Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection are often non-specific, and there is no definitive test for the accurate diagnosis of infection. The 'omics' approaches to identifying biomarkers from the host-response to bacterial infection are promising. In this study, lipidomic analysis was carried out with plasma samples obtained from febrile children with confirmed bacterial infection (n = 20) and confirmed viral infection (n = 20). We show for the first time that bacterial and viral infection produces distinct profile in the host lipidome. Some species of glycerophosphoinositol, sphingomyelin, lysophosphatidylcholine and cholesterol sulfate were higher in the confirmed virus infected group, while some species of fatty acids, glycerophosphocholine, glycerophosphoserine, lactosylceramide and bilirubin were lower in the confirmed virus infected group when compared with confirmed bacterial infected group. A combination of three lipids achieved an area under the receiver operating characteristic (ROC) curve of 0.911 (95% CI 0.81 to 0.98). This pilot study demonstrates the potential of metabolic biomarkers to assist clinicians in distinguishing bacterial from viral infection in febrile children, to facilitate effective clinical management and to the limit inappropriate use of antibiotics

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection are often non-specific, and there is no definitive test for the accurate diagnosis of infection. The 'omics' approaches to identifying biomarkers from the host-response to bacterial infection are promising. In this study, lipidomic analysis was carried out with plasma samples obtained from febrile children with confirmed bacterial infection (n = 20) and confirmed viral infection (n = 20). We show for the first time that bacterial and viral infection produces distinct profile in the host lipidome. Some species of glycerophosphoinositol, sphingomyelin, lysophosphatidylcholine and cholesterol sulfate were higher in the confirmed virus infected group, while some species of fatty acids, glycerophosphocholine, glycerophosphoserine, lactosylceramide and bilirubin were lower in the confirmed virus infected group when compared with confirmed bacterial infected group. A combination of three lipids achieved an area under the receiver operating characteristic (ROC) curve of 0.911 (95% CI 0.81 to 0.98). This pilot study demonstrates the potential of metabolic biomarkers to assist clinicians in distinguishing bacterial from viral infection in febrile children, to facilitate effective clinical management and to the limit inappropriate use of antibiotics

Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection ar

Psychoaktivní sloučeniny ve vodním prostředí a jejich účinky na ryby

Psychoactive substances are emerging compounds that have received an increasing interest in ecotoxicology as a result of their ubiquitous presence in the environment, and the possible effects over non-targeted fauna. They have been detected in continental waters at concentrations ranging from nanograms to micrograms per litre, mainly as a consequence of the ineffective removal in the sewage treatment plants. Within this group of substances, methamphetamine and tramadol were selected in this dissertation due to the lack of research about their potential effects despite of the high amounts reported in water. Methamphetamine, mainly consumed as an illicit drug, is an addictive psychostimulant with special relevance in Central Europe. Environmental relevant and higher concentrations of methamphetamine in water leaded to histopathological alterations in heart and liver in brown trout (Salmo trutta m. fario). The major changes in heart were microvascular injuries, infiltration and fibrosis; and cytoplasmatic vacuolation of hepatocytes in liver. In addition, apoptotic changes were observed in liver. The findings were very similar to those reported in human and experimental animals. The parent compound and the main metabolite, amphetamine, were detected in trout tissues following the order kidney > liver > brain > muscle > plasma. The concentrations of the metabolite were evidently higher comparing to the parent compound; therefore, the histological findings could be suspected to partially derivate from amphetamine. Behaviour - i.e. activity and place preference - and metabolome changes for the period of withdrawal were observed in trouts, linked to remnants of the parent compound and the metabolite in brain. Tramadol is an extensively used analgesic which singular mode of action provides added antidepressant and anxiolytic effects. Realistic concentration of tramadol in water was found to impair essential behavioural traits in the chub (Squalius cephalus) - a native fish species in Central Europe. The degree of the outcomes was correlated with the individual amounts of tramadol in brain. Exposed fish exhibited anxiolytic-like effects, illustrated by lesser bold and social individuals comparing to controls. In the boldness test, exposed fish were less frequently out of the shelter and moved a shorter distance, therefore, they explored the new environment less than control fish. The novel object recognition experiment indicated that, although they distinguished the new item, their activity was reduced, and they explored the new object less. The increased interindividual distance indicated that the shoal cohesion was disturbed. The behavioural traits were associated to the treatment, suggesting the influence of the pollutant over fish personality. Bioconcentration factors for tramadol and methamphetamine were low in all cases, thus, the probability of bioconcentration for these substances is very low. However, these compounds are continuously released into water, leading to their pseudo-persistence and the consequent presence in tissues. The occurrence in fish, and the parallelism in the target signalization result in similar actions in these organisms comparing to human and experimental models. Here we evidenced that the water pollution with the tested neuroactive substances in the aquatic compartment could lead to unexpected effects over fauna, and subsequent changes in the whole aquatic ecosystem

Environmental concentration of methamphetamine induces pathological changes in brown trout (Salmo trutta fario)

Methamphetamine, mainly consumed as an illicit drug, is a potent addictive psychostimulant that has been detected in surface water at concentrations ranging from nanograms to micrograms per litre, especially in Middle and East Europe. The aim of this study was to expose brown trout (Salmo trutta fario) to environmental (1 μg L−1) and higher (50 μg L−1) concentrations of methamphetamine for 35 days with a four-day depuration phase to assess the possible negative effects on fish health. Degenerative liver and heart alterations, similar to those described in mammals, were observed at both concentrations, although at different intensities. Apoptotic changes in hepatocytes, revealed by activated caspase-3, were found in exposed fish. The parent compound and a metabolite (amphetamine) were detected in fish tissues in both concentration groups, in the order of kidney > liver > brain > muscle > plasma. Bioconcentration factors ranged from 0.13 to 80. A therapeutic plasma concentration was reached for both compounds in the high-concentration treatment. This study indicates that chronic environmental concentrations of methamphetamine can lead to health issues in aquatic organisms

Periodontal regeneration using a xenogeneic bone substitute seeded with autologous periodontal ligament-derived mesenchymal stem cells: A 12-month quasi-randomized controlled pilot clinical trial.

Aim: To evaluate the safety and efficacy of autologous periodontal ligament-derived mesenchymal stem cells (PDL-MSCs) embedded in a xenogeneic bone substitute (XBS) for the regenerative treatment of intra-bony periodontal defects. Material and methods: This quasi-randomized controlled pilot phase II clinical trial included patients requiring a tooth extraction and presence of one intra-bony lesion (1-2 walls). Patients were allocated to either the experimental (XBS + 10 × 106 PDL-MSCs/100 mg) or the control group (XBS). Clinical and radiographical parameters were recorded at baseline, 6, 9 and 12 months. The presence of adverse events was also evaluated. Chi-square, Student's t test, Mann-Whitney U, repeated-measures ANOVA and regression models were used. Results: Twenty patients were included. No serious adverse events were reported. Patients in the experimental group (n = 9) showed greater clinical attachment level (CAL) gain (1.44, standard deviation [SD] = 1.87) and probing pocket depth (PPD) reduction (2.33, SD = 1.32) than the control group (n = 10; CAL gain = 0.88, SD = 1.68, and PPD reduction = 2.10, SD = 2.46), without statistically significant differences. Conclusion: The application of PDL-MSCs to XBS for the treatment of one- to two-wall intra-bony lesions was safe and resulted in low postoperative morbidity and appropriate healing, although its additional benefit, when compared with the XBS alone, was not demonstrated.Proyecto EC10-095 financiado por el Ministerio de SanidadDepto. de Especialidades Clínicas OdontológicasFac. de OdontologíaTRUEpu

Environmental and societal factors associated with COVID-19-related death in people with rheumatic disease: an observational study

Published by Elsevier Ltd.Background: Differences in the distribution of individual-level clinical risk factors across regions do not fully explain the observed global disparities in COVID-19 outcomes. We aimed to investigate the associations between environmental and societal factors and country-level variations in mortality attributed to COVID-19 among people with rheumatic disease globally. Methods: In this observational study, we derived individual-level data on adults (aged 18-99 years) with rheumatic disease and a confirmed status of their highest COVID-19 severity level from the COVID-19 Global Rheumatology Alliance (GRA) registry, collected between March 12, 2020, and Aug 27, 2021. Environmental and societal factors were obtained from publicly available sources. The primary endpoint was mortality attributed to COVID-19. We used a multivariable logistic regression to evaluate independent associations between environmental and societal factors and death, after controlling for individual-level risk factors. We used a series of nested mixed-effects models to establish whether environmental and societal factors sufficiently explained country-level variations in death. Findings: 14 044 patients from 23 countries were included in the analyses. 10 178 (72·5%) individuals were female and 3866 (27·5%) were male, with a mean age of 54·4 years (SD 15·6). Air pollution (odds ratio 1·10 per 10 μg/m3 [95% CI 1·01-1·17]; p=0·0105), proportion of the population aged 65 years or older (1·19 per 1% increase [1·10-1·30]; p<0·0001), and population mobility (1·03 per 1% increase in number of visits to grocery and pharmacy stores [1·02-1·05]; p<0·0001 and 1·02 per 1% increase in number of visits to workplaces [1·00-1·03]; p=0·032) were independently associated with higher odds of mortality. Number of hospital beds (0·94 per 1-unit increase per 1000 people [0·88-1·00]; p=0·046), human development index (0·65 per 0·1-unit increase [0·44-0·96]; p=0·032), government response stringency (0·83 per 10-unit increase in containment index [0·74-0·93]; p=0·0018), as well as follow-up time (0·78 per month [0·69-0·88]; p<0·0001) were independently associated with lower odds of mortality. These factors sufficiently explained country-level variations in death attributable to COVID-19 (intraclass correlation coefficient 1·2% [0·1-9·5]; p=0·14). Interpretation: Our findings highlight the importance of environmental and societal factors as potential explanations of the observed regional disparities in COVID-19 outcomes among people with rheumatic disease and lay foundation for a new research agenda to address these disparities.MAG is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (grant numbers K01 AR070585 and K24 AR074534 [JY]). KDW is supported by the Department of Veterans Affairs and the Rheumatology Research Foundation Scientist Development award. JAS is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (grant numbers K23 AR069688, R03 AR075886, L30 AR066953, P30 AR070253, and P30 AR072577), the Rheumatology Research Foundation (K Supplement Award and R Bridge Award), the Brigham Research Institute, and the R. Bruce and Joan M. Mickey Research Scholar Fund. NJP is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (T32-AR-007258). AD-G is supported by grants from the Centers for Disease Control and Prevention and the Rheumatology Research Foundation. RH was supported by the Justus-Liebig University Giessen Clinician Scientist Program in Biomedical Research to work on this registry. JY is supported by grants from the National Institutes of Health (K24 AR074534 and P30 AR070155).info:eu-repo/semantics/publishedVersio

Evaluation of a quality improvement intervention to reduce anastomotic leak following right colectomy (EAGLE): pragmatic, batched stepped-wedge, cluster-randomized trial in 64 countries

Background Anastomotic leak affects 8 per cent of patients after right colectomy with a 10-fold increased risk of postoperative death. The EAGLE study aimed to develop and test whether an international, standardized quality improvement intervention could reduce anastomotic leaks. Methods The internationally intended protocol, iteratively co-developed by a multistage Delphi process, comprised an online educational module introducing risk stratification, an intraoperative checklist, and harmonized surgical techniques. Clusters (hospital teams) were randomized to one of three arms with varied sequences of intervention/data collection by a derived stepped-wedge batch design (at least 18 hospital teams per batch). Patients were blinded to the study allocation. Low- and middle-income country enrolment was encouraged. The primary outcome (assessed by intention to treat) was anastomotic leak rate, and subgroup analyses by module completion (at least 80 per cent of surgeons, high engagement; less than 50 per cent, low engagement) were preplanned. Results A total 355 hospital teams registered, with 332 from 64 countries (39.2 per cent low and middle income) included in the final analysis. The online modules were completed by half of the surgeons (2143 of 4411). The primary analysis included 3039 of the 3268 patients recruited (206 patients had no anastomosis and 23 were lost to follow-up), with anastomotic leaks arising before and after the intervention in 10.1 and 9.6 per cent respectively (adjusted OR 0.87, 95 per cent c.i. 0.59 to 1.30; P = 0.498). The proportion of surgeons completing the educational modules was an influence: the leak rate decreased from 12.2 per cent (61 of 500) before intervention to 5.1 per cent (24 of 473) after intervention in high-engagement centres (adjusted OR 0.36, 0.20 to 0.64; P &lt; 0.001), but this was not observed in low-engagement hospitals (8.3 per cent (59 of 714) and 13.8 per cent (61 of 443) respectively; adjusted OR 2.09, 1.31 to 3.31). Conclusion Completion of globally available digital training by engaged teams can alter anastomotic leak rates. Registration number: NCT04270721 (http://www.clinicaltrials.gov)