scholarly journals Metabolomic profiling of microbial disease etiology in community-acquired pneumonia

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0252378
Author(s):  
Ilona den Hartog ◽  
Laura B. Zwep ◽  
Stefan M. T. Vestjens ◽  
Amy C. Harms ◽  
G. Paul Voorn ◽  
...  

Diagnosis of microbial disease etiology in community-acquired pneumonia (CAP) remains challenging. We undertook a large-scale metabolomics study of serum samples in hospitalized CAP patients to determine if host-response associated metabolites can enable diagnosis of microbial etiology, with a specific focus on discrimination between the major CAP pathogen groups S. pneumoniae, atypical bacteria, and respiratory viruses. Targeted metabolomic profiling of serum samples was performed for three groups of hospitalized CAP patients with confirmed microbial etiologies: S. pneumoniae (n = 48), atypical bacteria (n = 47), or viral infections (n = 30). A wide range of 347 metabolites was targeted, including amines, acylcarnitines, organic acids, and lipids. Single discriminating metabolites were selected using Student’s T-test and their predictive performance was analyzed using logistic regression. Elastic net regression models were employed to discover metabolite signatures with predictive value for discrimination between pathogen groups. Metabolites to discriminate S. pneumoniae or viral pathogens from the other groups showed poor predictive capability, whereas discrimination of atypical pathogens from the other groups was found to be possible. Classification of atypical pathogens using elastic net regression models was associated with a predictive performance of 61% sensitivity, 86% specificity, and an AUC of 0.81. Targeted profiling of the host metabolic response revealed metabolites that can support diagnosis of microbial etiology in CAP patients with atypical bacterial pathogens compared to patients with S. pneumoniae or viral infections.

2021 ◽  
Vol 10 (15) ◽  
pp. 3392
Author(s):  
Joeri Lambrecht ◽  
Mustafa Porsch-Özçürümez ◽  
Jan Best ◽  
Fabian Jost-Brinkmann ◽  
Christoph Roderburg ◽  
...  

(1) Background: Surveillance of at-risk patients for hepatocellular carcinoma (HCC) is highly necessary, as curative treatment options are only feasible in early disease stages. However, to date, screening of patients with liver cirrhosis for HCC mostly relies on suboptimal ultrasound-mediated evaluation and α-fetoprotein (AFP) measurement. Therefore, we sought to develop a novel and blood-based scoring tool for the identification of early-stage HCC. (2) Methods: Serum samples from 267 patients with liver cirrhosis, including 122 patients with HCC and 145 without, were collected. Expression levels of soluble platelet-derived growth factor receptor beta (sPDGFRβ) and routine clinical parameters were evaluated, and then utilized in logistic regression analysis. (3) Results: We developed a novel serological scoring tool, the APAC score, consisting of the parameters age, sPDGFRβ, AFP, and creatinine, which identified patients with HCC in a cirrhotic population with an AUC of 0.9503, which was significantly better than the GALAD score (AUC: 0.9000, p = 0.0031). Moreover, the diagnostic accuracy of the APAC score was independent of disease etiology, including alcohol (AUC: 0.9317), viral infection (AUC: 0.9561), and NAFLD (AUC: 0.9545). For the detection of patients with (very) early (BCLC 0/A) HCC stage or within Milan criteria, the APAC score achieved an AUC of 0.9317 (sensitivity: 85.2%, specificity: 89.2%) and 0.9488 (sensitivity: 91.1%, specificity 85.3%), respectively. (4) Conclusions: The APAC score is a novel and highly accurate serological tool for the identification of HCC, especially for early stages. It is superior to the currently proposed blood-based algorithms, and has the potential to improve surveillance of the at-risk population.


Author(s):  
Jianchun Xiao ◽  
Fiona Bhondoekhan ◽  
Eric C Seaberg ◽  
Otto Yang ◽  
Valentina Stosor ◽  
...  

Abstract Background Clinically useful predictors for fatal toxoplasmosis are lacking. We investigated the value of serological assays for antibodies to whole Toxoplasma antigens and to peptide antigens of the Toxoplasma cyst protein MAG1, for predicting incident toxoplasmic encephalitis (TE) in people living with HIV (PLWH). Methods We performed a nested case control study, conducted within the Multicenter AIDS Cohort Study (MACS), using serum samples obtained 2 years prior to diagnosis of TE from 28 cases, and 37 HIV disease-matched Toxoplasma seropositive controls at matched time-points. Sera were tested for Toxoplasma antibodies using a commercial assay and for antibodies to MAG1_4.2 and MAG1_5.2 peptides in ELISA. Results Two years prior to clinical diagnosis, 68% of TE cases were MAG1_4.2 seropositive compared with 16% of controls (OR 25.0, 95% CI 3.14-199.18). Corresponding results for MAG1_5.2 seropositivity were 36% and 14% (OR 3.6, 95% CI 0.95-13.42). Higher levels of antibody to MAG1_4.2 (OR 18.5 per doubling of the OD value, 95% CI 1.41-242) and to Toxoplasma (OR 2.91 for each OD unit increase, 95% CI 1.48-5.72) were also associated with the risk of TE. When seropositivity was defined as the presence of MAG1 antibody or relatively high levels of Toxoplasma antibody, the sensitivity was 89% and specificity was 68% for subsequent TE. Conclusions Antibodies to MAG1 showed predictive value on the occurrence of TE in PLWH, and the predictive performance was further improved by adding the levels of Toxoplasma antibody. These measures could be clinically useful for predicting subsequent diseases in multiple at-risk populations.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S27-S28
Author(s):  
Jeffrey Gruenglas ◽  
James Mond ◽  
Micaela Scobie ◽  
Cynthia Tolman ◽  
Joseph Martinez

Abstract Background S. pneumonia infection presents a significant challenge, accounting for 20–38% of hospital-acquired pneumonia, and the leading cause of community-acquired pneumonia despite availability of effective vaccines. Incidence is highest in children under 2 years, the immunocompromised, and elderly. CDC has reported the emergence of antibiotic resistance in ~30% of cases, adding to risk of morbidity and mortality. Fewer than half of the elderly are vaccinated and vulnerable to infection on admission. Passive immunotherapy as an adjunct to vaccines may improve outcomes in such populations. The objective of this study was to evaluate whether seroprotective response induced with a pneumococcal conjugate vaccine could rapidly yield protective opsonic levels of antibody within anticipated duration of hospitalization. Methods Healthy donors (n=30) were immunized with Prevnar. Blood was drawn on days 0, 3, 7, 10, 14, 21, and 28. Samples were pooled and tested for presence of functional opsonic antibodies recognizing capsular polysaccharides. Clearance mechanism of S. pneumonia was based on antibody recognition to pneumococcal capsular polysaccharide and opsonic titers used as an in vitro surrogate to evaluate the efficacy of vaccine. Results There was little to no opsonic activity against most serotypes on day 0, except for low antibody activity with serotypes 1, 3, 4, and 5. Titers increased, with protective levels achieved by day 10 for most serotypes (except 14 and 18C), peaking at day 14 or after across serotypes (Figures 1 and 2). Average titers rose from log2 titer 2 on day 0 to log2 titer 8 on days 21 and 28. Titers against most serotypes reached log2 10 (titer 1024) or higher. Patients remained susceptible to nosocomial infection for at least 10 days post admission until protective titers are reached. OPK titers (log2 scale) for serum samples on day 0 (pre), day 3, 7, 10, 14, 21, 28, and control for S. pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V. N=2. OPK titers (log2 scale) for serum samples on day 0 (pre), day 3, 7, 10, 14, 21, 28, and control for S. pneumoniae serotypes 14, 18C, 19A, 19F, and 23F. N=2. Conclusion Patients with no prior history of vaccination (or inability to mount response) with Prevnar or pneumovax remain vulnerable to S. pneumonia infection even if vaccinated on entry, due to delayed kinetics in reaching protective titers. These patients may require prophylactic intervention of hyperimmune Ig with high opsonic titers to S. pneumonia, providing protection until vaccine response elicits protective antibodies. Disclosures All Authors: No reported disclosures


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Niina Haiminen ◽  
Filippo Utro ◽  
Ed Seabolt ◽  
Laxmi Parida

AbstractIn response to the ongoing global pandemic, characterizing the molecular-level host interactions of the new coronavirus SARS-CoV-2 responsible for COVID-19 has been at the center of unprecedented scientific focus. However, when the virus enters the body it also interacts with the micro-organisms already inhabiting the host. Understanding the virus-host-microbiome interactions can yield additional insights into the biological processes perturbed by viral invasion. Alterations in the gut microbiome species and metabolites have been noted during respiratory viral infections, possibly impacting the lungs via gut-lung microbiome crosstalk. To better characterize microbial functions in the lower respiratory tract during COVID-19 infection, we carry out a functional analysis of previously published metatranscriptome sequencing data of bronchoalveolar lavage fluid from eight COVID-19 cases, twenty-five community-acquired pneumonia patients, and twenty healthy controls. The functional profiles resulting from comparing the sequences against annotated microbial protein domains clearly separate the cohorts. By examining the associated metabolic pathways, distinguishing functional signatures in COVID-19 respiratory tract microbiomes are identified, including decreased potential for lipid metabolism and glycan biosynthesis and metabolism pathways, and increased potential for carbohydrate metabolism pathways. The results include overlap between previous studies on COVID-19 microbiomes, including decrease in the glycosaminoglycan degradation pathway and increase in carbohydrate metabolism. The results also suggest novel connections to consider, possibly specific to the lower respiratory tract microbiome, calling for further research on microbial functions and host-microbiome interactions during SARS-CoV-2 infection.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hiroki Yoshikawa ◽  
Kosaku Komiya ◽  
Takashi Yamamoto ◽  
Naoko Fujita ◽  
Hiroaki Oka ◽  
...  

AbstractErector spinae muscle (ESM) size has been reported as a predictor of prognosis in patients with some respiratory diseases. This study aimed to assess the association of ESM size on all-cause in-hospital mortality among elderly patients with pneumonia. We retrospectively included patients (age: ≥ 65 years) admitted to hospital from January 2015 to December 2017 for community-acquired pneumonia who underwent chest computed tomography (CT) on admission. The cross-sectional area of the ESM (ESMcsa) was measured on a single-slice CT image at the end of the 12th thoracic vertebra and adjusted by body surface area (BSA). Cox proportional hazards regression models were used to assess the influence of ESMcsa/BSA on in-hospital mortality. Among 736 patients who were admitted for pneumonia, 702 patients (95%) underwent chest CT. Of those, 689 patients (98%) for whom height and weight were measured to calculate BSA were included in this study. Patients in the non-survivor group were significantly older, had a greater frequency of respiratory failure, loss of consciousness, lower body mass index, hemoglobin, albumin, and ESMcsa/BSA. Multivariate analysis showed that a lower ESMcsa/BSA independently predicted in-hospital mortality after adjusting for these variables. In elderly patients with pneumonia, quantification of ESMcsa/BSA may be associated with in-hospital mortality.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Ron Nudel ◽  
Rosa Lundbye Allesøe ◽  
Wesley K. Thompson ◽  
Thomas Werge ◽  
Simon Rasmussen ◽  
...  

Abstract Background Infections are a major disease burden worldwide. While they are caused by external pathogens, host genetics also plays a part in susceptibility to infections. Past studies have reported diverse associations between human leukocyte antigen (HLA) alleles and infections, but many were limited by small sample sizes and/or focused on only one infection. Methods We performed an immunogenetic association study examining 13 categories of severe infection (bacterial, viral, central nervous system, gastrointestinal, genital, hepatitis, otitis, pregnancy-related, respiratory, sepsis, skin infection, urological and other infections), as well as a phenotype for having any infection, and seven classical HLA loci (HLA-A, B, C, DPB1, DQA1, DQB1 and DRB1). Additionally, we examined associations between infections and specific alleles highlighted in our previous studies of psychiatric disorders and autoimmune disease, as these conditions are known to be linked to infections. Results Associations between HLA loci and infections were generally not strong. Highlighted associations included associations between DQB1*0302 and DQB1*0604 and viral infections (P = 0.002835 and P = 0.014332, respectively), DQB1*0503 and sepsis (P = 0.006053), and DQA1*0301 with “other” infections (a category which includes infections not included in our main categories e.g. protozoan infections) (P = 0.000369). Some HLA alleles implicated in autoimmune diseases showed association with susceptibility to infections, but the latter associations were generally weaker, or with opposite trends (in the case of HLA-C alleles, but not with alleles of HLA class II genes). HLA alleles associated with psychiatric disorders did not show association with susceptibility to infections. Conclusions Our results suggest that classical HLA alleles do not play a large role in the etiology of severe infections. The discordant association trends with autoimmune disease for some alleles could contribute to mechanistic theories of disease etiology.


2021 ◽  
Vol 13 (4) ◽  
pp. 581 ◽  
Author(s):  
Yuanyuan Fu ◽  
Guijun Yang ◽  
Xiaoyu Song ◽  
Zhenhong Li ◽  
Xingang Xu ◽  
...  

Rapid and accurate crop aboveground biomass estimation is beneficial for high-throughput phenotyping and site-specific field management. This study explored the utility of high-definition digital images acquired by a low-flying unmanned aerial vehicle (UAV) and ground-based hyperspectral data for improved estimates of winter wheat biomass. To extract fine textures for characterizing the variations in winter wheat canopy structure during growing seasons, we proposed a multiscale texture extraction method (Multiscale_Gabor_GLCM) that took advantages of multiscale Gabor transformation and gray-level co-occurrency matrix (GLCM) analysis. Narrowband normalized difference vegetation indices (NDVIs) involving all possible two-band combinations and continuum removal of red-edge spectra (SpeCR) were also extracted for biomass estimation. Subsequently, non-parametric linear (i.e., partial least squares regression, PLSR) and nonlinear regression (i.e., least squares support vector machine, LSSVM) analyses were conducted using the extracted spectral features, multiscale textural features and combinations thereof. The visualization technique of LSSVM was utilized to select the multiscale textures that contributed most to the biomass estimation for the first time. Compared with the best-performing NDVI (1193, 1222 nm), the SpeCR yielded higher coefficient of determination (R2), lower root mean square error (RMSE), and lower mean absolute error (MAE) for winter wheat biomass estimation and significantly alleviated the saturation problem after biomass exceeded 800 g/m2. The predictive performance of the PLSR and LSSVM regression models based on SpeCR decreased with increasing bandwidths, especially at bandwidths larger than 11 nm. Both the PLSR and LSSVM regression models based on the multiscale textures produced higher accuracies than those based on the single-scale GLCM-based textures. According to the evaluation of variable importance, the texture metrics “Mean” from different scales were determined as the most influential to winter wheat biomass. Using just 10 multiscale textures largely improved predictive performance over using all textures and achieved an accuracy comparable with using SpeCR. The LSSVM regression model based on the combination of the selected multiscale textures, and SpeCR with a bandwidth of 9 nm produced the highest estimation accuracy with R2val = 0.87, RMSEval = 119.76 g/m2, and MAEval = 91.61 g/m2. However, the combination did not significantly improve the estimation accuracy, compared to the use of SpeCR or multiscale textures only. The accuracy of the biomass predicted by the LSSVM regression models was higher than the results of the PLSR models, which demonstrated LSSVM was a potential candidate to characterize winter wheat biomass during multiple growth stages. The study suggests that multiscale textures derived from high-definition UAV-based digital images are competitive with hyperspectral features in predicting winter wheat biomass.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S52-S52
Author(s):  
Pegah Shakeraneh ◽  
Jeffrey Steele ◽  
Robert Seabury ◽  
Stephen J Thomas ◽  
Kristopher M Paolino ◽  
...  

Abstract Background Ceftriaxone and azithromycin are common empiric antibiotics for community-acquired pneumonia (CAP). Despite low suspicion for atypical infection, azithromycin is often continued for a full course. Negative laboratory data for atypical bacteria may assist with azithromycin de-escalation. Thus, a pharmacist-driven azithromycin de-escalation protocol was implemented for immunocompetent, non-intensive care unit (ICU) patients treated for CAP. The primary outcome was to compare azithromycin duration before and after protocol implementation. Secondary outcomes included hospital length of stay (LOS) and all-cause 30-day readmission. Methods This was a single-center, quasi-experimental study of hospitalized, non-ICU patients treated with azithromycin and a beta-lactam for CAP. The pre- and post-intervention cohorts were from 07/01/2018–04/30/2019 and 07/01/2019–04/30/2020, respectively. Patients were included if they were ≥18 years old, diagnosed with CAP, and had a negative Legionella pneumophila urinary antigen and negative nasopharyngeal swab PCR for Mycoplasma pneumoniae and Chlamydia pneumoniae. Patients were excluded if they were immunocompromised, admitted to an ICU, prescribed azithromycin for an alternative indication, or had evidence of atypical bacteria. Results After exclusion criteria were applied, 90 and 100 patients were included in the pre- and post-intervention cohorts, respectively. Demographic and clinical characteristics were mostly similar between cohorts. This initiative was associated with a statistically significant decrease in azithromycin duration (2 days (IQR 1–2.75) vs. 5 days (IQR 3–6), p < 0.001) and hospital LOS (3 days (IQR 2–5) vs. 5 days (IQR 3–8.25), p < 0.001). No statistically significant difference was observed for all-cause 30-day readmission (14 days (15.6%) vs 13 days (13.0%), p=0.614). Conclusion Implementation of a pharmacist-driven azithromycin de-escalation protocol for CAP was associated with reduced azithromycin duration and hospital LOS, but not all-cause 30-day readmission. Disclosures Jeffrey Steele, PharMD, Paratek Pharmaceuticals (Advisor or Review Panel member) Wesley D. Kufel, PharmD, Melinta (Research Grant or Support)Merck (Research Grant or Support)Theratechnologies, Inc. (Advisor or Review Panel member)


Author(s):  
Е.Е. Краснова ◽  
В.В. Чемоданов ◽  
Е.Г. Кузнецова

Пневмония – острое инфекционно-воспалительное заболевание легких преимущественно бактериальной этиологии, характеризующееся выраженной в разной степени дыхательной недостаточностью, токсическими и респираторными нарушениями, локальными физикальными симптомами, а также инфильтративными изменениями на рентгенограмме. Заболеваемость внебольничными пневмониями повышается в октябре-декабре, достигая максимума в январе-апреле, коррелируя с сезонным повышением уровня острых респираторных вирусных инфекций. Схожесть симптомов дебюта пневмонии с проявлениями острых респираторных вирусных инфекций может привести к несвоевременной ее диагностике и, как следствие, к отсроченному началу лечения. Поэтому в период сезонной заболеваемости респираторными инфекциями должна повышаться настороженность врачей-педиатров в отношении внебольничной пневмонии. Антибактериальная терапия оказывает решающее влияние на прогноз пневмонии, поэтому при достоверном диагнозе или у больного в тяжелом состоянии с вероятным диагнозом ее следует начать незамедлительно. Выбор антибиотика в каждом случае внебольничной пневмонии проводят индивидуально с учетом природной активности препаратов в отношении предполагаемого возбудителя и их возможной приобретенной резистентности, тяжести и течения заболевания, наличия у пациента противопоказаний к использованию тех или иных антибиотиков. В статье приводятся сведения о диагностических критериях внебольничных пневмоний. Рассмотрены вопросы антибактериального лечения типичной нетяжелой пневмонии у детей разных возрастных групп амоксициллином с клавулановой кислотой и показана его эффективность. Результаты проведенного исследования позволяют заключить, что пероральное использование одного курса защищенного аминопенициллина эффективно при лечении типичной внебольничной нетяжелой пневмонии у детей разного возраста, о чем свидетельствует ликвидация основных клинических проявлений болезни в короткие сроки. Pneumonia is an acute infectious and inflammatory lung disease of predominantly bacterial etiology, characterized by respiratory failure, toxic and respiratory disorders, local physical symptoms, and infiltrative changes on the roentgenogram. The incidence of community-acquired pneumonia increases in October-December, reaching a maximum in January-April, correlating with the seasonal increase in the level of acute respiratory viral infections. The similarity of the symptoms of the onset of pneumonia with the manifestations of acute respiratory viral infections can lead to its untimely diagnosis and, as a consequence, to a delayed start of treatment. Therefore, during the period of seasonal morbidity with respiratory infections, the alertness of pediatricians in relation to community-acquired pneumonia should increase. Antibiotic therapy has a decisive influence on the prognosis of pneumonia, therefore, with a reliable diagnosis or in a patient in serious condition with a probable diagnosis, it should be started immediately. The choice of antibiotic in each case of community-acquired pneumonia is carried out individually, taking into account the natural activity of the drugs in relation to the alleged pathogen and their possible acquired resistance, the severity and course of the disease, the patient's contraindications to the use of certain antibiotics. The article provides information on the diagnostic criteria for community-acquired pneumonia. The issues of antibacterial treatment of typical non-severe pneumonia in children of different age groups with amoxicillin with clavulanic acid are considered and its effectiveness is shown. The results of the study allow us to conclude that the oral use of one course of protected aminopenicillin is effective in the treatment of typical community-acquired non-severe pneumonia in children of different ages, as evidenced by the elimination of the main clinical manifestations of the disease in a short time.


2004 ◽  
Vol 1 (1) ◽  
pp. 131-142
Author(s):  
Ljupčo Todorovski ◽  
Sašo Džeroski ◽  
Peter Ljubič

Both equation discovery and regression methods aim at inducing models of numerical data. While the equation discovery methods are usually evaluated in terms of comprehensibility of the induced model, the emphasis of the regression methods evaluation is on their predictive accuracy. In this paper, we present Ciper, an efficient method for discovery of polynomial equations and empirically evaluate its predictive performance on standard regression tasks. The evaluation shows that polynomials compare favorably to linear and piecewise regression models, induced by the existing state-of-the-art regression methods, in terms of degree of fit and complexity.


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