48 hours post-treatment L-Carnitine Pharmacometabolomics in Sepsis (CaPS) Patients
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo Sapiens
TISSUE(S): Blood
DISEASE(S): Sepsis
PROVIDER: ST001354 | MetabolomicsWorkbench |
REPOSITORIES: MetabolomicsWorkbench
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| mwtab | Other |
Items per page: 5 1 - 1 of 1 |
Similar Datasets
Project description: Not available
| ST001319 | MetabolomicsWorkbench
Project description: Not available
| ST000785 | MetabolomicsWorkbench
Project description:Tomatidine, a natural steroidal alkaloid from unripe green tomatoes has been shown to exhibit many health benefits. We recently provided in vitro evidence that tomatidine reduces the infectivity of Dengue virus (DENV) and Chikungunya virus (CHIKV), two medically important arthropod-borne human infections for which no treatment options are available. The objective of this mass spectrometry analysis was to determine possible proteomic changes in the human cell line Huh7 induced by tomatidine which may be indicative of the underlying antiviral activity of tomatidine.
2021-11-18 | PXD028693 | Pride
Project description:Subjects with schizophrenia have high risks of metabolic abnormalities and bioenergetic dysfunction. Acyl-carnitines involved in bioenergetic pathways provide potential biomarker targets for identifying early changes and onset characteristics in subjects with schizophrenia. We measured 29 acyl-carnitine levels within well-characterized plasma samples of adults with schizophrenia and healthy controls using liquid chromatography-mass spectrometry (LC-MS). Subjects with schizophrenia were measured at baseline and after 8 weeks of treatment. A total of 225 subjects with schizophrenia and 175 age- and gender-matched healthy controls were enrolled and 156 subjects completed the 8-week follow-up. With respect to plasma acyl-carnitines, the individuals with schizophrenia at baseline showed significantly higher levels of C4-OH (C3-DC) and C16:1, but lower concentrations of C3, C8, C10, C10:1, C10:2, C12, C14:1-OH, C14:2, and C14:2-OH when compared with healthy controls after controlling for age, sex, body mass index (BMI), smoking, and drinking. For the comparison between pretreatment and posttreatment subjects, all detected acyl-carnitines were significantly different between the two groups. Only the concentration of C3 and C4 were increased after selection by variable importance in projection (VIP) value >1.0 and false discovery rate (FDR) q value <0.05. A panel of acyl-carnitines were selected for the ability to differentiate subjects of schizophrenia at baseline from controls, pre- from post-treatment, and posttreatment from controls. Our data implicated acyl-carnitines with abnormalities in cellular bioenergetics of schizophrenia. Therefore, acyl-carnitines can be potential targets for future investigations into their roles in the pathoetiology of schizophrenia.
| S-EPMC6336814 | biostudies-literature
Project description:BackgroundThe post-discharge prognosis of patients with sepsis remains a crucial issue; however, few studies have investigated the relationship between pre-sepsis health status and subsequent prognosis in a large population. This study aimed to examine the effect of the pre-sepsis care needs level on changes in care needs and mortality in patients with sepsis 1 year post-discharge.MethodsThis was a population-based retrospective cohort study including twelve municipalities in Japan that participated in the Longevity Improvement & Fair Evidence study between April 2014 and March 2022, with a total of 1,491,608 persons. The pre-hospitalization levels of care needs (baseline) were classified from low to high, as no care needs, support level and care needs level 1, care needs levels 2-3, and care needs levels 4-5 (fully dependent). The outcomes were changes in care needs level and mortality 1 year post-discharge, assessed by baseline care needs level using Cox proportional hazard models.ResultsThe care needs levels of 17,648 patients analyzed at baseline were as follows: no care needs, 7982 (45.2%); support level and care needs level 1, 3736 (21.2%); care needs levels 2-3, 3089 (17.5%); and care needs levels 4-5, 2841 (16.1%). At 1 year post-discharge, the distribution of care needs were as follows: no care needs, 4791 (27.1%); support level and care needs level 1, 2390 (13.5%); care needs levels 2-3, 2629 (14.9%); care needs levels 4-5, 3373 (19.1%); and death, 4465 (25.3%). Patients with higher levels of care needs exhibited an increased association of all-cause mortality 1 year post-discharge after adjusting for confounders [hazard ratios and 95% confidence intervals: support level and care needs level 1, 1.05 (0.96, 1.15); care needs levels 2-3, 1.46 (1.33, 1.60); and care needs levels 4-5, 1.92 (1.75, 2.10); P for trend < 0.001].ConclusionsElevated care needs and mortality were observed in patients with sepsis within 1 year post-discharge. Older patients with sepsis and higher baseline levels of care needs had a high association of all-cause mortality 1 year post-discharge.
| S-EPMC11363546 | biostudies-literature
Project description:Background: Septic shock is a life-threatening clinical condition characterized by a robust immune inflammatory response to disseminated infection. Little is known about its impact on the transcriptome of distinct human organs. Objective and Methods: To address this, we performed RNA sequencing of samples from the prefrontal cortex, hippocampus, heart, lung, kidney and colon of seven individuals who succumbed to sepsis and seven uninfected controls. Main Results: We identified that the lungs and colon were the most affected organs. While gene activation dominated, strong inhibitory signals were also detected, particularly in the lungs. Principal Conclusions: We found that septic shock is an extremely heterogeneous disease, not only when different individuals are investigated, but also when comparing different tissues of the same patient. However, several pathways, such as respiratory electron transport and other metabolic functions, revealed distinctive alterations, providing evidence that tissue specificity is a hallmark of sepsis. Strikingly, we found evident signals of accelerated ageing in our sepsis population.
2023-09-21 | GSE237861 | GEO
Project description:Sepsis therapeutics have a poor history of success in clinical trials, due in part to the heterogeneity of enrolled patients. Pharmacometabolomics could differentiate drug response phenotypes and permit a precision medicine approach to sepsis.To use existing serum samples from the phase 1 clinical trial of l-carnitine treatment for severe sepsis to metabolically phenotype l-carnitine responders and nonresponders.Serum samples collected before (T0) and after completion of the infusion (T24, T48) from patients randomized to either l-carnitine (12 g) or placebo for the treatment of vasopressor-dependent septic shock were assayed by untargeted (1)H-nuclear magnetic resonance metabolomics. The normalized, quantified metabolite data sets of l-carnitine- and placebo-treated patients at each time point were compared by analysis of variance with post-hoc testing for multiple comparisons. Pathway analysis was performed to statistically rank metabolic networks.Thirty-eight metabolites were identified in all samples. Concentrations of 3-hydroxybutyrate, acetoacetate, and 3-hydroxyisovalerate were different at T0 and over time in l-carnitine-treated survivors versus nonsurvivors. Pathway analysis of pretreatment metabolites revealed that synthesis and degradation of ketone bodies had the greatest impact in differentiating l-carnitine treatment response. Analysis of all patients based on pretreatment 3-hydroxybutyrate concentration yielded distinct phenotypes. Using the T0 median 3-hydroxybutyrate level (153 ?M), patients were categorized as either high or low ketone. l-Carnitine-treated low-ketone patients had greater use of carnitine as evidenced by lower post-treatment l-carnitine levels. The l-carnitine responders also had faster resolution of vasopressor requirement and a trend toward a greater improvement in mortality at 1 year (P = 0.038) compared with patients with higher 3-hydroxybutyrate.The results of this preliminary study, which were not readily apparent from the parent clinical trial, show a unique metabolite profile of l-carnitine responders and introduce pharmacometabolomics as a viable strategy for informing l-carnitine responsiveness. The approach taken in this study represents a concrete example for the application of precision medicine to sepsis therapeutics that warrants further study.
| S-EPMC4342803 | biostudies-literature
Project description:Sepsis is the leading cause of global death with the highest burden found in sub-Saharan Africa (sSA). The Universal Vital Assessment (UVA) score is a validated resource-appropriate clinical tool to identify hospitalized patients in sSA who are at risk of in-hospital mortality. Whether a decrease in the UVA score over 6 hours of resuscitation from sepsis is associated with improved outcomes is unknown. We aimed to determine (1) the association between 6-hour UVA score and in-hospital mortality, and (2) if a decrease in UVA score from admission to 6 hours was associated with improved in-hospital mortality. We analyzed data from participants with severe sepsis aged ≥14 years enrolled at the Mbarara Regional Referral Hospital in Uganda from October 2014 through May 2015. Among 197 participants, the median (interquartile range) age was 34 (27-47) years, 99 (50%) were female and 116 (59%) were living with HIV. At 6 hours, of the 65 participants in the high-risk group, 28 (43%) died compared to 28 (30%) of 94 in the medium-risk group (odds ratio [OR] 0.56, 95% confidence interval [CI] 0.29,1.08, p = 0.086) and 3 (9%) of 33 in the low-risk group (OR 0.13, 95% CI 0.03, 0.42, p = 0.002). In a univariate analysis of the 85 participants who improved their UVA risk group at 6 hours, 20 (23%) died compared to 39 (36%) of 107 participants who did not improve (OR 0.54, 95% CI 0.27-1.06, p = 0.055). In the multivariable analysis, the UVA score at 6 hours (adjusted OR [aOR] 1.26, 95%CI 1.10-1.45, p<0.001) was associated with in-hospital mortality. When adjusted for age and sex, improvement in the UVA risk group over 6 hours was associated with a non-statistically significant 43% decrease in odds of mortality (aOR 0.57, 95%CI 0.29-1.07, p = 0.08). Targeting a decrease in UVA score over 6 hours from admission may be a useful clinical endpoint for sepsis resuscitation in sSA, but this would need to be proven in a clinical trial.
| S-EPMC11495629 | biostudies-literature
Project description:Bloodstream infections (BSIs) and sepsis are major health problems, annually claiming millions of lives. Traditional blood culture techniques, employed to identify sepsis-causing pathogens and assess antibiotic susceptibility, usually take 2-4 days. Early and accurate antibiotic prescription is vital in sepsis to mitigate mortality and antibiotic resistance. This study aimed to reduce the wait time for sepsis diagnosis by employing shorter blood culture incubation times for BD BACTEC™ bottles using standard laboratory incubators, followed by real-time nanopore sequencing and data analysis. The method was tested on nine blood samples spiked with clinical isolates from the six most prevalent sepsis-causing pathogens. The results showed that pathogen identification was possible at as low as 102-104 CFU/mL, achieved after just 2 h of incubation and within 40 min of nanopore sequencing. Moreover, all the antimicrobial resistance genes were identified at 103-107 CFU/mL, achieved after incubation for 5 h and only 10 min to 3 h of sequencing. Therefore, the total turnaround time from sample collection to the information required for an informed decision on the right antibiotic treatment was between 7 and 9 h. These results hold significant promise for better clinical management of sepsis compared with current culture-based methods.
| S-EPMC10951244 | biostudies-literature
Project description:Samples from mice infected and then treated with vehicle, carnitine or benznidazole in the chronic stage of infection. Tissue samples extracted with 50% methanol followed by 3:1 dichloromethane:methanol. C8 chromatography with negative mode data acquisition
2023-11-13 | MSV000093394 | MassIVE