The present study assessed the criteria for initiating cytoreduction and response to conventional therapies in 1446 patients with essential thrombocythemia (ET), 267 (17%) of which were CALR‐mutated. ...In low risk patients, time from diagnosis to cytoreduction was shorter in CALR‐positive than in the other genotypes (2·8, 3·2, 7·4 and 12·5 years for CALR, MPL, JAK2V617F and TN, respectively, P < 0·0001). A total of 1104 (76%) patients received cytoreductive treatment with hydroxycarbamide (HC) (n = 977), anagrelide (n = 113), or others (n = 14). The estimated cumulative rates of complete haematological response (CR) at 12 months were 40 % and 67% in CALR and JAK2V617F genotypes, respectively. Median time to CR was 192 days for JAK2V617F, 343 for TN, 433 for MPL, and 705 for CALR genotypes (P < 0·0001). Duration of CR was shorter in CALR‐mutated ET than in the remaining patients (P = 0·003). In CALR‐positive patients, HC and anagrelide had similar efficacy in terms of response rates and duration. CALR‐mutated patients developed resistance/intolerance to HC more frequently (5%, 23%, 27% and 15% for JAK2V617F, CALR, MPL and TN, respectively; P < 0·0001). In conclusion, conventional cytoreductive agents are less effective in CALR‐mutated ET, highlighting the need for new treatment modalities and redefinition of haematologic targets for patients with this genotype.
Hyponatremia (HN) < 135 mmol/L is a frequent finding in children with community-acquired pneumonia (CAP). We aimed to determine the proportion of syndrome of inappropriate antidiuretic hormone ...secretion (SIADH) among patients with CAP and HN. Moreover, we wished to investigate the relationship between HN and inflammatory markers, bacterial etiology and prognosis in hospitalized children with CAP.
We carried out a prospective, observational, multicentre, prospective cohort study. Eligible participants were children from 1 month to 17 years old hospitalized due to CAP from 2012 to 2015.
A total of 150 children were analyzed. Forty-five (30%) patients had serum sodium levels of less than 135 mmol/L. Patients with HN had significantly higher concentrations of inflammatory biomarkers. They also had significantly lower osmolality and urine sodium. They also had longer hospitalizations and more days of fever. Only 16 out of the 45 (35%) patients with HN had confirmed calculated plasma osmolality (<275 mOsm/kg). Only 5 out of 37 (13%) patients with available measurements of plasma osmolality and urine sodium fulfilled the criteria for SIADH. Among the 16 patients with HN and hypo-osmolality, 15 had a fractional sodium excretion (EFNa) levels of less than 1%. We found a significant inverse linear correlation between serum sodium and C-reactive protein, as well as serum sodium and procalcitonin. We found a significant direct correlation between serum sodium and urine sodium.
HN is a common finding in hospitalized children with CAP. True SIADH is a rare event. HN has a good correlation with inflammatory biomarkers.
Several studies have analyzed the relationship between general personality traits and attitudes and behaviors, indicating that a person is more committed to the community. After raising the question ...of whether malevolent traits might also be related, the aim was to analyze the relationship between civic engagement and personality, delving into the contribution of the Dark Triad (narcissism, Machiavellianism, and psychopathy) and controlling for the association with the Big Five. The Civic Engagement Questionnaire, the Short Dark Triad, and the Big Five Inventory-10 were administered to 1175 Spanish students (convenience sampling). After performing statistical analyses using SPSS statistical software, it was obtained that the three Dark Triad traits explained 11% of the total explained variance of civic engagement, while 19% was reached when the Big Five were included. Narcissism and openness were the factors most strongly associated with engagement. The positive relationship between narcissism and general personality traits could explain why narcissistic people have more favorable attitudes. Furthermore, people with narcissistic traits may display these attitudes for their own benefit. This study provides further evidence of how the narcissistic personality trait differs from the other two malevolent traits. Given that these traits are also associated with maladaptive behaviors, knowing all their characteristics could facilitate the design of prevention programs aimed at reducing such maladaptive behaviors.
The mechanisms driving SARS-CoV-2 susceptibility remain poorly understood, especially the factors determining why unvaccinated individuals remain uninfected despite high-risk exposures. To understand ...lipid and metabolite profiles related with COVID-19 susceptibility and disease progression. We collected samples from an exceptional group of unvaccinated healthcare workers heavily exposed to SARS-CoV-2 but not infected ('non-susceptible') and subjects who became infected during the follow-up ('susceptible'), including non-hospitalized and hospitalized patients with different disease severity providing samples at early disease stages. Then, we analyzed their plasma metabolomic profiles using mass spectrometry coupled with liquid and gas chromatography. We show specific lipids profiles and metabolites that could explain SARS-CoV-2 susceptibility and COVID-19 severity. More importantly, non-susceptible individuals show a unique lipidomic pattern characterized by the upregulation of most lipids, especially ceramides and sphingomyelin, which could be interpreted as markers of low susceptibility to SARS-CoV-2 infection. This study strengthens the findings of other researchers about the importance of studying lipid profiles as relevant markers of SARS-CoV-2 pathogenesis.
A collection of 694 soil samples was taken from 367 sites (at a density of 1 site per 120 km2) in the western of Andalusia (SW Spain) to establish regional geochemical background of emerging critical ...elements on the < 2 mm soil fraction, and provide threshold values for anomaly detection to support mineral exploration in the survey area. The spatial distribution pattern of the soil geochemical anomalies is primarily influenced by the occurrence of magmatic alignments and metallogenic belts in the southern zones of the Iberian Massif. Soils over granitic parent materials are marked by W, Be, Ta and REE anomalies, whereas those derived from mafic igneous rocks contain anomalous concentrations of Sc, Co and V. Most of the threshold exceedances for Hf and Sb appear to be linked to soils on pelitic metasediments. The distribution of Sb and Co outliers is also related to sulfide ore occurrences in the bedrock and could be affected by anthropogenic influences. The Santa Olalla igneous complex, the granodioritic pluton of the Los Pedroches batholith and the magmatic alignment of Villaviciosa de Córdoba-La Coronada may represent exploration opportunities for high-tech elements, mainly for REE, although the identification of promising areas requires further investigation.
•Geochemical baselines of selected critical elements in soil were established.•Threshold values for mild and extreme anomaly detection were provided.•Bedrock lithology was inferred as the major source of soil geochemical anomalies.•Regional geology, parent rock and soil type influence the spatial distribution.
Extended-spectrum beta-lactamases (ESBL) constitute a key antibiotic-resistance mechanism affecting Gram-negative bacteria, and also an excellent model for studying evolution in real time. A shift in ...the epidemiology of ESBLs is being observed, which is characterized by the explosive diversification and increase in frequency of the CTX-M-type beta-lactamases in different settings. This provides a unique opportunity for studying a protein evolutionary radiation by the sequential acquisition of specific mutations enhancing protein efficiency and fitness concomitantly. The existence of driver antibiotic molecules favoring protein divergence has been investigated by combining evolutionary analyses and experimental site-specific mutagenesis. Phylogenetic reconstruction with all the CTX-M variants described so far provided a hypothetical evolutionary scenario showing at least three diversification events. CTX-M-3 was likely the enzyme at the origin of the diversification in the CTX-M-1 cluster, which was coincident with positive selection acting on several amino acid positions. Sixty-three CTX-M-3 derivatives containing all combinations of mutations under positively selected positions were constructed, and their phenotypic efficiency was evaluated. The CTX-M-3 diversification process can only be explained in a complex selective landscape with at least two antibiotics (cefotaxime and ceftazidime), indicating the need to invoke mixtures of selective drivers in order to understand the final evolutionary outcome. Under this hypothesis, we found congruent results between the in silico and in vitro analyses of evolutionary trajectories. Three pathways driving the diversification of CTX-M-3 towards the most complex and efficient variants were identified. Whereas the P167S pathway has limited possibilities of further diversification, the D240G route shows a robust diversification network. In the third route, drift may have played a role in the early stages of CTX-M-3 evolution. Antimicrobial agents should not be considered only as selectors for efficient mechanisms of resistance but also as diversifying agents of the evolutionary trajectories. Different trajectories were identified using a combination of phylogenetic reconstructions and directed mutagenesis analyses, indicating that such an approach might be useful to fulfill the desirable goal of predicting evolutionary trajectories in antimicrobial resistance.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This study aimed to assess the baseline characteristics and clinical outcomes of coronavirus disease 2019 (COVID-19) in pediatric patients with rheumatic and musculoskeletal diseases (RMD) and ...identify the risk factors associated with symptomatic or severe disease defined as hospital admission, intensive care admission or death.
An observational longitudinal study was conducted during the first year of the SARS-CoV-2 pandemic (March 2020-March 2021). All pediatric patients attended at the rheumatology outpatient clinics of six tertiary referral hospitals in Madrid, Spain, with a diagnosis of RMD and COVID-19 were included. Main outcomes were symptomatic disease and hospital admission. The covariates were sociodemographic and clinical characteristics and treatment regimens. We ran a multivariable logistic regression model to assess associated factors for outcomes.
The study population included 77 pediatric patients. Mean age was 11.88 (4.04) years Of these, 30 patients (38.96%) were asymptomatic, 41 (53.25%) had a mild-moderate COVID-19 and 6 patients (7.79%) required hospital admission. The median length of hospital admission was 5 (2-20) days, one patient required intensive care and there were no deaths. Previous comorbidities increased the risk for symptomatic disease and hospital admission. Compared with outpatients, the factor independently associated with hospital admission was previous use of glucocorticoids (OR 3.51; p = 0.00). No statistically significant risk factors for symptomatic COVID-19 were found in the final model.
No differences in COVID-19 outcomes according to childhood-onset rheumatic disease types were found. Results suggest that associated comorbidities and treatment with glucocorticoids increase the risk of hospital admission.
Tuberculosis (TB) is still a severe public health problem; the current diagnostic tests have limitations that delay treatment onset. Lipoarabinomannan (LAM) is a glycolipid that is a component of the ...cell wall of the bacillus
, the etiologic agent of TB. This glycolipid is excreted as a soluble form in urine. The World Health Organization has established that the design of new TB diagnostic methods is one of the priorities within the EndTB Strategy. LAM has been suggested as a biomarker to develop diagnostic tests based on its identification in urine, and it is one of the most prominent candidates to develop point-of-care diagnostic test because urine samples can be easily collected. Moreover, LAM can regulate the immune response in the host and can be found in the serum of TB patients, where it probably affects a wide variety of host cell populations, consequently influencing the quality of both innate and adaptive immune responses during TB infection. Here, we revised the evidence that supports that LAM could be used as a tool for the development of new point-of-care tests for TB diagnosis, and we discussed the mechanisms that could contribute to the low sensitivity of diagnostic testing.
Abstract Objectives Automated molecular analyzers have accelerated diagnosis, allowing earlier intervention and better patient follow-up. A recently developed completely automated molecular analyzer, ...Alinity™ m (Abbott), offers consolidated, continuous, and random-access testing that may improve molecular laboratory workflow. Methods An international, multicenter study compared laboratory workflow metrics across various routine analyzers and Alinity m utilizing assays for human immunodeficiency virus type 1 (HIV-1), hepatitis C virus (HCV), hepatitis B virus (HBV), high-risk human papillomavirus (HR HPV), and sexually transmitted infection (STI) ( Chlamydia trachomatis CT/ Neisseria gonorrhoeae NG/ Trichomonas vaginalis TV/ Mycoplasma genitalium MG). Three turnaround times (TATs) were assessed: total TAT (sample arrival to result), sample onboard TAT (sample loading and test starting to result), and processing TAT (sample aspiration to result). Results Total TAT was reduced from days with routine analyzers to hours with Alinity m, independent of requested assays. Sample onboard TATs for standard workflow using routine analyzers ranged from 7 to 32.5 h compared to 2.75–6 h for Alinity m. The mean sample onboard TAT for STAT samples on Alinity m was 2.36 h (±0.19 h). Processing TATs for Alinity m were independent of the combination of assays, with 100% of results reported within 117 min. Conclusions The consolidated, continuous, random-access workflow of Alinity m reduces TATs across various assays and is expected to improve both laboratory operational efficiency and patient care.
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