An increased risk of venous thromboembolism (VTE) in patients with COVID-19 pneumonia admitted to intensive care unit (ICU) has been reported. Whether COVID-19 increases the risk of VTE in non-ICU ...wards remains unknown. We aimed to evaluate the burden of asymptomatic deep vein thrombosis (DVT) in COVID-19 patients with elevated D-dimer levels.
In this prospective study consecutive patients hospitalized in non-intensive care units with diagnosis of COVID-19 pneumonia and D-dimer > 1000 ng/ml were screened for asymptomatic DVT with complete compression doppler ultrasound (CCUS). The study was approved by the Institutional Ethics Committee.
The study comprised 156 patients (65.4% male). All but three patients received standard doses of thromboprophylaxis. Median days of hospitalization until CCUS was 9 (IQR 5–17). CCUS was positive for DVT in 23 patients (14.7%), of whom only one was proximal DVT. Seven patients (4.5%) had bilateral distal DVT. Patients with DVT had higher median D-dimer levels: 4527 (IQR 1925-9144) ng/ml vs 2050 (IQR 1428-3235) ng/ml; p < 0.001. D-dimer levels > 1570 ng/ml were associated with asymptomatic DVT (OR 9.1; CI 95% 1.1–70.1). D-dimer showed an acceptable discriminative capacity (area under the ROC curve 0.72, 95% CI 0.61–0.84).
In patients admitted with COVID-19 pneumonia and elevated D-dimer levels, the incidence of asymptomatic DVT is similar to that described in other series. Higher cut-off levels for D-dimer might be necessary for the diagnosis of DVT in COVID-19 patients.
•An increased risk of VTE in patients with COVID-19 pneumonia admitted to intensive care unit has been reported.•The most consistent hemostatic abnormalities with COVID-19 include mild thrombocytopenia and increased D-dimer levels.•In COVID-19 patients with high D-dimer levels, the incidence of asymptomatic DVT is similar to that described in other series.•Higher cut-off levels for D-dimer might be necessary for the diagnosis of DVT in COVID-19 patients.
Summary
Background
Nonsteroidal anti‐inflammatory drugs (NSAIDs) are the main triggers of drug hypersensitivity, with NSAID‐induced acute urticaria/angioedema (NIUA) the most frequent phenotype. ...NSAID hypersensitivity is caused by cyclooxygenase 1 inhibition, which leads to an imbalance in prostaglandin (PG) and cysteinyl leukotriene (CysLT) synthesis. As only susceptible individuals develop NSAID hypersensitivity, genetic factors are believed to be involved; however, no study has assessed the overall genetic variability of key enzymes in PG and CysLT synthesis in NSAID hypersensitivity.
Objectives
To evaluate simultaneously variants in the main genes involved in PG and CysLT biosynthesis in NIUA.
Methods
Two independent cohorts of patients were recruited in Spain, alongside NSAID‐tolerant controls. The discovery cohort included only patients with NIUA; the replication cohort included patients with NSAID‐exacerbated respiratory disease (NERD). A set of tagging single‐nucleotide polymorphisms (tagSNPs) in PTGS1, PTGS2, ALOX5 and LTC4S was genotyped using mass spectrometry coupled with endpoint polymerase chain reaction.
Results
The study included 1272 individuals. Thirty‐five tagSNPs were successfully genotyped in the discovery cohort, with three being significantly associated after Bonferroni correction (rs10306194 and rs1330344 in PTGS1; rs28395868 in ALOX5). These polymorphisms were genotyped in the replication cohort: rs10306194 and rs28395868 remained associated with NIUA, and rs28395868 was marginally associated with NERD. Odds ratios (ORs) in the combined analysis (discovery and replication NIUA populations) were 1·7 for rs10306194 95% confidence interval (CI) 1·34–2·14; Pcorrected = 2·83 × 10–4) and 2·19 for rs28395868 (95% CI 1·43–3·36; Pcorrected = 0·002).
Conclusions
Variants of PTGS1 and ALOX5 may play a role in NIUA and NERD, supporting the proposed mechanisms of NSAID‐hypersensitivity and shedding light on their genetic basis.
What is already known about this topic?
Nonsteroidal anti‐inflammatory drugs (NSAIDs) are the main triggers of drug hypersensitivity reactions, with skin the most frequently affected organ.
The underlying mechanism is linked to cyclooxygenase (COX)‐1 inhibition and to imbalance in eicosanoid metabolism (mainly prostaglandins and cysteinyl leukotriene).
The idiosyncratic nature of NSAID hypersensitivity supports the involvement of genetic factors.
No study has simultaneously evaluated the potential role of genetic variants in the main eicosanoid synthesis enzymes in these reactions.
What does this study add?
rs10306194 (PTGS1) and rs28395868 (ALOX5) were associated with the risk of NSAID‐induced acute urticaria/angioedema in two independent populations, with the latter also being associated with NSAID‐exacerbated respiratory disease.
rs10306194 could help to discriminate those with NIUA from those whose respiratory symptoms are exacerbated after NSAID intake.
Our results add credence to the COX‐1 inhibition hypothesis in NSAID hypersensitivity and could help to differentiate its clinical phenotypes.
What is the translational message?
Diagnosis of NSAID hypersensitivity is a daily challenge in clinical settings as there is a lack of in vivo and in vitro tests, and drug provocation is not a risk‐free procedure.
Genetic research can provide substantial information not only to understand fully the underlying mechanism, but also to identify potential biomarkers for diagnosis and to develop targeted precision therapies.
Linked Comment: C. Flores. Br J Dermatol 2021; 185:697–698.
We report chemical abundances obtained by Sloan Digital Sky Survey (SDSS)-III/Apache Point Observatory Galactic Evolution Experiment for giant stars in five globular clusters located within 2.2 kpc ...of the Galactic Centre. We detect the presence of multiple stellar populations in four of those clusters (NGC 6553, NGC 6528, Terzan 5 and Palomar 6) and find strong evidence for their presence in NGC 6522. All clusters with a large enough sample present a significant spread in the abundances of N, C, Na and Al, with the usual correlations and anticorrelations between various abundances seen in other globular clusters. Our results provide important quantitative constraints on theoretical models for self-enrichment of globular clusters, by testing their predictions for the dependence of yields of elements such as Na, N, C and Al on metallicity. They also confirm that, under the assumption that field N-rich stars originate from globular cluster destruction, they can be used as tracers of their parental systems in the high-metallicity regime.
Atmospheric escape is key to explaining the long-term evolution of planets in our solar system and beyond, and in the interpretation of atmospheric measurements. Hydrodynamic escape is generally ...thought to be driven by the flux of extreme-ultraviolet photons that the planet receives from its host star. Here, we show that the escape from planets orbiting hot stars proceeds through a different yet complementary process: drawing its energy from the intense near-ultraviolet emission of the star that is deposited within an optically thin, high-altitude atmospheric layer of hydrogen excited into the lower state of the Balmer series. The ultra-hot exoplanet KELT-9b likely represents the first known instance of this Balmer-driven escape. In this regime of hydrodynamic escape, the near-ultraviolet emission from the star is more important at determining the planet mass loss than the extreme-ultraviolet emission, and uncertainties in the latter become less critical. Further, we predict that gas exoplanets around hot stars may experience catastrophic mass loss when they are less massive than 1-2 Jupiter masses and closer in than KELT-9b, thereby challenging the paradigm that all large exoplanets are stable to atmospheric escape. We argue that extreme escape will affect the demographics of close-in exoplanets orbiting hot stars.
GJ 3470b is a warm Neptune transiting an M-dwarf star at the edge of the evaporation desert. It offers the possibility of investigating how low-mass, close-in exoplanets evolve under the irradiation ...from their host stars. We observed three transits of GJ 3470b in the Lyman-α line with the Hubble Space Telescope (HST) as part of the Panchromatic Comparative Exoplanet Treasury (PanCET) program. Absorption signatures are detected with similar properties in all three independent epochs, with absorption depths of 35 ± 7% in the blue wing of the line, and 23 ± 5% in the red wing. The repeatability of these signatures, their phasing with the planet transit, and the radial velocity of the absorbing gas allow us to conclude that there is an extended upper atmosphere of neutral hydrogen around GJ 3470b. We determine from our observations the stellar radiation pressure and XUV irradiation from GJ 3470 and use them to perform numerical simulations of the upper atmosphere of GJ 3470b with the EVaporating Exoplanets (EVE) code. The unusual redshifted signature can be explained by the damping wings of dense layers of neutral hydrogen that extend beyond the Roche lobe and are elongated in the direction of the planet motion. This structure could correspond to a shocked layer of planetary material formed by the collision of the expanding thermosphere with the wind of the star. The blueshifted signature is well explained by neutral hydrogen atoms escaping at rates of about 1010 g s−1 that are blown away from the star by its strong radiation pressure and are quickly photoionized, resulting in a smaller exosphere than that of the warm Neptune GJ 436b. The stronger escape from GJ 3470b, however, may have led to the loss of about 4–35% of its current mass over its ~2 Gyr lifetime.
Solar water disinfection (SODIS) is one the cheapest and most suitable treatments to produce safe drinking water at the household level in resource-poor settings. This review introduces the main ...parameters that influence the SODIS process and how new enhancements and modelling approaches can overcome some of the current drawbacks that limit its widespread adoption. Increasing the container volume can decrease the recontamination risk caused by handling several 2 L bottles. Using container materials other than polyethylene terephthalate (PET) significantly increases the efficiency of inactivation of viruses and protozoa. In addition, an overestimation of the solar exposure time is usually recommended since the process success is often influenced by many factors beyond the control of the SODIS-user. The development of accurate kinetic models is crucial for ensuring the production of safe drinking water. This work attempts to review the relevant knowledge about the impact of the SODIS variables and the techniques used to develop kinetic models described in the literature. In addition to the type and concentration of pathogens in the untreated water, an ideal kinetic model should consider all critical factors affecting the efficiency of the process, such as intensity, spectral distribution of the solar radiation, container-wall transmission spectra, ageing of the SODIS reactor material, and chemical composition of the water, since the substances in the water can play a critical role as radiation attenuators and/or sensitisers triggering the inactivation process.
Summary
Patients with rheumatoid arthritis (RA) may be classified as seropositive or seronegative according to the presence of autoantibodies. An abnormal B cell phenotype and function could be one ...of the main components of the immunopathology of seropositive patients; however, there is little information regarding B cell defects in these patients. This study shows a broad characterization of the B cell phenotype and function in patients with seropositive RA. We focused mainly on the evaluation of subsets, the expression of modulatory molecules of cell activation (CD22, FcɣRIIb and FcµR), calcium mobilization, global tyrosine phosphorylation, expression of activation markers, cytokine and immunoglobulin (Ig) production, proliferation and the in‐vitro generation of plasma cells. Increased frequency of CD27−IgM−IgD− and CD21− B cells was observed in patients with seropositive RA compared with healthy donors (HD). Decreased expression of CD22 was primarily found in memory B cells of patients with RA regardless of seropositivity. B cells from seropositive patients exhibited normal proliferation, calcium mobilization kinetics and global tyrosine phosphorylation, but showed an increased frequency of CD86+ B cells compared with HD. B cells of seropositive patients secrete less interleukin‐10 after in‐vitro activation and showed a decreased frequency of plasma cell differentiation and IgM production compared with HD. Our data indicate that patients with seropositive RA have an increased frequency of atypical B cell populations previously associated with chronic activation and antigen exposure. This may result in the observed low responsiveness of these cells in vitro.
Patients with seropositive rheumatoid arthritis (RA) exhibit increased frequency of the atypical CD27−IgM−IgD− and CD21− B cell subsets compared with seronegative patients and healthy donors (HD). B cells of patients, mainly memory subsets, exhibit lower expression of CD22 compared with HD, regardless of seropositivity and disease activity. B cells from patients with seropositive RA showed high frequency of CD86+ cells, low levels of IL‐10, and decreased frequency of plasma cells after in vitro activation compared with HD. These results show the presence of atypical phenotype and altered response of B cells from patients with seropositive RA.
Terrestrial exoplanets orbiting within or near their host stars' habitable zone are potentially apt for life. It has been proposed that time-series measurements of reflected starlight from such ...planets will reveal their rotational period, main surface features and some atmospheric information. From imagery obtained with the Akatsuki spacecraft, here we show that Venus' brightness at 283, 365, and 2020 nm is modulated by one or both of two periods of 3.7 and 4.6 days, and typical amplitudes <10% but occasional events of 20-40%. The modulations are unrelated to the solid-body rotation; they are caused by planetary-scale waves superimposed on the super-rotating winds. Here we propose that two modulation periods whose ratio of large-to-small values is not an integer number imply the existence of an atmosphere if detected at an exoplanet, but it remains ambiguous whether the atmosphere is optically thin or thick, as for Earth or Venus respectively. Multi-wavelength and long temporal baseline observations may be required to decide between these scenarios. Ultimately, Venus represents a false positive for interpretations of brightness modulations of terrestrial exoplanets in terms of surface features.
Solar water disinfection (SODIS) is a simple, inexpensive and sustainable Household Water Treatment (HWT) that is appropriate for low-income countries or emergency situations. Usually, SODIS involves ...solar exposure of water contained in transparent polyethylene terephthalate (PET) bottles for a minimum of 6 h. Sunlight, especially UVB radiation, has been demonstrated to photoinactivate bacteria, viruses and protozoa. In this work, an in-depth study of the optical and mechanical properties, weathering and production prices of polymeric materials has been carried out to identify potential candidate materials for manufacturing SODIS devices. Three materials were ruled out (polystyrene (PS), polyvinyl chloride (PVC) and polyethylene (PE)) and four materials were initially selected for study: polymethylmethacrylate (PMMA), polypropylene (PP), polycarbonate (PC) and polyethylene terephthalate (PET). These plastics transmit sufficient solar radiation to kill waterborne pathogens with production costs compensated by their durability under solar exposure.
A predictive model has been developed to quantitatively estimate the radiation available for SODIS inside the device as a function of the material and thickness. This tool has two applications: to evaluate design parameters such as thickness, and to estimate experimental requirements such as solar exposure time. In this work, this model evaluated scenarios involving different plastic materials, device thicknesses, and pathogens (Escherichia coli bacterium, MS2 virus and Cryptosporidium parvum protozoon). The developed Solar UV Calculator model is freely available and can be also applied to other customized materials and conditions.
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•Revision of mechanical and optical properties, weathering and costs of plastics•Selection of optimal materials for SODIS container manufacturing•Development of a tool for estimating UV radiation available inside containers•Predictive evaluation of bacteria, viruses and protozoa solar inactivation•Freely available Solar UV Calculator for custom evaluation of solar irradiance
Fatigue is one of the most prevalent symptoms among cancer patients. Specifically, in metastatic castration-resistant prostate cancer (mCRPC) patients, fatigue is the most common adverse event ...associated with current treatments. The purpose of this study is to describe the prevalence of fatigue and its impact on quality of life (QoL) in patients with CRPC in routine clinical practice.
This was a cross-sectional, multicentre study. Male chemo-naïve adults with high-risk non-metastatic (M0) CRPC and metastatic (M1) CRPC (mCRPC) were eligible. Fatigue was measured using the Brief Fatigue Inventory (BFI) and QoL was assessed using the Functional Assessment of Cancer Therapy questionnaire for patients with prostate cancer (FACT-P) and the FACT-General (FACT-G) questionnaire. Data were analysed using Mann-Whitney or Kruskal-Wallis tests (non-parametric distribution), a T-test or an ANOVA (parametric distribution) and the Fisher or chi-squared tests (categorical variables).
A total of 235 eligible patients were included in the study (74 31.5% with M0; and 161 68.5% with M1). Fatigue was present in 74%, with 38.5% of patients reporting moderate-to-severe fatigue. Mean FACT-G and FACT-P overall scores were 77.6 ± 16.3 and 108.7 ± 21.4, respectively, with no differences between the CRPC M0 and CRPC M1 subgroups. Fatigue intensity was associated with decreased FACT-G/P scores, with no differences between groups. Among 151 mCRPC patients with available treatment data, those treated with abiraterone-prednisone ≥3 months showed a significant reduction in fatigue intensity (p = 0.043) and interference (p = 0.04) compared to those on traditional hormone therapy (HT). Patients on abiraterone-prednisone ≥3 months showed significantly better FACT-G/P scores than patients on HT (p = 0.046 and 0.018, respectively).
Our data show a high prevalence and intensity of fatigue and its impact on QoL in chemo-naïve CRPC patients. There is an association between greater fatigue and less QoL, irrespective of the presence or absence of metastasis. Chemo-naïve mCRPC patients receiving more than 3 months of abiraterone acetate plus prednisone showed an improvement of fatigue and QoL when compared to those on traditional HT.
Not applicable since it is not an interventional study.
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