Search

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Procalcitonin is a biomarker that can be used to diagnose bacterial infection and monitor treatment. Clinical practice guidelines are evidence-based recommendations by experts that aim to aid decision-making. In this systematic review, we searched for clinical practice guidelines and evaluated recommendations given regarding use of procalcitonin. Methods: Four biomedical databases (PubMed, Scopus, Cochrane Database and Web of Science) and various national medical sites were searched for clinical practice guidelines. Guidelines that mentioned procalcitonin were included in the review. Results: Seventeen guidelines were included. The earliest were published in 2009 and the latest in 2018. A majority (12/17) recommended use of procalcitonin or stated that it can be useful. One national guideline did not recommend procalcitonin, stating that there is no need for any biomarkers in diagnostics of community-acquired pneumonia in adults. Four guidelines stated no evidence to recommend or not recommend procalcitonin use. Thirteen of the guidelines commented on other concomitant or alternate biomarkers, mainly C-reactive protein. Five guidelines suggested decision limits for procalcitonin. None took a stand on how often procalcitonin should be analysed, and if it should be used as a single or as multiple measurements. Conclusions: One international and 11 national clinical practice guidelines endorse the use of procalcitonin in differential diagnosis of bacterial infections and/or to monitor antibiotic therapy. However, the evidence for or against the use of procalcitonin is weak. [ABSTRACT FROM AUTHOR]

The article reports that since 1991, Enterococcus faecium have been listed as the second leading nosocomial pathogen and are among the five most common causative agents of bloodstream infections.The issue of the emergence of Enterococcus faecium as a significant clinical problem at an adult haematology ward is discussed.

Asymmetric dimethylarginine (ADMA) has been recognized as an independent prognostic factor for sepsis mortality in intensive care units. No data are available on kinetics or prognostic value of ADMA in hematological patients. We evaluated the ability of ADMA to act as a predictor for complicated course of febrile neutropenia, defined as bacteremia and/or septic shock in adult hematological patients receiving intensive chemotherapy. This prospective study included 87 adult hematological patients with febrile neutropenia after an intensive chemotherapy for acute myeloid leukemia (AML) or after an autologous stem cell transplantation (ASCT). Plasma ADMA and serum C-reactive protein (CRP) levels were measured from the onset of fever (d0) and for 2 days (d1–d2) thereafter. The levels of ADMA were stable or had only minimal changes during the study period. There was no difference between the levels at any time-point in patients having complicated course compared to those without it. On the other hand, CRP levels were significantly higher on d1 (p = 0.016) in patients with bacteremia and/or septic shock than in those without. ADMA was not able to differentiate hematological patients with a complicated course from those without complications. Elevated ADMA levels are probably associated with organ dysfunction, which is rare in this group of patients, of whom about 95% can be successfully managed at the hematology ward. [ABSTRACT FROM PUBLISHER]

There are no data on serum cortisol of hematological patients at the onset of neutropenic fever and its possible association with the severity of infection. The purpose of this study was to evaluate the association of serum cortisol with the level of C-reactive protein (CRP) and procalcitonin (PCT), widely used markers of infection and inflammation, and with the development of severe sepsis in this patient group. All clinical data were collected prospectively at the hematology ward of Kuopio University Hospital. Altogether, 69 hematological patients with 93 periods of neutropenic fever were included. Nineteen patients received therapy for acute myeloid leukemia, and 50 patients were autologous stem cell transplantation recipients. Each period of neutropenic fever was classified as severe sepsis or not. Serum cortisol, CRP, and PCT were determined at the onset of fever on day 0 and then at 8-9 a.m. on days 1-4. Level of serum cortisol correlated positively with maximal CRP level during days 0 to 4 in neutropenic fever periods without severe sepsis, but no correlation was observed in fever periods with severe sepsis. To conclude, the level of cortisol correlated with the severity of infection measured as maximal CRP or elevated PCT in fever periods without severe sepsis, but in fever periods with severe sepsis, the cortisol response was attenuated. [ABSTRACT FROM AUTHOR]

This paper explores various forms of eco-industrial networks in advancing environmental sustainability. Prior research on environmental sustainability primarily identifies industrial actors as autonomous entities or considers the role of networks in advancing environmental sustainability from a rather narrow perspective. However, the networks of ties in which industrial firms are embedded profoundly impacts not only their own performance, but also the natural environment in which they operate. Based on a systematic literature review, we identify four forms of eco-industrial networks that have the potential to advance environmental sustainability: 1) symbiosis networks, 2) sustainable supply networks, 3) environmental issue networks and 4) environmental solution networks. The paper presents important insights on the operational logic for each of these network forms and the dimensions of their network architecture. The main implications of this comparison are that policy-makers and practitioners need to become aware of the various mechanisms through which inter-organisational networks can reduce environmental load. Furthermore, there is a need to build broad coalitions of organisations that are mobilised to address environmental issues. We suggest that network architecture which maximises its members' capability to self-organise while also including a coordinating organisation can be highly suitable for eco-industrial networks. We also suggest some fruitful avenues for future research on eco-industrial networks. In integrating research on eco-industrial networks with existing research on inter-organisational alliances and networks, the paper provides more understanding on the multifaceted role played by various forms of eco-industrial networks in advancing sustainability. [ABSTRACT FROM AUTHOR]

We compared biomarkers and their changes as predictors for bacteremia and severe sepsis during neutropenic fever after intensive chemotherapy in hematological patients. Serum C-reactive protein (CRP), semi-quantative procalcitonin, aminoterminal pro-brain natriuretic peptide (NT-proBNP), cortisol, lactate, plasma antithrombin and fibrinogen were measured daily from day 0 to day 3/day 4 in 89 neutropenic fever episodes of 65 hematological patients. The best predictors for bacteremia and gram-negative bacteremia were procalcitonin and its change, with odds ratios (ORs) and 95% confidence intervals of 2.63 (1.56-4.44) and 3.20 (1.77-5.80) for bacteremia and 4.14 (2.00-8.58) and 5.04 (2.18-11.63) for gram-negative bacteremia, respectively. For severe sepsis, the best predictors were CRP and fibrinogen, with ORs of 1.94 (1.07-3.52) and 1.92 (1.05-3.54). Factor analysis provided two predictive factors: procalcitonin-NT-proBNP-antithrombin factor predicted gram-negative bacteremia and CRP-fibrinogen predicted severe sepsis. Applying a combination of markers reflecting different aspects of infection might improve the recognition of risk for complications in patients with neutropenic fever. [ABSTRACT FROM AUTHOR]

Abstract: Bioenergy and biomass-based products offer the greatest new opportunities for diversifying business in the forest cluster. In particular, biorefineries, which can be integrated into the pulp and paper industry, seem to have immense future potential. This article aims to explore the biorefinery concept and related new products and business operations, as well as new business strategies and company models, which are part of the biorefinery value chain. These factors, which contribute to the establishment and success of forest biorefineries, were examined using internet survey responses and compared between Scandinavia, North America and South America. This article looks at the results of the survey – primarily from the Finnish perspective – to help identify competitive advantages upon which successful business operations in the Finnish forest cluster can be built. According to the survey, the outlooks for technical and raw material choices, as well as barriers to biorefinery diffusion, are very similar in all the studied areas. Biorefineries and related energy products are considered the way to sustainably guarantee the forest cluster’s success. An increase in the price of oil motivates the development of forest biorefineries and wood-based biofuels; however, it is obvious that there is a need to revaluate from a fresh perspective the utilisation of wood and the wood-refining chain in the forest cluster. The survey respondents consider wood-based biofuel and chemical production a serious business opportunity for the forest cluster. In Finland, there is a strong confidence in the production of biofuels. However, all the countries included in the study trust in their own national strengths and in their chance to be a leading actor in the forest biorefinery business worldwide. The forest biorefinery business seems to have market potential, and global competition can thus be expected. [Copyright &y& Elsevier]

Objective: To compare semi-quantitative procalcitonin with C-reactive protein in predicting bacteraemia in haematological patients with neutropenic fever. Methods: A total of 77 patients treated with intensive chemotherapy for haematological malignancy at Kuopio University Hospital were candidates for study entry. Eleven of these patients did not fulfil the criteria for neutropenic fever, and 66 patients were finally included. Nineteen patients had acute myeloid leukaemia and 47 had received high-dose chemotherapy supported by autologous stem cell transplant. Ninety neutropenic fever episodes in these 66 patients fulfilled the study entry criteria, with microbiological cultures, procalcitonin and C-reactive protein measurements available. Serum procalcitonin and C-reactive protein were analyzed at the onset of each neutropenic fever episode on day 0, and then daily from days 1 to 4. Results: Bacteraemia was observed in 21 episodes (23%) and the criteria for severe sepsis were fulfilled in 13 episodes (14%). Half of the bacteraemic episodes were caused by Gram-negative bacteria. The kinetics of procalcitonin and C-reactive protein were similar, with increasing levels for 2 to 4 days after the onset of fever. The procalcitonin level on days 1, 2, 3 and 4 was associated with bacteraemia and Gram-negative bacteraemia, but not with the development of severe sepsis. On day 1, a procalcitonin level above 0.5 ng/ml had a sensitivity of 57% and 70% and specificity of 81% and 77% to predict bacteraemia and Gram-negative bacteraemia, respectively. Conclusions: An elevated level of procalcitonin within 24 h after the onset of neutropenic fever predicts bacteraemia and Gram-negative bacteraemia in haematological patients. [ABSTRACT FROM AUTHOR]

Serum amino-terminal pro-brain natriuretic peptide (NT-proBNP) is considered as a prognostic marker in patients with severe sepsis or septic shock, but no data are available on NT-proBNP kinetics in hematological patients with neutropenic fever. Altogether 70 hematological patients with neutropenic fever were included in this prospective study. NT-proBNP and C-reactive protein (CRP) were determined at the beginning of the neutropenic fever (d0) and then daily up to 3–4 days. The median NT-proBNP (interquartile range) increased from 127 (57–393) ng/L on d0 to 542 (194–1385) ng/L on d4. The increment of CRP was from 35 (17–61) mg/L on d0 to 109 (56–109) mg/L on d2. Neither serial NT-proBNP nor CRP predicted development of severe sepsis, but NT-proBNP was significantly higher in patients with previous cardiovascular disease than in those without. NT-proBNP seemed to reflect cardiac distress, but it did not help to predict the development of severe sepsis in this patient group. [ABSTRACT FROM AUTHOR]

Elevated plasma lactate and impaired lactate clearance have been associated with poor outcome in patients with severe sepsis. No data are available on the kinetics or prognostic value of plasma lactate in haematological patients with neutropenic fever. A total of 70 haematological patients with 94 episodes of neutropenic fever were included into this prospective study during the period 2006–2008. The median age of the patients was 56 (range 18–70) y. Nineteen patients received therapy for acute myeloid leukaemia and 51 patients received autologous stem cell transplantation. At the onset and on days 1, 2, and 3 of each neutropenic fever episode, plasma lactate and serum C-reactive protein were determined. Criteria for severe sepsis were fulfilled in 13 neutropenic episodes. An elevated plasma lactate level was infrequent at the start of neutropenic fever (5%). There was no association of lactate level with the development of severe sepsis. Two patients died of septic shock, 1 patient with an exceptionally high and increasing level of lactate and the other patient with a normal lactate level. An elevated plasma lactate level at the start of neutropenic fever is not common and does not indicate severe sepsis, but high lactate and an impaired lactate decrease may signify a fatal course in neutropenic fever. [ABSTRACT FROM AUTHOR]

Objectives: Vascular endothelial growth factor (VEGF) is considered to be of importance in patients with sepsis. No data are available on VEGF kinetics in haematological patients with neutropenic fever. Methods: Forty-two haematological patients were included into this prospective study. Median age was 57 yr (range 18–70). Fifteen patients received therapy for acute myeloid leukaemia and 27 patients received autologous stem cell transplantation for haematological malignancy. Laboratory samples for the determination of C-reactive protein (CRP) and VEGF were collected at the start of fever (d0) and then daily. Results: The median serum VEGF concentrations were low in all study patients. In patients with severe sepsis ( n = 5) the median VEGF on d0 was higher than in septic patients without signs of hypoperfusion or hypotension ( n = 37) (77 pg/mL vs. 52 pg/mL, P = 0.061). Also on d1 the median VEGF concentration was higher in patients with severe sepsis (82 pg/mL vs. 56 pg/mL, P = 0.048). There were no statistically significant differences in CRP values on any day during the study period between patients with severe sepsis and those without. Time from d0 to the peak VEGF concentration (mean 1.02, SE 0.18 d) was shorter than that to the peak CRP concentration (mean 1.93, SE 0.15 d) ( P = 0.002). Conclusion: Compared to CRP, serum VEGF was a more rapid indicator for sepsis in our haematological patients with neutropenic fever. Those with severe sepsis had higher VEGF concentrations than those without on d0 and d1 after the onset of fever. Further studies on VEGF are warranted in haematological patients. [ABSTRACT FROM AUTHOR]

Infectious complications are the main reason for early treatment-related mortality after autologous stem cell transplantation (ASCT). We evaluated retrospectively microbiological aetiology, risk factors and clinical consequences of severe sepsis in this patient cohort. From 1996 to 2006 a total of 319 patients underwent ASCT at our institution. Antibacterial prophylaxis was not used. Neutropenic fever occurred in 83% (n=265) and was complicated by severe sepsis in 5% (n=17) of patients. Severe sepsis tended to be more common in patients with non-Hodgkin's lymphoma (NHL) than in other patients (9% vs 3%, p=0.009). Bacteraemia was observed more commonly in patients with severe sepsis (76% vs 22%, p<0.001); Pseudomonas sp. was found in 30% (n=5) of these patients. Kinetics of C-reactive protein (CRP) more commonly coincided with, rather than predicted, the development of severe sepsis. All other observed risk factors for severe sepsis (length of neutropenia, fever and blood culture findings) were late indicators. Severe sepsis was fatal in 9 patients (53%), and all had NHL (p=0.003 compared to other patients). Severe sepsis is an important cause of early mortality after ASCT, especially in NHL patients. Ways to prevent development of severe sepsis or predict its development might reduce early mortality among ASCT recipients. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate etiology and consequences of neutropenic fever in AML patients. Two hundred and ninety neutropenic periods following chemotherapy in 84 AML patients were retrospectively evaluated. Neutropenic fever was found in 280 periods (97%). Severe sepsis developed in 35 occasions (13%) and 9 patients (11%) died due to severe sepsis. In 165 episodes with neutropenic fever (59%), the potential causative organism was found in blood cultures. Gram-negative bacteria were more commonly found in patients who developed severe sepsis (40% vs. 23%, p = 0.03). CRP after 2 - 3 days from start with fever was higher in patients with severe sepsis (190 mg/L vs. 96 mg/L, p < 0.001) but the rise in CRP rather coincided than preceded with the development of severe sepsis. Severe sepsis is associated with significant mortality in AML patients. Earlier methods than CRP are needed to predict development of severe sepsis. [ABSTRACT FROM AUTHOR]

Aims: In this study, we examined the voluntary COVID-19 vaccine coverage among health care workers (HCWs) working in close patient contact. HCWs' beliefs about COVID-19 infection, their opinions of vaccination and reasons for having or declining the COVID-19 vaccination were also evaluated. Methods: In October 2021, a cross-sectional observational study was carried out in five hospitals in Central and Eastern Finland. The anonymous and voluntary survey was targeted at 5120 doctors and nurses working in close patient contact. Results: Some 1837 responses were included in the study. Ninety-seven per cent of the respondents had received at least one COVID-19 vaccine and 68% of the respondents agreed that all HCWs working in close patient contact should be vaccinated against COVID-19. Vaccination coverage and support for vaccination were higher among older HCWs and doctors. HCWs' main reasons for having the COVID vaccine were willingness to protect themselves, their family and their patients from COVID-19. Concerns about adverse reactions to the COVID-19 vaccine was the main reason for declining it. Conclusions: The overall COVID-19 vaccination coverage and support for vaccinations among HCWs working in close patient contact were high without actual mandatory policies being introduced. Prioritising HCWs for COVID-19 vaccinations and widespread vaccine availability, as well as low general vaccine hesitancy and high seasonal influenza vaccination coverage among the study population were check marks in achieving high COVID-19 vaccination coverage rapidly. [ABSTRACT FROM AUTHOR]

• IL-18 levels varied according to background hematological malignancy. • IL-18 levels did not predict complicated febrile neutropenia in all subjects. • IL-18 predicted complicated febrile neutropenia in non-Hodgkin lymphoma patients. • IL-18 levels were higher in non-Hodgkin lymphoma subgroup than in other subgroups. • IL-18 showed an inverse correlation with leukocyte count. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: Findings from a project aiming to improve eco-efficiency of a swimming hall in Finland are presented in this article. There are various opportunities for eco-efficiency improvements for a swimming hall, many of which belong to responsibilities of the staff. However, there are aspects where also customers could participate. Consequently, changes in the current behavior of the swimming hall management, staff and customers are required. Results from customer survey and staff interviews suggest that lack of knowledge about the swimming hall-specific environmental impacts and possibilities of the respondent (either staff or customers) to actively engage in pro-environmental work at the site are the greatest obstacles towards pro-environmental behavior. In this article, several options for how to promote pro-environmental behavior at a swimming hall are discussed. [Copyright &y& Elsevier]

Abstract: Copeptin, the surrogate marker of arginine vasopressin (AVP), has been suggested to be a useful biomarker in monitoring sepsis reflecting hemodynamic imbalance and stress state. This prospective study conducted at a hematology ward in a Finnish University Hospital aimed to investigate whether plasma copeptin predicts the development of complicated course of neutropenic fever (bacteremia or need for treatment at intensive care unit) in 100 hematological patients experiencing their first neutropenic fever episode after intensive chemotherapy for hematological malignancy. Contrary to study presumptions, not elevated copeptin but the lack of a proper initial increase of plasma copeptin (<0.02ng/mL from day 0 to day 1) predicted blood culture positive sepsis (p =0.023) and gram-negative bacteremia (p =0.045). No correlation was observed with plasma sodium, blood pressure or evaluated osmolality. Plasma copeptin correlated inversely with the same day pentraxin 3 on day 0–day 2 (all p-values <0.001) and with C-reactive protein on day 1 (p =0.015). In conclusion, copeptin did not correlate with disease severity, but the lack of a proper initial increase was associated with bacteremic complications of febrile neutropenia in hematological patients. The findings suggest the possibility of central dysregulation of AVP release and do not support the use of copeptin as a biomarker of septic complications in this patient group. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Nuclear factor κ light-chain enhancer of activated B cells (NF-κB) family of evolutionarily conserved transcription factors are involved in key cellular signaling pathways. Previously, hypogammaglobulinemia and common variable immunodeficiency (CVID)-like phenotypes have been associated with NFKB1 variants and loss-of-function NFKB1 variants have been reported as the most common monogenic cause for CVID among Europeans. Here, we describe a Finnish cohort of NFKB1 carriers consisting of 31 living subjects in six different families carrying five distinct heterozygous variants. In contrast to previous reports, the clinical penetrance was not complete even with advancing age and the prevalence of CVID/hypogammaglobulinemia was significantly lower, whereas (auto)inflammatory manifestations were more common (42% of the total cohort). At current stage of knowledge, routine genetic screening of asymptomatic individuals is not recommended, but counseling of potential adult carriers seems necessary. • Penetrance of NFKB1 haploinsufficiency is incomplete in screened families. • Inflammatory complications are more common than symptomatic antibody deficiency. • Routine genetic screening of all potential carriers is not recommended. • Genetic counseling of adult carriers and their parents seems imperative. [ABSTRACT FROM AUTHOR]

Neutropenic fever is common in patients receiving intensive chemotherapy for hematological malignancies. The clinical course may be aggravated by infectious complications like severe sepsis, septic shock or even death. We prospectively studied 100 patients with neutropenic fever and evaluated human plasma cell-free DNA (cfDNA) during the fi rst 3 days after the onset of fever as a prognostic biomarker for complicated clinical course, defined as sepsis or septic shock. Complicated course was observed in 21 patients (21%). There were no significant differences in cfDNA levels between the patients with or without complications on any study day when all the patients were analyzed as one group. In subgroups according to hematological malignancy, patients with acute myeloid leukemia (AML) had lower cfDNA levels than patients with lymphoma. Among AML patients d0 cfDNA/leukocyte ratio and among lymphoma patients d0 cfDNA was associated with subsequent development of sepsis or septic shock. cfDNA deserves further studies in hematological patients with sepsis. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in which the authors examine the use of a soluble urokinase-type plasminogen activator receptor as a biomarker to diagnose patients suffering from infectious complications and neutropenic fever resulting from intense chemotherapy for hematological malignancies.

Constitutive heterozygous GATA2 mutation is associated with deafness, lymphedema, mononuclear cytopenias, infection, myelodysplasia (MDS), and acute myeloid leukemia. In this study, we describe a cross-sectional analysis of 24 patients and 6 relatives with 14 different frameshift or substitution mutations of GATA2. A pattern of dendritic cell, monocyte, B, and natural killer (NK) lymphoid deficiency (DCML deficiency) with elevated Fms-like tyrosine kinase 3 ligand (Flt3L) was observed in all 20 patients phenotyped, including patients with Emberger syndrome, monocytopenia with Mycobacterium aviumcomplex (MonoMAC), and MDS. Four unaffected relatives had a normal phenotype indicating that cellular deficiency may evolve over time or is incompletely penetrant, while 2 developed subclinical cytopenias or elevated Flt3L. Patients with GATA2 mutation maintained higher hemoglobin, neutrophils, and platelets and were younger than controls with acquired MDS and wild-type GATA2. Frameshift mutations were associated with earlier age of clinical presentation than substitution mutations. Elevated Flt3L, loss of bone marrow progenitors, and clonal myelopoiesis were early signs of disease evolution. Clinical progression was associated with increasingly elevated Flt3L, depletion of transitional B cells, CD56bright NK cells, naïve T cells, and accumulation of terminally differentiated NK and CD8+ memory T cells. These studies provide a framework for clinical and laboratory monitoring of patients with GATA2 mutation and may inform therapeutic decision-making. [ABSTRACT FROM AUTHOR]

Abstract: Early diagnosis of complicated course in febrile neutropenia is cumbersome due to the non-specificity of clinical and laboratory signs of severe infection. This prospective study included 100 adult hematological patients with febrile neutropenia after intensive chemotherapy at the onset of fever (d0) and for 3days (d1–d3) thereafter. The study aim was to find early predictors for complicated course of febrile neutropenia, defined as bacteremia or septic shock. Interleukin 6 (IL-6), interleukin 10 (IL-10), procalcitonin (PCT) and C-reactive protein (CRP) all predicted complicated course of febrile neutropenia on d0, but only PCT was predictive throughout the study period. For IL-10 on d0–1 with cut-off 37ng/L, sensitivity was 0.71, specificity 0.82, positive predictive value 0.52 and negative predictive value 0.92. For PCT on d0–1 with cut-off 0.13μg/L, the respective measures were 0.95, 0.53, 0.36, and 0.98. For the combination of IL-10 and PCT on d0–1 with the same cut-offs, specificity improved to 0.85 and positive predictive value to 0.56. In conclusion, the present study confirms the high negative predictive value of PCT and provides new evidence for IL-10 as an early predictor for complicated course of febrile neutropenia in hematological patients. Combining IL-10 with PCT improves the early prediction for complicated course of febrile neutropenia. [Copyright &y& Elsevier]

Objectives: This study aimed at assessing the cut-off levels for pentraxin 3 (PTX3) in predicting complications of neutropenic fever (bacteraemia, septic shock) in haematological patients. Methods: A prospective study during 2006-2009 was performed at haematology ward in Kuopio University Hospital. A patient was eligible for the study if having neutropenic fever after intensive therapy for acute myeloid leukaemia (AML) ( n = 32) or non-Hodgkin lymphoma (NHL) ( n = 35). Blood cultures were taken, and maximal PTX3 and C-reactive protein (CRP) were evaluated during d0 to d3 from the beginning of fever onset. Results: The level of PTX3 was associated with both the underlying malignancy and the presence of complications, with highest level in NHL patients with complicated course of febrile neutropenia and lowest in AML patients with non-complicated course. The cut-off level of PTX3 to predict complications was ten-fold in patients with NHL (115 μg/L) in comparison with patients with AML (11.5 μg/L). In combined analysis based on separate cut-offs, PTX3 predicted complications of febrile neutropenia with sensitivity of 0.86, specificity of 0.83, positive predictive value of 0.57 and negative predictive value of 0.96. Conclusions: PTX3 was superior to CRP in predicting complicated course of febrile neutropenia, but only when the effect of the underlying malignancy had been taken into account. [ABSTRACT FROM AUTHOR]