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 Table of Contents  
ORIGINAL ARTICLE
Year : 2017  |  Volume : 4  |  Issue : 3  |  Page : 164-172

Diagnostic value of serum procalcitonin compared with c-reactive protein for postoperative wound infection of surgically treated trochanteric fracture


1 Department of Anesthesia and Surgical Intensive Care, Faculty of Medicine, Alexandria University, Alexandria, Egypt
2 Department of Orthopedic Surgery, Faculty of Medicine, Alexandria University, Alexandria, Egypt
3 Department of Clinical Pathology, Faculty of Medicine, Alexandria University, Alexandria, Egypt

Date of Submission09-Jan-2017
Date of Acceptance17-Mar-2017
Date of Web Publication5-Jul-2017

Correspondence Address:
Rabab S Saleh
33 Bahha El-Din El-Ghatwary Street, Smouha, Alexandria, 21131
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/roaic.roaic_3_17

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  Abstract 

Introduction
Because of the high prevalence of postoperative infection and its impact on mortality and morbidity in patients undergoing orthopedic and nonorthopedic procedures, a reliable marker for the diagnosis of infection would be of great importance. There has been an increasing use of procalcitonin (PCT) measurements in identifying systemic bacterial infections. This study was carried out to investigate the value of serum PCT level versus the C-reactive protein (CRP) in the diagnosis of postoperative inflammatory response with or without sepsis after trochanteric fracture surgery in the elderly.
Patients and methods
The study was carried out in El-Hadara University Hospital on 60 American Society of Anesthesiologists physical status I and II patients aged above 50 years scheduled for peritrochanteric hip fracture surgery [dynamic hip screw (DHS), dynamic condylar screw, gamma nail, cemented bipolar, cemented Thompson, and Austin Moore]. Blood samples for PCT, CRP, and white blood cells (WBCs) were drawn on day 0 (preoperatively) and days 1, 3, 5, and 7 postoperatively. The samples were collected at the same hour in the morning for each patient.
Results
The age ranged from 65.0 to 90.0 years with a mean of 77.0±8.66 years. There were 15 (25.0%) male and 45 (75.0%) female patients. Ten (16.7%) patients underwent cemented bipolar operation, 28 (46.7%) patients were treated with DHS, and four (6.7%) were treated with cemented Thompson, and 18 (30.0%) were treated with gamma nail. In the studied group, 15 (25%) patients had proven local wound sepsis on culture and sensitivity performed on day 3, and 45 (75%) patients were not infected. There was a significantly higher difference in the infected ones than in the noninfected ones as regards WBCs, PCT, and CRP changes. In the infected group seven (46.7%) patients were treated with DHS, four (26.7%) with cemented bipolar, two (13.3%) with cemented Thompson, and two (13.3%) were treated with gamma nail.
Conclusion
We could conclude that PCT is an earlier and more specific marker of wound infections compared with CRP or WBC count after trochanteric fractures in the elderly.

Keywords: c-reactive protein, postoperative infection, procalcitonin, trochanteric fracture


How to cite this article:
Saleh RS, Youssef AA, Demerdash HM. Diagnostic value of serum procalcitonin compared with c-reactive protein for postoperative wound infection of surgically treated trochanteric fracture. Res Opin Anesth Intensive Care 2017;4:164-72

How to cite this URL:
Saleh RS, Youssef AA, Demerdash HM. Diagnostic value of serum procalcitonin compared with c-reactive protein for postoperative wound infection of surgically treated trochanteric fracture. Res Opin Anesth Intensive Care [serial online] 2017 [cited 2017 Sep 20];4:164-72. Available from: http://www.roaic.eg.net/text.asp?2017/4/3/164/209667


  Introduction Top


The incidence of intertrochanteric fractures has been increasing significantly due to increasing life expectancy in the elderly population; it has been predicted that the total number of hip fractures will reach 2.6 million by 2025 and 4.5 million by 2050 [1]. Moreover, mortality after proximal femur fracture is increasing with a 1-year mortality rate of 14–36% [2],[3]. Surgical treatment represents the optimal strategy for managing intertrochanteric fractures, which allows early mobilization of the patient, reducing the risk for postoperative complications [4]. International recommendations suggest that patients with hip fractures undergo surgical treatment 24–48 h after diagnosis [5].

For elderly patients, who sometimes have cardiac, pulmonary, and psychiatric comorbidities, an immediate surgical procedure may initially carry too high a risk for substantial morbidity and mortality. Thus, a perioperative observational period was developed as a standard procedure for these patients. Monitoring in the postoperative period is also a part of current guidelines [6],[7]. The time needed to perform a complete medical evaluation and manage comorbidities in elderly patients with trochanteric fractures can delay surgery for at least 12–24 h [8],[9].

Postoperative infection is one of the most serious complications because of its impact on mortality and morbidity in patients undergoing orthopedic procedures. Its correct diagnosis is crucial for adequate surgical treatment. Moreover, it would allow the initiation of empirical antimicrobial therapy rapidly in patients with an infection and avoid unnecessary antimicrobial usage in patients without an infection, thereby saving healthcare costs and preventing the development of antimicrobial resistance [10].

In the early postoperative days, its detection is particularly difficult, and currently it can be established on the basis of several concurring parameters such as clinical presentation, laboratory markers, imaging study, and microbiologic testing. C-reactive protein (CRP) and, more recently, procalcitonin (PCT) are two laboratory tests of considerable usefulness in clinical practice [11].

CRP is the most available and widely used. CRP is a positive acute-phase protein whose plasma concentration increases rapidly up to 1000-fold from around 1 mg/l, during inflammatory disorders. CRP expression and its induction in the hepatocytes are mainly regulated transcriptionally by interleukin 6 through the activation of several transcription factors. CRP is used to monitor the postoperative course in surgical trauma following orthopedic implants and to detect prosthetic infection [12],[13].

PCT is a marker of infection; it is produced by the same cells in which calcitonin is synthesized. The short half-life (25–30 h in plasma) of PCT, coupled with its virtual absence in health and specificity for bacterial infections, gives it a clear advantage over the other markers when differentiating bacterial infection from noninfective causes of inflammation or viral infection [14],[15],[16]. Clinical studies in humans have shown that the highest serum PCT values occur in patients with sepsis [11],[17].

The aim of this study was to investigate the value of serum PCT level versus the CRP in the diagnosis of postoperative inflammatory response with or without sepsis after trochanteric fracture surgery in the elderly.


  Patients and methods Top


This study was carried out in El-Hadara University Hospital on 60 ASA physical status I and II patients aged above 50 years, of both sexes, scheduled for peritrochanteric hip fracture surgery [dynamic hip screw (DHS), dynamic condylar screw, gamma nail, cemented bipolar, cemented Thompson, and Austin Moore] with a duration of 1–2 h under spinal anesthesia.

Exclusion criteria

Patients fulfilling any of the following criteria were excluded from the study: age under 50 years, chronic organ failure, malignancy at terminal stage, pathological fractures, previous frequent blood transfusion, multiple trauma or fractures in multiple locations [due to triggering of systemic inflammatory response syndrome (SIRS)], surgery within the last 3 months, chronic rheumatoid disease, and contraindications for spinal anesthesia.

After approval of the medical ethical committee and obtaining informed written consent from all patients included in this study, they were assessed thoroughly by means of detailed medical and surgical history taking, full clinical examination, and routine laboratory investigations (e.g. complete blood count, prothrombin time, partial prothrombin time, international normalized ratio, serum urea and creatinine, serum glutamic oxaloacetic transaminase, and serum glutamic pyruvic transferase). Thereafter, serum samples for PCT, CRP, and white blood cell (WBC) count were drawn on day 0 preoperatively.

Anesthesia

Each patient was attached to a multichannels monitor (Trakmon Kontron Limited, Chichester, UK) to display the following: continuous ECG monitoring, heart rate monitoring, noninvasive blood pressure monitoring, and arterial oxygen saturation. An 18 G cannula was inserted and venous access was secured in all patients. Intravenous fluids, lactated Ringer’s solution, or normal saline was infused at a rate of 10 ml/kg over 30 min before spinal anesthesia. Subarachnoid anesthesia was instituted at either the L3/L4 or L4/L5 interspaces by injecting hyperbaric bupivacaine (5 mg/ml) 15 mg using a 22 G Quincke spinal needle. Before starting surgery, sensory block was assessed with a pinprick test at 5 min intervals until the desired block level was achieved. Supplemental oxygen (5 l/min) was delivered through facemask during the operation and the patient was placed in either supine or lateral position according to the procedure.

Blood sampling

Blood samples for PCT, CRP, and WBCs were drawn on day 0 (preoperatively), and days 1, 3, 5, and 7 postoperatively. The samples were collected at the same hour in the morning for each patient. Blood samples for CRP and PCT were collected in dry tubes and centrifuged at 3000 rpm for 10 min, and then the serum was separated. Serum samples were stored at −20°C until analysis. For both samples the enzyme-linked immunosorbent assay technique was applied using the ELISA reader MR‘-96 A Mindray (Shenzhen, China: Mindray Bio-Medical Electronics Co., Ltd.).

Surgical site infection was determined by the presence of superficial or deep incision infection and by culturing of septic wound specimen. Data were fed to the computer using IBM SPSS software package for Windows, version 20.0 (Armonk, NY: IBM Corp). Significance test results are quoted as two-tailed probabilities. Significance of the obtained results was judged at the 5% level.


  Results Top


The age ranged from 65.0 to 90.0 years with a mean of 77.0±8.66 years. There were 15 (25.0%) male and 45 (75.0%) female patients. Ten patients underwent cemented bipolar operation (16.7%), 28 (46.7%) patients were treated with DHS insertion, four (6.7%) patients were treated with cemented Thompson insertion, and 18 (30.0%) patients were treated with gamma nail. The duration of surgery ranged from 90 to 150 min with a mean of 120±19.13 min. In the studied group, 15 (25%) patients had proven local wound sepsis on culture and sensitivity performed on day 3, and 45 (75%) patients were not infected ([Table 1]).
Table 1 Distribution of studied patients according to different parameters

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White blood cells change in the studied cases

On comparing the infected patients with the noninfected patients, there was a significantly higher difference in the infected ones than in the noninfected ones (P≤0.001) on day 1 (P0.001), day 3 (P0.001), day 5 (P0.001), and day 7 (P0.001) ([Table 2] and [Figure 1]).
Table 2 Comparison between infected and noninfected cases in each period according to white blood cells, procalcitonin, and C-reactive protein

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Figure 1 Comparison between infected and noninfected cases in each period according to white blood cells (WBCs).

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Procalcitonin changes in the studied cases

There was a significantly higher difference in the infected cases than in the noninfected cases (P0.001) on day 0 (P0.001), day 1 (P0.001), day 3 (P0.001), day 5 (P0.001), and on day 7 (P0.001) ([Table 2] and [Figure 2]).
Figure 2 Comparison between infected and noninfected cases in each period according to procalcitonin (PCT).

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C-reactive protein changes in the study group

There was a significantly higher difference in the infected cases than in the noninfected cases (P0.005) on day 3 (P0.001), on day 5 (P0.001), and on day 7 (P0.000). However, on day 0 and day 1 there was no difference (P=0.369 and 0.300, respectively) ([Table 2] and [Figure 3]).
Figure 3 Comparison between infected and noninfected cases in each period according to C-reactive protein (CRP).

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Comparison between the patients according to the comorbid disease

In the infected cases, nine (60.0%) patients had controlled diabetes mellitus (DM) and hypertension. Six (40.0%) patients were medically free.

In the noninfected cases, 15 (33.3%) patients had controlled DM and hypertension. Fifteen (33.3%) patients had ischemic heart disease. Nine (20.0%) patients had controlled DM only, and six (13.3%) patients were medically free ([Table 3]).
Table 3 Comparison between the studied cases according to comorbid disease

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Comparison of studied patients according to the type of operation

In the infected group seven (46.7%) patients were treated with DHS, four (26.7%) with cemented bipolar, two (13.3%) with cemented Thompson, and two (13.3%) were treated with gamma nail ([Table 4]).
Table 4 Comparison between the studied groups according to operation

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Receiver operating characteristic curve during the study period for white blood cells, procalcitonin, and C-reactive protein

On day 0, the area under the curve (AUC) for WBCs was 0.693 with a P value of 0.026, whereas for PCT it was 0.733 with a P value of 0.007. However, for CRP it was 0.580 with a P value of 0.357. Therefore, both WBCs and PCT were significant ([Figure 4] and [Table 6]).
Figure 4 Receiver operating characteristic curve for WBCs, PCT, and CRP on day 0 in noninfected and infected cases. AUC, area under the curve; CRP, C-reactive protein; PCT, procalcitonin; WBC, white blood cell. *Statistically significant at P ≤ 0.05.

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By taking the cutoff value for WBCs of 14.0 K/ml, PCT of 187.5 pg/ml, and CRP of 18.5 mg/ml, the sensitivity, the specificity, the negative predictive value (NPV), and accuracy of WBCs, PCT, CRP on day 0 were 0, 100, 75, and 75%, respectively ([Table 5]). This was of no benefit.
Table 5 Agreement (sensitivity, specificity, and accuracy) for white blood cells, procalcitonin, and C-reactive protein on day 0 in noninfected and infected cases

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Table 6 Area under the curve and P value for white blood cells, procalcitonin, and C-reactive protein in noninfected and infected cases

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On day 1, the AUC for WBCs was 0.793 with a P value of 0.001, whereas for PCT it was 0.880 with P value less than 0.001. However, for CRP it was 0.393 with a P value of 0.219; therefore, both WBCs and PCT were significant ([Figure 5] and [Table 6]).
Figure 5 Receiver operating characteristic curve for WBCs, PCT, and CRP on day 1 in noninfected and infected cases. AUC, area under the curve; CRP, C-reactive protein; PCT, procalcitonin; WBC, white blood cell. *Statistically significant at P ≤ 0.05.

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The sensitivity, specificity, positive predictive value (PPV), NPV, and accuracy of WBCs were 40, 86.67, 50, 81, and 75%, respectively. However, those for PCT were 50, 100, 100, 64.29, and 73.68%, respectively. Moreover, those for CRP were 40, 40, 18.18, 66.67, and 40%, respectively, indicating that PCT had the highest sensitivity, specificity, and PPV ([Table 7]).
Table 7 Agreement (sensitivity, specificity, and accuracy) for white blood cells, procalcitonin, and C-reactive protein on day 1 in noninfected and infected cases

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On day 3, the AUC for WBCs was 1.000 with P value less than or equal to 0.001, for PCT it was 1.000 with P value less than or equal to 0.001, and for CRP it was 0.907 with P value less than 0.001. Therefore, they were all significant ([Figure 6] and [Table 6]).
Figure 6 Receiver operating characteristic curve for WBCs, PCT, and CRP on day 3 in noninfected and infected cases. AUC, area under the curve; CRP, C-reactive protein; PCT, procalcitonin; WBC, white blood cell. *Statistically significant at P ≤ 0.05.

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The sensitivity, specificity, PPV, NPV, and accuracy of WBCs and PCT were all 100%, whereas those for CRP were 100, 80, 62.5, 100, and 85%, respectively. Therefore, PCT and WBCs were better diagnostic markers ([Table 8]).
Table 8 Agreement (sensitivity, specificity, and accuracy) for white blood cells, procalcitonin, and C-reactive protein on day 3 in noninfected and infected cases

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On day 5, the AUC for all WBCs for PCT and CRP was 1.000 with P value less than or equal to 0.001; therefore, they were all significant ([Figure 7] and [Table 6]).
Figure 7 Receiver operating characteristic curve for WBCs, PCT, and CRP on day 5 in noninfected and infected cases showing that the three parameters have the same AUC. AUC, area under the curve; CRP, C-reactive protein; PCT, procalcitonin; WBC, white blood cell *Statistically significant at P ≤ 0.05.

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The sensitivity, specificity, PPV, NPV, and accuracy of all PCT, WBCs, and CRP were all 100%. This was of no benefit ([Table 9]).
Table 9 Agreement (sensitivity, specificity, and accuracy) for white blood cells, procalcitonin, and C-reactive protein on day 5 in noninfected and infected cases

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On day 7, the AUC for WBCs was 0.960 with P value less than 0.001, for PCT it was 1.000 with P value less than or equal to 0.001, and for CRP it was 0.867 with P value less than 0.001. Therefore, they were all significant ([Figure 8] and [Table 6]).
Figure 8 Receiver operating characteristic curve for WBCs, PCT, and CRP on day 7 in noninfected and infected cases. AUC, area under the curve; CRP, C-reactive protein; PCT, procalcitonin; WBC, white blood cell. *Statistically significant at P ≤ 0.05.

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The sensitivity, specificity, PPV, NPV, and the accuracy of WBCs and CRP were 40, 100, 100, 83.33, and 85%, respectively, whereas those for PCT were all 100%, indicating that PCT is a better prognostic marker ([Table 10]).
Table 10 Agreement (sensitivity, specificity, and accuracy) for white blood cells, procalcitonin, and C-reactive protein on day 7 in noninfected and infected cases

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  Discussion Top


Postoperative infection and its impact on mortality and morbidity in patients undergoing orthopedic and nonorthopedic procedures, needs a reliable marker for the diagnosis of infection. It would allow the initiation of empirical antimicrobial therapy rapidly in patients with an infection avoiding the complications of the delay in treating infected cases and also avoid unnecessary antimicrobial usage in patients without an infection, thereby saving healthcare costs and preventing the development of antimicrobial resistance [10].

In the present study, WBCs were statistically significant in the infected cases than in the noninfected cases on days 0, 1, 3, 5, and 7. As regards PCT, there was a significantly higher difference in the infected cases than in the noninfected cases on all days. As for CRP, there was a significantly higher difference in the infected cases than in the noninfected cases on days 3, 5, and 7.

Our results are, in fact, comparable to various studies that have demonstrated that serum PCT is a helpful diagnostic marker supporting clinical and microbiological findings for more reliable differentiation of infectious from noninfectious causes of fever after orthopedic surgery.

Hunziker et al. [10] evaluated 103 consecutive patients with new onset of fever within 10 days after orthopedic surgery. WBCs, CRP, and PCT were assessed on days 0, 1, and 3. Infection was diagnosed in 45 of 103 patients and involved the respiratory tract (18 patients), urinary tract (18 patients), joints (four patients), surgical site (two patients), bloodstream (two patients), and soft tissues (one patient). Unlike CRP levels and WBC counts, PCT values were significantly higher in patients with infection compared with patients without infection on days 1 and 3. Receiver operating characteristics curve demonstrated that PCT had the highest diagnostic accuracy.

Yasmin et al. [18] concluded that PCT may prove to be a useful parameter to identify early postoperative systemic infective complications after fracture surgery. They evaluated 21 patients who underwent surgery for peritrochanteric hip fractures. In contrast to CRP levels, which were above normal level in all patients, PCT levels were higher than the normal level only in patients who developed complications. The sensitivity and specificity of PCT to determine systemic complications were 100 and 100% on the first day, and 100 and 50% on the second day, respectively.

Castelli et al. [19] investigated the diagnostic value of PCT and CRP in septic complications after major trauma.

They concluded that elevation of PCT signifies possible septic complications during SIRS after major trauma. In addition, high PCT concentration at admission after trauma in ICU patients indicates an increased risk for septic complications.

Ahmadinejad et al. [20] studied 120 patients with positive SIRS admitted in the emergency department of a university hospital.

The serum PCT levels were compared between the two groups. PCT had a sensitivity of 88.7%, a specificity of 77.6%, a PPV of 85.1%, and a NPV of 82.6%. Serum level of PCT in the infectious group was significantly higher than that in the noninfectious group. PCT level was a predictor of mortality in patients with infectious SIRS.

Hochreiter et al. [21] found that monitoring of PCT is a helpful tool for guiding antibiotic treatment in surgical intensive care patients. Simon et al. [11] performed a meta-analysis to evaluate the accuracy of PCT and CRP levels for the diagnosis of bacterial infection. PCT level was more sensitive and more specific compared with CRP level for differentiating bacterial from noninfective causes of inflammation.

Piper et al. [22] concluded that CRP and ESR had poor sensitivity for the diagnosis of prosthetic implant infection. They analyzed preoperative CRP and ESR in 636 participants who underwent knee (n=297), hip (n=221), or shoulder (n=64) arthroplasty, or spine implant (n=54) removal. CRP and erythrocyte sedimentation rate values were higher in knee arthroplasty and spine implant patients than in hip arthroplasty patients with infection, and showed the lowest sensitivity for diagnosis of shoulder arthroplasty infection.

However, many studies found results that contradict our study as they proved that PCT is not a better marker of infection compared with CRP.

Ugarte et al. [23] studied 111 infected and 79 noninfected patients in a prospective, observational study in the Medicosurgical Department of Intensive Care.

There was no significant correlation between the maximum PCT and CRP concentrations in the infected and noninfected groups. This may be due to the discrepancy in the definition of day 0 in this study, as day 0 in the noninfected patients was the day of admission, whereas in the infected ones it was the day when the patients became infected and the antibiotic was started. The WBCs was elevated in both groups with no significant difference between the two, indicating that the WBCs may reflect the stress response to the inflammatory condition but it is not specific for infection.

Chan et al. [24] proved that PCT is not a better marker of bacterial infection compared with CRP for adult emergency department patients, but it is a useful marker of severity of infection. Compared with CRP, PCT had a comparable sensitivity, a lower specificity, and a lower area under the receiver operating characteristic curve. This may be attributed to the use of single PCT level only on admission to the emergency department, and hence the correlation with the outcome was suboptimal.

Kang et al. [25] performed a prospective study on 348 consecutive cases involving patients who underwent spinal surgery under general anesthesia. As a predictor for early wound infection, the sensitivity, specificity, PPV, and NPV for abnormal CRP responses were calculated as 100, 96.8, 31.3, and 100%, respectively. Therefore, CRP screening is a simple and reliable test for the detection of early infectious complications after spinal surgery.

Povoa et al. [26] undertook a prospective observational cohort study on the intensive care patients; they showed a significant difference between infected and noninfected patients. CRP was a good marker of infection prediction.

From the above discussion, most of the studies that compared the value of PCT and CRP for the diagnosis of infection after major orthopedic surgeries proved the preference of PCT being more sensitive and specific. However, many studies showed that both PCT and CRP can be a good marker for infection prediction, and hence we recommend systematic review and meta-analysis to analyze these controversial issues on the use of PCT compared with CRP.


  Conclusion Top


We could conclude that PCT is an earlier and more specific marker of wound infections compared with CRP or WBC count after trochanteric fractures in the elderly. The rise in PCT is faster compared with CRP, in response to infection, and also decreases faster as infection subsides. This rise in PCT is sensitive and specific on the 1st, 3rd, 5th, and 7th postoperative days. The kinetic characteristic allows anticipation of a diagnosis of sepsis 24–48 h before the CRP level would, and even before the results of cultures.

Acknowledgements

Rabab S. Saleh participated in the study design, conduct of the study, data collection, data analysis, and manuscript preparation; Amin A. Youssef participated in the study design, conduct of the study, data collection, data analysis, and manuscript preparation; Hala M. Demerdash participated in the study design, conduct of the study, data collection, data analysis, and manuscript preparation.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8], [Table 9], [Table 10]



 

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