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1.  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
2.  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
3.  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
4.  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.
5.  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
6.  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
7.  Evaluation of Clinical Alvarado Scoring System and CT Criteria in the Diagnosis of Acute Appendicitis 
Radiology Research and Practice  2016;2016:9739385.
Aim. The aim was to evaluate the clinical Alvarado scoring system and computed tomography (CT) criteria for the diagnosis of acute appendicitis. Material and Methods. 117 patients with acute abdominal pain who underwent abdominal CT were enrolled in this retrospective study. Patient demographics, clinical Alvarado scoring, CT images, and pathologic results of the patients were evaluated. Results. 39 of the 53 patients who were operated on had pathologically proven acute appendicitis. CT criteria of appendiceal diameter, presence of periappendiceal inflammation, fluid, appendicolith, and white blood cell (WBC) count were significantly correlated with the inflammation of the appendix. The best cut-off value for appendiceal diameter was 6.5 mm. The correlation between appendiceal diameter and WBC count was 80% (P = 0.01 < 0.05). The correlation between appendiceal diameter and Alvarado score was 78.7% (P = 0.01 < 0.05). Conclusion. Presence of CT criteria of appendiceal diameter above 6.5 mm, periappendiceal inflammation, fluid, and appendicolith should prompt the diagnosis of acute appendicitis. Since patients with acute appendicitis may not always show the typical signs and symptoms, CT is a helpful imaging modality for patients with relatively low Alvarado score and leukocytosis and when physical examination is confusing.
PMCID: PMC4868911  PMID: 27242926
8.  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
9.  Utility of Immature Granulocyte Percentage in Pediatric Appendicitis 
The Journal of surgical research  2014;190(1):230-234.
Acute appendicitis is the most common cause of abdominal surgery in children. Adjuncts are utilized to help clinicians predict acute or perforated appendicitis, which may affect treatment decisions. Automated hematologic analyzers can perform more accurate automated differentials including immature granulocyte percentages (IG%). Elevated IG% has demonstrated improved accuracy for predicting sepsis in the neonatal population than traditional immature to total neutrophil count (I/T) ratios. We intended to assess the additional discriminatory ability of IG% to traditionally assessed parameters in the differentiation between acute and perforated appendicitis.
Materials and Methods
We identified all patients with appendicitis from July 2012 to June 2013 by ICD-9 code. Charts were reviewed for relevant demographic, clinical, and outcome data, which were compared between acute and perforated appendicitis groups using Fischer’s exact and t-test for categorical and continuous variables, respectively. We utilized an adjusted logistic regression model utilizing clinical lab values to predict the odds of perforated appendicitis.
251 patients were included in the analysis. Those with perforated appendicitis had a higher white blood cell (WBC) count (p=0.0063), C-reactive protein (CRP) (p<0.0001), and IG% (p=0.0299). In the adjusted model, only elevated CRP (OR 3.46, 95% CI 1.40-8.54) and presence of left shift (OR 2.66, 95% CI 1.09-6.46) were significant predictors of perforated appendicitis. The c-statistic of the final model was 0.70, suggesting fair discriminatory ability in predicting perforated appendicitis.
IG% did not provide any additional benefit to elevated CRP and presence of left shift in the differentiation between acute and perforated appendicitis.
PMCID: PMC4277231  PMID: 24793450
appendicitis; pediatric; immature granulocyte percentage
10.  Diagnostic value of procalcitonin for acute complicated appendicitis 
A rapid and reliable test for detection of complicated appendicitis would be useful when deciding whether emergency surgery is required. We investigated the clinical usefulness of procalcitonin for identifying acute complicated appendicitis. We retrospectively analyzed 63 patients aged ≥15 years who underwent appendectomy without receiving antibiotics before admission and had preoperative data on the plasma procalcitonin level (PCT), body temperature (BT), white blood cell count (WBC), neutrophil / lymphocyte ratio (N/L ratio), and C-reactive protein level (CRP). Patients were classified into 3 groups: group A (inflammatory cell infiltration of the appendix with intact mural architecture), group B (inflammatory cell infiltration with destruction of mural architecture, but without abscess or perforation), and group C (macroscopic abscess and/or perforation). For identifying destruction of mural architecture, the diagnostic accuracy of PCT was similar to that of BT or CRP. However, the diagnostic accuracy of PCT was highest among the five inflammatory indices for identifying abscess and/or perforation, with the positive predictive value of PCT for abscess and/or perforation being higher than that of CRP (73% vs. 48%). Univariate analysis of the predictors of abscess and/or perforation revealed that a plasma PCT level ≥0.46 ng/mL had the highest odds ratio (30.3 [95% confidence interval: 6.5–140.5] versus PCT <0.46 ng/mL). These findings indicate that procalcitonin is a useful marker of acute appendicitis with abscess and/or perforation.
PMCID: PMC4767516  PMID: 27019529
procalcitonin; appendicitis; C-reactive protein
11.  Important CT findings for prediction of severe appendicitis: involvement of retroperitoneal space 
Determination of the severity of appendicitis and differentiation between complicated and uncomplicated appendicitis are clinically important. Severe appendicitis frequently affects extraperitoneal spaces. We have investigated CT findings of retroperitoneal space (RPS) in patients with appendicitis to create a model for identification of complicated appendicitis.
CT images of 223 patients with pathologically proven appendicitis were reviewed. The total number of the segments in RPS where inflammatory changes were located (RPS count) was obtained as well as appendiceal diameter, appendicolithiasis, WBC count, and CRP level. Data were analyzed to identify factors indicating complicated appendicitis. Univariate analysis was conducted to identify statistically significant variables. A multivariable logistic regression analysis was performed in order to find independent predictors of complicated appendicitis.
Patients with complicated appendicitis were more likely to have higher RPS count (P < 0.001), appendicolithiasis (P = 0.002), higher CRP level (P < 0.001), and greater appendix diameter (P < 0.001) than patients with uncomplicated appendicitis. Statistical analysis showed RPS count was the most helpful predictor of complicated appendicitis.
Radiologists and surgeons should be aware of the importance of CT findings in RPS when treating patients with appendicitis. Complicated appendicitis can be predicted by RPS count, diameter of the appendix, appendicolithiasis, and CRP level.
PMCID: PMC4293097  PMID: 25587352
Appendicitis; Complicated; Retroperitoneal space; Extraperitoneal space; CT
12.  Should appendectomy be performed laparoscopically? Clinical prospective randomized trial 
Laparoscopic appendectomy (LA) has been described in 1983, and its superiority over open appendectomy (OA) is still being debated. Currently, there is no agreement on the advantages of LA. Postoperative pain is reported to be lower along with a faster return to normal activities in LA. However, some studies do not support these findings. In our study, we aimed to compare the outcomes and cost effectiveness of LA and OA.
Material and Methods:
Patients were prospectively randomized into LA (31 patients) and OA (32 patients) groups. Demographic data, pre- and postoperative C-reactive protein (CRP) levels, white blood cell (WBC) count, duration of surgery and hospitalization, complications, and pain scores (VAS) were recorded. Cost was calculated for both groups. Return to normal activities was evaluated by phone calls at the first and second week and 1 month after surgery.
There was a significant postoperative decrease in WBC count in the LA group (p<0.01). There were no differences between LA and OA groups in terms of postoperative CRP levels (p>0.05). The rates of wound infection and abscess were similar (p>0.05), while post-operative pain and time to return to normal activities were higher in the OA group (p<0.01). There was a positive correlation between BMI and operative time in the LA group (p<0.01), while BMI and operative time did not show a correlation in the OA group (p>0,05). The average cost in the LA and OA groups were 1960.5±339.05 and 687.115±159.5 TL, respectively.
LA is an effective method in the treatment of acute appendicitis due to less pain and faster recovery. LA can be the choice of treatment in acute appendicitis, with utilization of re-useable and cheaper vascular sealing devices.
PMCID: PMC4674044  PMID: 26668531
Acute appendicitis; laparoscopic appendectomy; open appendectomy
13.  Predictive Factors to Distinguish Between Patients With Noncomplicated Appendicitis and Those With Complicated Appendicitis 
Annals of Coloproctology  2015;31(5):192-197.
Recently, randomized controlled trials have reported that conservative therapy can be a treatment option in patients with noncomplicated appendicitis. However, preoperative diagnosis of noncomplicated appendicitis is difficult. In this study, we determined predictive factors to distinguish patients with noncomplicated appendicitis from those with complicated appendicitis.
A total of 351 patients who underwent surgical treatment for acute appendicitis from January 2011 to December 2012 were included in this study. We classified patients into noncomplicated or complicated appendicitis groups based on the findings of abdominal computed tomography and pathology. We performed a retrospective analysis to find factors that could be used to discriminate between noncomplicated and complicated appendicitis.
The mean age of the patients in the complicated appendicitis group (54.5 years) was higher than that of the patients in the noncomplicated appendicitis group (40.2 years) (P < 0.001), but the male-to-female ratios were similar. In the univariate analysis, the appendicocecal junction's diameter, appendiceal maximal diameter, appendiceal wall enhancement, periappendiceal fat infiltration, ascites, abscesses, neutrophil proportion, C-reactive protein (CRP), aspartate aminotransferase, and total bilirubin were statistically significant factors. However, in the multivariate analysis, the appendiceal maximal diameter (P = 0.018; odds ratio [OR], 1.129), periappendiceal fat infiltration (P = 0.025; OR, 5.778), ascites (P = 0.038; OR, 2.902), and CRP (P < 0.001; OR, 1.368) were statistically significant.
Several factors can be used to distinguish between noncomplicated and complicated appendicitis. Using these factors, we could more accurately distinguish patients with noncomplicated appendicitis from those with complicated appendicitis.
PMCID: PMC4644707  PMID: 26576398
Appendicitis; Appendectomy
14.  Bedside Ultrasonography as an Adjunct to Routine Evaluation of Acute Appendicitis in the Emergency Department 
Appendicitis is a common condition presenting to the emergency department (ED). Increasingly emergency physicians (EP) are using bedside ultrasound (BUS) as an adjunct diagnostic tool. Our objective is to investigate the test characteristics of BUS for the diagnosis of appendicitis and identify components of routine ED workup and BUS associated with the presence of appendicitis.
Patients four years of age and older presenting to the ED with suspected appendicitis were eligible for enrollment. After informed consent was obtained, BUS was performed on the subjects by trained EPs who had undergone a minimum of one-hour didactic training on the use of BUS to diagnose appendicitis. They then recorded elements of clinical history, physical examination, white blood cell count (WBC) with polymophonuclear percentage (PMN), and BUS findings on a data form. We ascertained subject outcomes by a combination of medical record review and telephone follow-up.
A total of 125 subjects consented for the study, and 116 had adequate image data for final analysis. Prevalence of appendicitis was 40%. Mean age of the subjects was 20.2 years, and 51% were male. BUS was 100% sensitive (95% CI 87–100%) and 32% specific (95% CI 14–57%) for detection of appendicitis, with a positive predictive value of 72% (95% CI 56–84%), and a negative predictive value of 100% (95% CI 52–100%). Assuming all non-diagnostic studies were negative would yield a sensitivity of 72% and specificity of 81%. Subjects with appendicitis had a significantly higher occurrence of anorexia, nausea, vomiting, and a higher WBC and PMN count when compared to those without appendicitis. Their BUS studies were significantly more likely to result in visualization of the appendix, appendix diameter >6mm, appendix wall thickness >2mm, periappendiceal fluid, visualization of the appendix tip, and sonographic Mcburney’s sign (p<0.05). In subjects with diagnostic BUS studies, WBC, PMN, visualization of appendix, appendix diameter >6mm, appendix wall thickness >2mm, periappendiceal fluid were found to be predictors of appendicitis on logistic regression.
BUS is moderately useful for appendicitis diagnosis. We also identified several components in routine ED workup and BUS that are associated with appendicitis generating hypothesis for future studies.
PMCID: PMC4251223  PMID: 25493122
15.  Evaluation of procalcitonin as a biomarker of diagnosis, severity and postoperative complications in adult patients with acute appendicitis 
Background: Delay in diagnosis and treatment of acute appendicitis (AA) results in an increased rate of perforation, postoperative morbidity, mortality and hospital length of stay. Several biochemical parameters including white blood cell (WBC) count, C-reactive protein (CRP), interleukin-6 (IL6) and Procalcitonin (PCT) have been used to further improve the clinical diagnosis of AA. The aim of this study was to assess the value of procalcitonin as a predictor of diagnosis and severity of appendicitis in order to improve the clinical decision making, since other studies have been unable to demonstrate a diagnostic value for PCT elevation in acute appendicitis.
Methods: One-hundred patients who underwent open appendectomy, including 75 men and 25 women with a mean age of 28 years were included in this study. Procalcitonin values were measured by an immunofluorescent method). Serum PCT>0.5 ng/ml was considered positive. The PCT serum values were measured in four different categories, including ˂0.5ng/ml, 0.5-2 ng/ml, 2-10ng/ml and more than 10ng/ml.
Results: The sensitivity and specificity of PCT level measurement for acute appendicitis diagnosis were 44% and 100% respectively. The value of PCT increased with the severity of appendicitis and also with the presence of peritonitis and infection, at the site of surgery.
Conclusions: Procalcitonin measurement cannot be used as a diagnostic test for adult patients with acute appendicitis and its routine use in such patients is not cost effective and conclusive. Procalcitonin values can be used as a prognostic marker and predictor of infectious complications following surgery and it can help to carry out timely surgical intervention which is highly recommended in patients with PCT values more than 0.5ng/ml.
PMCID: PMC4219879  PMID: 25405116
Appendicitis; Procalcitonin; Diagnosis; Prognosis
16.  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.
17.  White Blood Cell Count in Women: Relation to Inflammatory Biomarkers, Haematological Profiles, Visceral Adiposity, and Other Cardiovascular Risk Factors 
The role of white blood cell (WBC) count in pathogenesis of diabetes, cardiovascular disease, and obesity-related disorders has been reported earlier. Recent studies revealed that higher WBC contributes to atherosclerotic progression and impaired fasting glucose. However, it is unknown whether variations in WBC and haematologic profiles can occur in healthy obese individuals. The aim of this study is to further evaluate the influence of obesity on WBC count, inflammatory biomarkers, and metabolic risk factors in healthy women to establish a relationship among variables analyzed. The sample of the present study consisted of 84 healthy women with mean age of 35.56±6.83 years. They were categorized into two groups based on their body mass index (BMI): obese group with BMI >30 kg/m2 and non-obese group with BMI <30 kg/m2. We evaluated the relationship between WBC and platelet count (PLT) with serum interleukin 6 (IL-6), C-reactive protein (CRP), angiotensin Π (Ang Π), body fat percentage (BF %), waist-circumference (WC), and lipid profile. WBC, PLT, CRP, and IL-6 in obese subjects were significantly higher than in non-obese subjects (p< 0.05). The mean WBC count in obese subjects was 6.4±0.3 (×109/L) compared to 4.4±0.3 (×109/L) in non-obese subjects (p=0.035). WBC correlated with BF% (r=0.31, p=0.004), CRP (r=0.25, P=0.03), WC (r=0.22, p=0.04), angiotensin Π (r=0.24, p=0.03), triglyceride (r=0.24, p=0.03), and atherogenic index of plasma (AIP) levels (r=0.3, p=0.028) but not with IL-6. Platelet count was also associated with WC and waist-to-hip ratio (p<0.05). Haemoglobin and haematocrit were in consistent relationship with LDL-cholesterol (p<0.05). In conclusion, obesity was associated with higher WBC count and inflammatory parameters. There was also a positive relationship between WBC count and several inflammatory and metabolic risk factors in healthy women.
PMCID: PMC3702359  PMID: 23617205
Angiotensin Π; C-reactive protein; Interleukin 6; Obesity; White blood cell count
18.  Plasma total anti-oxidant capacity correlates inversely with the extent of acute appendicitis: a case control study 
The role of free oxygen radicals in inflammatory conditions is well known. Free radicals cause lipid peroxidation of cellular membranes resulting in cell death. The purpose of this study was to investigate the levels of total anti-oxidant status (TAS), as a marker of anti-oxidant defense system and malondialdehyde (MDA), as a marker of oxidative stress, in the plasma of patients with acute appendicitis.
Fifty-one adult patients with a median age of 31 years who underwent operations with a preoperative diagnosis of acute appendicitis were included in this prospective study. Blood samples for C-reactive protein (CRP), MDA and TAS were collected preoperatively. Groups were compared by using the Mann-Whitney U test.
There were 27 patients with acute phlagmenous appendicitis and 19 patients with advanced appendicitis (10 gangrenous and 9 perforated appendicitis), while 5 negative explorations were documented. No significant differences in WBC counts and MDA levels between groups were encountered. Plasma CRP was significantly higher in patients with perforated appendicitis, but not in the other groups. In advanced appendicitis group, TAS level was significantly lower than the other groups. On the other hand, plasma TAS level in acute phlagmenous appendicitis group was significantly higher.
A decrease in plasma total anti-oxidant capacity might be a predictor of the progression of inflammation to the perforation in acute appendicitis.
PMCID: PMC1475839  PMID: 16759345
19.  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
20.  Accuracy and Feasibility of Point-Of-Care White Blood Cell Count and C-Reactive Protein Measurements at the Pediatric Emergency Department 
PLoS ONE  2015;10(6):e0129920.
Several point-of-care (POC) tests are available for evaluation of febrile patients, but the data about their performance in acute care setting is sparse. We investigated the analytical accuracy and feasibility of POC tests for white blood cell (WBC) count and C-reactive protein (CRP) at the pediatric emergency department (ED).
In the first part of the study, HemoCue WBC and Afinion AS100 CRP POC analyzers were compared with laboratory’s routine WBC (Sysmex XE-2100) and CRP (Modular P) analyzers in the hospital central laboratory in 77 and 48 clinical blood samples, respectively. The POC tests were then adopted in use at the pediatric ED. In the second part of the study, we compared WBC and CRP levels measured by POC and routine methods during 171 ED patient visits by 168 febrile children and adolescents. Attending physicians performed POC tests in capillary fingerprick samples.
In parallel measurements in the laboratory both WBC and CRP POC analyzers showed good agreement with the reference methods. In febrile children at the emergency department (median age 2.4 years), physician performed POC determinations in capillary blood gave comparable results with those in venous blood analyzed in the laboratory. The mean difference between POC and reference test result was 1.1 E9/L (95% limits of agreement from -6.5 to 8.8 E9/L) for WBC and -1.2 mg/L (95% limits of agreement from -29.6 to 27.2 mg/L) for CRP.
POC tests are feasible and relatively accurate methods to assess CRP level and WBC count among febrile children at the ED.
PMCID: PMC4452774  PMID: 26034987
21.  Diagnosing Appendicitis: Evidence-Based Review of the Diagnostic Approach in 2014 
Acute appendicitis is the most common abdominal emergency requiring emergency surgery. However, the diagnosis is often challenging and the decision to operate, observe or further work-up a patient is often unclear. The utility of clinical scoring systems (namely the Alvarado score), laboratory markers, and the development of novel markers in the diagnosis of appendicitis remains controversial. This article presents an update on the diagnostic approach to appendicitis through an evidence-based review.
We performed a broad Medline search of radiological imaging, the Alvarado score, common laboratory markers, and novel markers in patients with suspected appendicitis.
Computed tomography (CT) is the most accurate mode of imaging for suspected cases of appendicitis, but the associated increase in radiation exposure is problematic. The Alvarado score is a clinical scoring system that is used to predict the likelihood of appendicitis based on signs, symptoms and laboratory data. It can help risk stratify patients with suspected appendicitis and potentially decrease the use of CT imaging in patients with certain Alvarado scores. White blood cell (WBC), C-reactive protein (CRP), granulocyte count and proportion of polymorphonuclear (PMN) cells are frequently elevated in patients with appendicitis, but are insufficient on their own as a diagnostic modality. When multiple markers are used in combination their diagnostic utility is greatly increased. Several novel markers have been proposed to aid in the diagnosis of appendicitis; however, while promising, most are only in the preliminary stages of being studied.
While CT is the most accurate mode of imaging in suspected appendicitis, the accompanying radiation is a concern. Ultrasound may help in the diagnosis while decreasing the need for CT in certain circumstances. The Alvarado Score has good diagnostic utility at specific cutoff points. Laboratory markers have very limited diagnostic utility on their own but show promise when used in combination. Further studies are warranted for laboratory markers in combination and to validate potential novel markers.
PMCID: PMC4251237  PMID: 25493136
22.  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
23.  C-Reactive Protein and White Blood Cell Count as Triage Test Between Urgent and Nonurgent Conditions in 2961 Patients With Acute Abdominal Pain 
Medicine  2015;94(9):e569.
The purpose of this article is to assess the diagnostic accuracy of C-reactive protein (CRP) and white blood cell (WBC) count to discriminate between urgent and nonurgent conditions in patients with acute abdominal pain at the emergency department, thereby guiding the selection of patients for immediate diagnostic imaging.
Data from 3 large published prospective cohort studies of patients with acute abdominal pain were combined in an individual patient data meta-analysis. CRP levels and WBC counts were compared between patients with urgent and nonurgent final diagnoses. Parameters of diagnostic accuracy were calculated for clinically applicable cutoff values of CRP levels and WBC count, and for combinations.
A total of 2961 patients were included of which 1352 patients (45.6%) had an urgent final diagnosis. The median WBC count and CRP levels were significantly higher in the urgent group than in the nonurgent group (12.8 ×109/L; interquartile range [IQR] 9.9–16) versus (9.3 ×109/L; IQR 7.2–12.1) and (46 mg/L; IQR 12–100 versus 10 mg/L; IQR 7–26) (P < 0.001).
The highest positive predictive value (PPV) (85.5%) and lowest false positives (14.5%) were reached when cutoff values of CRP level >50 mg/L and WBC count >15 ×109/L were combined; however, 85.3% of urgent cases was missed.
A high CRP level (>50 mg/L) combined with a high WBC count (>15 ×109/L) leads to the highest PPV. However, this applies only to a small subgroup of patients (8.7%). Overall, CRP levels and WBC count are insufficient markers to be used as a triage test in the selection for diagnostic imaging, even with a longer duration of complaints (>48 hours).
PMCID: PMC4553955  PMID: 25738473
24.  Ability of serum C-reactive protein and white blood cell cout in predicting acute schemic stroke. A short -term follow-up study 
Stroke is one of the leading causes of mortality and long-term morbidity. The aim of the present study was to determine the ability of baseline serum C-reactive protein (CRP) and white blood cell count (WBC) values in predicting the outcome of acute ischemic stroke (AIS).
This study consisted of patients with first AIS referred to Poursina Hospital, Rasht, Iran. Severity of stroke was determined according to the National Institute of Health (NIH) Stroke Scale at the time of admission. Serum CRP levels and WBC count were measured at the time of admission. All patients were followed-up for 90 days after discharge and the severity of stroke was assessed using modified Rankin Scale. Receiver operating characteristic curve analysis was used for calculating the most appropriate cutoff point of CRP and WBC count for differentiating patients with and without poor outcome at the end of the study period.
A total of 53 out of 102 patients (52%) had poor outcome. The most appropriate cutoff value for CRP in differentiating patients with and without poor outcome was 8.5mg/l (sensitivity: 73.1%, specificity: 69.4%) and for WBC the difference did not reach to a significant level. The cutoff points of CRP > 10.5 mg/ml yielded a predictive ability at sensitivity: 75%, specificity: 63.8% whereas predictive ability of WBC for mortality was at a borderline level.
These findings indicate that high levels of serum CRP in AIS at the time of admission is associated with poor prognosis. However, this study found no ability for WBC in predicting AIS outcome.
PMCID: PMC5062180  PMID: 27757207
C reactive protein; White blood cell count; Ischemic Stroke; Prognosis. Outcome
25.  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

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