Neutrophil to Lymphocyte Ratio as a Predictor of Complicated Acute Diverticulitis

Study Overview
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Brief Summary
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Introduction: Various biomarkers have been studied to predict the severity of acute diverticulitis (AD), such as the leukocyte count and CRP, which are useful but lack sufficient sensitivity. The neutrophil-lymphocyte ratio (NLR) has been identified as a new inflammatory biomarker in several abdominal pathologies. However, few studies determine its association with the severity of AD. The objective of the present study was to determine the utility and diagnostic precision of NLR in complicated acute diverticulitis (cAD). Material and methods: Descriptive, retrospective and analytical study. Patients older than 18 years with a diagnosis of AD were included, from 2013 - 2018. Demographic variables, days of hospitalization, leukocyte count, neutrophils, lymphocytes, ESR, CRP, and NLR were analyzed. The sensitivity and specificity for the diagnosis of cAD were determined using ROC curves.

Detailed Description
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Introduction Acute diverticulitis (AD) is present in 10-25% of patients with diverticular disease, being most common in sigmoid colon, with around 200.000 hospitalizations yearly . As much as one fifth of patients are younger than 50 at the moment of diagnosis and around 5% under the age of 40 . Confirming the diagnosis requires the utilization of imaging studies, therefore, American Society of Colon and Rectal Surgeons (ASCRS) established that computed tomography (CT) is the standard method for the diagnosis of AD, with a sensitivity of 98% and a specificity of 99%. The tomographic findings vary according the severity of diverticular disease, which is categorized through a modified Hinchey classification system. Approximately 10-15% of AD patients may develop complications that imply the onset of abscesses, fistulas, stenosis, obstruction and/or perforation. Recently, interest has been raised in the role of biomarkers in diverticular disease as non-invasive, reliable, inexpensive tools that may help in the early diagnosis of complicated AD, such as C-reactive protein (CRP), useful marker in the prediction of the level of inflammation and severity of AD. In 2001 identified the neutrophil-lymphocyte ratio (NLR) as an inflammation marker in critical patients, defining as the absolute neutrophil count divided by the absolute lymphocyte count. Over the last decade, NLR effectiveness has been recognized in various pathologies, both benign and malignant; finding that the levels of neutrophils rise as a part of the inflammatory cascade, whereas lymphocytes diminish during sepsis, making a novel subclinical biomarker with a prognostic value in oncological, cardiovascular and infectious diseases, among others. The NLR may be obtained from the blood count data, which represents a lower cost regarding other known biomarkers. It was also demonstrated that high values of NLR are associated with severe abdominal infections and worse outcomes, reason why it started to be applied as a predictor to evaluate results in surgical patients. Currently, the debate on usefulness of NLR as a predictor of complications in AD remains open, specially, the relation to the severity of the disease, the clinical impact and the necessity of minimally invasive or emergency surgical procedures. On the other hand, its diagnostic efficacy has not been studied even in our field. Up until now, there are only four studies published in Ireland, Israel, and South Korea. The purpose of the study was to determine the usefulness and diagnostic accuracy of NLR in complicated acute diverticulitis (cAD). Material and methods Study population A descriptive, retrospective cohort and analytical study was undertaken. Medical histories and an electronic database from General Surgery Service were reviewed. All the patients over the age of 18 with AD diagnosis through CT were included, since January 2013 until January 2018 in a University Hospital of Cordoba, Argentina, with third level reference. Patients were excluded if they had chronic diseases, susceptible to modify the immune inflammatory response, extra-abdominal infections, immunosuppression and neoplasias, and those who supplied incomplete data in their electronic clinical histories. Study of variables Demographic variables (sex and age), days of inpatient stay, level of severity in diverticular process (objectified by CT) were analyzed. It was recorded the value of serum leukocyte, neutrophil, and lymphocyte concentration, Erythrocyte Sedimentation Rate (ESR), CRP and NLR at the moment of consultation on call. Variable definition NLR: It can be obtained from the blood count (the absolute neutrophil count divided by the absolute lymphocyte count) CRP: normal value under 5 mg/l. Statistical analysis The categorical variables were expressed as frequency (percentage), the continuous variables as mean value (standard deviation, SD) or median (range) according to the distribution of data; Mann Whitney test was used to compare the continuous variables, Chi-square and Fisher's tests were used to compare categorical variables among patients with simple acute diverticulitis (sAD) and cAD. A value of p<0.05 was considered as statistically significant. ROC (Receiver Operating Characteristic) curves were used as diagnostic tests to evaluate the diagnostic accuracy of NLR as predictor of complicated AD, determining sensitivity (Se), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV). Youden index was used to find the cut-off point with the best diagnostic yield for NLR in cAD. SPSS 26 software and GraphPad 7 software were used for statistical analysis.

Official Title
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Neutrophil to Lymphocyte Ratio as a Predictor of Complicated Acute Diverticulitis: A Retrospective Cohort Study

Conditions
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Acute Diverticulitis

Intervention / Treatment
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* Diagnostic Test: Neutrophil to Lymphocyte Ratio


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients older than 18 years. Patients with a diagnosis of acute diverticulitis confirmed by computed tomography. Exclusion Criteria: Patients under 18 years of age. Patients with hematological diseases. Patients with extra abdominal infections. Patients with oncological diseases

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 92 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| simple acute diverticulitis<br>Ninety-one percent (n=295) were categorized as simple acute diverticulitis | Diagnostic Test: Neutrophil to Lymphocyte Ratio<br>* Zahorec et al. identified the neutrophil-lymphocyte ratio (NLR) as an inflammation marker in critical patients, defining as the absolute neutrophil count divided by the absolute lymphocyte count<br>|
| complicated acute diverticulitis<br>9% (n=30) presented were categorized as complicated acute diverticulitis | Diagnostic Test: Neutrophil to Lymphocyte Ratio<br>* Zahorec et al. identified the neutrophil-lymphocyte ratio (NLR) as an inflammation marker in critical patients, defining as the absolute neutrophil count divided by the absolute lymphocyte count<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Demographic variables | sex and age | 2013-2018 | 
| inpatient stay | days | 2013-2018 | 
| level of severity in diverticular process | confirmed by computed tomography | 2013-2018 | 
| value of C-reactive protein | normal value under 5 mg/l | 2013-2018 | 
| value of Neutrophil to Lymphocyte Ratio | It can be obtained from the blood count (the absolute neutrophil count divided by the absolute lymphocyte count) | 2013-2018 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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neutrophil-to-lymphocyte ratio, C-reactive protein, biomarkers