Background
The COMET-ICE trial demonstrated that sotrovimab clinically and statistically significantly reduces the risk of all-cause > 24-h hospitalization or death due to any cause among patients ...with COVID-19 at high risk of disease progression. Patient-reported outcomes are important to capture symptom burden of COVID-19 and assess treatment effectiveness. This study investigated symptoms and their impact over the acute phase of COVID-19 infection among patients on sotrovimab versus placebo.
Methods
Randomized (1:1), double-blind, multicenter, placebo-controlled, phase 2/3 study in 57 centers across five countries. Participants were non-hospitalized patients with symptomatic, mild-to-moderate COVID-19 and ≥ 1 baseline risk factor for disease progression (aged ≥ 55 years or ≥ 1 of the following: diabetes requiring medication, obesity, chronic kidney disease, congestive heart failure, chronic obstructive pulmonary disease, or moderate-to-severe asthma). An intravenous infusion of sotrovimab 500 mg or placebo was administered on Day 1. The FLU-PRO Plus questionnaire was administered once-daily with 24-h recall from Day 1–21, and at Day 29. Intensity and duration of COVID-19 symptoms were determined from area under the curve (AUC) and mean change in total and individual domain scores through Days 7, 14, and 21. Time to symptom alleviation was assessed.
Results
In total, 1057 patients were randomized to sotrovimab (n = 528) or placebo (n = 529). At Day 7, mean decrease in FLU-PRO Plus total score (measured by AUC) was statistically significantly greater for patients on sotrovimab (–3.05 95% confidence interval (CI) –3.27 to –2.83) than placebo (–1.98 95% CI –2.20 to –1.76; difference –1.07 95% CI –1.38 to –0.76;
p
< 0.001). Significant differences were also observed at Days 14 and 21. A more rapid decline in symptom severity was observed with sotrovimab versus placebo through Week 1 and the first 21 days post-treatment. By Day 21, 41% of patients on sotrovimab and 34% on placebo reported symptom resolution. In a post-hoc analysis, median time to symptom alleviation was 4 and 6 days, respectively.
Conclusions
Sotrovimab provides significant and rapid improvements in patient-reported COVID-19 symptoms, as measured by the FLU-PRO Plus. These results further show the benefits of sotrovimab in alleviating symptoms among high-risk patients with COVID-19.
Trial registration
ClinicalTrials.Gov: NCT04545060 (
https://clinicaltrials.gov/ct2/show/NCT04545060
). Date of registration: September 10, 2020 (retrospectively registered).
This study aims to evaluate the safety, efficacy, and renal function preservation of percutaneous cryoablation (PCA) for small renal masses (SRMs) in inherited RCC syndromes. Patients with inherited ...T1N0M0 RCCs (<7 cm) undergoing PCA from 2015 to 2021 were identified from the European Registry for Renal Cryoablation (EuRECA). The primary outcome was local recurrence-free survival (LRFS). The secondary outcomes included technical success, peri-operative outcomes, and other oncological outcomes estimated using the Kaplan-Meier method. Simple proportions, chi-squared tests, and
-tests were used to analyse the peri-operative outcomes. A total of 68 sessions of PCA were performed in 53 patients with RCC and 85 tumours were followed-up for a mean duration of 30.4 months (SD ± 22.0). The overall technical success rate was 99%. The major post-operative complication rate was 1.7%. In total, 7.4% (2/27) of patients had >25% reduction in renal function. All oncological events were observed in VHL patients. Estimated 5-year LRFS, metastasis-free survival, cancer-specific survival, and overall survival were 96.0% (95% CI 75-99%), 96.4% (95% CI 77-99%), 90.9% (95% CI 51-99%), and 90.9% (95% CI 51-99%), respectively. PCA of RCCs for patients with hereditary RCC SRMs appears to be safe, offers low complication rates, preserves renal function, and achieves good oncological outcomes.
Common variants of about 20 genes contributing to AD risk have so far been identified through genome-wide association studies (GWAS). However, there is still a large proportion of heritability that ...might be explained by rare but functionally important variants. One of the so far identified genes with rare AD causing variants is ADAM10. Using whole-genome sequencing we now identified a single rare nonsynonymous variant (SNV) rs142946965 p.R215I in ADAM17 co-segregating with an autosomal-dominant pattern of late-onset AD in one family. Subsequent genotyping and analysis of available whole-exome sequencing data of additional case/control samples from Germany, UK, and USA identified five variant carriers among AD patients only. The mutation inhibits pro-protein cleavage and the formation of the active enzyme, thus leading to loss-of-function of ADAM17 alpha-secretase. Further, we identified a strong negative correlation between ADAM17 and APP gene expression in human brain and present in vitro evidence that ADAM17 negatively controls the expression of APP. As a consequence, p.R215I mutation of ADAM17 leads to elevated Aß formation in vitro. Together our data supports a causative association of the identified ADAM17 variant in the pathogenesis of AD.
Diabetic retinopathy is the most common microvascular complication of diabetes and is a major cause of blindness, but an understanding of the pathogenesis of the disease has been hampered by a lack ...of accurate animal models. Here, we explore the dynamics of retinal cellular changes in the Nile rat (Arvicanthis niloticus), a carbohydrate-sensitive model for type 2 diabetes. The early retinal changes in diabetic Nile rats included increased acellular capillaries and loss of pericytes that correlated linearly with the duration of diabetes. These vascular changes occurred in the presence of microglial infiltration but in the absence of retinal ganglion cell loss. After a prolonged duration of diabetes, the Nile rat also exhibits a spectrum of retinal lesions commonly seen in the human condition including vascular leakage, capillary non-perfusion, and neovascularization. Our longitudinal study documents a range and progression of retinal lesions in the diabetic Nile rat remarkably similar to those observed in human diabetic retinopathy, and suggests that this model will be valuable in identifying new therapeutic strategies.
BackgroundLittle is known about the natural history and impact of irritable bowel syndrome (IBS)‐type symptoms on psychological health and quality of life in inflammatory bowel disease (IBD). We ...aimed to address this in a 12‐month longitudinal follow‐up study of secondary care patients.MethodsWe collected demographic, Rome III IBS‐type symptom, psychological, and quality of life data, with questionnaires at 3‐month intervals, over 12 months of follow‐up in patients with IBD in clinical remission at baseline. We assessed the natural history of Rome III IBS‐type symptoms over the 12 months of the study and compared psychological and quality of life data between those reporting Rome III IBS‐type symptoms at each of the points of follow‐up with those not reporting such symptoms.Key ResultsAmong 206 patients with IBD in clinical remission at baseline (104 50.5% women, mean age 56.9 years range 18–83 years, 79 38.3% Crohn's disease), 33 (16.0%) reported Rome III IBS‐type symptoms at baseline and 72 (35.0%) reported Rome III IBS‐type symptoms at one or more time points. Among the 33 patients with Rome III IBS‐type symptoms at baseline, symptoms resolved in 6 (18.2%) patients, were present throughout in 6 (18.2%) patients, and fluctuated in the remaining 21 (63.6%) patients. Among the 39 patients with new onset of Rome III IBS‐type symptoms after baseline, 24 (65.1%) had symptoms at one point in time only, 10 (25.6%) at two points, four (10.3%) at three points, and one (2.6%) at four points. At each point in time, reporting IBS‐type symptoms was associated with significantly higher anxiety, depression, or somatoform symptom‐reporting scores, and/or lower quality of life scores.Conclusions & InferencesIn this 12‐month follow‐up study, one‐third of patients with IBD reported presence of Rome III IBS‐type symptoms at any point in time. Reporting such symptoms was associated with significant impacts on psychological health and/or quality of life.
Background The long‐term natural history and impact of irritable bowel syndrome (IBS)‐type symptoms on outcomes in inflammatory bowel disease (IBD) are uncertain. Aim To assess this in a longitudinal ...follow‐up study of patients in secondary care Methods We assessed the natural history of IBS‐type symptoms in IBD via Rome III criteria applied at baseline, and 2 and 6 years. We defined longitudinal disease activity as the need for glucocorticosteroids or flare, escalation, hospitalisation or intestinal resection. To assess healthcare utilisation, we recorded the number of outpatient clinic attendances and investigations. We also collected anxiety, depression and somatoform symptom scores and quality of life scores during follow‐up. Results Among 125 individuals with Rome III data at all three time points, only 41 (32.8%) never reported IBS‐type symptoms. Fifteen patients (12.0%) had IBS‐type symptoms at baseline that resolved, 19 (15.2%) had fluctuating symptoms, 35 (28.0%) had new‐onset symptoms, and 15 (12.0%) had persistent symptoms. Among more than 300 patients with IBD activity data, IBS‐type symptoms were not associated with an increased likelihood of the need for glucocorticosteroids or flare, escalation, hospitalisation or intestinal resection. However, the mean numbers of outpatient appointments and endoscopic investigations were significantly higher among those with IBS‐type symptoms. Anxiety, depression and somatoform symptom scores were significantly higher, and quality of life scores were significantly lower, in those reporting IBS‐type symptoms at least once during the study. Conclusions IBS‐type symptoms affected more than two‐thirds of patients with IBD during >6 years of follow‐up and were associated with increased healthcare utilisation, and worse anxiety, depression, somatoform symptom and quality of life scores, but not adverse disease activity outcomes.
For quality, interpretation, reproducibility and sharing value, microscopy images should be accompanied by detailed descriptions of the conditions that were used to produce them. Micro-Meta App is an ...intuitive, highly interoperable, open-source software tool that was developed in the context of the 4D Nucleome (4DN) consortium and is designed to facilitate the extraction and collection of relevant microscopy metadata as specified by the recent 4DN-BINA-OME tiered-system of Microscopy Metadata specifications. In addition to substantially lowering the burden of quality assurance, the visual nature of Micro-Meta App makes it particularly suited for training purposes.
Objectives
To evaluate the use of pre-cryoablation biopsy for small renal masses (SRMs) and the effects of increasing uptake on histological results of treated SRMs.
Methods
From 2015 to 2019, ...patients with sporadic T1N0M0 SRMs undergoing percutaneous, laparoscopic, or open cryoablation from 14 European institutions within the European Registry for Renal Cryoablation (EuRECA) were included for the retrospective analysis. Univariate and multivariate logistic models were used to evaluate the trends, histological results, and the factors influencing use of pre-cryoablation biopsy.
Results
In total, 871 patients (median (IQR) age, 69 (14), 298 women) undergoing cryoablation were evaluated. The use of pre-cryoablation biopsy has significantly increased from 42% (65/156) in 2015 to 72% (88/122) in 2019 (
p
< 0.001). Patients treated for a benign histology are significantly more likely to have presented later in the trend, where pre-cryoablation biopsy is more prevalent (OR: 0.64, 95% CI 0.51–0.81,
p
< 0.001). Patients treated for undiagnosed histology are also significantly less likely to have presented in 2018 compared to 2016 (OR 0.31, 95% CI 0.10–0.97,
p
= 0.044). Patients aged 70+ are less likely to be biopsies pre-cryoablation (
p
< 0.05). R.E.N.A.L. nephrometry score of 10+ and a Charlson Comorbidity Index > 1 are factors associated with lower likelihood to not have received a pre-cryoablation biopsy (
p
< 0.05).
Conclusion
An increased use of pre-cryoablation biopsy was observed and cryoablation patients treated with a benign histology are more likely to have presented in periods where pre-cryoablation biopsy is not as prevalent. Comparative studies are needed to draw definitive conclusions on the effect of pre-cryoablation biopsy on SRM treatments.
Key Points
•
The use of biopsy pre-ablation session has increased significantly from 42% of all patients in 2015 to 74% in 2019
.
•
Patients are less likely to be treated for a benign tumour if they presented later in the trend, where pre-cryoablation biopsy is more prevalent, compared to later in the trend (OR 0.64, 95% CI 0.51–0.81, p < 0.001)
.
•
Patients with comorbidities or a complex tumour (R.E.N.A.L. nephrometry score > 10) are less likely to not undergo biopsy as a separate session to cryoablation
.
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