Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

SARS-CoV-2-specific nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination

BACKGROUND: Most studies of immunity to SARS-CoV-2 focus on circulating antibody, giving limited insights into mucosal defences that prevent viral replication and onward transmission. We studied nasal and plasma antibody responses one year after hospitalisation for COVID-19, including a period when SARS-CoV-2 vaccination was introduced. METHODS: In this follow up study, plasma and nasosorption samples were prospectively collected from 446 adults hospitalised for COVID-19 between February 2020 and March 2021 via the ISARIC4C and PHOSP-COVID consortia. IgA and IgG responses to NP and S of ancestral SARS-CoV-2, Delta and Omicron (BA.1) variants were measured by electrochemiluminescence and compared with plasma neutralisation data. FINDINGS: Strong and consistent nasal anti-NP and anti-S IgA responses were demonstrated, which remained elevated for nine months (p < 0.0001). Nasal and plasma anti-S IgG remained elevated for at least 12 months (p < 0.0001) with plasma neutralising titres that were raised against all variants compared to controls (p < 0.0001). Of 323 with complete data, 307 were vaccinated between 6 and 12 months; coinciding with rises in nasal and plasma IgA and IgG anti-S titres for all SARS-CoV-2 variants, although the change in nasal IgA was minimal (1.46-fold change after 10 months, p = 0.011) and the median remained below the positive threshold determined by pre-pandemic controls. Samples 12 months after admission showed no association between nasal IgA and plasma IgG anti-S responses (R = 0.05, p = 0.18), indicating that nasal IgA responses are distinct from those in plasma and minimally boosted by vaccination. INTERPRETATION: The decline in nasal IgA responses 9 months after infection and minimal impact of subsequent vaccination may explain the lack of long-lasting nasal defence against reinfection and the limited effects of vaccination on transmission. These findings highlight the need to develop vaccines that enhance nasal immunity. FUNDING: This study has been supported by ISARIC4C and PHOSP-COVID consortia. ISARIC4C is supported by grants from the National Institute for Health and Care Research and the Medical Research Council. Liverpool Experimental Cancer Medicine Centre provided infrastructure support for this research. The PHOSP-COVD study is jointly funded by UK Research and Innovation and National Institute of Health and Care Research. The funders were not involved in the study design, interpretation of data or the writing of this manuscript

Large-scale phenotyping of patients with long COVID post-hospitalization reveals mechanistic subtypes of disease

One in ten severe acute respiratory syndrome coronavirus 2 infections result in prolonged symptoms termed long coronavirus disease (COVID), yet disease phenotypes and mechanisms are poorly understood1. Here we profiled 368 plasma proteins in 657 participants ≥3 months following hospitalization. Of these, 426 had at least one long COVID symptom and 233 had fully recovered. Elevated markers of myeloid inflammation and complement activation were associated with long COVID. IL-1R2, MATN2 and COLEC12 were associated with cardiorespiratory symptoms, fatigue and anxiety/depression; MATN2, CSF3 and C1QA were elevated in gastrointestinal symptoms and C1QA was elevated in cognitive impairment. Additional markers of alterations in nerve tissue repair (SPON-1 and NFASC) were elevated in those with cognitive impairment and SCG3, suggestive of brain–gut axis disturbance, was elevated in gastrointestinal symptoms. Severe acute respiratory syndrome coronavirus 2-specific immunoglobulin G (IgG) was persistently elevated in some individuals with long COVID, but virus was not detected in sputum. Analysis of inflammatory markers in nasal fluids showed no association with symptoms. Our study aimed to understand inflammatory processes that underlie long COVID and was not designed for biomarker discovery. Our findings suggest that specific inflammatory pathways related to tissue damage are implicated in subtypes of long COVID, which might be targeted in future therapeutic trials

Enzymeimmunoassay of 17-alphahydoxyprogesterone

SIGLEAvailable from British Library Document Supply Centre- DSC:DX95199 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Relationships between Visual Field Sensitivity and Spectral Absorption Properties of the Neuroretinal Rim in Glaucoma by Multispectral Imaging

NoTo investigate the relationship between neuroretinal rim (NRR) differential light absorption (DLA, a measure of spectral absorption properties) and visual field (VF) sensitivity in primary open-angle glaucoma (POAG). atients diagnosed with (n = 22) or suspected of having (n = 7) POAG were imaged with a multispectral system incorporating a modified digital fundus camera, 250-W tungsten-halogen lamp, and fast-tuneable liquid crystal filter. Five images were captured sequentially within 1.0 second at wavelengths selected according to absorption properties of hemoglobin (range, 570–610 nm), and a Beer-Lambert law model was used to produce DLA maps of residual NRR from the images. Patients also underwent VF testing. Differences in NRR DLA in vertically opposing 180° and 45° sectors either side of the horizontal midline were compared with corresponding differences in VF sensitivity on both decibel and linear scales by Spearman's rank correlation. The decibel VF sensitivity scale showed significant relationships between superior–inferior NRR DLA difference and sensitivity differences between corresponding VF areas in 180° NRR sectors (Spearman ρ = 0.68; P < 0.0001), superior-/inferior-temporal 45° NRR sectors (ρ = 0.57; P < 0.002), and superior-/inferior-nasal 45° NRR sectors (ρ = 0.59; P < 0.001). Using the linear VF sensitivity scale significant relationships were found for 180° NRR sectors (ρ = 0.62; P < 0.0002) and superior–inferior–nasal 45° NRR sectors (ρ = 0.53; P < 0.002). No significant difference was found between correlations using the linear or decibel VF sensitivity scales. Residual NRR DLA is related to VF sensitivity in POAG. Multispectral imaging may provide clinically important information for the assessment and management of POAG.College of Optometrists (UK) PhD Studentship (JD), Central Manchester NHS Foundation Trust Grant RO1180, the Manchester Academic Health Sciences Centre (MAHSC), and the NIHR Manchester Biomedical Research Centre

Spatial and spectral imaging of retinal laser photocoagulation burns

NoThe purpose of this research was to correlate in vivo spatial and spectral morphologic changes of short- to long-pulse 532 nm Nd:YAG retinal laser lesions using Fourier-domain optical coherence tomography (FD OCT), autofluorescence (AF), fluorescein angiography (FA), and multispectral imaging. Ten eyes with treatment-naive preproliferative or proliferative diabetic retinopathy were studied. A titration grid of laser burns at 20, 100, and 200 milliseconds was applied to the nasal retina and laser fluence titrated to produce four grades of laser lesion visibility: subvisible (SV), barely visible (BV, light-gray), threshold (TH, gray-white), and suprathreshold (ST, white). The AF, FA, FD-OCT, and multispectral imaging were performed 1 week before laser, and 1 hour, 4 weeks, and 3 and 6 months post-laser. Multispectral imaging measured relative tissue oxygen concentration. Laser burn visibility and lesion size increased in a linear relationship according to fixed fluence levels. At fixed pulse durations, there was a semilogarithmic increase in lesion size over 6 months. At 20 milliseconds, all grades of laser lesion were reduced significantly in size after 6 months: SV, 51%; BV, 54%; TH, 49%; and ST, 50% (P < 0.001), with retinal pigment epithelial proliferation and photoreceptor infilling. At 20 milliseconds, there was healing of photoreceptor inner segment/outer segment junction layers compared with 100- and 200-millisecond lesions. Significant increases in mean tissue oxygenation (range, four to six units) within the laser titration area and in oxygen concentration across the laser lesions (P < 0.01) were detected at 6 months. For patients undergoing therapeutic laser, there may be improved tissue oxygenation, higher predictability of burn morphology, and more spatial localization of healing responses of burns at 20 milliseconds compared with longer pulse durations over timeOptimedica Corp., the Manchester Academic Health Sciences Centre, and the NIHR Manchester Biomedical Research Centre. JD was funded by a College of Optometrists PhD Studentship, United Kingdom

High-resolution hyperspectral imaging of the retina with a modified fundus camera

NoThe purpose of the research was to examine the practical feasibility of developing a hyperspectral camera from a Zeiss fundus camera and to illustrate its use in imaging diabetic retinopathy and glaucoma patients. The original light source of the camera was replaced with an external lamp filtered by a fast tunable liquid-crystal filter. The filtered light was then brought into the camera through an optical fiber. The original film camera was replaced by a digital camera. Images were obtained in normals and patients (primary open angle glaucoma, diabetic retinopathy) recruited at the Manchester Royal Eye Hospital. A series of eight images were captured across 495- to 720-nm wavelengths, and recording time was less than 1.6s. The light level at the cornea was below the ANSI limits, and patients judged the measurement to be very comfortable. Images were of high quality and were used to generate a pixel-to-pixel oxygenation map of the optic nerve head. Frame alignment is necessary for frame-to-frame comparison but can be achieved through simple methods. We have developed a hyperspectral camera with high spatial and spectral resolution across the whole visible spectrum that can be adapted from a standard fundus camera. The hyperspectral technique allows wavelength-specific visualization of retinal lesions that may be subvisible using a white light source camera. This hyperspectral technique may facilitate localization of retinal and disc pathology and consequently facilitate the diagnosis and management of retinal disease