scholarly journals Serum caspase-cleaved cytokeratin-18 fragment as a prognostic biomarker in hematological patients with febrile neutropenia

2021 ◽  
Author(s):  
Carina Intke ◽  
Sini Korpelainen ◽  
Marika Lappalainen ◽  
Matti Vänskä ◽  
Sari Hämäläinen ◽  
...  
Keyword(s):  
Severe Sepsis ◽  
Blood Culture ◽  
Febrile Neutropenia ◽  
Prognostic Marker ◽  
Fatal Outcome ◽  
University Hospital ◽  
Cell Transplant ◽  
Cytokeratin 18 ◽  
Intensive Care Unit Treatment ◽  
Hematological Patients

AbstractThe study aim was to determine the benefit of the measurement of serum caspase-cleaved cytokeratin-18 (CK-18) fragment as a prognostic marker of febrile neutropenia (FN) in hematological patients. The study population consisted of 86 consecutive patients with FN who received intensive chemotherapy for hematological malignancy at the adult hematology ward of Kuopio University Hospital. Twenty-three patients (27%) had acute myeloid leukemia, and 63 patients (73%) were autologous stem cell transplant recipients. Serum caspase-cleaved CK-18 fragment M30, C-reactive protein (CRP) and procalcitonin (PCT) were measured at the onset of FN (d0), on day 1 (d1), and on day 2 (d2). Eight patients (9%) developed severe sepsis, including three patients with septic shock. Eighteen patients (21%) had a blood culture-positive infection. Serum CK-18 fragment peaked on the first day after fever onset in patients with severe sepsis. Higher CK-18 level was associated with severe sepsis, intensive care unit treatment, and fatal outcome, but not with blood culture positivity. In ROC curve analysis, d1 serum CK-18 fragment predicted severe sepsis with an area under the curve (AUC) of 0.767, CRP with an AUC of 0.764, and PCT with an AUC of 0.731. On d2, the best predictive capacity was observed for CRP with an AUC of 0.832. The optimal cutoff of caspase-cleaved CK-18 fragment M30 for predicting severe sepsis was 205 U/L on d1. In hematological patients, serum CK-18 fragment was found to be a potential prognostic marker of severe sepsis at early stages of FN.

scholarly journals Soluble CD14 as a Diagnostic and Prognostic Biomarker in Hematological Patients with Febrile Neutropenia

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Sini Korpelainen ◽  
Carina Intke ◽  
Sari Hämäläinen ◽  
Esa Jantunen ◽  
Auni Juutilainen ◽  
...  
Keyword(s):  
Septic Shock ◽  
Severe Sepsis ◽  
Blood Culture ◽  
Febrile Neutropenia ◽  
Clinical Course ◽  
Surface Glycoprotein ◽  
Intensive Chemotherapy ◽  
Soluble Cd14 ◽  
Cell Surface Glycoprotein ◽  
Hematological Patients

Objective. Elevated levels of a cell surface glycoprotein, soluble cluster of differentiation 14 (sCD14), have been observed in patients with sepsis. Only scarce data are available on sCD14 in hematological patients with chemotherapy-induced febrile neutropenia. The study aim was to investigate sCD14 as an early biomarker in febrile neutropenia after intensive chemotherapy to detect a rapidly deteriorating clinical course early enough to avoid serious infectious complications.Patients and Methods. This prospective study included 87 adult hematological patients at the start of febrile neutropenia after intensive chemotherapy for acute myeloid leukemia or after autologous stem cell transplantation. The study endpoints were septic shock, severe sepsis, and positive blood culture findings. sCD14 was analyzed from day 0 to day 2, and its prognostic capacity was compared to that of C-reactive protein and procalcitonin.Results. Plasma level of sCD14 predicted the development of septic shock on day 1 (p=0.001) and day 2 but not the development of severe sepsis or blood culture positivity in hematological patients with chemotherapy-induced febrile neutropenia.Conclusions. Soluble CD14 did not predict an overall complicated course at the early stages of febrile neutropenia. However, it was helpful in predicting the progression of the clinical course of neutropenic fever to septic shock.

Retrospective study on the management of patients admitted for febrile neutropenia and considered to be at low risk at the Centre Hospitalier Universitaire de Québec.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18762-e18762
Author(s):  
Tommy Jean ◽  
Julie Lemieux ◽  
Geneviève Soucy ◽  
Francis Caron ◽  
Dominique Leblanc
Keyword(s):  
Retrospective Study ◽  
Febrile Neutropenia ◽  
Outpatient Treatment ◽  
Significant Proportion ◽  
Low Risk ◽  
University Hospital ◽  
Quebec City ◽  
Cell Transplant ◽  
Transplant Patients ◽  
Mascc Score

e18762 Background: Febrile neutropenia is a serious complication of chemotherapy leading to hospitalization in cancer patients. According to a practice guidelines published by ASCO (American Society of clinical Oncology) and IDSA (Infectious Diseases Society of American) in 2018, patients meeting the criteria for low-risk neutropenia according to the MASCC score (Multinational Association for Supportive Care in Cancer Score) could be treated as outpatient and thus avoid hospitalization. The objective of the study was to assess the number and proportion of patients who were hospitalized for febrile neutropenia in university hospital that would have met the low risk criteria of febrile neutropenia. We also wanted to know if these patients had experienced a favorable outcome during hospitalization. Methods: We performed a retrospective study including all patients admitted for febrile neutropenia in 3 hospitals in Quebec City during the period from January 1, 2018 to December 31, 2019. We excluded patients with leukemia, as well as stem cell transplant patients. The chart review retrospectively established the MASCC score for each patient. We also established according to predefined criteria whether the clinical course was favorable or unfavorable. Results: A total of 177 hospitalizations met our inclusion criteria. We found that 101/177 (57.1%) of hospitalized patients met the criteria for low-risk neutropenia according to the MASCC score (score of 21 and above). Of this number 74/177 (41.8%) presented all the criteria suggested for receiving outpatient treatment. In these patients 70/177 (39.5%) presented a favorable evolution during hospitalization and thus 4/177 (2.3%) presented an unfavorable evolution. Among these, 2 patients presented with infections considered major (2 bacteremia), 1 patient developed acute renal failure, and 1 other patient developed delirium. There was no death or admission to the intensive care unit in these 4 patients. Conclusions: According to this retrospective study, about 40% of patients admitted for febrile neutropenia filled the criteria of low risk febrile neutropenia and could be treated as outpatient. Given this represents a significant proportion of patients, a protocol for systematic follow-up of outpatient treatment with low-risk febrile neutropenia should be put in place.

MMP-10 and TIMP-1 as indicators of severe sepsis in adult hematological patients with febrile neutropenia

2019 ◽  
Vol 60 (12) ◽  
pp. 3036-3043 ◽  
Author(s):  
Stefan Becker ◽  
Sini Korpelainen ◽  
Miika Arvonen ◽  
Sari Hämäläinen ◽  
Esa Jantunen ◽  
...  
Keyword(s):  
Severe Sepsis ◽  
Febrile Neutropenia ◽  
Hematological Patients

scholarly journals 203. Opportunities for Antimicrobial Stewardship in Febrile Neutropenia

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S105-S106
Author(s):  
Christopher Shoff ◽  
Jordan Baskett ◽  
Julia A Messina ◽  
Arthur W Baker ◽  
Nicholas A Turner ◽  
...  
Keyword(s):  
Blood Culture ◽  
Febrile Neutropenia ◽  
Antimicrobial Stewardship ◽  
Positive Blood Culture ◽  
Treatment Duration ◽  
University Hospital ◽  
Research Support ◽  
Gram Negative ◽  
Gaussian Density ◽  
Culture Negative

Abstract Background Emerging evidence suggests antibiotics may be safely discontinued before neutropenia resolves in patients without identifiable infection. We estimated the volume of encounters and antibiotic use for future stewardship interventions shortening FN treatment duration. Methods This retrospective cohort study used electronic health records from inpatient encounters on the hematologic malignancies ward at Duke University Hospital from 5/21/2018 to 12/31/2019 where patients received at least one antibiotic for an indication of “neutropenic fever.” The primary outcome was length of therapy (LOT) of broad Gram-negative (GN) agents, including cefepime, piperacillin-tazobactam, meropenem, or aztreonam. FN LOT was counted by calendar day, starting with the first day of administration of a broad GN agent and ending with antibiotic discontinuation or hospital discharge. Encounters with at least one positive blood culture (positive cohort) were compared to those with no positive blood cultures (negative cohort) to assess if culture positivity was associated with differences in FN LOT. We included the first FN LOT from each encounter in the negative cohort and the FN LOT associated with the first positive blood culture in the positive cohort. We used descriptive statistics and a Gaussian density function to calculate the percent of encounters exceeding FN LOT of 14 days and the percent of broad GN agent days. Results We evaluated 15,678 GN antibiotic administrations from 471 unique FN encounters. Blood culture results were available for 443 encounters— 122 (27.5%) in the positive cohort, and 321 (72.5%) encounters in the negative cohort. Thirty percent of encounters (36/122) in the positive cohort received more than one GN treatment course, compared to 10% (32/321) of those in the negative cohort. FN LOT was significantly longer in the positive cohort (median 10.5, IQR 13 days vs. 6, IQR 8 days, p < 0.001). Among encounters with negative cultures, 57 (17.8%) had a first FN LOT greater than 14 days, accounting for 44% of broad GN agent days within that population (Figure 1). Gram-Negative Antibiotic Therapy in Blood Culture-Negative Febrile Neutropenia Conclusion Nearly 20% of blood culture-negative encounters received initial GN treatment courses exceeding 14 days, representing a sizeable target for antimicrobial stewardship interventions focused on FN treatment duration. Disclosures Rebekah W. Moehring, MD, MPH, Agency for Healthcare Quality and Research (Grant/Research Support)Centers for Disease Control and Prevention (Grant/Research Support)

scholarly journals Clinical Considerations of Isavuconazole Administration in High-Risk Hematological Patients: A Single-Center 5-Year Experience

2021 ◽  
Author(s):  
Ilona Kronig ◽  
Stavroula Masouridi-Levrat ◽  
Yves Chalandon ◽  
Emmanouil Glampedakis ◽  
Nathalie Vernaz ◽  
...  
Keyword(s):  
Real Life ◽  
Liver Function Tests ◽  
Primary Objective ◽  
University Hospital ◽  
Cell Transplant ◽  
Qtc Interval ◽  
Single Center ◽  
Hematopoietic Cell Transplant ◽  
Allogeneic Hematopoietic Cell Transplant ◽  
Hematological Patients

Abstract Background There are limited real-life data on isavuconazole prophylaxis and treatment of invasive mold infections (IMI) in hematological patients and allogeneic hematopoietic cell transplant (HCT) recipients. Objectives Primary objective was to describe the indications of real-life isavuconazole administration at a university hospital. Secondary objectives included the description of liver function tests and QTc interval between baseline and end of treatment (EOT), clinical outcomes and breakthrough IMI by the EOT. Patients/Methods This was a 5-year single-center retrospective study of all adult patients with acute myeloid leukemia and/or allogeneic HCT recipients who received isavuconazole as prophylaxis and/or treatment between June 1, 2016, and July 31, 2020. Results Among 30 identified patients, the indications for isavuconazole administration were adverse events associated with prior antifungal treatment (N: 18, 60%: hepatotoxicity, renal insufficiency, long QTc interval, neurotoxicity, and potential drug–drug interactions in 6, 4, 3, 1 and 4 patients, respectively), clinical efficacy (N: 5, 16.6%), and other reasons (N: 10, 33.3%; 5/10 patients treated with isavuconazole to facilitate hospital discharge with orally administered appropriate treatment). Alanine aminotransferase significantly decreased from baseline (mean: 129 IU/L, range: 73, 202) to a mean of 48 IU/L (range: 20, 80) by day 14 (P-value: 0.02), 23.5 IU/L (range: 20, 27) by day 28 (P-value: 0.03) and 16.5 IU/L (range: 16, 17) by day 42 (P-value: 0.009). The QTc interval decreased from baseline (mean: 456.8 ms, range: 390, 533) to EOT (mean: 433.8 ms, range: 400, 472; P-value: 0.03). The mean isavuconazole plasma concentration was 2.9 mg/L (range: 0.9, 6.7). There was no breakthrough IMI observed. Conclusion Isavuconazole is a safe and reliable antifungal agent in complex hematological patients, with relatively low hepatotoxicity and QTc interval shortening properties.

scholarly journals Cost-Effectiveness Analysis Comparing Two Approaches for Empirical Antifungal Therapy in Hematological Patients with Persistent Febrile Neutropenia

2013 ◽  
Vol 57 (10) ◽  
pp. 4664-4672 ◽  
Author(s):  
Almudena Martín-Peña ◽  
M. Victoria Gil-Navarro ◽  
Manuela Aguilar-Guisado ◽  
Ildefonso Espigado ◽  
Maite Ruiz Pérez de Pipaón ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Febrile Neutropenia ◽  
Antifungal Therapy ◽  
Standard Approach ◽  
Sensitivity Analyses ◽  
Treatment Pathways ◽  
Hematological Patients ◽  
Wide Range ◽  
Empirical Antifungal Therapy ◽  
The Cost

ABSTRACTNew approaches of empirical antifungal therapy (EAT) in selected hematological patients with persistent febrile neutropenia (PFN) have been proposed in recent years, but their cost-effectiveness has not been studied. The aim of this study was to compare the cost-effectiveness of two different approaches of EAT in hematological patients with PFN: the diagnosis-driven antifungal therapy (DDAT) approach versus the standard approach of EAT. A decision tree to assess the cost-effectiveness of both approaches was developed. Outcome probabilities and treatment pathways were extrapolated from two studies: a prospective cohort study following the DDAT approach and a randomized clinical trial following the standard approach. Uncertainty was undertaken through sensitivity analyses and Monte Carlo simulation. The average effectiveness and economic advantages in the DDAT approach compared to the standard approach were 2.6% and €5,879 (33%) per PFN episode, respectively. The DDAT was the dominant approach in the 99.5% of the simulations performed with average cost-effectiveness per PFN episode of €32,671 versus €52,479 in the EAT approach. The results were robust over a wide range of variables. The DDAT approach is more cost-effective than the EAT approach in the management of PFN in hematological patients.

scholarly journals Differences in Hypotensive vs. Non-Hypotensive Sepsis Management in the Emergency Department: Door-to-Antibiotic Time Impact on Sepsis Survival

2018 ◽  
Vol 6 (4) ◽  
pp. 91
Author(s):  
Leonor Ballester ◽  
Rafael Martínez ◽  
Juan Méndez ◽  
Gloria Miró ◽  
Manel Solsona ◽  
...  
Keyword(s):  
Emergency Department ◽  
Severe Sepsis ◽  
Clinical Laboratory ◽  
University Hospital ◽  
Antibiotic Administration ◽  
Process Of Care ◽  
Sepsis Management ◽  
Initial Management ◽  
Sepsis Diagnosis ◽  
Community Onset

Background: Sepsis diagnosis can be incorrectly associated with the presence of hypotension during an infection, so the detection and management of non-hypotensive sepsis can be delayed. We aimed to evaluate how the presence or absence of hypotension, on admission at the emergency department, affects the initial management and outcomes of patients with community-onset severe sepsis. Methods: Demographic, clinical, laboratory, process of care, and outcome variables were recorded for all patients, at the emergency department of our university hospital, who presented with community-onset severe sepsis, between 1 March and 31 August in three consecutive years. Patient management consisted of standardized bundled care with five measures: Detection, blood cultures and empirical antibiotics, oxygen supplementation and fluid resuscitation (if needed), clinical monitoring, and noradrenalin administration (if needed). We compared all variables between patients who had hypotension (mean arterial pressure <65 mmHg), on admission to the emergency department, and those who did not. Results: We identified 153 episodes (84 (54.5%) men; mean age 73.6 ± 1.2; mean Sequential Organ Failure Assessment (SOFA) score 4.9 ± 2.7, and 41.2% hospital mortality). Hypotension was present on admission to the emergency department in 57 patients (37.2%). Hemodynamic treatment was applied earlier in patients who presented hypotension initially. Antibiotics were administered 48 min later in non-hypotensive sepsis (p = 0.08). A higher proportion of patients without initial hypotension required admission to the intensive care unit (ICU) (43.1% for patients initially hypotensive vs. 56.9% in those initially non-hypotensive, p < 0.05). Initial hypotension was not associated with mortality. A delay in door-to-antibiotic administration time was associated with mortality [OR 1.150, 95%CI: 1.043–1.268). Conclusions: Initial management of patients with community-onset severe sepsis differed according to their clinical presentation. Initial hypotension was associated with early hemodynamic management and less ICU requirement. A non-significant delay was observed in the administration of antibiotics to initially non-hypotensive patients. The time of door-to-antibiotic administration was related to mortality.

scholarly journals Bloodstream infections in patients with hematologic malignancies and febrile neutropenia - a single center experience

2021 ◽  
Vol 74 (3-4) ◽  
pp. 83-89
Author(s):  
Marina Dragicevic-Jojkic ◽  
Ivana Urosevic ◽  
Amir El Farra ◽  
Borivoj Sekulic ◽  
Ivanka Percic ◽  
...  
Keyword(s):  
Febrile Neutropenia ◽  
Fatal Outcome ◽  
Antibiotic Sensitivity ◽  
Bloodstream Infections ◽  
Hematologic Malignancies ◽  
High Rate ◽  
Antibiotics Resistance ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Acinetobacter Spp

Introduction. Bacterial blood infections during febrile neutropenia episodes are urgent medical conditions which were and still are the main cause of morbidity and mortality among patients with hematologic malignancies. The aim of this study was to determine the incidence and clinical characteristics of bacteremia, infectious agents, presence and incidence of antibiotic resistance, as well as the treatment outcome of bloodstream infections in patients with hematologic malignancies. Material and Methods. A three-year retrospective study included 107 patients with hematologic malignancies and positive blood culture results during febrile neutropenia. Results. The most common isolates were Gram-negative bacteria (58.5%), with Escherichia coli being the most frequent pathogen. The Gram-negative microorganisms were mostly sensitive to carbapenems in 70.7%, whereas sensitivity to other antibiotics was as follows: piperacillin/ tazobactam 62%, amikacin 58.5%, and third-generation cephalosporins 50.5%. Acinetobacter spp. was sensitive only to colistin (94.1%). The antibiotic sensitivity among Gram-positive bacteria was highest to linezolid (97.1%), followed by teicoplanin (81.4%) and vancomycin (81.4%). In our patients, the mortality rate during the first 28 days from the moment of positive isolates was high (37.4%). Most patients died within the first seven days. Bacterial blood infections caused by Gram-negative bacteria were associated with significantly higher mortality (?2 = 4.92, p = 0.026). Acinetobacter spp. was isolated in almost half of the patients with fatal outcome, of whom 62.5% died in the first 24 hours. Conclusion. Bacterial bloodstream infections are severe complications with a high rate of mortality in febrile neutropenic hematological patients. Gram-negative bacteria were the most common isolates in our Clinic, with high mortality. It is of utmost importance to constantly monitor the resistance of bacteria to antibiotics, as well as to prevent and control the spread of resistant strains. Antibiotics resistance patterns should regularly be followed.

scholarly journals A Thrombomodulin Promoter Gene Polymorphism, rs2239562, Influences Both Susceptibility to and Outcome of Sepsis

2022 ◽  
Vol 8 ◽  
Author(s):  
Eizo Watanabe ◽  
Osamu Takasu ◽  
Youichi Teratake ◽  
Teruo Sakamoto ◽  
Toshiaki Ikeda ◽  
...  
Keyword(s):  
Severe Sepsis ◽  
Protein C ◽  
Validation Cohort ◽  
University Hospital ◽  
Coagulation Cascade ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Functional Polymorphisms ◽  
Promoter Gene ◽  
Control Study

Objective: Disseminated intravascular coagulation plays a key role in the pathophysiology of sepsis. Thrombomodulin is essential in the protein C system of coagulation cascade, and functional polymorphisms influence the human thrombomodulin gene (THBD). Therefore, we conducted a multicenter study to evaluate the influence of such polymorphisms on the pathophysiology of sepsis.Methods: A collaborative case-control study in the intensive care unit (ICU) of each of five tertiary emergency centers. The study included 259 patients (of whom 125 displayed severe sepsis), who were admitted to the ICU of Chiba University Hospital, Chiba, Japan between October 2001 and September 2008 (discovery cohort) and 793 patients (of whom 271 patients displayed severe sepsis), who were admitted to the five ICUs between October 2008 and September 2012 (multicenter validation cohort). To assess the susceptibility to severe sepsis, we further selected 222 critically ill patients from the validation cohort matched for age, gender, morbidity, and severity with the patients with severe sepsis, but without any evidence of sepsis.Results: We examined whether the eight THBD single nucleotide polymorphisms (SNPs) were associated with susceptibility to and/or mortality of sepsis. Higher mortality on severe sepsis in the discovery and combined cohorts was significantly associated with the CC genotype in a THBD promoter SNP (−1920*C/G; rs2239562) [odds ratio [OR] 2.709 (1.067–6.877), P = 0.033 and OR 1.768 (1.060–2.949), P = 0.028]. Furthermore, rs2239562 SNP was associated with susceptibility to severe sepsis [OR 1.593 (1.086–2.338), P = 0.017].Conclusions: The data demonstrate that rs2239562, the THBD promoter SNP influences both the outcome and susceptibility to severe sepsis.

scholarly journals Galectin-3 in Critically Ill Patients with Sepsis and/or Trauma: A Good Predictor of Outcome or Not?

2018 ◽  
Vol 0 (0) ◽  
Author(s):  
Jasna Jevdjic ◽  
Maja Surbatovic ◽  
Snezana Milosavljevic ◽  
Goran Rondovic ◽  
Ivan Stanojevic ◽  
...  
Keyword(s):  
Severe Sepsis ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Good Predictor ◽  
Injury Severity ◽  
Area Under The Curve ◽  
University Hospital ◽  
Youden Index ◽  
Lethal Outcome ◽  
Galectin 3

Abstract Severe sepsis and/or trauma complicated with multiple organ dysfunction syndrome are leading causes of death in critically ill patients. The aim of this prospective, observational, single centre study was to assess the prognostic value of galectin-3 regarding outcome in critically ill patients with severe trauma and/or severe sepsis. The outcome measure was hospital mortality. In total, 75 critically ill patients who were admitted to the intensive care unit of the tertiary university hospital were enrolled in a prospective observational study. Blood samples were collected upon fulfilling Sepsis-3 criteria and for a traumatized Injury Severity Score > 25 points. Levels of galectin-3 were significantly higher in nonsurvivors on the day of enrolment - Day 1 (p<0.05). On Day 1, the area under the curve (AUC) for the galectin-3 for lethal outcome was 0.602. At a cut-off level of 262.82 ng/mL, the sensitivity was 53%, and the specificity was 69.7%, which was objectively determined by a Youden index of 0.20. The discriminative power of galectin-3 in predicting outcome was statistically significant. Galectin-3 on Day 1 is a fairly good predictor of lethal outcome.

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