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1.  Correlation of serum C-reactive protein, white blood count and neutrophil percentage with histopathology findings in acute appendicitis 
Background
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.
Results
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.
Conclusion
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.
doi:10.1186/1749-7922-7-27
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.
Background
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.
Methods
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.
Results
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.
Conclusion
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.
doi:10.1186/1471-2482-6-15
PMCID: PMC1712352  PMID: 17132173
3.  A Prospective Bicenter Study Investigating the Diagnostic Value of Procalcitonin in Patients with Acute Appendicitis 
Background
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.
Methods
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.
Results
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.
Conclusions
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.
doi:10.1159/000232939
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.
doi:10.7150/ijms.4733
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 
Objectives
To assess the accuracy of novel and traditional biomarkers in patients with suspected appendicitis as a function of duration of symptoms.
Methods
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.
Results
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.
Conclusions
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.
doi:10.1111/j.1553-2712.2011.01095.x
PMCID: PMC3117273  PMID: 21676053
6.  The diagnostic values of preoperative laboratory markers in children with complicated appendicitis 
Purpose
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.
Methods
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.
Results
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%.
Conclusion
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.
doi:10.4174/jkss.2012.83.4.237
PMCID: PMC3467390  PMID: 23091796
Appendicitis; Child; Leukocytes; C-reactive protein; Bilirubin
7.  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
8.  Sex based levels of C-reactive protein and white blood cell count in subjects with metabolic syndrome: Isfahan Healthy Heart Program 
Background:
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.
Results:
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.
Conclusion:
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.  Clinical value of total white blood cells and neutrophil counts in patients with suspected appendicitis: retrospective study 
Introduction
Acute appendicitis (AA) is common surgical problem associated with acute-phase reaction. Blood tests role in decision-making process is unclear. This retrospective study aimed to determine diagnostic value of preoperative evaluation of white blood cells (WBCs) and neutrophils and its value in predicting AA severity.
Methods
Medical records of 456 patients who underwent appendectomy during 4-years period were retrospectively reviewed. Patients were subdivided according to histological finding into: normal appendix (n = 29), uncomplicated inflamed appendix (n = 350), complicated appendicitis (n = 77). Diagnostic performances of WBCs and neutrophils were analyzed using receiver operating characteristic (ROC) curves.
Results
WBCs and neutrophils counts were higher in patients with inflamed and complicated appendix than normal appendix and in complicated than inflamed appendix. In patients, WBCs count 9.400 × 103/mL had sensitivity of 76.81%, specificity of 65.52%, positive predictive value (PPV) of 97.0%, negative predictive value (NPV) of 16.1%, positive likelihood ratio [LR(+)] of 2.23, negative LR(−) of 0.35. Neutrophil count 7.540 × 103/mL had sensitivity of 70.96%, specificity of 65.52%, PPV of 96.8%, NPV of 13.3%, LR(+) of 2.06, LR(−) of 0.44. Areas under ROC curve were 0.701, 0.680 for elevated WBCs and neutrophils count.
Conclusions
Clinicians should not rely on either elevated WBCs or neutrophils count as appendicitis indicator as clinical data are superior in decision-making appendectomy.
doi:10.1186/1749-7922-7-32
PMCID: PMC3502286  PMID: 23031349
Acute appendicitis; Diagnosis; White blood cells; Histological diagnosis; Neutrophil count; Receiver operating characteristic curves
10.  Leukocyte Count versus C-Reactive Protein Levels in Obese Portuguese Patients Aged 6-12 Years Old 
Objectives:
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.
Results:
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.
Conclusions:
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.
doi:10.2174/1874091X01004010072
PMCID: PMC2911598  PMID: 20676221
Leukocytes; C-reactive protein; children obesity.
11.  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
12.  Diagnostic accuracy of white cell count and C-reactive protein for assessing the severity of paediatric appendicitis 
JRSM Short Reports  2011;2(7):59.
Objectives
Simple investigations like white cell count (WCC) and C-reactive protein (CRP) may help to improve the accuracy of diagnosis in paediatric appendicitis. We evaluated the diagnostic accuracy of WCC and CRP for the severity of acute appendicitis in children.
Design
Cross-sectional study.
Setting
This study was conducted on all children who underwent open appendectomy from January 2007 to December 2008 at a District General Hospital. Data regarding demographics, WCC, CRP, histology and postoperative complications were analysed.
Participants
All children who underwent open appendectomy during the study period.
Main outcome measures
Diagnostic accuracy of WCC and CRP for simple acute appendicitis and a perforated appendix.
Results
Out of 204 patients, 112 (54.9%) were girls. At surgery, appendix was grossly inflamed in 175 of which 32 had perforation. Histology revealed simple acute appendicitis in 135 (66.2%) and gangrenous appendicitis in 32 (15.7%). The rest were normal. The duration of symptoms, temperature, length of stay, WCC and CRP were significantly worse in the perforated group (P value <0.05). Postoperative complications included wound infection (n = 18), pelvic collection (n = 5) and intestinal obstruction (n = 6); and were more common among patients with a perforated appendix (P value <0.05). WCC had a higher diagnostic accuracy and higher sensitivity than CRP in diagnosing simple acute appendicitis. The combined sensitivity of WCC and CRP increased to 95% and 100% for the diagnosis of simple acute appendicitis and a perforated appendix, respectively.
Conclusion
Accuracy of WCC is higher than CRP for diagnosing simple acute appendicitis. The combined sensitivity of WCC and CRP increases for simple acute appendicitis as well as a perforated appendix.
doi:10.1258/shorts.2011.011025
PMCID: PMC3147235  PMID: 21847441
13.  Plasma total anti-oxidant capacity correlates inversely with the extent of acute appendicitis: a case control study 
Background
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.
Methods
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.
Results
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.
Conclusion
A decrease in plasma total anti-oxidant capacity might be a predictor of the progression of inflammation to the perforation in acute appendicitis.
doi:10.1186/1749-7922-1-6
PMCID: PMC1475839  PMID: 16759345
14.  High mobility group box protein-1 (HMGB-1) as a new diagnostic marker in patients with acute appendicitis 
Background
The aim of this prospective study was therefore to evaluate the diagnostic value of preoperative serum High Mobility Group Box Protein-1 (HMGB-1) levels in patients with Acute Appendicitis (AA) who show normal white blood cell count (WBC) counts.
Method
Our study was carried out from October 2010 through November 2010 and included 20 healthy control group participants and 60 patients who presented at the emergency department of Erzurum Training and Research Hospital in Turkey with acute abdominal pain complaints, who were pathologically diagnosed with AA after laparotomy, and who agreed to participate in the study.
Results
Of the 60 patients who underwent appendectomies, 36 were male and 24 were female, and of the healthy group, 12 were male and 8 female. The age averages of the patients in Groups 1, 2 and 3 were, respectively, 31.3+15.4, 34.0+16.3 and 31.0+13.1 years. The WBC averages of Groups 1, 2 and 3 were, respectively, 7.41+2.02 (x109/L), 15.71+2.85 (x109/L) and 8.51+1.84 (x109/L). The HMGB-1 levels for Groups 1 (healthy persons), 2 (AA patients with high WBC counts ) and 3 (AA patients with normal WBC counts) were, respectively, 21.71 ± 11.36, 37.28+13.37 and 36.5 ± 17.73 ng/ml. The average HMGB-1 level of the patients with AA was 36.92 ± 15.43 ng/ml while the average HMGB-1 value of the healthy group was 21.71 ± 11.36 ng/ml.
Conclusion
The significantly higher levels of HMGB-1 in AA patients compared to healthy persons infer that HMGB-1 might be useful in the diagnosis of AA. Use of HMGB-1, especially in patients with normal WBC counts, will reduce the number of unnecessary explorations.
doi:10.1186/1757-7241-19-27
PMCID: PMC3094252  PMID: 21507210
15.  Bedside Ultrasonography as an Adjunct to Routine Evaluation of Acute Appendicitis in the Emergency Department 
Introduction
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.
Methods
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.
Results
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.
Conclusion
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.
doi:10.5811/westjem.2014.9.21491
PMCID: PMC4251223  PMID: 25493122
16.  The diagnostic value of white cell count, C-reactive protein and bilirubin in acute appendicitis and its complications 
Introduction
Inflammatory markers such as white cell count (WCC) and C-reactive protein (CRP) and, more recently, bilirubin have been used as adjuncts in the diagnosis of appendicitis. The aim of this study was to determine the diagnostic accuracy of the above markers in acute and perforated appendicitis as well as their value in excluding the condition.
Methods
A retrospective analysis of 1,169 appendicectomies was performed. Patients were grouped according to histological examination of appendicectomy specimens (normal appendix = NA, acute appendicitis = AA, perforated appendicitis = PA) and preoperative laboratory test results were correlated. Receiver operating characteristic (ROC) curve area analysis (area under the curve [AUC]) was performed to examine diagnostic accuracy.
Results
ROC analysis of all laboratory variables showed that no independent variable was diagnostic for AA. Good diagnostic accuracy was seen for AA when all variables were combined (WCC/CRP/bilirubin combined AUC: 0.8173). In PA, the median CRP level was significantly higher than that of AA (158mg/l vs 30mg, p<0.0001). CRP also showed the highest sensitivity (100%) and negative predictive value (100%) for PA. CRP had the highest diagnostic accuracy in PA (AUC: 0.9322) and this was increased when it was combined with WCC (AUC: 0.9388). Bilirubin added no diagnostic value in PA. Normal levels of WCC, CRP and bilirubin could not rule out appendicitis.
Conclusions
CRP provides the highest diagnostic accuracy for PA. Bilirubin did not provide any discriminatory value for AA and its complications. Normal inflammatory markers cannot exclude appendicitis, which remains a clinical diagnosis.
doi:10.1308/003588413X13511609957371
PMCID: PMC4165248  PMID: 23827295
White cell count; C-reactive protein; Bilirubin; Appendicitis; Perforated appendicitis; Normal appendix
17.  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.
Background
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.
Methods
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.
Results
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.
Conclusion
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.
doi:10.1186/1465-9921-10-65
PMCID: PMC2714042  PMID: 19594893
18.  Diagnosing Appendicitis: Evidence-Based Review of the Diagnostic Approach in 2014 
Introduction
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.
Methods
We performed a broad Medline search of radiological imaging, the Alvarado score, common laboratory markers, and novel markers in patients with suspected appendicitis.
Results
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.
Conclusion
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.
doi:10.5811/westjem.2014.9.21568
PMCID: PMC4251237  PMID: 25493136
19.  Effects of fluoxetine and escitalopram on C-reactive protein in patients of depression 
Objective:
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.
Results:
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).
Conclusion:
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.
doi:10.4103/0976-500X.77091
PMCID: PMC3117562  PMID: 21701640
Anti-inflammatory activity; C-reactive protein; erythrocyte sedimentation rate; Hamilton rating scale for depression; white blood cell count
20.  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.
Purpose
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).
Methods
Prospective observational study, applying receiver operating characteristics curve analysis to compare the sensitivity and specificity of the tested variables.
Results
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.
Conclusions
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.
doi:10.1007/s12262-009-0074-8
PMCID: PMC3452791  PMID: 23133170
Acute appendicitis; Hyperbilirubinaemia; Perforated appendicitis; Hepatic dysfunction in sepsis
21.  Effects of Smoking Intensity and Cessation on Inflammatory Markers in a Large Cohort of Active Smokers 
American heart journal  2010;160(3):458-463.
Background
Cigarette smoking has been associated with increases in C-reactive protein (CRP) and leukocyte counts (WBC); however, the effects of smoking intensity and smoking cessation on inflammatory markers have not been evaluated prospectively in a large, modern cohort of current smokers.
Methods
WBC count and high-sensitivity CRP were measured in current smokers enrolled in a randomized, prospective clinical trial of five smoking cessation pharmacotherapies. Smoking intensity parameters included: cigarettes/day, pack-years, Fagerstrom Test of Nicotine Dependence (FTND) score, and carbon monoxide (CO) levels. CRP also was measured after 1 year with assessment of abstinence status.
Results
The 1,504 current smokers (58% female) were mean (standard deviation): 44.7 (11.1) years old, smoked 21.4 (8.9) cigarettes/day and had a smoking burden of 29.4 (20.4) pack-years. Log (CRP) was not associated with any marker of smoking intensity, except for a weak correlation with pack-years (r=0.05, p=0.047). In contrast, statistically significant correlations were observed between all 4 markers of smoking intensity and WBC count (all p≤0.011). In multivariable models, waist circumference (p<0.001) and triglycerides (p<0.05), but no markers of smoking intensity, were associated with log(CRP). However, pack-years (p=0.002), cigarettes/day (p=0.013), CO (p<0.001), and FTND (p<0.001) were independently associated with WBC count. After 1 year, log(CRP) (p=0.296) and changes in log(CRP) (p=0.455) did not differ between abstainers and continuing smokers.
Conclusions
Smoking intensity is associated with increased WBC count, but not CRP levels. Smoking cessation does not reduce CRP. The relationship between CRP and smoking intensity may be masked by CRP’s stronger relationship with adiposity.
doi:10.1016/j.ahj.2010.06.006
PMCID: PMC2937015  PMID: 20826253
C-reactive protein; Inflammation; Leukocytes; Risk factors; Smoking
22.  Diagnostic value of urine sTREM-1 for sepsis and relevant acute kidney injuries: a prospective study 
Critical Care  2011;15(5):R250.
Introduction
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).
Methods
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.
Results
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.
Conclusions
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
ClinicalTrial.gov identifier NCT01333657
doi:10.1186/cc10508
PMCID: PMC3334801  PMID: 22023777
urine; soluble triggering receptor expressed on myeloid cells-1(sTREM-1); sepsis; severity; prognosis; acute kidney injury (AKI); sensitivity; specificity
23.  Hyponatremia Is a Specific Marker of Perforation in Sigmoid Diverticulitis or Appendicitis in Patients Older Than 50 Years 
Introduction. This study aimed to evaluate symptoms and signs, inflammation markers, electrolytes, and ECG signs of increased vagal tone as markers of colon perforation in sigmoid diverticulitis or appendicitis. Methods. The records of all patients older than fifty years (only these had routine ECG done) admitted to our emergency station between January 2008 and December 2010 with sigmoid diverticulitis (n = 198, diagnosed by computer tomography) or appendicitis (n = 84, diagnosed intraoperatively) were retrospectively evaluated. Pain score, heart rate, blood pressure, and body temperature were assessed at presentation. Before starting infusion therapy, blood was taken to do a blood count and to analyze CRP, the electrolytes, and creatinine levels. Then an ECG was done. Results. The perforation rate was 37% (n = 103). Body temperature, heart rate, sodium, CRP, and leukocytes correlated significantly with infectious colon perforation. However, only body temperature, CRP, and sodium correlated significantly with infectious colon perforation if compared by logistic regression analysis. The prevalence of hyponatremia (sodium level <136 mmol/L) was 29% in the group with infectious colon perforation and 16% in the group without (P = 0.013). Conclusion. Hyponatremia is a specific marker of infectious colon perforation in patients older than fifty years.
doi:10.1155/2013/462891
PMCID: PMC3586515  PMID: 23476637
24.  Acute phase proteins and white blood cell levels for prediction of infectious complications in status epilepticus 
Critical Care  2011;15(6):R274.
Introduction
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.
Methods
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.
Results
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.
Conclusions
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.
doi:10.1186/cc10555
PMCID: PMC3388641  PMID: 22099124
25.  Risk factors of converting to laparotomy in laparoscopic appendectomy for acute appendicitis 
Purpose
Laparoscopic appendectomy (LA) for acute appendicitis has several advantages over open appendectomy (OA). In cases of complicated appendicitis, LA is converted to OA at a constant rate, though converting appendectomy (CA) has several disadvantages. We retrospectively determined preoperative risk factors for failure of LA and subsequent conversion to OA.
Methods
Consecutive cases of preoperative computed tomography (CT) and attempted LA were retrieved from our hospital database and grouped by procedure (LA versus CA). Patients with negative appendectomies (n = 28), opened appendectomy (n = 210), delayed interval appendectomy (n = 3), or who were <14 years of age were excluded.
Results
Average patient age, preoperative C-reactive protein (CRP) level, and diffuse peritonitis were significantly different between the groups. CT inflammation and occurrence of complicated appendicitis were significantly higher in CA than LA. Conversion to OA was mostly because of dense adhesions, diffuse peritonitis, and difficulties in excision of the appendix due to perforation or severe inflammation from surgical point of view. Postoperative complications were significantly lower in LA than CA, although the rate of intraoperative abscess was not different.
Conclusion
Most patients with acute appendicitis can be successfully treated with LA. We identified the following significant risk factors of CA: CT inflammation grade 4 or 5; complicated appendicitis; higher preoperative CRP level; and diffuse peritonitis.
doi:10.2147/CEG.S41571
PMCID: PMC3706257  PMID: 23869174
laparotomy; laparoscopic appendectomy; acute appendicitis

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