It has been widely observed that adult men of all ages are at higher risk of developing serious complications from COVID-19 when compared with women. This study aimed to investigate the association ...of COVID-19 positivity and severity with estrogen exposure in women, in a population based matched cohort study of female users of the COVID Symptom Study application in the UK. Analyses included 152,637 women for menopausal status, 295,689 women for exogenous estrogen intake in the form of the combined oral contraceptive pill (COCP), and 151,193 menopausal women for hormone replacement therapy (HRT). Data were collected using the COVID Symptom Study in May-June 2020. Analyses investigated associations between predicted or tested COVID-19 status and menopausal status, COCP use, and HRT use, adjusting for age, smoking and BMI, with follow-up age sensitivity analysis, and validation in a subset of participants from the TwinsUK cohort. Menopausal women had higher rates of predicted COVID-19 (P = 0.003). COCP-users had lower rates of predicted COVID-19 (P = 8.03E-05), with reduction in hospital attendance (P = 0.023). Menopausal women using HRT or hormonal therapies did not exhibit consistent associations, including increased rates of predicted COVID-19 (P = 2.22E-05) for HRT users alone. The findings support a protective effect of estrogen exposure on COVID-19, based on positive association between predicted COVID-19 with menopausal status, and negative association with COCP use. HRT use was positively associated with COVID-19, but the results should be considered with caution due to lack of data on HRT type, route of administration, duration of treatment, and potential unaccounted for confounders and comorbidities.
Immune-checkpoint inhibitors (ICIs) have revolutionised the therapeutic landscape for multiple malignancies and the health of the gut microbiome (GM) is strongly linked with therapeutic responses to ...ICI. This review explores the implications of diet and medication on the GM for patients receiving ICI. Clinical trials are underway to explore the impact of factors such as faecal microbiota transfer, probiotics, prebiotics, bacteria consortia and a number of dietary interventions on patients receiving ICI. Randomised controlled trials are lacking, and inferences are currently based on short-term clinical and observational studies. Antibiotics should be avoided before ICI initiation, and depending on prospective data, future consideration may be given to temporary delay of initiation of non-urgent ICI if patient has had broad spectrum antibiotics within 1 month of planned treatment initiation. Proton pump inhibitor use should be discontinued when not clearly indicated and potential switch to a histamine H2-receptor antagonist considered. Patients should be advised to minimise animal meat intake and maximise plants, aiming to consume ≥30 plant types weekly. A high fibre intake (>30 g/day) has been seen to be beneficial in increasing the chance of ICI response. Fermented foods may have a beneficial effect on the GM and should be introduced where possible. Ideally, all patients should be referred to a nutritionist or dietician with knowledge of GM before commencing ICI.
•Therapeutic response to immune-checkpoint inhibitor (ICI) is linked to the gut microbiome.•Care needs to be given to protecting the microbiome, both by clinicians and patients.•Patients' diets should focus on diversity, variety, plentiful plants, protein and dietary fibres.•Antibiotics and many other common medications can adversely affect responses to ICI.•Before and during ICI patients should have access to nutritional support.
The current outbreak of Ebola virus in West Africa is unprecedented, causing more cases and fatalities than all previous outbreaks combined, and has yet to be controlled. Several post-exposure ...interventions have been employed under compassionate use to treat patients repatriated to Europe and the United States. However, the in vivo efficacy of these interventions against the new outbreak strain of Ebola virus is unknown. Here we show that lipid-nanoparticle-encapsulated short interfering RNAs (siRNAs) rapidly adapted to target the Makona outbreak strain of Ebola virus are able to protect 100% of rhesus monkeys against lethal challenge when treatment was initiated at 3 days after exposure while animals were viraemic and clinically ill. Although all infected animals showed evidence of advanced disease including abnormal haematology, blood chemistry and coagulopathy, siRNA-treated animals had milder clinical features and fully recovered, while the untreated control animals succumbed to the disease. These results represent the first, to our knowledge, successful demonstration of therapeutic anti-Ebola virus efficacy against the new outbreak strain in nonhuman primates and highlight the rapid development of lipid-nanoparticle-delivered siRNA as a countermeasure against this highly lethal human disease.
Increasing CO2 threatens human nutrition Myers, Samuel S; Zanobetti, Antonella; Kloog, Itai ...
Nature (London),
06/2014, Letnik:
510, Številka:
7503
Journal Article
Recenzirano
Odprti dostop
Dietary deficiencies of zinc and iron are a major global public health problem. An estimated two billion people suffer these deficiencies causing a loss of 63 million life years annually. Most of ...these people depend upon grains and legumes as their primary dietary source of zinc and iron. This manuscript reports findings from the analysis of 540 pairs of crop samples grown at contemporary and elevated CO2 from six different FACE experiments involving six food crops. We tested the nutrient concentrations of the edible portions of rice (Oryza sativa, 18 cultivars), wheat (Triticum aestivum, 8 cultivars), maize (Zea mays, 2 cultivars), soybeans (Glycine max, 7 cultivars), field peas (Pisum sativum, 4 cultivars) and sorghum (Sorghum bicolor, 1 cultivar). In all six experiments, the elevated CO2 was in the range of 550-584 ppm. Each crop sample grown at elevated CO2 was paired with an identical cultivar grown under the same conditions but at contemporary CO2. Our main outcomes were fractional changes in concentrations of the nutrients between samples grown at elevated and contemporary CO2 levels, estimated using a linear mixed effects statistical model. We found that elevated CO2 was associated with significant decreases in the concentrations of zinc and iron in all C3 grasses and legumes. For example, in wheat grains grown at elevated CO2 compared with contemporary CO2, zinc decreased 9.6% and iron decreased 5.2%. We also found that elevated CO2 was associated with lower protein in C3 grasses with a 6.5% decrease in wheat grains and a 7.9% (95% CI: -8.9, -6.9) decrease in rice grains. Elevated CO2 showed no significant effect on protein in C3 legumes or C4 crops. Response differences between cultivars suggest breeding crops for reduced sensitivity to elevations in atmospheric CO2. Such breeding efforts may partly address the new challenges to global health that these findings highlight.
This decade has brought significantly improved outcomes for patients with advanced melanoma with immunotherapies and targeted treatments offering utility in a variety of settings. In 2020, we can ...hope for durable long-term responses, and complete remission in a subset of patients with metastatic disease. In the adjuvant setting, approximately 50% improvements in recurrence-free survival are seen both with targeted and immunotherapies. Early data from neoadjuvant immunotherapy clinical trials are very promising. However, responses to treatment are heterogeneous and not always durable; further advances are required, and several emerging strategies are of particular interest. We review the systemic treatment of melanoma, discussing the treatment of unresectable stage III-IV and recurrent disease, outlining curative treatment of cutaneous melanoma in the adjuvant setting and briefly discussing neoadjuvant systemic therapies for advanced melanoma.
The novel method accurately detected 8/10 RT-PCR positive cases and identified a further 3 positive cases. Eight further cases were negative using both methods. Using repeated RT-PCR as a "gold ...standard", the sensitivity and specificity of a single novel test were 80 and 73% respectively. PPV was 73% and NPV was 83%. Incorporating retesting of low signal RT-LAMP positives improved the specificity to 100%. We also speculate that hypothermia may be a significant early clinical sign of COVID-19. RT-LAMP testing for SARS-CoV-2 was found to be promising, fast and to work equivalently to RT-PCR methods. RT-LAMP has the potential to transform COVID-19 detection, bringing rapid and accurate testing to the PoC. RT-LAMP could be deployed in mobile community testing units, care homes and hospitals to detect disease early and prevent spread.
Abstract
Background
Frailty, increased vulnerability to physiological stressors, is associated with adverse outcomes. COVID-19 exhibits a more severe disease course in older, comorbid adults. ...Awareness of atypical presentations is critical to facilitate early identification.
Objective
To assess how frailty affects presenting COVID-19 symptoms in older adults.
Design
Observational cohort study of hospitalised older patients and self-report data for community-based older adults.
Setting
Admissions to St Thomas’ Hospital, London with laboratory-confirmed COVID-19. Community-based data for older adults using the COVID Symptom Study mobile application.
Subjects
Hospital cohort: patients aged 65 and over (n = 322); unscheduled hospital admission between 1 March 2020 and 5 May 2020; COVID-19 confirmed by RT-PCR of nasopharyngeal swab. Community-based cohort: participants aged 65 and over enrolled in the COVID Symptom Study (n = 535); reported test-positive for COVID-19 from 24 March (application launch) to 8 May 2020.
Methods
Multivariable logistic regression analysis performed on age-matched samples from hospital and community-based cohorts to ascertain association of frailty with symptoms of confirmed COVID-19.
Results
Hospital cohort: significantly higher prevalence of probable delirium in the frail sample, with no difference in fever or cough. Community-based cohort: significantly higher prevalence of possible delirium in frailer, older adults and fatigue and shortness of breath.
Conclusions
This is the first study demonstrating higher prevalence of probable delirium as a COVID-19 symptom in older adults with frailty compared to other older adults. This emphasises need for systematic frailty assessment and screening for delirium in acutely ill older patients in hospital and community settings. Clinicians should suspect COVID-19 in frail adults with delirium.
Background. Convalescent serum and blood were used to treat patients during outbreaks of Zaire ebolavirus (ZEBOV) infection in 1976 and 1995, with inconclusive results. During the recent 2013-2016 ...West African epidemic, serum/plasma from survivors of ZEBOV infection was used to treat patients in the affected countries and several repatriated patients. The effectiveness of this strategy remains unknown. Methods. Nine rhesus monkeys were experimentally infected with ZEBOV-Makona. Beginning on day 3 after exposure (at the onset of viremia), 4 animals were treated with homologous ZEBOV-Makona convalescent macaque sera, 3 animals were treated in parallel with heterologous Sudan ebolavirus (SEBOV) convalescent macaque sera, and 2 animals served as positive controls and were not treated. Surviving animals received additional treatments on days 6 and 9. Results. Both untreated control animals died on postinfection day 9. All 4 ZEBOV-Makona-infected macaques treated with homologous ZEBOV-Makona convalescent sera died on days 8-9. One macaque treated with heterologous SEBOV convalescent sera survived, while the other animals treated with the heterologous SEBOV sera died on days 7 and 9. Conclusions. The findings suggest that convalescent sera alone is not sufficient for providing 100% protection against lethal ZEBOV infection when administered at the onset of viremia.
Marburg virus (MARV) and the closely related filovirus Ebola virus cause severe and often fatal hemorrhagic fever (HF) in humans and nonhuman primates with mortality rates up to 90%. There are no ...vaccines or drugs approved for human use, and no postexposure treatment has completely protected nonhuman primates against MARV-Angola, the strain associated with the highest rate of mortality in naturally occurring human outbreaks. Studies performed with other MARV strains assessed candidate treatments at times shortly after virus exposure, before signs of disease are detectable. We assessed the efficacy of lipid nanoparticle (LNP) delivery of anti-MARV nucleoprotein (NP)-targeting small interfering RNA (siRNA) at several time points after virus exposure, including after the onset of detectable disease in a uniformly lethal nonhuman primate model of MARV-Angola HF. Twenty-one rhesus monkeys were challenged with a lethal dose of MARV-Angola. Sixteen of these animals were treated with LNP containing anti-MARV NP siRNA beginning at 30 to 45 min, 1 day, 2 days, or 3 days after virus challenge. All 16 macaques that received LNP-encapsulated anti-MARV NP siRNA survived infection, whereas the untreated or mock-treated control subjects succumbed to disease between days 7 and 9 after infection. These results represent the successful demonstration of therapeutic anti-MARV-Angola efficacy in nonhuman primates and highlight the substantial impact of an LNP-delivered siRNA therapeutic as a countermeasure against this highly lethal human disease.
Purpose
Trastuzumab improves survival in patients with HER2+ early breast cancer. However, cardiotoxicity remains a concern, particularly in the curative setting, and there are limited data on its ...incidence outside of clinical trials. We retrospectively evaluated the cardiotoxicity rates left ventricular ejection fraction (LVEF) decline, congestive heart failure (CHF), cardiac death or trastuzumab discontinuation and assessed the performance of a proposed model to predict cardiotoxicity in routine clinical practice.
Methods
Patients receiving curative trastuzumab between 2011 and 2018 were identified. Demographics, treatments, assessments and toxicities were recorded. Fisher’s exact test, Chi-squared and logistic regression were used.
Results
931 patients were included in the analysis. Median age was 54 years (range 24–83) and Charlson comorbidity index 0 (0–6), with 195 patients (20.9%) aged 65 or older. 228 (24.5%) were smokers. Anthracyclines were given in 608 (65.3%). Median number of trastuzumab doses was 18 (1–18). The HFA-ICOS cardiovascular risk was low in 401 patients (43.1%), medium in 454 (48.8%), high in 70 (7.5%) and very high in 6 (0.6%). Overall, 155 (16.6%) patients experienced cardiotoxicity: LVEF decline ≥ 10% in 141 (15.1%), falling below 50% in 55 (5.9%), CHF NYHA class II in 42 (4.5%) and class III–IV in 5 (0.5%) and discontinuation due to cardiac reasons in 35 (3.8%). No deaths were observed. Cardiotoxicity rates increased with HFA-ICOS score (14.0% low, 16.7% medium, 30.3% high/very high;
p
= 0.002).
Conclusions
Cardiotoxicity was relatively common (16.6%), but symptomatic heart failure on trastuzumab was rare in our cohort. The HFA-ICOS score identifies patients at high risk of cardiotoxicity.
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