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1.  Diagnostic value of blood inflammatory markers for detection of acute appendicitis in children 
BMC Surgery  2006;6:15.
Acute appendicitis (AA) is a common surgical problem that is associated with an acute-phase reaction. Previous studies have shown that cytokines and acute-phase proteins are activated and may serve as indicators for the severity of appendicitis. The aim of this study was to compare diagnostic value of different serum inflammatory markers in detection of phlegmonous or perforated appendicitis in children.
Data were collected prospectively on 211 consecutive children. Laparotomy was performed for suspected AA for 189 patients. Patients were subdivided into groups: nonsurgical abdominal pain, early appendicitis, phlegmonous or gangrenous appendicitis, perforated appendicitis.
White blood cell count (WBC), serum C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), acid α1-glycoprotein (α1GP), endotoxin, and erythrocyte sedimentation reaction (ESR) were estimated ad the time of admission. The diagnostic performance was analyzed using receiver operating characteristic (ROC) curves.
WBC count, CRP and IL-6 correlated significantly with the severity of appendiceal inflammation. Identification of children with severe appendicitis was supported by IL-6 or CRP but not WBC. Between IL-6 and CRP, there were no significant differences in diagnostic use.
Laboratory results should be considered to be integrated within the clinical assessment. If used critically, CRP and IL-6 equally provide surgeons with complementary information in discerning the necessity for urgent operation.
PMCID: PMC1712352  PMID: 17132173
2.  A Prospective Bicenter Study Investigating the Diagnostic Value of Procalcitonin in Patients with Acute Appendicitis 
Procalcitonin (PCT) is an established laboratory marker for disease severity in patients with infection and sepsis. In addition, PCT has been shown to be an effective marker for a limited number of localized infections. However, whether or not PCT has any diagnostic value for acute appendicitis, still remains unclear. The purpose of this prospective bicenter study was, therefore, to determine whether or not the PCT levels in the serum of patients with acute appendicitis have any diagnostic value.
This prospective study included 103 patients who received an appendectomy, based on the clinical diagnosis of acute appendicitis, in a surgical department of an academic teaching hospital in Germany or in a county hospital in Spain. White blood cell count (WBC), C-reactive protein (CRP) and procalcitonin (PCT) values were determined preoperatively. All appendectomy specimens were sent for routine histopathological evaluation. Based on this information, the patients were assigned to 1 of 5 groups that reflected the severity of the appendicitis.
Of the 103 patients who were included in the study, 98 had appendicitis. Fourteen (14.3%) showed an increase in PCT values. Of those 14, 4 had a serum PCT >0.5 ng/ml, 9 had a PCT value >2–10 ng/ml and 1 had a PCT value >10 ng/ml. The sensitivity of PCT was calculated to be 0.14. The mean WBC value was 13.0/nl (± 5.2, 3.4–31), and for CRP it was 8.8 mg/dl (± 13, 0–60.2). The values of CRP, WBC and PCT increased with the severity of the appendicitis.
PCT is potentially increased in rare cases of severe inflammation and, in particular, after appendiceal perforation or gangrenous appendicitis. However, its remarkably low sensitivity prohibits its routine use for the diagnosis of appendicitis.
PMCID: PMC2790741  PMID: 19672084
Procalcitonin; Appendicitis; Diagnostic
3.  Procalcitonin and C-Reactive Protein in the Diagnosis and Prediction of Spontaneous Bacterial Peritonitis Associated With Chronic Severe Hepatitis B 
Annals of Laboratory Medicine  2013;33(6):449-454.
Procalcitonin (PCT), C-reactive protein (CRP), and white blood cells (WBCs) are inflammatory markers used to diagnose severe bacterial infections. We evaluated the diagnostic role of these markers and compared their accuracy for spontaneous bacterial peritonitis (SBP) associated with chronic severe hepatitis B (CSHB).
PCT and CRP concentrations, WBC count, and other hematological parameters were measured in serum from 84 well-characterized patients with CSHB, of whom 42 had SBP. Receiver operating characteristics (ROC) curve analysis was performed to assess the diagnostic accuracy.
PCT and CRP concentrations were significantly higher in the CSHB patients with SBP (n=42) than CSHB patients without SBP (n=42). PCT and CRP concentrations were more accurate than WBC count for the diagnosis of CSHB-associated SBP. The optimal cutoff value of PCT was 0.48 ng/mL. The PCT concentration was significantly correlated with the CRP concentration and WBC count.
Serum PCT and CRP seems to be better markers than WBC for the diagnosis of CSHB patients with SBP.
PMCID: PMC3819445  PMID: 24205495
Chronic severe hepatitis B; Procalcitonin; C-reactive protein; White blood cell
4.  Inflammatory parameters predict etiologic patterns but do not allow for individual prediction of etiology in patients with CAP – Results from the German competence network CAPNETZ 
Respiratory Research  2009;10(1):65.
Aim of this study was to evaluate the correlation of inflammatory markers procalcitonin (PCT), C-reactive protein (CRP) and leukocyte count (WBC) with microbiological etiology of CAP.
We enrolled 1337 patients (62 ± 18 y, 45% f) with proven CAP. Extensive microbiological workup was performed. In all patients PCT, CRP, WBC and CRB-65 score were determined. Patients were classified according to microbial diagnosis and CRB-65 score.
In patients with typical bacterial CAP, levels of PCT, CRP and WBC were significantly higher compared to CAP of atypical or viral etiology. There were no significant differences in PCT, CRP and WBC in patients with atypical or viral etiology of CAP. In contrast to CRP and WBC, PCT markedly increased with severity of CAP as measured by CRB-65 score (p < 0.0001). In ROC analysis for discrimination of patients with CRB-65 scores > 1, AUC for PCT was 0.69 (95% CI 0.66 to 0.71), which was higher compared to CRP and WBC (p < 0.0001). CRB-65, PCT, CRP and WBC were higher (p < 0.0001) in hospitalised patients in comparison to outpatients.
PCT, CRP and WBC are highest in typical bacterial etiology in CAP but do not allow individual prediction of etiology. In contrast to CRP and WBC, PCT is useful in severity assessment of CAP.
PMCID: PMC2714042  PMID: 19594893
5.  CRP and leukocyte-count after lumbar spine surgery: fusion vs. nucleotomy 
Acta Orthopaedica  2011;82(4):489-493.
Despite the fact that C-reactive protein (CRP) levels and white blood cell (WBC) count are routine blood chemistry parameters for the early assessment of wound infection after surgical procedures, little is known about the natural history of their serum values after major and minimally invasive spinal procedures.
Pre- and postoperative CRP serum levels and WBC count in 347 patients were retrospectively assessed after complication-free, single-level open posterior lumbar interlaminar fusion (PLIF) (n = 150) for disc degeneration and spinal stenosis and endoscopically assisted lumbar discectomy (n = 197) for herniated lumbar disc. Confounding variables such as overweight, ASA classification, arterial hypertension, diabetes mellitus, and perioperative antibiotics were recorded to evaluate their influence on the kinetics of CRP values and WBC count postoperatively.
In both procedures, CRP peaked 2–3 days after surgery. The maximum CRP level was significantly higher after fusion: mean 127 (SD 57) (p < 0.001). A rapid fall in CRP within 4–6 days was observed for both groups, with almost normal values being reached after 14 days. Only BMI > 25 and long duration of surgery were associated with higher peak CRP values. WBC count did not show a typical and therefore interpretable profile.
CRP is a predictable and responsive serum parameter in postoperative monitoring of inflammatory responses in patients undergoing spine surgery, whereas WBC kinetics is unspecific. We suggest that CRP could be measured on the day before surgery, on day 2 or 3 after surgery, and also between days 4 and 6, to aid in early detection of infectious complications.
PMCID: PMC3237042  PMID: 21657968
6.  White Blood Cells, Neutrophils, and Reactive Oxygen Metabolites among Asymptomatic Subjects 
Chronic inflammation and oxidative stress are associated with health and the disease status. The objective of the present study was to investigate the association among white blood cell (WBC) counts, neutrophil counts as a WBC subpopulation, and diacron reactive oxygen metabolites (d-ROMs) levels in an asymptomatic population.
The clinical data, including general cardiovascular risk variables and high-sensitivity C-reactive protein (hs-CRP), were collected from 100 female subjects (mean age, 62 years) in outpatient clinics. The correlation of the d-ROMs with hs-CRP, WBC, and neutrophil counts was examined.
The mean/median levels were WBC counts 5.9 × 109/L, neutrophil counts 3.6 × 109/L, hs-CRP 0.06 mg/dL, and d-ROMs 359 CURR U. A simple correlation analysis showed a significant positive correlation of the d-ROMs with the WBC counts, neutrophil counts, or hs-CRP levels. The correlation between d-ROMs and neutrophil counts (β = 0.22, P < 0.05), as well as that between d-ROMs and hs-CRP (β = 0.28, P < 0.01), remained significant and independent in a multiple linear regression analysis adjusted for other variables. A multiple linear regression analysis showed that WBC counts had only a positive correlation tendency to the d-ROMs.
Neutrophils may be slightly but more involved in the oxidative stress status, as assessed by d-ROMs, in comparison to the overall WBC. Further studies are needed to clarify the biologic mechanism(s) of the observed relationship.
PMCID: PMC3389441  PMID: 22783470
C-reactive protein; inflammation; leukocyte; neutrophil; oxidative stress
7.  Effect of Intensive Non-Surgical Treatment on the Level of Serum Inflammatory Markers in Advanced Periodontitis 
To assess whether non-surgical periodontal treatment is associated with changes in serological markers of systemic inflammation.
Materials and Methods:
Thirty-five systemically healthy subjects with severe generalized periodontitis meeting the inclusion criteria participated in a four-month single blind interventional trial of which thirty-two completed the study. Periodontal parameters and inflammatory markers [C-reactive protein (CRP) and plasma fibrinogen] and also the white blood cell count (WBC) were evaluated prior to and four months after delivery of intensive non-surgical periodontal therapy with simultaneous lavage of chlorhexidine 0.1% from the tip of the ultrasonic instrument into the pockets.
Significant differences in serum CRP levels were observed four months after treatment compared to the baseline (1.85, SD=1.93 vs 2.46, SD=2.32, respectively, P<0.0001). Periodontal treatment also resulted in a significant difference in WBC and neutrophil counts compared to the baseline (P<0.0001). The reduction in fibrinogen levels was not significant at the end of the research period. Significant improvement in the pocket probing depth and clinical attachment level for pockets with initially 4–6 mm and then more than 7 mm depth was observed. Changes in plaque and bleeding scores were also statistically significant (82.75 vs. 35.84 and 19.03 vs. 1.81, respectively).
Periodontal treatment is effective in reducing CRP levels and white blood cell count, while fibrinogen levels are not influenced by periodontal therapy. Periodontal treatment may therefore decrease the systemic inflammatory burden in patients with advanced periodontitis.
PMCID: PMC3184718  PMID: 21998772
Periodontal Index; Periodontal Diseases; C-Reactive Protein; Root Planing
8.  Leukocyte Count versus C-Reactive Protein Levels in Obese Portuguese Patients Aged 6-12 Years Old 
to evaluate whether total and differential WBC counts are altered in young obese patients (aged 6-12 years) and if a relationship exists between WBC counts and the severity of obesity as well as with CRP level.
Materials and Methods:
a group of 77 obese patients [32 males and 45 females] and 19 controls [7 males and 12 females] were studied. Total WBC count was performed by using an automatic blood cell counter. Blood cell morphology and WBC differential count were evaluated in Wright stained blood films. The plasma levels of CRP were evaluated by immunoturbidimetry.
obese participants presented with a statistically significant higher neutrophil percentage and CRP levels when compared to controls; the median CRP value was about 5 times higher than that observed in controls. Absolute neutrophil count and neutrophil/lymphocyte ratio were also higher in patients, though without statistical significance. The parameters that were statistically significant related with adiposity markers were neutrophil count and CRP levels. The neutrophil count was positively and statistically correlated with body mass index (BMI), BMI z-score, waist circumference and waist/height ratio, and also with CRP levels. In multiple regression analysis, the only variable that remained statistically associated with neutrophil count was CRP (neutrophil count = 2.612 + 0.439lnCRP; standardised coefficient/beta: 0.384, P=0.001). When performing multiple regression without CRP, the only variable that remained statistically associated with neutrophil count was BMI.
our results demonstrated in obese patients aged 6-12 years, a significant change in the differential leukocyte count towards neutrophilia, together with a significant higher CRP concentration, and that absolute neutrophil count correlates with obesity markers and with CRP levels. Our data also indicate that neutrophil count, a current clinically used low-cost parameter, may be used as an obesity-related inflammatory marker in young obese patients.
PMCID: PMC2911598  PMID: 20676221
Leukocytes; C-reactive protein; children obesity.
9.  Correlation of serum C-reactive protein, white blood count and neutrophil percentage with histopathology findings in acute appendicitis 
Acute appendicitis is one of the most common surgical emergencies. Accurate diagnosis of acute appendicitis is based on careful history, physical examination, laboratory and imaging investigation. The aim of the study is to analyze the role of C-reactive protein (CRP), white blood count (WBC) and Neutrophil percentage (NP) in improving the accuracy of diagnosis of acute appendicitis and to compare it with the intraoperative assessment and histopathology findings.
Materials and methods
This investigation was a prospective double blinded clinical study. The study was done on 173 patients surgically treated for acute appendicitis. The WBC, NP, and measurement of CRP were randomly collected pre-operatively from all involved patients. Macroscopic assessment was made from the operation. Appendectomy and a histopathology examination were performed on all patients. Gross description was compared with histopathology results and then correlated with CRP, WBC, and NP.
The observational accuracy was 87,3%, as compared to histopathological accuracy which was 85.5% with a total of 173 patients that were operated on. The histopathology showed 25 (14.5%) patients had normal appendices, and 148 (85.5%) patients had acutely inflamed, gangrenous, or perforated appendicitis. 52% were male and 48% were female, with the age ranging from 5 to 59 with a median of 19.7. The gangrenous type was the most frequent (52.6%). The WBC was altered in 77.5% of the cases, NP in 72.3%, and C-reactive protein in 76.9% cases. In those with positive appendicitis, the CRP and WBC values were elevated in 126 patients (72.8%), whereas NP was higher than 75% in 117 patients (67.6%). Out of 106 patients with triple positive tests, 101 (95.2%) had appendicitis. The sensitivity, specificity, and positive predictive values of the 3 tests in combination were 95.3%, 72.2%, and 95.3%, respectively.
The raised value of the CRP was directly related to the severity of inflammation (p-value <0.05). CRP monitoring enhances the diagnostic accuracy of acute appendicitis. The diagnostic accuracy of CRP is not significantly greater than WBC and NP. A combination of these three tests significantly increases the accuracy. We found that elevated serum CRP levels support the surgeon's clinical diagnosis.
PMCID: PMC3469372  PMID: 22866907
Acute appendicitis; CRP correlation; White blood count; Neutrophil percentage; Histopathology findings
10.  Comparative Value of Simple Inflammatory Markers in the Prediction of Left Ventricular Systolic Dysfunction in Postacute Coronary Syndrome Patients 
Mediators of Inflammation  2009;2009:826297.
Objectives. We sought to assess the comparative value of inflammatory markers on the occurrence of left ventricular systolic dysfunction (LVSD) after an acute coronary syndrome (ACS). Methods. During 2006–2008, 760 patients with an ACS were enrolled. C-reactive protein (CRP) and white blood cell (WBC) count were measured during the first 12 hours of hospital admission. Results. CRP levels and WBC count were significantly higher in those who developed LVSD compared to those who did not. The analysis revealed that a 10 mg/dL increase of CRP levels and a 1000/μL increase in WBC are associated with a 6% and a 7% increase in the likelihood of developing LVSD, respectively. Furthermore, WBC count at entry and CRP have almost the same predictive value for development of LVSD after an ACS (R2 = 0.109 versus R2 = 0.093). Conclusions. Serum CRP levels and WBC count at entry are almost equally powerful independent predictors of LVSD, after an ACS.
PMCID: PMC2686251  PMID: 19503842
11.  Marked increase of procalcitonin after the administration of anti-thymocyte globulin in patients before hematopoietic stem cell transplantation does not indicate sepsis: a prospective study 
Critical Care  2009;13(2):R37.
Procalcitonin (PCT) and C-reactive protein (CRP) are established markers of infection in the general population. In contrast, several studies reported falsely increased PCT levels in patients receiving T-cell antibodies. We evaluated the validity of these markers in patients scheduled for hemopoietic stem cell transplantation receiving anti-thymocyte globulin (ATG) during conditioning. We also assessed renal and liver functions and their relationship to PCT and CRP changes.
Twenty-six patients without clinical signs of infection were prospectively studied. ATG was administered in up to three doses over the course of 5 days. PCT, CRP, white blood cell (WBC) count, urea, creatinine, glomerular filtration rate, bilirubin, alanin amino-transferase (ALT), and gamma-glutamyl transferase (GGT) were assessed daily during ATG administration. Pharyngeal, nose, and rectal swabs and urine samples were cultured twice weekly. Blood cultures were obtained if clinical symptoms of infection were present.
Baseline (BL) levels of both PCT and CRP before ATG administration were normal. WBC count decreased after ATG administration (P = 0.005). One day after ATG administration, both PCT and CRP levels increased significantly, returning to BL levels on day 4. Microbiological results were clinically unremarkable. There was no interrelationship between PCT levels and BL markers of renal or liver functions (P > 0.05 for all comparisons). Bilirubin and GGT were increased on days 2 to 5 and ALT was increased on day 3 (P < 0.05 versus BL). No difference in renal functions was observed. Three patients developed bacterial infection on days 7 to 11 with different dynamics of PCT and CRP. There was no association between the number of ATG doses and PCT levels or between the risk of developing infection and previous PCT levels.
ATG triggered a marked early surge in PCT and CRP followed by a steady decrease over the course of 3 days. The dynamics of both PCT and CRP were similar and were not associated with infection. PCT levels were independent of renal and liver functions and were not predictive of further infectious complications. A direct effect of ATG on T lymphocytes could be the underlying mechanism. Hepatotoxic effect could be a contributing factor. Neither PCT nor CRP is a useful marker that can identify infection in patients receiving ATG.
PMCID: PMC2689473  PMID: 19291300
12.  Is hyperbilirubinaemia in appendicitis a better predictor of perforation than C-reactive protein? — a prospective study 
The Indian Journal of Surgery  2009;71(5):265-272.
To compare the performance for the prediction of perforated appendicitis of total bilirubin versus C-reactive protein (CRP), white blood cell count, the time period of symptoms’ evolution, and systemic inflammatory response syndrome (SIRS).
Prospective observational study, applying receiver operating characteristics curve analysis to compare the sensitivity and specificity of the tested variables.
The period of symptom’s evolution was prolonged (105.2 ± 79.3 hours vs. 38.6 ± 17.5 hours), and CRP levels were higher in perforated appendicitis (176 ± 82.6 mg/l vs. 80 ± 76 mg/l). Most patients with perforated appendicitis had a SIRS score higher than 3 points. CRP (>76.7 mg/l), the time period of symptoms’ evolution (>34.5 hours), and SIRS (3 points or more), were the best cutoff values to predict perforated appendicitis.
Perforated appendicitis may be suspected based on CRP, SIRS and the time period of symptoms’ evolution. We do not recommend the use of total bilirubin to predict perforation in appendicitis.
PMCID: PMC3452791  PMID: 23133170
Acute appendicitis; Hyperbilirubinaemia; Perforated appendicitis; Hepatic dysfunction in sepsis
13.  The Diagnostic Value of D-dimer, Procalcitonin and CRP in Acute Appendicitis 
BACKGROUND: The early diagnosis of acute abdomen is of great importance. To date, several inflammatory markers have been used for the diagnosis of acute abdominal conditions, including acute appendicitis. The aim of this study was to evaluate the diagnostic utility of D-dimer, Procalcitonin (PCT) and C-reactive protein (CRP) measurements in the acute appendicitis.
METHODS: This prospective study was conducted between March 1st, 2010 and July 1st, 2011. In this period, seventy-eight patients were operated with the diagnosis of acute appendicitis, and D-dimer, PCT and CRP levels of the patients were measured. The patients were grouped as phlegmonous appendicitis (Group 1), gangrenous appendicitis (Group 2), perforated appendicitis (Group 3) and negative appendectomy (Group 4) according to the surgical findings and histopathological results.
RESULTS: Of 78 patients, 54 (69.2 %) were male and 24 (30.8 %) were female, and the mean age was 25.4 ± 11.1 years (range, 18 to 69 years). 66 (84.6 %) patients had increased leukocyte count (white blood cell count). The PCT values were higher than the upper normal limit in 20 (25.6%) patients, followed by D-dimer in 22 (28.2 %) patients and CRP in 54 (69.2 %) patients. The diagnostic value of leukocyte count and CRP in acute appendicitis was higher than that of the other markers, whereas leukocyte count showed very low specificity. CRP values were higher in perforated appendicitis when compared with the phlegmonous appendicitis (p<0.05). However, PCT and D-dimer showed lower diagnostic values (26% and 31%, respectively).
CONCLUSION: An increase in CRP levels alone is not sufficient to make the diagnosis of acute appendicitis. However, CRP levels may differentiate between phlegmonous appendicitis and perforated appendicitis. Due to their low sensitivity and diagnostic value, PCT and D-dimer are not better markers than CRP for the diagnosis of acute appendicitis.
PMCID: PMC3520016  PMID: 23236260
Appendicitis; D-dimer; Procalcitonin; C-reactive protein.
14.  Patients with Clinical Acute Appendicitis Should have Pre-operative Full Blood Count and C-Reactive Protein Assays 
The role of inflammatory markers in the diagnosis of acute appendicitis has not been clearly defined. The aims of this prospective audit were to define the role of the serum markers of inflammation total white cell count, neutrophil count and C-reactive protein in the diagnosis of acute appendicitis with particular reference to the discrimination between uncomplicated and complicated appendicitis, and the prediction of abscess.
The author compiled a prospective database over a 13-month period of all appendicectomies performed. After five exclusions (three having no notes for review and two having confounding second morbidity in the presence of a normal appendix), the data relating to 75 patients were analysed.
In patients judged on clinical grounds to require laparotomy for suspected acute appendicitis, white cell count and neutrophil count distinguish acute appendicitis from normal appendices when used as categorical variables, though they do not reflect the presence of abscess. C-reactive protein neither distinguishes appendicitis from normal, nor predicts abscess when used as a categorical variable, though higher levels suggest abscess.
Laboratory tests of the white cell count, neutrophil count and C-reactive protein are more effective in supporting a clinical diagnosis of acute appendicitis in patients with typical clinical features than in excluding the diagnosis.
PMCID: PMC1963644  PMID: 16460636
Appendicitis; Inflammatory markers; Audit
15.  Diagnostic value of urine sTREM-1 for sepsis and relevant acute kidney injuries: a prospective study 
Critical Care  2011;15(5):R250.
We explored the diagnostic value of a urine soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) for early sepsis identification, severity and prognosis assessment, and for secondary acute kidney injury (AKI). We compared this with white blood cell (WBC) counts, serum C-reactive protein (CRP), serum procalcitonin (PCT), urine output, creatinine clearance (CCr), serum creatinine (SCr), and blood urea nitrogen (BUN).
We enrolled 104 subjects admitted to the ICU: 16 cases with systemic inflammatory response syndrome (SIRS); 35 with sepsis and 53 with severe sepsis. Results for urine sTREM-1, WBC, serum CRP and serum PCT were recorded on days 1, 3, 5, 7, 10, and 14. For 17 sepsis cases diagnosed with secondary AKI, comparisons between their urine sTREM-1, urine output, CCr, SCr and BUN at diagnosis and 48 h before diagnosis were made.
On the day of admission to the ICU, and compared with the SIRS group, the sepsis group exhibited higher levels of urine sTREM-1 and Acute Physiologic Assessment and Chronic Health Evaluation II (APACHE II) scores (P < 0.05). Areas under the curve (AUC) shaped by the scores were 0.797 (95% CI 0.711 to 0.884) and 0.722 (95% CI 0.586 to 0.858), respectively. On days 1, 3, 5, 7, 10, and 14, urine sTREM-1, serum PCT and WBC levels registered higher in the severe sepsis group in contrast to the sepsis group (P < 0.05). Urine sTREM-1 and serum PCT levels continuously increased among non-survivors, while WBC and serum CRP levels in both groups declined. For 17 patients with AKI, urine sTREM-1, SCr and BUN levels at 48 h before AKI diagnosis were higher, and CCr level was lower than those for non-AKI subjects (P < 0.05). AUC for urine sTREM-1 was 0.922 (95% CI 0.850 to 0.995), the sensitivity was 0.941, and the specificity was 0.76 (based on a cut-off point of 69.04 pg/ml). Logistic regression analysis showed that urine sTREM-1 and severity were risk factors related to AKI occurrence.
Besides being non-invasive, urine sTREM-1 testing is more sensitive than testing WBC, serum CRP, and serum PCT for the early diagnosis of sepsis, as well as for dynamic assessments of severity and prognosis. It can also provide an early warning of possible secondary AKI in sepsis patients.
Trial Registration identifier NCT01333657
PMCID: PMC3334801  PMID: 22023777
urine; soluble triggering receptor expressed on myeloid cells-1(sTREM-1); sepsis; severity; prognosis; acute kidney injury (AKI); sensitivity; specificity
16.  The diagnostic values of preoperative laboratory markers in children with complicated appendicitis 
Accurate diagnosis and optimal management of acute appendicitis, despite being the most common surgical emergency encountered in emergency departments, is often delayed in pediatric patients due to nonspecific symptoms and communication barriers, often leading to more complicated cases. The aim of this study is to investigate the diagnostic significance of common laboratory markers.
A total of 421 patients aged 15 and younger underwent surgical treatment for acute appendicitis. We conducted a retrospective analysis for white blood cell (WBC), C-reactive protein (CRP) and bilirubin. All patients were classified into simple or complicated appendicitis groups based on postoperative histology.
The mean age of the patients in the complicated appendicitis group was younger than that in the simple group (P = 0.005). WBC, CRP and bilirubin levels were significantly higher in the complicated appendicitis group (P < 0.001, <0.001, 0.002). The relative risk for complicated appendicitis was calculated using age, WBC, CRP and bilirubin. Elevated CRP levels were associated with the highest risk for complicated appendicitis (hazard ratio [HR], 2.53; 95% confidence interval [CI], 1.38 to 4.65) followed by WBC (HR, 2.42; 95% CI, 1.07 to 5.46) and bilirubin (HR, 2.04; 95% CI, 1.09 to 3.82). The most sensitive markers for diagnosing complicated appendicitis were WBC (95.2%) and CRP (86.3%). Bilirubin levels showed the highest specificity at 74.8%.
The risk of complicated appendicitis was significantly higher in patients younger than 10 years old. Preoperative WBC, CRP and bilirubin have clinical value in diagnosing complicated appendicitis with a HR of 2.0 to 2.5. Our results suggest that the utilization of WBC, CRP, and bilirubin can assist in the diagnosis of complicated appendicitis in pediatric patients, allowing prompt diagnosis and optimal management.
PMCID: PMC3467390  PMID: 23091796
Appendicitis; Child; Leukocytes; C-reactive protein; Bilirubin
17.  Inflammation Biomarkers and Risk of All-Cause Mortality in the Reasons for Geographic and Racial Differences in Stroke Cohort 
American Journal of Epidemiology  2011;174(3):284-292.
Inflammation biomarkers, including higher high-sensitivity C-reactive protein (hsCRP) levels, higher white blood cell (WBC) counts, and lower serum albumin levels, are associated with an increased risk of all-cause mortality. Many studies have examined these biomarkers individually, but less is known about their joint association with mortality. hsCRP, WBC count, and serum albumin were measured at baseline in the Reasons for Geographic and Racial Differences in Stroke Study cohort members, who were enrolled in 2003–2007. Over 4.5 years, there were 1,062 deaths in 17,845 participants. High-risk categories were defined as hsCRP or WBC levels above the 75th percentile (5.1 mg/L and 6.9 × 109 cells/L, respectively) and albumin levels below the 25th percentile (4.00 g/dL). The authors derived 4 groups that corresponded to 0 (n = 8,341), 1 (n = 6,277), 2 (n = 2,635), or 3 (n = 592) biomarkers in the high-risk category. After adjustment for age, sex, waist circumference, race, region, smoking, alcohol use, income, educational level, physical activity frequency, and medical history and compared with those with no biomarkers in the high-risk category, the hazard ratios for all-cause mortality for 1, 2, and 3 biomarkers in the high-risk category were 1.56 (95% confidence interval: 1.33, 1.82), 2.19 (95% confidence interval: 1.84, 2.62), and 2.96 (95% confidence interval: 2.30, 3.80), respectively (Ptrend < 0.0001). Adding the 3 inflammation biomarkers to a fully adjusted model improved risk discrimination by 23.7% (95% confidence interval: 9.3, 39.9). Measurement of more than 1 biomarker is more useful in risk prediction than single biomarkers.
PMCID: PMC3202158  PMID: 21685411
biological markers; cohort studies; C-reactive protein; inflammation; leukocytes; mortality; prospective studies
18.  Retrospective Reports of Weight Change and Inflammation in the US National Health and Nutrition Examination Survey 
Journal of Obesity  2013;2013:601534.
Purpose. This study investigated the association between weight change and inflammation in a nationally representative population of US adults aged 40 and older. Methods. Using the US National Health and Nutrition Examination Survey (2005–2008), logistic regression models were used to determine the relationship between high levels of inflammation (C-reactive protein [CRP]) and infection (white blood cell count [WBC]) with 1- and 10-year change in self-reported weight status. Results. Change in 1- and 10-year weight was associated with high CRP but not high WBC. Individuals who gained or lost ≥10 kg had an odds of having high CRP that was 1.96 (95% CI 1.11–3.50) and 1.61 (95% CI 1.02–2.46) as high, respectively, as those who maintained a stable weight (<4 kg change) in the past year. The increased risk of elevated CRP among individuals who experienced at least 10 kg of weight loss or weight gain was also observed for weight change that occurred over the past 10 years; however, weight loss over the 10-year period was no longer associated with high inflammation. Conclusions. These results suggest that adult respondents who retrospectively self-reported weight loss or gain had higher levels of inflammation relative to their weight stable counterparts.
PMCID: PMC3583126  PMID: 23476750
19.  Discriminative Accuracy of Novel and Traditional Biomarkers in Children with Suspected Appendicitis Adjusted for Duration of Abdominal Pain 
To assess the accuracy of novel and traditional biomarkers in patients with suspected appendicitis as a function of duration of symptoms.
This was a prospective cohort study, conducted in a tertiary care emergency department (ED). The authors enrolled children 3 to 18 years old with acute abdominal pain of less than 96 hours, and measured serum levels of Interleukin-6 (IL-6), Interleukin-8 (IL-8), C - reactive protein (CRP), white blood cell count (WBC), and absolute neutrophil count (ANC). Final diagnosis was determined by histopathology or telephone follow-up. Trends in biomarker levels were examined based on duration of abdominal pain. The accuracy of biomarkers was assessed with receiver operating characteristic (ROC) curves. Optimal cut-points and test performance characteristics were calculated for each biomarker.
Of 280 patients enrolled, the median age was 11.3 years (IQR 8.6 to 14.8), 57% were male, and 33% had appendicitis. Median IL-6, median CRP, mean WBC, and mean ANC differed significantly (p < 0.001) between patients with non-perforated appendicitis and those without appendicitis; median IL-8 levels did not differ between groups. In non-perforated appendicitis, median IL-6, WBC, and ANC levels were maximal at less than 24 hrs of pain, while CRP peaked between 24 and 48 hours. In perforated appendicitis, median IL-8 levels were highest by 24 hours, WBC and IL-6 by 24 to 48 hours, and CRP after 48 hours of pain. The WBC appeared to be the most useful marker to predict appendicitis in those with fewer than 24 or more than 48 hours of pain, while CRP was the most useful in those with 24 to 48 hours of pain.
In this population, the serum levels and accuracy of novel and traditional biomarkers varies in relation to duration of abdominal pain. IL-6 shows promise as a novel biomarker to identify children with appendicitis.
PMCID: PMC3117273  PMID: 21676053
20.  Effects of fluoxetine and escitalopram on C-reactive protein in patients of depression 
To study the anti-inflammatory activity of fluoxetine and escitalopram in newly diagnosed patients of depression and also to evaluate the association between depression and inflammation.
Materials and Methods:
Ninety-eight newly diagnosed patients of depression were recruited as cases. From these, 48 had started treatment with fluoxetine (20 mg/day) and 50 had started treatment with escitalopram (20 mg/day). After 2 months of treatment of these patients, Hamilton rating scale for depression (HRSD scale), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and white blood cell (WBC) count were measured and compared to their respective baseline values before starting treatment. One hundred healthy volunteers were recruited as controls and their baseline of CRP, ESR and WBC count were measured and compared with their respective baseline values of cases. Severity of depression was measured by HRSD scale and anti-inflammatory activity was measured by reduction CRP, ESR and WBC count.
On baseline comparison between cases and controls, there were significant increases in the levels of CRP (P = 0.014), ESR (P = 0.023) and WBC count (P = 0.020) in cases. In fluoxetine (20 mg/day) treatment group, there was a significant reduction in the levels of CRP (P = 0.046), ESR (P = 0.043) and WBC count (P = 0.021) after 2 months of treatment but no significant reduction in HRSD scale (P = 0.190). Similarly, in escitalopram treatment group, there was a significant reduction in CRP (P = 0.041), ESR (P = 0.030) and WBC count (P = 0.017) after 2 months of treatment but no significant reduction in HRSD scale (P = 0.169).
In newly diagnosed patients of depression, inflammatory markers such as CRP, ESR and WBC count were significantly raised and Selective serotonin reuptake inhibitors SSRIs such as fluoxetine and escitalopram reduced them independent of their antidepressant effect. So, SSRIs have some anti-inflammatory activity independent of their antidepressant action.
PMCID: PMC3117562  PMID: 21701640
Anti-inflammatory activity; C-reactive protein; erythrocyte sedimentation rate; Hamilton rating scale for depression; white blood cell count
21.  Differentiation of bacterial and viral pneumonia in children 
Thorax  2002;57(5):438-441.
Background: A study was undertaken to investigate the differential diagnostic role of chest radiographic findings, total white blood cell count (WBC), erythrocyte sedimentation rate (ESR), and serum C reactive protein (CRP) in children with community acquired pneumonia of varying aetiology.
Methods: The study population consisted of 254 consecutive children admitted to hospital with community acquired pneumonia diagnosed between 1993 and 1995. WBC, ESR, and CRP levels were determined on admission. Seventeen infective agents (10 viruses and seven bacteria) were searched for. Chest radiographs were retrospectively and separately reviewed by three paediatric radiologists.
Results: A potential causative agent was found in 215 (85%) of the 254 cases. Bacterial infection was found in 71% of 137 children with alveolar infiltrates on the chest radiograph, while 72% of the 134 cases with a bacterial pneumonia had alveolar infiltrates. Half of the 77 children with solely interstitial infiltrates on the chest radiograph had evidence of bacterial infection. The proportion of patients with increased WBC or ESR did not differ between bacterial and viral pneumonias, but differences in the CRP levels of >40 mg/l, >80 mg/l, and >120 mg/l were significant although the sensitivity for detecting bacterial pneumonia was too low for use in clinical practice.
Conclusions: Most children with alveolar pneumonia, especially those with lobar infiltrates, have laboratory evidence of a bacterial infection. Interstitial infiltrates are seen in both viral and bacterial pneumonias.
PMCID: PMC1746322  PMID: 11978922
22.  Genetic Effects on Postprandial Variations of Inflammatory Markers in Healthy Individuals 
Obesity (Silver Spring, Md.)  2009;18(7):1417-1422.
Circulating levels of inflammatory markers predict the risk of cardiovascular disease (CVD), mediated perhaps in part by dietary fat intake, through mechanisms only partially understood. To evaluate post-fat load changes in inflammatory markers and genetic influences on these changes, we administered a standardized high-fat meal to 838 related Amish subjects as part of the Heredity and Phenotype Intervention (HAPI) Heart Study and measured a panel of inflammatory markers, including C-reactive protein (CRP), interleukin-1 β (IL-1β), matrix metalloproteinase-1 and -9 (MMP-1 and MMP-9), and white blood cell (WBC) count, before and 4 hours post-fat challenge (CRP pre-challenge only). Heritabilities (h2 ± SD) of basal inflammatory levels ranged from 16 ± 8% for MMP-9 (P = 0.02) to 90 ± 7% for MMP-1 (P < 0.0001). Post-fat load, circulating levels of WBC, MMP-1 and MMP-9 increased by 16%, 32% and 43% (all P < 0.0001), with no significant changes in IL-1β. Postprandial changes over the 4-hour period were modestly heritable for WBC (age- and sex-adjusted h2 = 14 ± 9%, P = 0.04), but the larger MMP-1 and MMP-9 changes appeared to be independent of additive genetic effects. These results reveal that a high fat meal induces a considerable inflammatory response. Genetic factors appear to play a significant role influencing basal inflammatory levels but to have minimal influence on post-fat intake inflammatory changes.
PMCID: PMC3066005  PMID: 19910936
Inflammation; Fat Intake; Dietary; Genetic Epidemiology
23.  Acute phase proteins and white blood cell levels for prediction of infectious complications in status epilepticus 
Critical Care  2011;15(6):R274.
Infections in status epilepticus (SE) patients result in severe morbidity making early diagnosis crucial. As SE may lead to inflammatory reaction, the value of acute phase proteins and white blood cells (WBC) for diagnosis of infections during SE may be important. We examined the reliability of C-reactive protein (CRP), procalcitonin (PCT), and WBC for diagnosis of infections during SE.
All consecutive SE patients treated in the ICU from 2005 to 2009 were included. Clinical and microbiological records, and measurements of CRP and WBC during SE were analyzed. Subgroup analysis was performed for additional PCT measurements in the first 48 hours of SE.
A total of 22.5% of 160 consecutive SE patients had infections during SE. Single levels of CRP and WBC had no association with the presence of infections. Their linear changes over the first three days after SE onset were significantly associated with the presence of infections (P = 0.0012 for CRP, P = 0.0137 for WBC). Levels of PCT were available for 31 patients and did not differ significantly in patients with and without infections. Sensitivity of PCT and CRP was high (94% and 83%) and the negative predictive value of CRP increased over the first three days to 97%. Specificity was low, without improvement for different cut-offs.
Single levels of CRP and WBC are not reliable for diagnosis of infections during SE, while their linear changes over time significantly correlate with the presence of infections. In addition, low levels of CRP and PCT rule out hospital-acquired infections in SE patients.
PMCID: PMC3388641  PMID: 22099124
24.  Sex based levels of C-reactive protein and white blood cell count in subjects with metabolic syndrome: Isfahan Healthy Heart Program 
C-reactive protein (CRP) and white blood cell (WBC) are proinflammatory markers. They are major pathophysiological for the development of metabolic syndrome (MetS). This study aimed to address the independent associations between MetS and WBC counts and serum CRP levels and evaluation of their magnitude in relation to the MetS, based on the sex in the Iranian adults.
Materials and Methods:
In this cross-sectional study, subjects who met the MetS criteria, based on the Adult Treatment Panel III were selected from the Isfahan Healthy Heart Program database. A questionnaire containing the demographic data, weight, height, waist, and hip circumference of the respondents was completed for each person. Blood pressure was measured and the anthropometric measurements were done, and fasting blood samples were taken for 2 h postload plasma glucose (2 hpp). Serum [total, high-density lipoprotein (HDL), and low-density lipoprotein] levels of cholesterol, triglyceride, and CRP as well as WBC counts were determined. The univariate analyses were carried out to assess the relation between the CRP levels, WBC counts with the MetS in both sexes the.
In men with the abdominal obesity, the higher levels of WBC count, high serum triglyceride and blood glucose levels, a low serum HDL level, and raised systolic and diastolic blood pressure were observed. However, the higher serum CRP levels were only observed in those with the low serum HDL-cholesterol levels. The mean values of the WBC counts were statistically different between the men with and without MetS, but the mean values of the CRP levels were similar between the two groups. In women, the mean values of WBC count and CRP levels were statistically different in the subjects with and without a MetS components (except for the low serum HDL levels and high diastolic blood pressure for the WBC measures and abdominal obesity for the CRP measures) and for those with and without MetS. The age and smoking adjusted changes in the CRP levels and WBC counts correlated with the number of Mets components in the women.
The findings of this study suggest substantial implications for the prevention and management of the MetS and atherosclerotic diseases, as these involve the suppression of inflammatory conditions rather than the incitement of anti-inflammatory conditions.
PMCID: PMC3818614  PMID: 24250693
C-reactive protein level; metabolic syndrome; white blood cell count
25.  Markers of lower respiratory tract infections in emergency departments 
Acute respiratory tract infections are the common causes for admission to emergency department. Appropriate diagnosis and initiating treatment on time are important for reducing morbidity and mortality rate due to lower respiratory tract infection (LRTI). The aim of this study is to determine if C-reactive protein (CRP) levels and white blood cells (WBC) count are considerable markers to help rapid diagnosis and prediction of antibiotic need for lower respiratory infections in emergency departments. The relationships between infectious agents and those markers have also been evaluated.
Study subjects and control group were selected by defined criteria. Patients were analyzed and assessed for CRP and WBC, sputum Gram stain and culture besides routine laboratory tests and chest X-Rays.
One hundred and ninety four episodes out of 175 patients were evaluated for the study. CRP level and WBC count were detected significantly higher in patients ofstudy group than in those of control group. Pseudomonas aeruginosa and Haemophilus influenzae were the pathogens most often isolated.
In conclusion, CRP and WBC sputum are important markers for diagnosis of LRTI at the emergency departments and results of microbiological analysis of respiratory specimens were correlated with these markers.
Trial registration
Registation number of ethic committee of Dr. Suat Seren Chest Diseases and Surgery Training and Research Hospital: 28.04.2006/114
PMCID: PMC3610129  PMID: 23497669
C-reactive protein; Gram stain; Lower respiratory tract infections; Sputum culture; White blood cells

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