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.     

Comparison of C-reactive protein levels before and after coronary stenting and restenosis among patients treated with sirolimus-eluting versus bare metal stents

We prospectively studied the inflammatory response to coronary stenting (calculated as the difference between the highest postprocedural C-reactive protein [CRP] and baseline CRP levels [DeltaCRP]) and restenosis in 301 patients who received a sirolimus-eluting stent (n = 149) or a bare stent (n = 152) in the setting of a randomized trial. Median values of DeltaCRP were 3.1 mg/L in the sirolimus-eluting stent group and 3.0 mg/L in the bare stent group (p = 0.71). In the sirolimus-eluting group, restenotic rates were 9.7% in the subgroup with DeltaCRP higher than the median and 11.5% in the subgroup with DeltaCRP no higher than the median (p = 0.37). In the bare stent group, restenotic rates were 28.6% in the subgroup with DeltaCRP higher than the median and 15.4% in the subgroup with DeltaCRP no higher than the median (p = 0.04).     

Can procalcitonin measurement help in differentiating between bacterial infection and other kinds of inflammatory processes?

OBJECTIVE: To study the levels of procalcitonin (PCT) in various inflammatory states seen in an internal medicine department and to evaluate the possible discriminative role of PCT in differentiating bacterial infection from other inflammatory processes. METHODS: PCT, C reactive protein (CRP), and white blood cell count (WBC) were measured in patients admitted to the department for fever or biological inflammatory syndrome, or both. The serum of 173 consecutive patients was analysed according to the aetiological diagnosis. The patients were divided into two groups: group I (n=60) with documented bacterial or fungal infection; group II (n=113) with abacterial inflammatory disease. RESULTS: PCT levels were >0.5 ng/ml in 39/60 (65%) patients in group I. In group II, three patients with a viral infection had slightly increased PCT levels (0.7, 0.8, and 1.1 ng/ml) as did two others, one with crystal arthritis and the other with vasculitis (0.7 ng/ml in both cases). All other patients in group II had PCT levels <0.5 ng/ml. In this study a value of PCT >0.5 ng/ml was taken as the marker of bacterial infection (sensitivity 65%, specificity 96%). PCT values were more discriminative than WBC and CRP in distinguishing a bacterial infection from another inflammatory process. CONCLUSION: PCT levels only rose significantly during bacterial infections. In this study PCT levels >1.2 ng/ml were always evidence of bacterial infection and the cue for starting antibiotic treatment.     

Evaluation of C-reactive protein, interleukin-6, and procalcitonin levels in allogeneic hematopoietic stem cell recipients

BACKGROUND: Prompt detection of transplant-related complications (TRC) as infections, acute graft-versus-host disease (aGVHD), microangiopathic hemolytic anemia, or veno-occlusive disease following allogeneic hematopoietic stem cell transplantation (HSCT) is essential. PATIENTS AND METHODS: We conducted a prospective trial on clinical significance of C-reactive protein (CRP), interleukin-6 (IL-6) and procalcitonin (PCT) serum levels in TRC. A total of 350 stem cell recipients were admitted. CRP, IL-6 and PCT were analyzed prior to conditioning and weekly until 8 wk after HSCT. TRC were recorded weekly throughout the study. RESULTS: CRP (4.4 mg/dL vs. 12.8 mg/dL; P < 0.001), IL-6 (93 ng/mL vs. 1.138 ng/mL; P < 0.001) and PCT (0.8 ng/dL vs. 5.7 ng/dL; P < 0.001) were increased in infectious complications. Only PCT differentiated between infection and other TRC. Exclusive aGVHD did not increase CRP (4.4 mg/dL vs. 5.7 mg/dL; n.s.), IL-6 (93 ng/mL vs. 153 ng/mL; n.s.) and PCT (0.8 ng/dL vs. 0.8 ng/dL; n.s.). CRP (6.1 mg/dL vs. 3.1 mg/dL; P < 0.001) and IL-6 (295 ng/mL vs. 122 ng/mL; P = 0.001) were decreased during steroid therapy, but not PCT (2.3 ng/dL vs. 2.0 ng/dL; n.s.). CONCLUSION: Our study confirmed CRP, IL-6 and PCT serum levels as helpful markers for TRC. PCT can differentiate infection from GVHD despite steroid therapy. Further trials are needed focusing on the identification of patients who benefit from early risk stratification.     

Evaluation of serum procalcitonin and C-reactive protein levels as biomarkers of Henoch-Schönlein purpura in pediatric patients

Henoch-Schönlein purpura (HSP) is a vasculitic disorder resulting from autoinflammatory-mediated tissue injury. Procalcitonin (PCT) and C-reactive protein (CRP) are two biomarkers of the immune response that recognize bacterial infection and inflammation, respectively. This study tested whether levels of PCT and CRP were associated with selected clinical features, disease severity, and organ damage in HSP. Eighty-nine pediatric patients with HSP were analyzed for clinical manifestations and organ damage. Serum CRP, PCT, and occult blood in the urine and stool (prior to steroid therapy) were measured. Disease severity was classified according to previously established clinical classifications. Sixty patients (67.4 %) had a low clinical score (LCS) of <4 (group A) while 29 patients (32.5 %) had a high clinical score (HCS) of ≥4 (group B). When patients were then classified by the presence of gastrointestinal bleeding, 66 (74.2 %) cases lacked alimentary tract hemorrhage (group C) while 23 (25.8 %) cases presented with gastrointestinal bleeding (group D). There were no significant differences in CRP (group A: median?=?5.26, range?=?1.00–77.60 vs. group B: median?=?8.59, range?=?1.00–144.00 mg/l; u?=?1.397) or PCT levels (group A: median?=?0.05, range?=?0.05–0.24 vs. group B: median?=?0.08, range?=?0.05–1.02 ng/ml; u?=?1.709) between groups A and B. When serum PCT levels were examined in relation to gastrointestinal bleeding, the levels of serum PCT were higher in group D than group C patients (group D: median?=?0.09, range?=?0.05–1.02 vs. group C: median?=?0.05, range?=?0.05–0.32 ng/ml; u?=?2.849). It is important to note that the average PCT level was below the threshold for a systemic bacterial infection (0.5 ng/ml). We did not observe a correlation between CRP levels and the absence or presence of GI bleeding in groups C or D (group C: median?=?4.66, range?=?1.00–144.00 vs. group D: median?=?9.44, range?=?1.06–124.00 mg/l; u?=?1.783), respectively. In all patients, there was a significant correlation between the concentrations of PCT and CRP (r?=?0.721, p?=?0.002). In patients with HSP, inflammatory markers are not uniformly associated with the disease and instead, show variable association depending on the clinical severity and level of organ damage. In patients with severe HSP, elevated serum PCT was significantly associated with gastrointestinal bleeding. In contrast, CRP was not a specific predictor for different clinical classifications of HSP, despite a similar pattern of concentration changes to PCT.     

Serum procalcitonin concentration in patients with Kawasaki disease

BACKGROUND: Procalcitonin (PCT) is a new parameter of inflammation, the clinical usefulness of which is currently being evaluated. MATERIALS AND METHODS: We determined simultaneously the serum concentrations of PCT and C-reactive protein (CRP) as well as the white blood cell (WBC) count in 25 patients with Kawasaki disease (KD), 17 with bacterial infections, 10 with systemic autoimmune diseases, 17 with viral infections and 18 healthy children. The optimal cut-off value of each parameter for predicting coronary aneurysms was determined using receiver operating characteristic curves. RESULTS: Significantly higher serum concentrations of PCT were observed in patients with KD (2.3 +/- 3.0 ng/ml) and bacterial infections (2.2 +/- 2.9 ng/ml) than in patients with autoimmune diseases (0.4 +/- 0.4 ng/ml) or viral infections (0.4 +/- 0.3 ng/ml), or in healthy children (0.2 +/- 0.1 ng/ml). The serum PCT but not the WBC count or CRP, differentiated the KD patients from the patients with autoimmune diseases. The optimal cut-off value of 3.0 ng/ml of PCT increased the prediction rate of coronary aneurysms that subsequently occurred in 4 (16%) patients with KD. CONCLUSIONS: The serum PCT may be clinically useful for determining the severity of KD and for narrowing the differential diagnosis of patients with inflammatory diseases.     

Diagnostic value of serum and synovial procalcitonin in acute arthritis: a prospective study of 42 patients

OBJECTIVE: To determine the diagnostic value of serum and synovial procalcitonin (PCT) for bacterial arthritis and to determine the cellular origin of synovial PCT. METHODS: A prospective study enrolled 42 patients with acute arthritis including 11 bacterial arthritis, 18 rheumatoid arthritis and 13 crystal induced arthritis. Diagnostic values of serum and synovial PCT levels were determined by a immunoluminometric assay (Lumitest PCT) and compared to those of classical inflammatory markers (C-reactive protein, erythrocyte sedimentation rate, synovial fluid cellularity and both serum and synovial IL-6 and TNF alpha). Using fibroblast-like synoviocyte (FLS) cultures derived from rheumatoid arthritis (n = 4) and osteo-arthritis (n = 3) synovium, with or without stimulation by lipopolysaccharid or recombinant streptococcal protein 1/II, we attempted to determine whether synovial cells could be a source of PCT. RESULTS: Serum PCT was the best parameter to distinguish patients with acute bacterial arthritis from patients with crystal induced arthritis or rheumatoid arthritis. In setting of an acute arthritis serum PCT (> 0.5 ng/mL) achieved 55% sensitivity and 94% specificity for the diagnosis of bacterial arthritis, while CRP (> 50 mg/L) had 100% sensitivity but poor specificity (40%). Serum PCT appeared to be higher in patients with septic arthritis resulting from "systemic infection" than in cases resulting from direct inoculation. Synovial PCT was not useful to discriminate between infectious and non infectious arthritis in clinical practice. PCT could not be detected at significant levels in the conditioned medium from fibroblast-like synoviocyte cultures. CONCLUSION: Serum PCT is a poorly sensitive but specific marker of bacterial arthritis. Use of serum PCT in association with CRP could nevertheless be useful in an emergency situation for the diagnosis of bacterial arthritis.     

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%).     

C-reactive protein and fever in neutropenic patients

The predictive value of daily C-reactive protein (CRP) monitoring to distinguish causes of fever in neutropenic patients was studied retrospectively. A total of 143 fever episodes during 113 consecutive hospitalizations were studied in 71 patients who had been referred for chemotherapy or haemopoietic stem cell transplantation (HSCT). There were, on average, 1.3 fever episodes per hospital stay, attributed to: infection (55, 27 invasive bacterial, 5 fungal, 3 viral and 20 probable infections); acute graft vs host disease (GvHD) (20); drugs (22); transfusions (7); and not attributable (39). 130 (91%) fever episodes were accompanied by a rise in CRP, 6 (4%) episodes were fatal. Maximal CRP levels (CRPmax) and maximal temperature (Tmax) were higher in invasive bacterial infections than in aGvHD and higher in aGvHD than in drug- or transfusion-related fever (p < 0.0001). Temperature and CRP rose in parallel. A total of 16 patients developed grade II-IV aGvHD by day 11 (9-21) (median, range) after allogeneic HSCT. Acute GvHD was preceded by fever for 3 d (1-7), and by CRP increase for 5 d (0-15) (p < 0.0001). CRP monitoring may be useful to distinguish between causes of fever. Very high CRP levels tend to be associated with invasive bacterial infections. CRP is not an early warning sign. An increase in CRP and fever may precede other clinical manifestations of aGvHD.     

CD64、CRP、PCT及NLR对儿童社区获得性肺炎的诊断价值

目的探讨中性粒细胞CD64、C反应蛋白(CRP)、降钙素原(PCT)及中性粒细胞与淋巴细胞比值(NLR)在儿童社区获得性肺炎(CAP)中的诊断价值。方法选取海口市人民医院收治的CAP患儿186例,依据病原体不同分为细菌性肺炎组(95例),支原体肺炎组(43例)和病毒性肺炎组(48例)。细菌性肺炎患儿依据入院病情严重程度分为轻症组(75例)和重症组(20例)。采用流式细胞术检测外周血中性粒细胞CD64的表达,同时检测CRP、PCT及NLR水平。应用ROC曲线分析CD64、CRP、PCT及NLR水平对细菌性肺炎的诊断价值。结果细菌性肺炎组治疗前CD64(8.85±3.40 vs 2.26±0.74,2.42±0.95,2.38±0.80)、CRP(38.62±8.50 vs 3.25±0.96,3.42±1.15,4.16±1.53,mg/L)、PCT(6.17±1.40 vs 0.15±0.03,0.34±0.12,0.62±0.28,ng/mL)及NLR(7.84±3.25 vs 2.05±0.96,1.37±0.62,2.48±1.16)水平均明显高于对照组、病毒性肺炎组和支原体肺炎组(P<0.01)。细菌性肺炎患儿治疗后CD64(2.70±1.06 vs 8.85±3.40)、CRP(4.63±1.58 vs 38.62±8.50,mg/L)、PCT(0.21±0.06 vs 6.17±1.40,ng/mL)及NLR(2.28±1.07 vs 7.84±3.25)水平均明显低于治疗前(P<0.01)。重症细菌性肺炎患儿CD64(10.42±4.36 vs 7.60±2.58)、CRP(43.25±10.47 vs 34.85±8.16,mg/L)、PCT(9.26±2.18 vs 4.62±1.15,ng/mL)及NLR(9.75±4.12 vs 6.53±2.90)水平均明显高于轻症细菌性肺炎(P<0.01)。ROC曲线分析显示,CD64、CRP、PCT及NLR单项指标诊断细菌性肺炎的最佳截值分别为3.25、14.80 mg/L、1.83 ng/mL、4.37,四项联合诊断细菌性肺炎的AUC(0.948,95%CI:0.887~0.992)最大,其敏感度和特异度为96.2%和89.3%。Pearson相关分析显示,细菌性肺炎患儿CD64与CRP、PCT及NLR呈正相关(r=0.573、0.729、0.536,P<0.01),CRP与PCT及NLR呈正相关(r=0.602、0.497,P<0.01),PCT与NLR呈正相关(r=0.514,P<0.01)。结论CD64、CRP、PCT及NLR四项联合检测有助于提高细菌性肺炎的诊断价值,并可作为判断CAP患儿病情严重程度的实验室指标。     

Diagnostic and Prognostic Significance of Serum C-Reactive Protein Levels in Patients Admitted to the Department of Medicine

BackgroundDespite its apparent role as a marker of different disease processes, to date, no study has presented comprehensive comparative data regarding the distribution of serum C-reactive protein (CRP) levels in all admitted patients. We aimed to examine the distribution of serum CRP levels in internal medicine patients and to find whether initial serum CRP value had a diagnostic and prognostic significance.MethodsSerum CRP levels together with epidemiologic, clinical, and laboratory data were analyzed for 370 consecutive adult patients admitted to the department of internal medicine during a 2-month period.ResultsThe median CRP level on admission was 24 mg/L, with a range between 0 and 346 mg/L. Infections had significantly higher median CRP than noninfections (99 versus 11 mg/L), and bacterial infections had distinctively higher CRP (120 mg/L) compared with nonbacterial infections (32 mg/L). The highest noninfectious median CRP was recorded in inflammatory bowel disease exacerbation (107 mg/L). Moreover, serum CRP was divided into 5 ranges. Very high CRP >200 mg/L was a marker of sepsis. In contrast, low CRP range (<10 mg/L) was characteristic to cardiovascular diseases and viral infections, but included none of the patients with severe infections or sepsis. Furthermore, higher CRP was significantly associated with mortality, the need for intubation, and longer hospitalization, and had better distinguishing ability compared with erythrocyte sedimentation rate or platelets count for the comparison of major disease categories, such as bacterial infections, inflammatory and rheumatic disease, viral infections, and cardiovascular disorders.ConclusionsInitial serum CRP has an important role as a diagnostic and prognostic tool in patients admitted to internal medicine.     

红细胞沉降率/C反应蛋白比值联合降钙素原在鉴别诊断系统性红斑狼疮活动和细菌性感染中的价值

目的 评价红细胞沉降率(ESR)/C反应蛋白(CRP)比值联合降钙素原(PCT)在鉴别诊断系统性红斑狼疮(SLE)活动和细菌性感染中的价值。方法 将167例SLE患者分为活动组（SLE活动患者）64例和感染组（SLE合并细菌性感染患者）103例,比较两组患者的ESR、CRP、ESR/CRP比值及PCT水平,采用受试者工作特征（ROC）曲线评估上述指标鉴别诊断SLE活动和细菌性感染的价值。结果 活动组患者CRP及PCT均低于感染组,ESR和ESR/CRP比值均高于感染组（P<0.05）。PCT联合ESR/CRP比值鉴别诊断SLE活动和细菌性感染的灵敏度均高于单独检测PCT、CRP、ESR/CRP比值及PCT联合CRP（P<0.05）;而上述5项指标的特异度比较差异均无统计学意义（P>0.05）。PCT联合ESR/CRP比值鉴别诊断SLE活动和细菌性感染的ROC曲线下面积（AUC）均高于CRP、ESR、PCT、ESR/CRP比值、PCT联合CRP（P<0.05）,CRP、ESR、PCT、ESR/CRP比值的约登指数（YI）分别为0.36、0.23、0.40、0.54,对应值分别为22.02mg/L、39mm/h、1.69ng/ml、11.75。结论 PCT和CRP水平在SLE合并细菌性感染者中升高,ESR/CRP比值可作为鉴别诊断SLE活动与细菌性感染的新指标,且ESR/CRP比值<11.75提示SLE合并细菌性感染的可能性大,PCT联合ESR/CRP比值更能提高鉴别诊断SLE活动与细菌性感染的价值。     

Diagnostic value of C-reactive protein for predicting activity level of Crohn's disease.

BACKGROUND AND AIMS: Measuring Crohn's disease (CD) activity is useful in clinical trials as well as in clinical practice, but each available instrument to measure such activity has some limitations. C-reactive protein (CRP) is a sensitive marker for inflammation and tissue injury. The aims of the study were: to assess the diagnostic value of low level of CRP for predicting a low CD activity, and to calculate optimal CRP cutoff value for selecting patients with moderate or high CD activity. METHODS: One hundred fifty consecutive patients with active or nonactive CD were included in the study without any pre-selection criteria. CRP was measured, and CD activity was calculated by means of the van Hees index (VHI). RESULTS: The median VHI score was 154.4 (interquartile range, 126.0-193.4), and the median CRP was 19.1 mg/L (interquartile range, 6.1-50.1 mg/L; upper limit of normal [N], 4 mg/L). Forty-nine percent of our patients had CRP >20 mg/L. CRP was significantly correlated to VHI (P = .0001). The probability that VHI was <150 if CRP was below upper limit of normal was equal to 1 (confidence interval, 0.891-1.000). The diagnostic value for CRP predicting a VHI > or =150 was high; the area under the receiver operating characteristic curve was equal to 0.844 (confidence interval, 0.783-0.906; P = .0001) with an optimal cutoff value of 21.6 mg/L, about 5 x N. CONCLUSIONS: CRP appears useful to evaluate CD activity, especially to predict inactive or low activity CD.     

Procalcitonin and C-reactive protein as early markers of postoperative intra-abdominal infection in patients operated on colorectal cancer

Purpose

The aim of this study was to evaluate the accuracy of serum procalcitonin (PCT) and C-reactive protein (CRP) for early diagnosis of postoperative intra-abdominal infections (PIAI) after elective surgery for colorectal cancer.

Methods

Prospective observational study including patients operated on for colorectal cancer between January and December of 2015 was performed. Serum PCT and CRP levels were measured before surgery and daily until postoperative day 3.

Results

One hundred twenty patients were included. Seven patients (5.8%) had PIAI. PCT levels were significantly higher in patients with PIAI on postoperative days 1 and 3, whereas CRP levels only were significantly more elevated on postoperative day 3. The ratio between CRP levels on postoperative day 3 and CRP levels on postoperative days 2 (CRP D3/CRP D2) and 1 (CRP D3/CRP D1) was significantly higher in patients with PIAI. PCT on postoperative day 3, for a cutoff of 0.45 ng/mL, had the best sensitivity (100%) with a specificity of 73.8%. The ratio CRP D3/CRP D1 yielded the higher specificity and positive predictive value (90.9 and 27.3%, respectively, for a cutoff of 1.8). The higher negative predictive value was obtained for PCT on postoperative days 1 and 3 (100%, with cutoff of 0.76 and 0.45 ng/mL, respectively) and for CRP on postoperative day 3 (100% with cutoff of 10 mg/dL).

Conclusion

PCT and CRP serum levels are associated with the appearance of PIAI after colorectal cancer surgery, although the positive predictive values were low for both PCT and CRP. However, the negative predictive values were high.

     

Procalcitonin in acute myocardial infarction

OBJECTIVE: Procalcitonin (PCT) is released in severe bacterial infections, sepsis and in infection independent cases such as major surgery, multiple trauma, cardiogenic shock, burns, resuscitation, and after cardiac surgery. The aim of this study was to determine the levels and the kinetics of PCT in AMI and to investigate their possible correlation with the release of IL-6 and CRP. DESIGN-PATIENTS: The study included 60 patients (47 men, 63.2+/-14.8 years) with the diagnosis of AMI at admission. In all patients, serum levels of PCT, IL-6, CK-MB, TnI and CRP were measured at admission, at 3, 6, 12, 24, 48 and 72 h and at the seventh day. RESULTS: PCT was elevated in all patients with AMI. It was initially detected in serum approximately 2-3 h after the onset of the symptoms. The median value at admission was 1.3 ng/ml (95% CI: 0.89 to 1.80). The value of PCT showed an increase and reached a plateau after 12-24 h. The median value at 24 h was 3.57 ng/ml (95% CI: 2.89 to 4.55). PCT values fell to baseline (<0.5 ng/ml) by the seventh day. PCT was detected in serum earlier than CK-MB or TnI in 56 of the 60 patients (93.3%). The kinetics of PCT was similar to those of CK-MB and TnI. The maximal values of PCT were positively correlated with the maximal values of IL-6 (r = 0.59, P = 0.00) and of CRP (r = 0.65, P = 0.001). The maximal values of IL-6 were positively correlated with max CRP (r = 0.35, P = 0.045). CONCLUSIONS: PCT could be considered as a novel sensitive myocardial index. Its release in AMI is probably due to the inflammatory process that occurs during AMI.     

Native pentameric C-reactive protein displays more potent pro-atherogenic activities in human aortic endothelial cells than modified C-reactive protein

Inflammation is pivotal in atherogenesis. Numerous prospective studies have shown that levels of high sensitive C-reactive protein (CRP) predict cardiovascular events. Recently, data suggests that CRP could be a mediator in atherothrombosis. Loss of pentameric symmetry in CRP has been shown to result in the formation of modified CRP (mCRP). The main aim of this study was to examine the biological effects of the native, pentameric form of CRP compared to a modified form in human aortic endothelial cells. Human pentameric native CRP (n-CRP) from two different sources (recombinant and serum) was purified and used. It was then subjected to EDTA chelation and urea treatment to prepare modified CRP (m-CRP). Purity of both n-CRP and m-CRP preparations was checked by gel electrophoresis. Both n-CRP and m-CRP were incubated with human aortic endothelial cells (HAEC) and biological activities was tested by assaying for interleukin-8 (IL-8), plasminogen activator inhibitor-1(PAI-1), cyclic GMP and prostaglandin F1-alpha. n-CRP significantly upregulated IL-8 at concentrations > or = 10 microg/mL while m-CRP upregulated IL-8 only at concentrations of 50 microg/mL (p < 0.05). PAI-1 levels were significantly increased to a greater extent with native compared to m-CRP (p < 0.05). While both decreased PGF1-alpha at concentrations of 50 microg/mL, the effect of native CRP was more pronounced and was evident at 10 microg/mL (p < 0.05). The most pronounced difference was observed with regard to inhibition of eNOS activity as assessed by cGMP which was observed at 10 microg/ml of native CRP but only at 50 microg/mL for m-CRP (native CRP versus mCRP: p < 0.001). Thus, native pentameric CRP compared to modified CRP exerts more potent atherogenic effects in human aortic endothelial cells.     

Could procalcitonin be a predictive biological marker in systemic fungal infections?. Study of 14 cases

BACKGROUND: Procalcitonin (PCT) is a recently described inflammatory marker that has been shown to increase significantly in patients with severe systemic bacterial infections or sepsis. Reports on the diagnostic and predictive value of PCT in systemic fungal infections are limited. METHODS: In order to evaluate the role of PCT in systemic mycosis, 14 patients (mean age 40 years) with proven or probable systemic fungal infections were investigated. Blood samples were collected on days 1, 3, 5, and 10 after the onset of signs and symptoms of systemic fungal infection (clinical and/or laboratory diagnosis and/or radiographic evidence). PCT measurements were performed using an immunoluminometric assay. RESULTS: In five patients with severe fungal infection and an unfavorable course (patient group 2), PCT levels were moderately elevated on day 3 (0.5-1.0 ng/ml), whereas they were normal in the patients who recovered (patient group 1). High PCT levels (>/=1.11 ng/ml) were detected on the 10th day of the course of the illness in patient group 2. A normal or moderate elevation of PCT on day 10 was observed in patient group 1. The difference in mean PCT levels in patient groups 1 and 2 on days 3 and 10 were statistically significant. CONCLUSIONS: PCT levels seem to correlate with the severity and outcome of systemic fungal infection. If this finding can be confirmed in a larger number of patients, it could serve as a prognostic indicator.     

Invasive pulmonary aspergillosis in patients with hematologic malignancies: survival and prognostic factors

BACKGROUND AND OBJECTIVES: Despite improvements made in its early diagnosis and effective treatment, invasive pulmonary aspergillosis (IPA) remains a devastating opportunistic infection. In this retrospective study we have reviewed all consecutive cases of IPA diagnosed in adult patients with hematologic malignancies in our center from 1995 to 2000 to determine survival and prognostic factors. DESIGN AND METHODS: Forty-one patients were included in the study. Ante-mortem classification of cases of IPA were: 4 definite, 10 highly probable, 19 probable and 8 possible cases; all these last eight patients were later upgraded to definite IPA at post-mortem examination. Clinical charts were reviewed and factors possibly affecting the outcome of IPA were analyzed. RESULTS: All but two patients received chemotherapy and/or immunosuppresive therapy before the onset of IPA (conventional chemotherapy = 24, allogeneic stem cell transplantation [SCT] = 12, autologous SCT = 3). At IPA diagnosis 28 patients were neutropenic (< 0.5 x 10(9)/L) for a median of 25 days (range 7-135), and 10 allogeneic SCT patients were receiving corticosteroids for graft-versus-host-disease. All but two patients received antifungal treatment for IPA. The median delay from diagnosis to start of therapy was two days (range 0-20). The median follow-up after the first symptom or sign of IPA was 42 days with a maximum follow-up of 61 months. The actuarial 4-month infection-free survival was 40% (95% CI 25% to 55%). Thirty-three patients died during follow-up and IPA was implicated in the patients' death in 24 cases (75%). In multivariate analysis prolonged survival was associated with recovery of neutropenia during treatment (p = 0.001) and not having received an allogeneic SCT (p = 0.003). INTERPRETATION AND CONCLUSIONS: Despite prompt initiation of antifungal therapy, survival of patients with a hematologic malignancy and IPA is currently low. Perhaps the introduction of more sensitive diagnostic methods will allow the onset of intensive therapy prior to the appearance of more advanced clinical symptoms and/or radiological signs, and the time will come to test whether earlier and more intensive therapy will improve survival.     

Role of procalcitonin and C-reactive protein in differentiation of mixed bacterial infection from 2009 H1N1 viral pneumonia

Please cite this paper as: Ahn et al. (2011) Role of procalcitonin and C‐reactive protein in differentiation of mixed bacterial infection from 2009 H1N1 viral pneumonia. Influenza and Other Respiratory Viruses 5(6), 398–403. Background Mixed bacterial infection is an important contributor to morbidity and mortality during influenza pandemics. We evaluated procalcitonin (PCT) and C‐reactive protein (CRP) in differentiating pneumonia caused by mixed bacterial and 2009 H1N1 influenza infection from 2009 H1N1 influenza infection alone. Methods Data were collected retrospectively over a 7‐month period during the 2009 H1N1 influenza pandemic. Patients visiting emergency department and diagnosed as community‐acquired pneumonia caused by 2009 H1N1 infection were included (n = 60). Results Mixed bacterial and viral infection pneumonia (n = 16) had significantly higher PCT and CRP levels than pneumonia caused by 2009 H1N1 influenza alone (n = 44, P = 0·019, 0·022 respectively). The sensitivity and specificity for detection of mixed bacterial infection pneumonia was 56% and 84% for PCT > 1·5 ng/ml, and 69% and 63% for CRP > 10 mg/dl. Using PCT and CRP in combination, the sensitivity and specificity were 50% and 93%, respectively. Conclusion Procalcitonin and CRP alone and their combination had a moderate ability to detect pneumonia of mixed bacterial infection during the 2009 H1N1 pandemic. Considering high specificity, combination of low CRP and PCT result may suggest that pneumonia is unlikely to be caused by mixed bacterial infection.     

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.