Assessment of procalcitonin as a diagnostic marker of underlying infection in patients with febrile neutropenia.

The novel inflammatory marker procalcitonin (PCT) was assessed as an index of infection in patients with febrile neutropenia. Blood samples were obtained from 115 patients with febrile neutropenia for determination of PCT levels before onset of fever and daily until the resolution of fever. The median PCT level on the first day of fever was 8.23 ng/mL in patients with bacteremia, compared with 0.86 ng/mL in patients with localized bacterial infections (P=.017). The median PCT level on the first day of fever was 2.62 ng/mL in patients with severe sepsis, compared with 0.57 ng/mL in patients with clinically localized infections (P<.001). A dramatic decrease in PCT levels was documented after resolution of the infection; PCT levels were elevated when the infection worsened. Pronounced PCT levels were also found in patients with fever of unknown origin who were responding to antimicrobial chemotherapy, compared with those not responding to treatment with antibiotics. PCT levels were particularly elevated in patients with bacteremia and severe sepsis. These findings provide new insight into the application of PCT in clinical trials as a diagnostic tool of the severity of an infection in patients with febrile neutropenia and of the need to change antimicrobial regimen.     

Procalcitonin (PCT) and C-reactive Protein (CRP) as severe systemic infection markers in febrile neutropenic adults

Background  

Procalcitonin (PCT) is an inflammatory marker that has been used as indicator of severe bacterial infection. We evaluated the concentrations of PCT as a marker for systemic infection compared to C-reactive protein (CRP) in patients neutropenic febrile.     

Diagnostic value of procalcitonin measurement in febrile patients with systemic autoimmune diseases

OBJECTIVE: To determine the usefulness of plasma procalcitonin (PCT) measurement to suspect infectious etiology in febrile patients with systemic autoimmune disease. METHODS: PCT, C-Reactive protein (CRP), erythrocyte sedimentation rate (ESR) and white blood cell count (WBC) were measured in 44 consecutive inpatients with a diagnosis of systemic autoimmune disease and fever >38 masculine C. After careful microbiologic screening no obvious infection was demonstrated in 24 patients (Group A) while an infectious bacterial complication was diagnosed in 20 cases (Group B). RESULTS: Median PCT levels were significantly higher in the group B (1.11 vs 0.24 ng/ml; p = 0.0007), whereas the differences for CRP, WBC and ESR did not reach statistical significance. PCT also exhibited a good sensitivity and specificity (75%) in differentiating patients with infection from those with disease flare. With respect to positive and negative predictive values (71.4% and 78.2%), PCT markedly exceeded the other variables. By analyzing PCT values by disease we identified a false positive subgroup of patients suffering from adult onset Still's disease (AOSD), showing markedly elevated PCT levels in absence of infection. By excluding these patients, PCT showed a very good sensitivity and specificity (73.6% and 89.4%) and the area under receiver operating characteristics (ROC) curve rose from 0.801 to 0.904. CONCLUSION: Our data indicate that elevated PCT concentrations offer good sensitivity and specificity for the diagnosis of systemic bacterial infection in febrile patients with systemic autoimmune diseases. However, in fever associated with AOSD PCT may be elevated even in the absence of infectious complication.     

Serum cortisol and inflammatory response in neutropenic fever

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.     

Can procalcitonin be used to distinguish between disease flare and infection in patients with systemic lupus erythematosus: a systematic literature review

Distinction between infection and febrile disease flare in patients with systemic lupus erythematosus (SLE) is fundamental but often difficult to make, because clinical presentation can be similar. A systematic review of all articles indexed in PubMed through October 2013 was performed, in order to examine the potential role of procalcitonin (PCT) for the discrimination between SLE flare and infection. Among the 12 papers identified, 5 articles reported on PCT levels in SLE patients without infection, 6 compared PCT levels between SLE patients with flare versus those with infection, and 1 analyzed PCT levels in active patients with and without bacterial infection. These data suggest the absence of correlation between PCT levels and SLE disease activity. Furthermore, PCT levels detected during disease flares are lower than those observed during bacterial infections. PCT can therefore be used accurately in the early differentiation between bacterial infection and flare in febrile SLE patients. Raised PCT levels ≥0.5 μg/L should strongly suggest bacterial infection in the context of SLE, keeping in mind the limited data available in case of hemophagocytic syndrome. Elevated PCT levels in SLE patients should always prompt a thorough search for sources of potential infection.     

Fever and solid tumor: diagnostic value of procalcitonin and C-reactive protein

PURPOSE: Evaluate the clinical utility of procalcitonin (PCT) and C-reactive protein (CRP) as diagnostic of paraneoplastic fever. METHOD: A prospective analysis of serum levels of PCT and CRP has been conducted on 68 consecutive febrile patients with solid tumour and no neutropenia. The samples were collected at hospital admission. RESULTS: Out of 68 patients, 57 had head and neck cancer. Forty-three patients had signs of infection and 19 had paraneoplastic fever. CRP was not significantly different between the two groups (infected patients: median: 134 mg/L, extremes: 20-569; paraneoplastic fever patients: median: 154 mg/L, extremes: 26-267; P = 0.75 with Mann-Whitney test). On the other hand, PCT was significantly higher in case of infection (median: 0.44 ng/mL, extremes: 0.09-57.4) than in the case of paraneoplastic fever (median: 0.26 ng/mL, extremes: 0.05-1.17; P = 0.01 with Mann-Whitney test). CONCLUSION: In our study, no paraneoplastic fever patient had PCT level equal or above 2 ng/mL (negative predictive value of 100%).     

Piperacillin–Tazobactum Plus Amikacin Versus Ceftazidime Plus Amikacin as Empirical Therapy for Fever in Neutropenic Patients with Hematological Malignancies

Infections are one of the main cause of death in cancer patients particularly when granulocytopenia is present. A number of drugs have been used for the treatment of neutropenic patients with fever. Most published literature has shown piperacillin–tazobactum in combination with amikacin to be significantly more effective than ceftazidime plus amikacin in empirical treatment of febrile episodes in patients with neutropenia. In view of the reported literature we have tried this combination in our febrile neutropenic patients with haematological malignancies at PGIMS Rohtak. It was an open randomized trial. Patients were divided into two groups of 20 each. In the first group (group A) piperacillin–tazobactum (4 + 0.5 g 6 hourly) with single daily dose of amikacin 20 mg/kg was given. In the second group (group B) ceftazidime 40 mg/kg every 8 hourly with single daily dose of amikacin 20 mg/kg was given. The most common site of infection was blood followed by urinary tract, respiratory tract and oral cavity. 13 (65%) patients in group A and 12 (60%) patient in group B showed clinical success. In our study however in our patients a better response was seen in patients with piperacillin–tazobactum + amikacin (65% vs. 60%). So it is recommended that piperacillin–tazobactum + amikacin should be given in febrile neutropenic patients with haematological malignancies.     

An Exploration of the Happiness-enhancing Activities Engaged in by Older Adults

Although happiness has been found to relate to positive outcomes across a number of areas, there has been little research conducted on how to increase and sustain it. Intentional happiness-enhancing activities have been identified as a promising avenue of inquiry, but again this area is under-researched, particularly in relation to older adults. We address this gap by exploring the happiness-enhancing activities older adults engage in, with a thematic analysis of interview data from 23 adults (56–76 years old). Four main themes—‘other-focused’, ‘personal recreation and interests’, ‘thoughts and attitudes’, and ‘achievement-related’ activities—are identified and discussed, along with ‘spiritual activities’ and ‘self-concordant work’, which were found to span multiple themes. The findings fit with and add to extant research and theory related to enhancing happiness and will be used as the basis for inventory items to be included in the next wave of a major longitudinal study of older adults.     

Diagnostic value of sTREM-1, IL-8, PCT,and CRP in febrile neutropenia after autologous stem cell transplantation

Infections and infectious complications are the major cause of morbidity and mortality in febrile neutropenic patients after autologous stem cell transplantation. Laboratory biomarkers are helpful for early identification of critically ill patients and optimal therapy management. Several studies in adult non-neutropenic patients proposed sTREM-1 as a superior biomarker for identification of septic patients as well as a predictor for survival in these patients compared with procalcitonin (PCT), C-reactive protein (CRP), or interleukin-8 (IL-8). Here, to assess the utility of PCT, CRP, IL-8, and sTREM-1 in febrile neutropenia, 44 patients presenting with febrile neutropenia after autologous stem cell transplantation were recruited in a single-center prospective pilot study. We analyzed PCT and CRP as well as IL-8 and sTREM-1 levels pre- and post-transplantation at defined time points. In 20 of 44 patients, concentration of sTREM-1 was under the detection level at appearance of febrile neutropenia. Mean levels of PCT, IL-8, and CRP were significantly increased in infections of critically ill patients who by dysfunction or failure of one or more organs/system depend on survival from advanced instruments of monitoring and therapy. However, all tested biomarkers could not distinguish between presence and absence of bloodstream infection. The combination of the biomarkers PCT and IL-8 achieved a high sensitivity of 90% and specificity of 74% for the identification of serious complications in febrile neutropenia, whereas the combination of CRP and PCT or IL-8 achieved a high sensitivity of 100%, but with the addition of a low specificity of 47or 41%. In conclusion, we found that the measurement of sTREM-1 concentration at presentation of febrile neutropenia is not useful to identify bacterial bloodstream infections and critically ill patients. PCT and IL-8 are useful biomarkers for the early identification of critically ill patients, compared to CRP and sTREM-1 in febrile neutropenia. PCT or IL-8 in combination with clinical parameters should be considered in routine measurement to identify critically ill patients as early as possible.     

The clinical role of procalcitonin in hematopoietic SCT

Infectious disease following hematopoietic SCT (HSCT) is a major cause of TRM. The more valuable markers to distinguish infections disease from non-infectious complications are needed. Procalcitonin (PCT) and C-reactive protein (CRP) were measured periodically throughout the clinical course of consecutive 28 patients who underwent HSCT. The diagnoses of 103 febrile episodes were analyzed. PCT and CRP level on the first day of fever significantly increased in systemic bacterial or fungal infection (P<0.001 and <0.001, respectively). PCT is more valuable than CRP for discrimination between systemic bacterial or fungal infection and intracellular infection (P=0.022 and 0.447, respectively). The area under receiver-operator characteristics curve for detection of bacterial or fungal infection was 0.82 for PCT and 0.76 for CRP. When PCT levels did not increase over 0.25?ng/mL through the fifth day of fever, PCT yielded a specificity of 100.0%. In multivariate analysis, the maximum level of PCT during a whole course of HSCT>=2?ng/mL was independently associated with worse overall survival as post-transplant predictors (adjusted hazard ratio 6.42, P=0.035). PCT provide additional information for discrimination between bacterial or fungal infection and other causes and predicting the patient's prognosis after HSCT.     

Utilización de procalcitonina y proteína C reactiva como marcadores de infección en la neutropenia febril de pacientes sometidos a trasplante de progenitores hematopoyéticos

Introduction and objective

Neutropenia is a frequent sign in patients who are going to have a haematopoietic stem cell transplant (HSCT). Infection is an important complication in these patients, which is favoured by immunosuppression and the degree of neutropenia. This study aims to evaluate the diagnostic usefulness of procalcitonin (PCT) and C-reactive protein (CRP) in onco-haematological patients undergoing chemotherapy and HSCT to determine the origin of the fever.

Patients and methods

PCT and CRP values were measured in 30 episodes of febrile neutropenia: before starting chemotherapy, appearance of neutropenia, onset of fever, days 1, 2, 3 and 6 after the onset of fever, and when the febrile episode ended. The episodes were classified as 5 bacteraemia, 3 microbiologically documented infections, 10 clinical infections, and 12 fevers of unknown origin.

Results

The highest PCT mean values corresponded to the group of patients with bacteraemia. Statistically significant differences (P = .04) were found on the second day after the onset of fever. The cut-off point of 0.5 ng/ml showed a sensitivity of 66% and a specificity of 75%. PCR results showed statistically significant differences on days 1, 2 and 3 after the onset of fever (P = .01, P = .003, and P = .002, respectively). The cut-off point of 7.5 mg/L had a sensitivity of 88% and a specificity of 58%.

Conclusions

The combination of PCT and CRP is an insufficient method to detect bacterial infections and may not replace the proper clinical and microbiological diagnosis.     

Assessment of systemic inflammation markers to differentiate a stable from a deteriorating clinical course in patients with febrile neutropenia

In this study, we evaluated the predictive values of procalcitonin (PCT), C-reactive protein (CRP), interleukin-6 (IL-6) and serum amyloid A (SAA) for determining the clinical course in febrile neutropenic patients. Daily plasma analyses during the fever course were performed in 101 episodes with fever and chemotherapy-induced neutropenia (neutrophil count <0.5 x 10(9)/L). Procalcitonin (PCT) and IL-6 values were significantly higher in febrile episodes in patients who developed complications. Procalcitonin with a cut-off value of < or =0.4 ng/mL or IL-6 < or =50 pg/mL 3 d after fever onset indicated daily high negative predictive values (NPVs) (91-100%) for episodes with complications. No marker could predict deterioration; however, daily low plasma concentrations of PCT or IL-6 during the first 8 d of fever were found to be a good predictor of no subsequent complications in neutropenic patients and therefore to be a helpful tool for limiting anti-microbial therapy.     

Procalcitonin and C-reactive protein do not discriminate between febrile reaction to anti-T-lymphocyte antibodies and Gram-negative sepsis

Treatment with antibodies against T-lymphocytes usually triggers a febrile response potentially mimicking or masking infection. Procalcitonin (PCT) is considered a sensitive and specific marker of systemic bacterial and fungal infection. It was the aim of this study to investigate the characteristics of PCT and C-reactive protein (CRP) during treatment with polyclonal or monoclonal anti-T-cell antibodies, in order to examine the ability of these parameters to distinguish between systemic bacterial infection and reaction to antibody treatment. Thus, 15 consecutive febrile episodes after T-cell antibody infusion without clinical signs of infection were compared with nine episodes of Gram-negative sepsis. After T-cell antibody infusion PCT and CRP serum levels increased to a similar extent as in Gram-negative sepsis. Therefore, during T-cell antibody treatment neither PCT nor CRP are adequate for differentiating between fever due to infection or to unspecific cytokine release.     

A review of the reported cases of chronic intestinal pseudo-obstruction in Japan and an investigation of proposed new diagnostic criteria

Intestinal pseudo-obstruction is a clinical syndrome in which the clinical symptoms of intestinal obstruction appear without mechanical obstruction of the intestine. We searched for articles from Japana Centra Revuo Medicina for the period 1983−2009 using the keywords ‘chronic’ and ‘intestinal pseudo-obstruction’. 124 articles were identified, and of these 121 cases were investigated using our diagnostic criteria. The patients were between 0 (just after birth) and 84 years of age, indicating that chronic intestinal pseudo-obstruction (CIP) can occur at any age. The mean age was 43.6 years and the median age was 47 years. Forty-nine patients were male and 72 were female, showing a slight tendency towards female predominance. Five cases (4.2%) had a definitive family history. Of the identified causes of secondary CIP, systemic sclerosis was the most common. Abdominal bloating was the most common initial symptom, seen in 90 (81%) patients. Patients having poor intestinal peristalsis with stagnation of the contents of the small intestines causing fatty stools and bacterial overgrowth complained of diarrhea. The interval between the initial symptoms and diagnosis ranged from 0 to 60 years, with a mean and median interval of 7.3 and 2 years, respectively. In case reports of CIP in Japan, the sensitivity of our diagnostic criteria was found to be 85.9%, indicating that the criteria are useful. For improvement in the rate of recognition of CIP and practical application of the diagnostic criteria in Japan, it is important to conduct further studies.     

Procalcitonin: a useful discriminator between febrile conditions of different origin in hemato-oncological patients?

Plasma concentrations of procalcitonin (PCT) have been shown to be elevated in bacterial and fungal infections. In contrast to C-reactive protein (CRP), PCT is not elevated in inflammations of noninfectious origin. Febrile inflammatory conditions are frequent in patients with hemato-oncological diseases. A reliable marker to discriminate infectious inflammations from drug-related and tumor-associated fever is still lacking. To evaluate the impact of PCT in this setting, PCT and CRP were prospectively measured in 95 febrile hemato-oncological patients. Infections could be identified in 40 of 95 patients: 38 of 95 had fever of unknown origin (FUO), 9 patients were suspected to suffer from drug-related fever, and 8 patients from tumor-associated fever. In the noninfection group (drug-related and tumor-associated fever), PCT levels were significantly lower than in patients with infections (P<0.001) or FUO (P<0.001). Differences were still highly significant comparing patients with suspected drug-related or tumor-associated fever alone with the infection or the FUO cohort. All eight patients with tumor-associated fever as well as eight of the nine patients with drug-related fever had PCT levels within the normal range (<0.5 micro g/l). CRP values only partially allowed discrimination between the various subgroups. Differences were significant between patients with drug-related fever and the infection (P=0.001) or FUO group (P=0.004). However, as CRP levels were far above the normal range also in the patients with drug-related fever, the significance of individual values was rather limited. In conclusion, PCT may provide useful additional information to assess the clinical significance of febrile conditions. PCT may facilitate the decision on when to initiate antimicrobial or cytotoxic therapy.     

Hormones and gallbladder cancer in women

Epidemiological evidence suggests that the incidence of gallstone disease and gallbladder cancer is higher in women. We analyzed the literature on estrogen and progesterone receptor expression in gallbladder cancer in women. A systematic search was done using Medline, Embase, and Cochrane Central Register of Controlled Trials for the years 1983–2009. The search terms used included ‘gallbladder’, ‘gallstone’, ‘oestrogen/estrogen’, ‘progesterone’, ‘cancer’, ‘cholelithiasis’, ‘hormone,’ and ‘motility’. Hormone receptor expression in gallbladder cancer was analyzed in 11 studies of which immunohistochemistry was used in 10 and enzyme immunoassay in one study. Sample sizes varied 141. Estrogen and/or progesterone receptor expression was detectable in gallbladder cancer tissue samples in nine studies, whereas four studies failed to confirm these findings. The data on the association of hormone receptor expression to tumor differentiation is contradictory and needs further evaluation.     

The role of new basal insulin analogues in the initiation and optimisation of insulin therapy in type 2 diabetes

Intensive insulin therapy aimed at achieving normoglycaemia is becoming increasingly accepted in the treatment of type 2 diabetes (T2DM) to reduce the risk of diabetes-related complications. Insulin therapy is increasingly combined with oral antidiabetic drugs (OADs) to moderate insulin dosage, reduce weight gain and confer cardiovascular protection. However, traditional insulins are associated with limitations that may act as barriers to initiation, and intensive use of insulin therapy. The advent of newer, longer-acting, basal insulin analogues, such as insulin glargine (glargine) and insulin detemir (detemir), offer improved pharmacokinetic and pharmacodynamic profiles compared with neutral protamine Hagedorn insulin (NPH). This potentially provides concomitant improvements in safety, efficacy and variability of glycaemic control. This paper reviews the properties of these new long-acting, basal insulin analogues and their potential roles in facilitating the initiation and optimisation of insulin therapy. Studies that reported the use of insulin and insulin analogues for the treatment of T2DM were identified using Medline. Key search terms included: ‘insulin glargine’, ‘insulin detemir’, ‘NPH insulin’, ‘basal insulin’, ‘long-acting insulin’, ‘insulin analogue’, ‘pharmacokinetics’, ‘pharmacodynamics’, ‘dose titration’, ‘algorithms’ and ‘type 2 diabetes’. Abstracts presented at the American Diabetes Association and the European Association for the Study of Diabetes annual congresses were also searched. The data show that the long-acting insulin analogues glargine and detemir both offer a low risk of hypoglycaemia and improved glycaemic control. Aggressive dose titration with glargine and detemir facilitates attainment of glycaemic control targets. The goal of achieving good glycaemic control with a low risk of hypoglycaemia may be more feasible with newer insulin therapies as part of a simple basal insulin regimen with continued OADs.     

Fever associated with chemotherapy-induced neutropenia: a review of current therapeutic approaches

The numbers of cancer patients subjected to chemotherapy-induced neutropenia steadily grows as the new indications for systemic treatment expand. When these patients develop fever, or other signs of infection, they must receive immediate medical attention. This paper discusses the current therapeutic strategy for febrile neutropenia in cancer patients and reviews some of the newer approaches, which include empirical monotherapy, outpatient protocols, antibiotic prophylaxis and the use of haematopoietic growth factors.