High pentraxin 3 level predicts septic shock and bacteremia at the onset of febrile neutropenia after intensive chemotherapy of hematologic patients.
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ABSTRACT:
SUBMITTER: Vanska M
PROVIDER: S-EPMC3166112 | biostudies-literature | 2011 Sep
REPOSITORIES: biostudies-literature
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High pentraxin 3 level predicts septic shock and bacteremia at the onset of febrile neutropenia after intensive chemotherapy of hematologic patients.
Vänskä Matti M Koivula Irma I Hämäläinen Sari S Pulkki Kari K Nousiainen Tapio T Jantunen Esa E Juutilainen Auni A
Haematologica 20110901 9
We evaluated pentraxin 3 as a marker for complications of neutropenic fever in 100 hematologic patients receiving intensive chemotherapy. Pentraxin 3 and C-reactive protein were measured at fever onset and then daily to day 3. Bacteremia was observed in 19 patients and septic shock in 5 patients (three deaths). In comparison to C-reactive protein, pentraxin 3 achieved its maximum more rapidly. Pentraxin 3 correlated not only with the same day C-reactive protein but also with the next day C-react ...[more]
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Project description:ObjectiveTo evaluate the usefulness of a new marker, pentraxin, as a prognostic marker in septic shock patients.Materials and methodsSingle-centre prospective observational study that included all consecutive patients 18 years or older who were admitted to the intensive care unit (ICU) with septic shock. Serum levels of procalcitonin (PCT), C-reactive protein (CRP) and pentraxin (PTX3) were measured on ICU admission.ResultsSeventy-five septic shock patients were included in the study. The best predictors of in-hospital mortality were the severity scores: SAPS II (AUC = 0.81), SOFA (AUC = 0.79) and APACHE II (AUC = 0.73). The ROC curve for PTX3 (ng/mL) yielded an AUC of 0.70, higher than the AUC for PCT (0.43) and CRP (0.48), but lower than lactate (0.79). Adding PTX3 to the logistic model increased the predictive capacity in relation to SAPS II, SOFA and APACHE II for in-hospital mortality (AUC 0.814, 0.795, and 0.741, respectively). In crude regression models, significant associations were found between in-hospital mortality and PTX3. This positive association increased after adjusting for age, sex and immunosuppression: adjusted OR T3 for PTX3 = 7.83, 95% CI 1.35-45.49, linear P trend = 0.024.ConclusionOur results support the prognostic value of a single determination of plasma PTX3 as a predictor of hospital mortality in septic shock patients.
| S-EPMC7728227 | biostudies-literature
Project description:BackgroundCancer chemotherapy-associated febrile neutropenia (FN) is a common condition that is deadly when bacteremia is present. Detection of bacteremia depends on culture, which takes days, and no accurate predictive tools applicable to the initial evaluation are available. We utilized metabolomics and transcriptomics to develop multivariable predictors of bacteremia among FN patients.MethodsWe classified emergency department patients with FN and no apparent infection at presentation as bacteremic (cases) or not (controls), according to blood culture results. We assessed relative metabolite abundance in plasma, and relative expression of 2,560 immunology and cancer-related genes in whole blood. We used logistic regression to identify multivariable predictors of bacteremia, and report test characteristics of the derived predictors.ResultsFor metabolomics, 14 bacteremic cases and 25 non-bacteremic controls were available for analysis; for transcriptomics we had 7 and 22 respectively. A 5-predictor metabolomic model had an area under the receiver operating characteristic curve of 0.991 (95%CI: 0.972,1.000), 100% sensitivity, and 96% specificity for identifying bacteremia. Pregnenolone steroids were more abundant in cases and carnitine metabolites were more abundant in controls. A 3-predictor gene expression model had corresponding results of 0.961 (95%CI: 0.896,1.000), 100%, and 86%. Genes involved in innate immunity were differentially expressed.ConclusionsClassifiers derived from metabolomic and gene expression data hold promise as objective and accurate predictors of bacteremia among FN patients without apparent infection at presentation, and can provide insights into the underlying biology. Our findings should be considered illustrative, but may lay the groundwork for future biomarker development.
| S-EPMC5955575 | biostudies-literature
Project description:Febrile neutropenia (FN) is a common condition in children receiving chemotherapy. Our goal in this study was to develop a model for predicting blood stream infection (BSI) and transfer to intensive care (TIC) at time of presentation in pediatric cancer patients with FN. We conducted an observational cohort analysis of pediatric and adolescent cancer patients younger than 24 years admitted for fever and chemotherapy-induced neutropenia over a 7-year period. We excluded stem cell transplant recipients who developed FN after transplant and febrile non-neutropenic episodes. The primary outcome was onset of BSI, as determined by positive blood culture within 7 days of onset of FN. The secondary outcome was transfer to intensive care (TIC) within 14 days of FN onset. Predictor variables include demographics, clinical, and laboratory measures on initial presentation for FN. Data were divided into independent derivation (2009-2014) and prospective validation (2015-2016) cohorts. Prediction models were built for both outcomes using logistic regression and random forest and compared with Hakim model. Performance was assessed using area under the receiver operating characteristic curve (AUC) metrics. A total of 505 FN episodes (FNEs) were identified in 230 patients. BSI was diagnosed in 106 (21%) and TIC occurred in 56 (10.6%) episodes. The most common oncologic diagnosis with FN was acute lymphoblastic leukemia (ALL), and the highest rate of BSI was in patients with AML. Patients who had BSI had higher maximum temperature, higher rates of prior BSI and higher incidence of hypotension at time of presentation compared with patients who did not have BSI. FN patients who were transferred to the intensive care (TIC) had higher temperature and higher incidence of hypotension at presentation compared to FN patients who didn't have TIC. We compared 3 models: (1) random forest (2) logistic regression and (3) Hakim model. The areas under the curve for BSI prediction were (0.79, 0.65, and 0.64, P < 0.05) for models 1, 2, and 3, respectively. And for TIC prediction were (0.88, 0.76, and 0.65, P < 0.05) respectively. The random forest model demonstrated higher accuracy in predicting BSI and TIC and showed a negative predictive value (NPV) of 0.91 and 0.97 for BSI and TIC respectively at the best cutoff point as determined by Youden's Index. Likelihood ratios (LRs) (post-test probability) for RF model have potential utility of identifying low risk for BSI and TIC (0.24 and 0.12) and high-risk patients (3.5 and 6.8) respectively. Our prediction model has a very good diagnostic performance in clinical practices for both BSI and TIC in FN patients at the time of presentation. The model can be used to identify a group of individuals at low risk for BSI who may benefit from early discharge and reduced length of stay, also it can identify FN patients at high risk of complications who might benefit from more intensive therapies at presentation.
| S-EPMC9076887 | biostudies-literature
Project description:Sepsis, which is the leading cause of death in intensive care units (ICU), has been acknowledged as a global health priority by the WHO in 2017. Identification of biomarkers allowing early stratification and recognition of patients at higher risk of death is crucial. One promising biomarker candidate is pentraxin-3 (PTX3); initially elevated and persistently increased plasma concentration in septic patients has been associated with increased mortality. PTX3 is an acute phase protein mainly stored in neutrophil granules. These cells are responsible for rapid and prompt release of PTX3 in inflammatory context, but the cellular origin responsible for successive days' elevation in sepsis remains unknown. Upon inflammatory stimulation, PTX3 can also be produced by other cell types, including endothelial and immune cells. As in septic patients immune alterations have been described, we therefore sought to investigate whether such cells participated in the elevation of PTX3 over the first days after septic shock onset. To address this point, PTX3 was measured in plasma from septic shock patients at day 3 after ICU admission as well as in healthy volunteers (HV), and the capacity of whole blood cells to secrete PTX3 after inflammatory stimulation was evaluated ex vivo. A significantly mean higher (100-fold) concentration of plasma PTX3 was found in patients compared to HV, which was likely due to the inflammation-induced initial release of the pre-existing PTX3 reservoir contained in neutrophils. Strikingly, when whole blood was stimulated ex vivo with LPS no significant difference between patients and HV in PTX3 release was found. This was in contrast with TNFα which decreased production was illustrative of the endotoxin tolerance phenomenon occurring in septic patients. Then, the release of PTX3 protein from a HV neutrophil-free PBMC endotoxin tolerance model was investigated. At the transcriptional level, PTX3 seems to be a weakly tolerizable gene similar to TNFα. Conversely, increased protein levels observed in anergy condition reflects a non-tolerizable phenotype, more likely to an anti-inflammatory marker. Hence, altered immune cells still have the ability to produce PTX3 in response to an inflammatory trigger, and therefore circulating white blood cell subset could be responsible of the sustained PTX3 plasma levels over the first days of sepsis setting.
| S-EPMC6338061 | biostudies-literature
Project description: Not available
| S-EPMC3381405 | biostudies-literature
Project description:We herein report a case of presumed septic shock due to Actinotignum schaalii bacteremia with urinary tract infection. A 65-year-old Japanese man suffering from a fever was diagnosed with septic shock due to urinary tract infection. A urine sample was additionally incubated under 5% CO2 and anaerobic conditions after A. schaalii was identified in a blood culture, but A. schaalii was not detected in the urine culture. If Gram-positive rods are observed on Gram staining of a urine sample in symptomatic patients with a predisposing urogenital condition, 5% CO2 and an anaerobic culture of a urine sample should be performed immediately.
| S-EPMC8263186 | biostudies-literature
Project description:The aim of this study is to investigate if neutrophil CD64 expression in febrile neutropenia patients could be used as an early indicator of bacteremia.All consecutive patients older than 18 years of age who had developed febrile neutropenia episodes due to hematological malignancies were included in the study. Those patients who had significant growth in their blood cultures constituted the case group, while those who had febrile neutropenia without any growth in their cultures and who did not have any documented infections formed the control group. Blood culture bottles were incubated in the Bact ALERT 3D system (bioMerieux, France), identification and susceptibility testing were performed using an automated broth microdilution method (VITEK 2, bioMerieux), and CD64 expression analysis was performed by the flow cytometry method. C-reactive protein (CRP) was measured by turbidimetric methods (Biosystems, Spain) and erythrocyte sedimentation rate (ESR) was measured by the Wintrobe method.In total, we prospectively evaluated 31 febrile episodes. The case group consisted of 17 patients while the control group included 14 patients. CD64 was found on neutrophils of the case group patients with a mean count of 8006 molecules/cell and of control group with a mean count of 2786 molecules/cell. CD64 levels of the case group were significantly higher than those of the control group (p=0.005). In the differentiation of the case group from the control group, a 2500 cut-off value for CD64 had significant [AUC=0.792 (0.619-0.965)] predictive value (p=0.001). In the prediction of patients with a 2500 cut-off value for CD64, sensitivity was 94.1%, positive predictive value was 76.2%, specificity was 64.3%, and negative predictive value was 90.0%. CRP levels and ESR values did not differ significantly between the groups (p=0.005).Neutrophil CD64 expression could be a good predictor as an immune parameter with high sensitivity and a negative predictive value for bacteremia in febrile neutropenic patients.
| S-EPMC5440869 | biostudies-other
Project description:BACKGROUND:Serum procalcitonin (PCT) and C-reactive protein (CRP) are biomarkers of infection. In patients with hematologic disorders with or without hematopoietic stem cell transplantation (HSCT), it is difficult to distinguish bloodstream infections from aseptic causes of febrile episodes. The objective of this study was to investigate diagnostic values of PCT and CRP in predicting systemic bacterial infection in patients with hematologic malignancies. METHODS:Clinical and laboratory data of 614 febrile episode cases from 511 patients were analyzed. Febrile episodes were classified into four groups: (1) culture-positive bacterial infection by Gram-positive cocci (GPC), (2) culture-positive bacterial infection by Gram-negative bacilli (GNB), (3) fungal infection, and (4) viral infection or a noninfectious etiology. RESULTS:Of 614 febrile cases, systemic bacterial infections were confirmed in 99 (16.1%) febrile episodes, including 38 (6.2%) GPC and 61 (9.9%) GNB infections. PCT levels were significantly higher in GNB infectious episodes than those in febrile episodes caused by fungal infection (0.58 ng/mL (95% CI: 0.26-1.61) vs. 0.22 ng/mL (0.16-0.38), P = 0.047). Bacterial infectious episodes showed higher PCT and CRP levels than non-bacterial events (PCT: 0.49 (0.26-0.93) ng/mL vs. 0.20 (0.18-0.22) ng/mL, P < 0.001; CRP: 76.6 (50.5-92.8) mg/L vs. 58.0 (51.1-66.5) mg/L, P = 0.036). For non-neutropenic febrile episodes, both PCT and CRP discriminated bacteremia from non-bacteremia. However, in neutropenic febrile episodes, PCT only distinguished bacteremia from non-bacteremia. In non-neutropenic episode, both PCT and CRP showed good diagnostic accuracy (AUC: 0.757 vs. 0.763). In febrile neutropenia, only PCT discriminated bacteremia from non-bacterial infection (AUC: 0.624) whereas CRP could not detect bacteremia (AUC: 0.500, 95% CI: 0.439-0.561, P > 0.05). CONCLUSIONS:In this single-center observational study, PCT was more valuable than CRP for discriminating between bacteremia and non-bacteremia independent of neutropenia or HSCT.
| S-EPMC6903763 | biostudies-literature
Project description:BackgroundThe source of bacterial infection in neutropenic acute leukemia patients is detected in about 20-30% of cases. Bacterial cultures may require a long incubation period and risk false-positive and false- negative results. Therefore, biomarkers distinguishing septic febrile neutropenia from other etiologies in acute leukemia patients play the important role in patient assessment and treatment planning. This study aims to determine the role of procalcitonin (PCT) and presepsin (PSPN) in infectious complication in comparison to C-reactive protein (CRP) on the first and third day at the onset of febrile neutropenia in patients with acute leukemia.MethodsBetween June 2018 and February 2019, 60 acute leukemia patients with febrile neutropenia receiving chemotherapy. The 41 acute myeloid leukemia patients and 19 acute lymphoblastic leukemia patients were recruited in this study. Their ages ranged from 14 to 65 years. PCT and PSPN were measured and were compared to CRP at the onset of febrile neutropenia and after 48 hours. 20 patients had a fever of unknown origin (FUO) and 40 patients had a bacterial infection.FindingsOur results showed that the values of these markers were higher in patients with infection than patients without. The area under the curve (AUC) of PCT were 0.931 and 0.813 on day one and three respectively, which was the best in determination of infection. The cut-off values of PCT were 1.27 and 1.23 ng/mL and the cut off values of PSPN were 1.75 and 2.9 μg/L in the successive days, their clinical sensitivities were high. PCT and PSPN were capable of distinguishing the cause of febrile neutropenia from the onset of infection and predicting its complications (p<0.05). The PSPN level couldn't differentiate gram-positive or gram-negative bacterial infection. Significant differences were found between the mean values of the PSPN during the successive days in all patients and patients with bacteremia. This study illustrated a weak positive correlation between PCT and Sequential Organ Failure Assessment (SOFA) score, the negligible correlation between CRP and SOFA score and no significant correlation between PSPN and SOFA score.InterpretationPCT is an accurate biomarker in identifying infection in acute leukemia patients, its concentration is associated with the severity of bacterial sepsis. PSPN is superior to PCT for follow-up of patients.
| S-EPMC8321513 | biostudies-literature
Project description:Background and Objectives: Teicoplanin (TEIC) is an effective drug for patients with febrile neutropenia (FN); however, it has been reported that these patients may have increased TEIC clearance compared with patients who do not have FN. The purpose of this study was to study therapeutic drug monitoring in patients with FN when the TEIC dosing design was based on the population mean method. Materials and Methods: Thirty-nine FN patients with hematological malignancy were included in the study. To calculate the predicted blood concentration of TEIC, we used the two population pharmacokinetic (population PK) parameters (parameters 1 and 2) reported by Nakayama et al. and parameter 3, which is a modification of the population PK of Nakayama et al. We calculated the mean prediction error (ME), an indicator of prediction bias, and the mean absolute prediction error (MAE), an indicator of accuracy. Furthermore, the percentage of predicted TEIC blood concentration within 25% and 50% of the measured TEIC blood concentration was calculated. Results: The ME values were -0.54, -0.25, and -0.30 and the MAE values were 2.29, 2.19, and 2.22 for parameters 1, 2, and 3, respectively. For all of the three parameters, the ME values were calculated as minus values, and the predicted concentrations tended to be biased toward smaller values relative to the measured concentrations. Patients with serum creatinine (Scr) < 0.6 mg/dL and neutrophil counts < 100/μL had greater ME and MAE values and a smaller percentage of predicted TEIC blood concentration within 25% of measured TEIC blood concentrations compared with other patients. Conclusions: In patients with FN, the accuracy of predicting TEIC blood concentrations was good, with no significant differences between each parameter. However, patients with a Scr < 0.6 mg/dL and a neutrophil count < 100/μL showed slightly inferior prediction accuracy.
| S-EPMC10145105 | biostudies-literature