Novel biomarkers to identify complicated course of febrile neutropenia in hematological patients receiving intensive chemotherapy.

Febrile neutropenia (FN) is a common consequence of intensive chemotherapy in hematological patients. More than 90% of the patients with acute myeloid leukemia (AML) develop FN, and 5%-10% of them die from subsequent sepsis. FN is very common also in autologous stem cell transplant recipients, but the risk of death is lower than in AML patients. In this review, we discuss biomarkers that have been evaluated for diagnostic and prognostic purposes in hematological patients with FN. In general, novel biomarkers have provided little benefit over traditional inflammatory biomarkers, such as C-reactive protein and procalcitonin. The utility of most biomarkers in hematological patients with FN has been evaluated in only a few small studies. Although some of them appear promising, much more data is needed before they can be implemented in the clinical evaluation of FN patients. Currently, close patient follow-up is key to detect complicated course of FN and the need for further interventions such as intensive care unit admission. Scoring systems such as q-SOFA (Quick Sequential Organ Failure Assessment) or NEWS (National Early Warning Sign) combined with traditional and/or novel biomarkers may provide added value in the clinical evaluation of FN patients.

Central Obesity is Associated with Increased Left Ventricular Maximal Wall Thickness and Intrathoracic Adipose Tissue Measured with Cardiac Magnetic Resonance.

INTRODUCTION: Central obesity (CO), characterized by an increased waist circumference increases the risk of cardiovascular disease (CVD) and morbidity, yet the underlying mechanisms are not fully understood. CO is often associated with general obesity, hypertension, and abnormal glucose tolerance, confounding the independent contribution of CO to CVD. AIM: We investigated the relationship of CO (without associated disorders) with left ventricular (LV) characteristics and intrathoracic adipose tissue (IAT) by cardiac magnetic resonance. METHODS: LV characteristics, epicardial (EAT), and mediastinal adipose tissue (MAT) were measured from 29 normoglycemic, normotensive males with CO but without general obesity (waist circumference >100 cm, body mass index (BMI) <30 kg/m2) and 18 non-obese male controls. RESULTS: LV maximal wall thickness (LVMWT) and IAT but not LV mass or volumes were increased in CO subjects compared to controls (LVMWT, 12.3±1.2 vs. 10.7±1.5 mm, p < 0.001; EAT, 5.5±3.0 vs. 2.2±2.0 cm2, p = 0.001; MAT, 31.0±12.8 vs. 15.4±10.7 cm2, p < 0.001). The LVMWT was ≥12 mm in 69% of subjects with CO and 22% of controls (p = 0.002). In CO suspects, EAT correlated inversely with LV end-diastolic volume index (r = - 0.403, p = 0.037) and LV stroke volume (SV) (r = - 0.425, p = 0.027). MAT correlated inversely with SV (r = - 0.427, p=0.026) and positively with LVMWT (r = 0.399, p = 0.035). Among CO subjects, the waist-to-hip ratio (WHR) was an independent predictor of LVMWT (B = 22.4, ß = 0.617, p < 0.001). The optimal cut-off with Youden's index for LV hypertrophy was identified at WHR 0.98 (sensitivity 85%, specificity 89%). CONCLUSIONS: CO independent of BMI is associated with LV hypertrophy and intrathoracic adipose tissue contributing to cardiovascular burden.

Sex Differences in Red Blood Cell Transfusions and 30-Day Mortality in Cardiac Surgery: A Single Center Observational Study.

In cardiac surgery, women have higher short-term mortality and a higher risk of receiving red blood cell (RBC) transfusions than men. This study's aim was to evaluate possible sex differences in RBC transfusions in cardiac surgery and their association with preoperative hemoglobin levels, body mass index, and 30-day mortality. A single-center retrospective study was conducted with 1583 patients (1181 men and 402 women) undergoing cardiac surgery. A total of 64.4% of the women and 33.0% of the men received an RBC transfusion. In a multivariable analysis, female sex was an independent predictor of RBC transfusion (OR 3.88, 95% CI 2.95-5.11, p < 0.001). Other independent predictors of RBC transfusion were age, preoperative hemoglobin level, and body mass index. The women were more likely to receive RBC transfusions than the men, regardless of the type of cardiac surgery. Decreased transfusion risk was found in all higher-than-normal weight categories in the women, but only in the severe obesity category in the men. Preoperative hemoglobin was similarly associated with RBC transfusion in the men and women. The crude 30-day mortality rate was higher in the women than in the men (2.5% vs. 0.9%, p = 0.018). In both sexes, RBC transfusion was associated with an increased probability of death within 30 days.

Association of body mass index with 30-day mortality and red blood cell transfusions in open heart surgery.

OBJECTIVES: Obesity is associated with increased burden of cardiovascular risk factors, morbidity and mortality. However, several studies have counterintuitively shown better outcome after cardiac surgery in obese than in normal weight patients, a phenomenon known as obesity paradox. Furthermore, obesity has been linked with decreased need of red blood cell (RBC) transfusions. The purpose of this study was to evaluate the impact of body mass index (BMI) on 30-day mortality and RBC transfusions in patients undergoing cardiac surgery, a clinically important topic with conflicting previous data. METHODS: We retrospectively investigated 1691 patients who underwent coronary and/or valve or aortic root surgery using cardiopulmonary bypass between 2013 and 2016. The patients were categorized by BMI based on the World Health Organization classification. For analysis, logistic regression was used with adjustment for potential confounding factors. RESULTS: Of the patients, 28.7% were normal weight, 43.3% overweight, 20.5% mildly obese and 7.5% severely obese. Thirty-day mortality was 1.9% without significant differences between the BMI groups. 41.0% of patients received RBC transfusion. Overweight [odds ratio (OR) 0.75, 95% confidence interval (CI) 0.56-0.99, P = 0.045], mildly (OR 0.65, 95% CI 0.46-0.92, P = 0.016) and severely obese (OR 0.41, 95% CI 0.24-0.70, P = 0.001) patients needed less frequently RBC transfusions than patients with normal weight. CONCLUSIONS: Obesity was not associated with 30-day mortality but was associated with lower use of RBC transfusions in cardiac surgery.

Impact of perfusion method on perioperative red blood cell transfusions and new-onset postoperative atrial fibrillation in mitral valve surgery patients.

INTRODUCTION: Red blood cell (RBC) transfusions are common in cardiac surgery and reportedly associated with increased mortality and morbidity, including increased risk of postoperative new-onset atrial fibrillation (NOAF). The aim of this study was to compare minimal invasive extracorporeal circulation (MiECC) and conventional extracorporeal circulation (CECC) in terms of RBC transfusions and the incidence of NOAF in mitral valve surgery. METHODS: The study population consisted of 89 MiECC and 169 CECC patients undergoing mitral valve surgery as an isolated procedure (80.6% of the patients) or in combination with coronary artery bypass grafting (19.4% of patients). 79.4% of the patients were male and the mean age was 62.1 years. RESULTS: 30.0% of patients aged < 65 years and 48.1% of patients aged ≥ 65 years needed RBC transfusion. The overall need for RBC transfusions did not differ between the treatment groups. Among patients < 65 years of age transfusions of ≥ 3 units were less frequent in MiECC than in CECC patients (OR 0.31, 95% CI 0.10-0.98, p = 0.045). The overall incidence of NOAF was 41.8% with no significant difference between MiECC and CECC groups. Red blood cell transfusions were associated with an increased risk of NOAF in an unadjusted analysis but not after adjustment for age and sex (OR 1.25, 95% CI 0.64-2.43, p = 0.515). CONCLUSIONS: In mitral valve surgery MiECC compared to CECC was associated with less need of RBC units and platelets, particularly in patients aged < 65 years. Use of RBC transfusions was associated with increased risk of NOAF significantly only in unadjusted analysis.

Impact of minimal invasive extracorporeal circulation on perioperative intravenous fluid management in coronary artery bypass surgery.

OBJECTIVE: Compare the use of blood products and intravenous fluid management in patients scheduled for coronary artery bypass surgery and randomized to minimal invasive extracorporeal circulation (MiECC) and conventional extracorporeal circulation (CECC). METHODS: A total of 240 patients who were scheduled for their first on-pump CABG, were randomized to MiECC or CECC groups. The study period was the first 84 hours after surgery. Hemoglobin <80 g/l was used as transfusion trigger. RESULTS: Red blood cell transfusions intraoperatively were given less often in the MiECC group (23.3% vs 9.2%, p = 0.005) and the total intravenous fluid intake was significantly lower in the MiECC group (3300 ml [2950-4000] vs 4800 ml [4000-5500], p < 0.001). Hemoglobin drop also was lower in the MiECC group (35.5 ± 8.9 g/l vs 50.7 ± 9 g/l, p < 0.001) as was hemoglobin drop percent (25.3 ± 6% vs 35.3 ± 5.9%, p < 0.001). Chest tube drainage output was higher in the MiECC group (645 ml [500-917.5] vs 550 ml [412.5-750], p = 0.001). Particularly, chest tube drainage in up to 600 ml category, was in benefit of CECC group (59.1% vs 40.8%, p = 0.003). ROC curve analysis showed that patients with hemoglobin level below 95 g/l upon arrival to intensive care unit was associated with increased risk of developing postoperative atrial fibrillation (POAF) (p = 0.002, auc = 0.61, cutoff <95, sensitivity = 0.47, positive predictive value = 0.64). CONCLUSION: MiECC reduced the intraoperative need for RBC transfusion and intravenous fluids compared to the CECC group, also reducing hemoglobin drop compared to the CECC group in CABG surgery patients. Postoperative hemoglobin drop was a predictor of POAF.

Prevention of Atrial Fibrillation After Cardiac Surgery: A Review of Literature and Comparison of Different Treatment Modalities.

Atrial fibrillation is the most common arrhythmia to occur after cardiac surgery, with an incidence of 10% to 50%. It is associated with postoperative complications including increased risk of stroke, prolonged hospital stays and increased costs. Despite new insights into the mechanisms of atrial fibrillation, no specific etiologic factor has been identified as the sole perpetrator of the arrhythmia. Current evidence suggests that the pathophysiology of atrial fibrillation in general, as well as after cardiac surgery, is multifactorial. Studies have also shown that new-onset postoperative atrial fibrillation following cardiac surgery is associated with a higher risk of short-term and long-term mortality. Furthermore, it has been demonstrated that prophylactic medical therapy decreases the incidence of postoperative atrial fibrillation after cardiac surgery. Of note, the incidence of postoperative atrial fibrillation has not changed during the last decades despite the numerous preventive strategies and operative techniques proposed, although the perioperative and postoperative care of cardiac patients as such has improved.

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

The 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.

Accuracy of 1-Hour Plasma Glucose During the Oral Glucose Tolerance Test in Diagnosis of Type 2 Diabetes in Adults: A Meta-analysis.

OBJECTIVE: One-hour plasma glucose (1-h PG) during the oral glucose tolerance test (OGTT) is an accurate predictor of type 2 diabetes. We performed a meta-analysis to determine the optimum cutoff of 1-h PG for detection of type 2 diabetes using 2-h PG as the gold standard. RESEARCH DESIGN AND METHODS: We included 15 studies with 35,551 participants from multiple ethnic groups (53.8% Caucasian) and 2,705 newly detected cases of diabetes based on 2-h PG during OGTT. We excluded cases identified only by elevated fasting plasma glucose and/or HbA1c. We determined the optimal 1-h PG threshold and its accuracy at this cutoff for detection of diabetes (2-h PG ≥11.1 mmol/L) using a mixed linear effects regression model with different weights to sensitivity/specificity (2/3, 1/2, and 1/3). RESULTS: Three cutoffs of 1-h PG, at 10.6 mmol/L, 11.6 mmol/L, and 12.5 mmol/L, had sensitivities of 0.95, 0.92, and 0.87 and specificities of 0.86, 0.91, and 0.94 at weights 2/3, 1/2, and 1/3, respectively. The cutoff of 11.6 mmol/L (95% CI 10.6, 12.6) had a sensitivity of 0.92 (0.87, 0.95), specificity of 0.91 (0.88, 0.93), area under the curve 0.939 (95% confidence region for sensitivity at a given specificity: 0.904, 0.946), and a positive predictive value of 45%. CONCLUSIONS: The 1-h PG of ≥11.6 mmol/L during OGTT has a good sensitivity and specificity for detecting type 2 diabetes. Prescreening with a diabetes-specific risk calculator to identify high-risk individuals is suggested to decrease the proportion of false-positive cases. Studies including other ethnic groups and assessing complication risk are warranted.

Preoperative atrial fibrillation in association with reduced haemoglobin predicts increased 30-d mortality after cardiac surgery.

OBJECTIVES: Atrial fibrillation is the most common arrhythmia occurring after cardiac surgery. Less attention has been focused on preoperative atrial fibrillation and anaemia as risk factors for mortality after cardiac surgery. The aim of this study was to determine preoperative risk factors for 30-d mortality after open-heart surgery. Design. The study population consisted of 2015 patients (73.4% men; mean age 68 years) undergoing coronary artery bypass grafting (CABG) (52.0%), aortic valve replacement (AVR) (18.6%), AVR and CABG (10.0%), mitral valve plasty or replacement (14.0%), and AVR and aortic root reconstruction (ARR) (5.5%) in Kuopio University Hospital from January 2013 to December 2016. Univariate and multivariate Cox proportional hazards models were used for statistical analyses. Kaplan-Meier survival curves were generated. Results. Total 30-d mortality was 1.8%. By Cox regression analysis, predictors of 30-d mortality (hazard ratio [HR] [95% confidence interval [CI]]) included female gender (1.95 [1.00-3.77]), preoperative atrial fibrillation, (2.38 [1.12-5.03]) reduced haemoglobin level (3.40 [1.47-7.90]), and pulmonary congestion (3.16 [1.52-6.55]). The combination of preoperative reduced haemoglobin and preoperative atrial fibrillation was a strong predictor (12.37 [4.40-34.77], p < .001). Estimated glomerular filtration rate (eGFR) predicted 30-d mortality in univariate models but was not an independent predictor in multivariate models. Conclusions. According to the main findings of our study, the combination of preoperative atrial fibrillation and reduced haemoglobin level substantially increase the risk of 30-d mortality after cardiac surgery. Identification of high-risk patients pre-operatively could help to make optimal clinical decisions for timing of operation and perioperative treatment.

Febrile neutropenia in patients with acute myeloid leukemia: Outcome in relation to qSOFA score, C-reactive protein, and blood culture findings.

OBJECTIVES: To evaluate quick Sequential Organ Failure Assessment (qSOFA) score during febrile neutropenia (FN) in adult patients receiving intensive chemotherapy for acute myeloid leukemia (AML). METHODS: qSOFA score, as well as the association of qSOFA score with ICU admission, infectious mortality, blood culture findings, and C-reactive protein (CRP) measurements during FN were assessed among 125 adult AML patients with 355 FN periods receiving intensive chemotherapy in a tertiary care hospital from November 2006 to December 2018. RESULTS: The multivariate model for qSOFA score ≥ 2 included CRP ≥ 150 mg/L on d0-2 [OR 2.9 (95% CI 1.1-7.3), P = .026], Gram-negative bacteremia [OR 2.7 (95% CI 1.1-6.9), P = .034], and treatment according to AML-2003 vs more recent protocols [OR 2.7 (95% CI 1.0-7.4), P = .047]. Age or gender did not gain significance in the model. qSOFA score ≥ 2 was associated with ICU treatment and infectious mortality during FN with sensitivity and specificity of 0.700 and 0.979, and 1.000 and 0.971, respectively. CONCLUSION: qSOFA offers a useful tool to evaluate the risk of serious complications in AML patients during FN.

Plasma level of interleukin-18 and complicated course of febrile neutropenia in hematological patients after intensive chemotherapy.

In search of a biomarker for complicated course of febrile neutropenia (FN), plasma IL-18 was measured in 92 hematological patients after intensive chemotherapy at the beginning of FN (days 0-3). Complicated course was defined as blood culture positivity or septic shock. IL-18 varied according to background hematological malignancy and showed an inverse correlation with leukocyte count. IL-18 was not associated with complicated course of FN, defined as blood culture positivity or septic shock, in the whole study group, but an association was observed on d1 and d2 after the onset of FN in the subgroup of autologous stem cell transplant recipients with non-Hodgkin lymphoma.

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

Commonly used indicators of sepsis are nonspecific and insufficient for predicting the course of febrile neutropenia (FN) in hematological patients. We analyzed data from 91 adult FN patients who received intensive chemotherapy for acute myeloid leukemia or autologous stem cell transplantation. Compared to patients with non-severe sepsis, patients with severe sepsis had significantly higher serum levels of tissue inhibitor of metalloproteinases-1 on the day of first occurrence of fever (day 0: 172 vs. 112 µg/L, p= .002) and for the two following days (day 1: 219 vs. 128 µg/L, p< .001; day 2: 443 vs. 128 µg/L, p= .001), and significantly higher serum levels of matrix metalloproteinase-10 on day 1 (1975 vs. 876 ng/L, p= .001) and day 2 (2020 vs. 841 ng/L, p< .001). We conclude that the measurement of these biomarkers may be useful in predicting the severity of sepsis in FN patients.

Interleukin-1 receptor antagonist as a biomarker of sepsis in neutropenic haematological patients.

OBJECTIVE: The study aim was to compare the performance of interleukin-1 receptor antagonist (IL-1Ra) to C-reactive protein (CRP) and procalcitonin (PCT) in early prediction of the clinical course of febrile neutropenia. METHODS: The study population consisted of 86 consecutive patients with febrile neutropenia who received intensive chemotherapy for haematological malignancy between November 2009 and November 2012 at the adult haematology ward of Kuopio University Hospital. Twenty-three (27%) patients had acute myeloid leukaemia and 63 (73%) patients were autologous stem cell transplant recipients. IL-1Ra, CRP and procalcitonin were measured at the onset of fever (d0), on day 1 (d1) and on day 2 (d2). RESULTS: Eight patients developed severe sepsis, including three patients with septic shock. Eighteen patients had bacteraemia. After the onset of febrile neutropenia Youden´s indices (with their 95% confidence intervals) to identify severe sepsis were for IL-1Ra on d0 0.57 (0.20-0.71) and on d1 0.65 (0.28-0.78), for CRP on d0 0.41 (0.04-0.61) and on d1 0.47 (0.11-0.67) and for PCT on d0 0.39 (0.05-0.66) and on d1 0.52 (0.18-0.76). CONCLUSIONS: In haematological patients, IL-1Ra has a comparable capacity with CRP and PCT to predict severe sepsis at the early stages of febrile neutropenia.

Effector T Cell Resistance to Suppression and STAT3 Signaling during the Development of Human Type 1 Diabetes.

Dysregulation of regulatory T cell (Treg)-mediated suppression and, in particular, resistance of CD4+ effector T cells (Teffs) to suppression have been implicated in the pathogenesis of human type 1 diabetes (T1D). However, the mechanistic basis behind this resistance and the time frame during which it develops in relation to the onset of clinical T1D remain unclear. In this study, we analyzed the capacity of peripheral blood Teffs isolated both from patients with T1D and from prediabetic at-risk subjects positive for multiple diabetes-associated autoantibodies (AAb+) to be suppressed by Tregs. Because STAT3 activation through IL-6 has previously been implicated in mediating Teff resistance, we also investigated the surface expression of IL-6R as well as IL-6- and TCR-mediated phosphorylation of STAT3 in T cells from our study subjects. Teff resistance to suppression was observed both in patients with newly diagnosed and long-standing T1D but not in AAb+ subjects and was shown to be STAT3 dependent. No alterations in IL-6R expression or IL-6-mediated STAT3 activation were observed in T cells from patients with T1D or AAb+ subjects. However, faster STAT3 activation after TCR stimulation without concomitant increase in IL-6 expression was observed in T cells from patients with T1D. These experiments suggest that Teff resistance in T1D patients is STAT3 dependent but not directly linked with the capacity of Teffs to produce or respond to IL-6. In conclusion, Teff resistance to Treg-mediated suppression is likely a feature of disease progression in human T1D and can potentially be targeted by immune therapies that block STAT3 activation.

Novel Biomarker Candidates for Febrile Neutropenia in Hematological Patients Using Nontargeted Metabolomics.

BACKGROUND: Novel potential small molecular biomarkers for sepsis were analyzed with nontargeted metabolite profiling to find biomarkers for febrile neutropenia after intensive chemotherapy for hematological malignancies. METHODS: Altogether, 85 patients were included into this prospective study at the start of febrile neutropenia after intensive chemotherapy for acute myeloid leukemia or after autologous stem cell transplantation. The plasma samples for the nontargeted metabolite profiling analysis by liquid chromatography-mass spectrometry were taken when fever rose over 38° and on the next morning. RESULTS: Altogether, 90 differential molecular features were shown to explain the differences between patients with complicated (bacteremia, severe sepsis, or fatal outcome) and noncomplicated courses of febrile neutropenia. The most differential compounds were an androgen hormone, citrulline, and phosphatidylethanolamine PE(18:0/20:4). The clinical relevance of the findings was evaluated by comparing them with conventional biomarkers like C-reactive protein and procalcitonin. CONCLUSION: These results hold promise to find out novel biomarkers for febrile neutropenia, including citrulline. Furthermore, androgen metabolism merits further studies.

Secular Trends in Infection-Related Mortality after Kidney Transplantation.

BACKGROUND AND OBJECTIVES: Infections are the most common noncardiovascular causes of death after kidney transplantation. We analyzed the current infection-related mortality among kidney transplant recipients in a nationwide cohort in Finland. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Altogether, 3249 adult recipients of a first kidney transplant from 1990 to 2012 were included. Infectious causes of death were analyzed, and the mortality rates for infections were compared between two eras (1990-1999 and 2000-2012). Risk factors for infectious deaths were analyzed with Cox regression and competing risk analyses. RESULTS: Altogether, 953 patients (29%) died during the follow-up, with 204 infection-related deaths. Mortality rate (per 1000 patient-years) due to infections was lower in the more recent cohort (4.6; 95% confidence interval, 3.5 to 6.1) compared with the older cohort (9.1; 95% confidence interval, 7.6 to 10.7); the incidence rate ratio of infectious mortality was 0.51 (95% confidence interval, 0.30 to 0.68). The main causes of infectious deaths were common bacterial infections: septicemia in 38% and pulmonary infections in 45%. Viral and fungal infections caused only 2% and 3% of infectious deaths, respectively (such as individual patients with Cytomegalovirus pneumonia, Herpes simplex virus meningoencephalitis, Varicella zoster virus encephalitis, and Pneumocystis jirovecii infection). Similarly, opportunistic bacterial infections rarely caused death; only one death was caused by Listeria monocytogenes, and two were caused by Mycobacterium tuberculosis. Only 23 (11%) of infection-related deaths occurred during the first post-transplant year. Older recipient age, higher plasma creatinine concentration at the end of the first post-transplant year, diabetes as a cause of ESKD, longer pretransplant dialysis duration, acute rejection, low albumin level, and earlier era of transplantation were associated with increased risk of infectious death in multivariable analysis. CONCLUSIONS: The risk of death due to infectious causes after kidney transplantation in Finland dropped by one half since the 1990s. Common bacterial infections remained the most frequent cause of infection-related mortality, whereas opportunistic viral, fungal, or unconventional bacterial infections rarely caused deaths after kidney transplantation.

Changes in the microbiological epidemiology of febrile neutropenia in autologous stem cell transplant recipients.

BACKGROUND: The aim of the study was to explore the incidence, microbiological etiology and outcome of febrile neutropenia among adult hematological patients following autologous stem cell transplantation (ASCT). METHODS: The study population consisted of patients who received ASCT between 1 December 2006 and 30 November 2012. The epidemiology was compared to a retrospective series covering eleven previous years at the same institution. Non-Hodgkin lymphoma (NHL) patients, who had been identified as a risk group in the retrospective study, received ciprofloxacin prophylaxis from January 2008. RESULTS: Altogether, 142 out of 178 of the included patients (80%) developed febrile neutropenia. The blood cultures were positive in 24 cases (17%). Of all bacteremia's, 88% were caused by Gram-positive and 12% by Gram-negative bacteria. The number of Gram-negative bacteremia were significantly lower in the prospective study compared to the retrospective study (3/142, 2.1% vs. 23/265, 8.7%, p = .01). Pseudomonas aeruginosa was prevalent in the retrospective series but not discovered in the present series. Enterococcus faecium was found more frequently in the prospective study (6/142, 4.2 vs. 2/265, 0.8%, p = .02). The infectious mortality among patients with febrile neutropenia was 4/142 (2.8%) in the present series and 9/265 (3.4%) in those who received ASCT in 1996-2006. CONCLUSION: Most patients who received ASCT developed febrile neutropenia and a minority had bacteraemia. In comparison to the earlier time period, the incidence of Gram-negative bacteraemias decreased, probably due to ciprofloxacin prophylaxis in NHL patients, but simultaneously the incidence of Enterococcus bacteraemias increased. Infectious mortality during febrile neutropenia was low in both series.

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

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.