whole population (CA1-3 -0.68%/year; subiculum -0.99%/year; and CA4-DG -1.39%/year; p less then 0.0001). On the other hand, the annualized rate of CA1-3 atrophy was associated with an increased risk of developing Alzheimer's clinical syndrome over time, independently of age, gender, educational level, and ApoE4 genotype (HR = 2.0; CI 95% 1.4-3.0). These results illustrate the natural history of hippocampal subfields atrophy during aging and AD by showing that the dentate gyrus is the most vulnerable subfield to the effects of aging while the cornu-ammonis is the primary target of AD pathophysiological processes, years before symptom onset. click here BACKGROUND New jurisdictionally-based vaccination programs were established providing free quadrivalent influenza vaccine (QIV) for preschool Australian children in 2018. This was in addition to the National Immunisation Program (NIP) funded QIV for Indigenous children and children with comorbid medical conditions. We assessed the impact of this policy change on influenza disease burden and vaccine coverage, as well as report on 2018 vaccine effectiveness in a hospital-based surveillance system. METHODS Subjects were recruited prospectively from twelve PAEDS-FluCAN sentinel hospital sites (April until October 2018). Children aged ≤16 years hospitalised with an acute respiratory illness (ARI) and laboratory-confirmed influenza were considered cases. Hospitalised children with ARI who tested negative for influenza were considered controls. VE estimates were calculated from the adjusted odds ratio of vaccination in cases and controls. RESULTS A total of 458 children were hospitalised with influenza 31.7% were lmortality. Whether to vaccinate or not is currently a hot topic in social discourse. Despite the majority view that childhood vaccination is safe and effective, websites and social media content opposing such vaccination are common. In this study, we searched the internet platforms Google, Facebook and YouTube for childhood vaccine information. We made every attempt to minimise selection bias generated by internet algorithms. We compared the displayed stances of vaccine information retrieved. Most of the information had a clearly stated stance on vaccines or made some sort of recommendation on whether or not to vaccinate. Despite our careful attempt to search comprehensively and systematically for vaccine information with as little bias as possible, this search yielded a sizeable minority of vaccine negative information. This research shows that negative vaccine information persists and is readily accessible online despite algorithm and policy changes in recent years, even when searching in the least biased way possible. It is important that vaccine-promoting entities and agencies continue to make every effort to maximize their presence online so that parents searching the internet to answer the question 'should I vaccinate my child?' continue to receive vaccine positive information. Despite a critical need for a respiratory syncytial virus (RSV) vaccine and decades of development efforts, a vaccine to protect infants, elderly, and other at-risk populations from RSV infection remains elusive. We have previously generated a new, live-attenuated vaccine candidate against RSV using rational, computer-aided gene design and chemical synthesis through a process termed viral gene "deoptimization." In this study, we assessed the attenuation, immunogenicity, and efficacy of this synthetic, live-attenuated RSV vaccine candidate, RSV-MinL4.0, in African Green Monkeys. RSV-MinL4.0 was produced under good-manufacturing-practice (GMP) in Vero cells. Vaccination with RSV-MinL4.0 resulted in minimal virus shedding after vaccination, generation of robust humoral and cellular immune responses (despite the presence of baseline RSV neutralizing antibodies in one animal) that were comparable to a wildtype infection, and protection from virus shedding post-challenge with wildtype RSV. These findings demonstrate the promise of RSV-MinL4.

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