Neutrophil to Lymphocyte Ratio Predicts Infections in First Week of Acute Pancreatitis

doi:10.21203/rs.3.rs-4721339/v1

Download PDF

Research Article

Neutrophil to Lymphocyte Ratio Predicts Infections in First Week of Acute Pancreatitis

https://doi.org/10.21203/rs.3.rs-4721339/v1

This work is licensed under a CC BY 4.0 License

You are reading this latest preprint version

Background

Differentiating infections from sterile inflammation is crucial in early AP management.

Aim

This study aimed to analyse the source, microbiological profile, and impact of infections in AP and to assess the capability of Neutrophil to Lymphocyte Ratio(NLR) and procalcitonin to discriminate between sterile inflammation and infections in the first week of illness.

Methods

Consecutive patients presenting within 5 days of symptom onset were included. Microbiological profiles and serious adverse events(SAEs:in-hospital mortality or discharge in critical state)were analysed. Blood count obtained at fever onset was used for calculating the NLR. The ability of NLR and procalcitonin to discriminate infection from sterile inflammation in the first week was assessed.

Results

Of 505 AP patients, 150 developed fevers. 48(32%)had sterile inflammation while 102(68%)had infections. Within infections,44 had infected pancreatic necrosis, 68 had extra-pancreatic infections,and 10 had both.Lower respiratory tract infection was the most common extra-pancreatic infection.Of 54 patients with culture-positive infections, 36(66.7%)had grown multidrug-resistant(MDR) organisms. Fungal isolates were identified in 5 patients. Patients with infections had higher SAE incidence(21.6% vs 4.2%,p = 0.007)than those with sterile inflammation. The SAE incidence was higher with MDR infections than those without MDR(37.5% vs 9.3%,p < 0.01).Most patients(n = 98,65.3%) developed fever during the first week of illness(sterile inflammation(n = 43)& infections(n = 55)).NLR demonstrated good accuracy in discriminating infections from sterile inflammation in the first week(AUROC 0.70,p = 0.001),outperforming procalcitonin(AUROC 0.54,p = 0.58).

Conclusions

Infections in AP occur early in the course of illness. NLR could serve as a reliable biomarker to distinguish infections from sterile inflammation in the early course of AP,aiding timely management. Patients with MDR infections have higher serious adverse outcomes.

Acute pancreatitis

Infections

Microbiological profile

Neutrophil to lymphocyte ratio

Acute pancreatitis (AP) is one of the most common gastrointestinal emergencies in the world. [1] The estimated incidence of the disease ranges between 110 and 140 per 100,000 population. [2] The inflammatory reaction in AP is initially local, but it may amplify systemically, leading to a systemic inflammatory response syndrome (SIRS) which manifests as fever, tachycardia and tachypnea. [1] The course of illness which starts as SIRS progresses over time to a compensatory anti-inflammatory response syndrome (CARS). In the phase of CARS, the immune response is downregulated making the person susceptible to infections. [2] Approximately 50% of patients develop infections in the first week of the illness, which significantly impacts outcome. [3]

Considering the high incidence of adverse events in patients with infections in AP, it is crucial to discriminate sterile inflammation from infection-driven inflammation in the early course of the illness. However, there is a lack of established parameters to distinguish between fever caused by inflammation and fever resulting from infection. Several biomarkers have been proposed as discriminants between infection and sterile inflammation. Neutrophil to Lymphocyte ratio (NLR) characterizes the balance between the initial innate and adaptive immune responses. Low-grade inflammation just slightly elevates the level of NLR. Whereas during bacterial infection, bacterial lipopolysaccharide in the circulation causes a temporary decrease, followed by an increase in neutrophil cell numbers within a few hours, and a parallel decrease in lymphocyte numbers, causing a significant rise in NLR. [4] Procalcitonin is a prohormone for calcitonin with distinct biological activities. A number of studies have suggested the use of procalcitonin as a valuable marker for diagnosis of bacterial infections. [5]

We undertook this study to analyze the source, microbiological profile, and impact of infections in AP, and to assess the capability of NLR and procalcitonin to discriminate between sterile inflammation and infections in the first week of illness.

Patients with AP admitted in Department of Gastroenterology, at a major tertiary care center in India, from October 2018 to October 2022 were identified from a prospectively maintained database. Inclusion criteria were 1) The first episode of AP, 2) Patients presenting within 5 days of symptom onset, 3) Patients with fever or other evidence of infection during illness. Patients were excluded if they had recurrent acute pancreatitis, chronic pancreatitis, or presented more than 5 days after symptom onset. The Institutional Review Board approved the study (IRB Approval Number 15760).

Data collection and definitions:

Demographic data, history, examination, investigations, details of medical management and intervention if done were recorded in standard data forms. Charlson comorbidity index (CCI) was calculated for every patient. [6]

AP was diagnosed on the basis of two out of three features: 1) Abdominal pain consistent with AP, 2) Serum lipase or amylase levels at least three times greater than the upper limit of normal, and 3) Characteristic findings of AP on imaging. [7] Patients were classified into mild, moderately severe and severe subgroups based on Revised Atlanta classification. [7] BISAP score was calculated for every patient. [8] For calculating NLR, the white cell count obtained from the blood count sent at the time of fever was used.

Definitions

Systemic Inflammatory Response Syndrome (SIRS)	Defined by the satisfaction of any two of the following criteria: 1) Body temperature > 38⁰ or < 36⁰C, 2) Heart rate > 90 beats/minute, 3) Respiratory rate > 20 breaths/minute or partial pressure of CO2 < 32 mmHg, 4) Leukocyte count > 12000 or < 4000 /microliters or over 10% immature forms or bands.[2]
Organ failures (OF)	Defined as score of ≥ 2 using Modified Marshall Scoring System. [9] OF were further classified on the basis of duration as transient (< 48 hours) and persistent OF (> 48 hours).
Serious Adverse Events (SAE)	In-hospital mortality or discharge in a critical state were considered as SAEs.
Sterile inflammation	Fever during the first two weeks of illness, was considered to be part of sterile inflammation and SIRS, in patients who did not have any objective evidence of infection or clinical suspicion of infection. Antibiotics were not started for sterile inflammation. [10]
Extra-pancreatic infections (EPI)	Documented infections occurring at sites other than pancreas were labelled as EPI, for example- lower respiratory tract infection, cholangitis, urinary tract infection, bacteremia. [11]
Bacteremia	Defined as positive blood cultures. It was essential for a minimum of two blood culture samples to be positive for non-pathogens, such as coagulase-negative staphylococci. [3]
Infected pancreatic necrosis (IPN)	The diagnosis of IPN was considered definite if the patient had 1) Positive culture of pancreatic necrosis from either fine needle aspiration (FNA), the initial percutaneous, endoscopic or surgical drainage, 2) Air foci inside the necrotic collection without the evidence of bowel communication, [12] or suspected infected necrosis if the patient had fever accompanied by deteriorating clinical signs and symptoms in the form of new or persistent organ failure, increased requirement of organ support or increasing C- reactive protein and received antibiotics. [13]
Carbapenem Resistant Organisms (CRO)	Organisms that test resistant to at least one of the carbapenem antibiotics or produce a carbapenemase are called CRO. [14]
Extended spectrum beta-lactamases (ESBLs) producing bacteria	Bacteria producing enzymes that are able to hydrolyze extended spectrum cephalosporins. [15]
Multidrug-resistant (MDR) bacteria	Bacteria which are not susceptible to at least 1 agent in at least 3 microbial categories. [16]
Neutrophil to lymphocyte ratio (NLR)	NLR was calculated by dividing the absolute neutrophil count by the absolute lymphocyte count, given by the differential white blood cell count. [17] Blood count obtained at fever onset was used for calculating the NLR.

Treatment protocol:

AP patients were monitored with 6-hourly charting of temperature, pulse, blood pressure, respiratory rate, and pain score. Patients received intravenous fluids, analgesics and were encouraged to be on enteral feeds. No prophylactic antibiotics were administered. Patients with single organ failure requiring mechanical ventilation, inotropic agents, or those with multi-organ failure were admitted to the Intensive Care Unit (ICU) for organ support including ventilation, vasopressors, and hemodialysis as clinically indicated. Upon developing fever during hospitalization, samples were collected to evaluate for infection, including a complete blood count with white blood cell differential, blood cultures, chest X-rays, urine cultures, serum procalcitonin levels and other relevant diagnostic tests based on clinical judgment. For calculating NLR the white cell count obtained from the blood count sent at the time of fever was used. For patients with suspected or confirmed infections, broad-spectrum antibiotic therapy was initiated and then tailored based on culture sensitivity results. Upon failure to improve with antibiotics, interventional drainage of IPN was pursued endoscopically or percutaneously based on location of fluid collections and illness duration. Patients unresponsive to drainage underwent necrosectomy using a step-up approach.

Statistical analysis:

Continuous data were summarized using medians and interquartile ranges and categorical variables were presented as frequencies and percentages. For the analysis, the Mann-Whitney U test was employed to compare continuous variables between groups, while categorical variables were compared using Chi-square tests or Fisher's exact tests when appropriate. Binary logistic regression modeling was conducted to identify predictors of outcomes. Receiver operating characteristic (ROC) curve was plotted to evaluate the predictive value NLR and Procalcitonin to identify infection in the first week of AP. A p-value < 0.05 was the threshold used to determine statistical significance for all analyses. The analysis was carried out using SPSS software, version 21.0.

Study population:

During the study period 505 patients were admitted within 5 days of onset of illness. Of them, 363 (71.9%) were males. The median age was 41 (IQR 32–55) years. Of the 505, 150 patients developed fever during hospitalization (Fig. 1). Among these 150 individuals, 48 (32%) had sterile inflammation while 102 (68%) had infections (Table 1).

Table 1

Baseline Characteristics
Variable	Patients with fever (n = 150)	Sterile inflammation (n = 48)	Infections (n = 102)	p value
Age	42 (31.7–54)	35 (29–51)	43(34.7–56.5)	0.03
Sex, Male	124 (82.7)	39 (81.2)	85 (83.3)	0.75
Charlson comorbidity score	0 (0–1)	0 (0–0)	0 (0–1)	0.06
Addictions	69 (46)	23 (47.9)	46 (45.1)	0.86
Aetiology of AP Alcohol Biliary Idiopathic Hypertriglyceridemia Hypercalcemia Post ERCP Others	69 (46) 42 (28) 19 (12.7) 4 (2.7) 3 (2) 6 (4) 7 (4.7)	22 (45.8) 17 (35.4) 6 (12.5) 2 (4.2) 0 (0) 0 (0) 1 (2.1)	47 (46.1) 25 (24.5) 13 (12.7) 2 (2) 3 (2.9) 6 (5.9) 6 (5.9)	0.30
Severity Mild Moderately severe Severe	41 (27.3) 36 (24) 73 (48.7)	25 (52.1) 11 (22.9) 12 (25)	16 (15.7) 25 (24.5) 61 (59.8)	< 0.001
BISAP score	0 (1-2.2)	1 (0–1)	2 (1–3)	< 0.001
Necrosis	77 (51.3)	13 (28.9)	64 (64)	< 0.001
Day of illness at admission	2 (1–4)	2 (1-3.7)	2 (1–4)	0.76
Hematocrit at admission, %	42.2 (36.4–48.1)	42 (36.1–46.2)	42.2 (36.8–50.1)	0.27
Data expressed as median (IQR) or number (%) as appropriate; BISAP, Bedside Index of Severity of Acute Pancreatitis

Figure 2 illustrates the temporal trends in the causes of fever in AP. Most patients developed fever during the first week of illness (n = 98). Out of these, 43 patients (43.9%) had sterile inflammation, while 55 patients (56.1%) had infections within the first week itself. Among those with infections in the first week, the majority (n = 44) had extra-pancreatic infections. Beyond two weeks, the most common cause of fever was infected pancreatic necrosis, accounting for 14 cases (82.3%).

Source of infections:

Out of 102 patients with infections, 44 had infected pancreatic necrosis (IPN). Extra-pancreatic infections (EPI) were observed in 68 patients. 10 patients suffered from both IPN and EPI concurrently. (Supplementary Fig. 1)

Infected pancreatic necrosis (IPN): (n = 44)

IPN was considered in 44 patients. Among them, 20 patients had definitive evidence of IPN, with 13 patients demonstrating positive pancreatic fluid cultures, and 7 patients having radiological imaging findings suggestive of IPN, such as the presence of air within the collections. Furthermore, 24 patients had a high clinical suspicion of IPN, based on persistent fever, SIRS, new onset organ failures, or increasing requirements of organ support.

Of those 13 culture-positive patients, 10 had grown MDR organisms. Most common organism was Klebsiella pneumoniae (n = 7) followed by Enterococcus (n = 6). Fungal culture positivity was noted in 3 patients (Candida tropicalis in 2 patients and Candida glabrata in one).

Percutaneous drainage was required in 12 patients while endoscopic ultrasound guided drainage was done in 6 patients.

Extra-pancreatic infections: (n = 68)

Lower respiratory tract infection (LRTI) was identified as the most prevalent EPI, seen in twenty-three cases. The most common causative organism being Acinetobacter baumanii, isolated in 16 cases (80%) of the 20-culture positive LRTIs. The most common isolate from bile was Klebsiella pneumoniae, seen in all five cases of bile culture positivity. The predominant isolate from blood culture was Klebsiella pneumoniae (n = 16) followed by Escherichia coli (n = 13).

Microbiological profile:

Among the patients with culture-positive infections (n = 54), 29 had monomicrobial while rest 25 had polymicrobial infections. (Details of microbiological isolates are provided in Supplementary Table S1 and Figure S2)

Gram-negative bacteria (GNB):

A total of 94 GNB strains were isolated. Among them, Klebsiella pneumoniae was the most frequently encountered, with 32 individual isolates identified.

Gram-positive bacteria (GPC):

A total of 15 GPC strains were isolated. Enterococcus species were the most identified GPCs, with 12 isolates.

Drug resistance:

Among the 54 patients with culture-positive infections, 36 (66.7%) patients were found to have disease caused by MDR organisms. Further analysis of the 94 GNB isolates revealed that 5 (5.3%) were ESBL producers, while a notable 25 (26.6%) isolates exhibited resistance to carbapenem antibiotics, categorized as CROs. Turning to the GPC isolates, out of the 15 identified, three were found to be Vancomycin-resistant Enterococci (VRE). Two isolates of Methicillin-resistant Staphylococcus aureus (MRSA) were detected among the GPC isolates.

Fungal infections:

There were fungal isolates identified in six culture samples obtained from 5 distinct patients. Candida tropicalis was identified in five cultures, including two samples of endotracheal tube aspirate and pancreatic fluid each and one sample of blood. Candida glabrata was identified in a single pancreatic collection culture.

Among the subset of 102 patients with infections, those who developed fungal infections had a significantly longer median duration of prior antibiotic use compared to those who did not develop fungal infections. The median duration was 3 (IQR 2–7) weeks for patients with fungal infections, while it was 2 (IQR 1–3) weeks for those without fungal infections (p value = 0.032). Additionally, 4 out of the 5 patients (80%) who developed fungal infections were admitted to the intensive care unit (ICU).

Impact of infections on Serious adverse events (SAE):

The incidence of SAE was higher in patients with infections (n = 22, 21.6%) compared to those with sterile inflammation (n = 2, 4.2%), with an odds ratio of 6.3 (95% CI: 1.4–28.1, p = 0.007). The incidence of organ failures as well ICU admissions were significantly more in the infection group (Table 2).

Table 2

Outcomes
Outcomes	Sterile inflammation (n = 48)	Infections (n = 102)	p value
Serious adverse events (SAE)	2 (4.2)	22 (21.6)	0.007
Organ failures	13 (27.1)	71 (69.6)	< 0.001
ICU admission	4 (8.3)	44 (43.1)	< 0.001
Data expressed as number (%)

The incidence of SAE was significantly higher among patients with multidrug-resistant (MDR) infections compared to those without MDR infections (37.5% vs 9.3%, p < 0.01).

First week of AP:

Similar to the study of Besselink et al we also noted a very high incidence of infections in the first week of AP. [3] Among patients with fever in the first week of illness, 56% had pancreatic and extra-pancreatic infections. Given the high incidence of SAE amongst patients with infection, it is vital to discriminate infection from inflammation-driven fever. We explored the role of procalcitonin and NLR in discriminating between infection and inflammation in the first week of pancreatitis. We constructed a receiver operating characteristic (ROC) curve of NLR and Procalcitonin to identify infection in the first week of AP (Fig. 3). NLR was a better predictor of infection in the first week of AP with an AUROC of 0.7, p = 0.001 (Table 3). At a cut-off of 6.2, the NLR had 77% sensitivity and 58% specificity for predicting infections. NLR > 9 demonstrated a specificity of over 80% in predicting infections (Supplementary Table S2). Further, patients who had NLR > 9 experienced a higher rate of SAE as compared those with NLR between 6 to 9 (27.4% vs 10.5%, p = 0.04).

Table 3

ROC comparison of NLR and procalcitonin in predicting infections in the first week
Parameter	AUROC	95% CI	p value
NLR	0.70	0.60–0.81	0.001
Procalcitonin	0.54	0.38–0.68	0.58
NLR, Neutrophil to lymphocyte ratio; AUROC, Area Under the ROC Curve

In this study we analyzed the source, microbiological profile, and impact of infections among a large cohort of 150 patients with AP who developed fever during acute pancreatitis. We characterized the temporal patterns, distinctive features, microbiological profiles, and outcomes associated with infectious complications in patients with AP.

A large proportion of our patients had extra-pancreatic infections. This aligns with previous reported literature on infections in AP. [18,19] Among these extra-pancreatic infections, lower respiratory tract infections were most common followed by cholangitis and bacteremia.

The occurrence of definite infected pancreatic necrosis is lower in our study as compared to the previously reported literature. [20] Notably, we did not perform per protocol FNAC for suspected IPN. Performing FNAC for suspected infected pancreatic necrosis has been a matter of debate. Studies have shown that infected necrosis can be reliably diagnosed on basis of clinical signs. [13] At our center we do not routinely perform FNAC for pancreatitis and 24 patients received antibiotics on the clinical suspicion of infected necrosis.

Of the 54 patients with culture-confirmed infections, 36 (66.7%) had infections caused by multidrug-resistant (MDR) organisms. Among patients with infected pancreatic necrosis who had positive cultures, 10 out of 13 (77.9%) grew MDR organisms. These findings highlight the high prevalence of MDR infections, especially in infected pancreatic necrosis. Previous studies also reported a high incidence of MDR infections in AP. [12,20,21] This highlights the importance of local antibiograms in guiding empiric antibiotic therapy for suspected infections. Patients with MDR infections had a considerably higher occurrence of serious adverse events (SAE) compared to patients without MDR infections, aligning with previous studies. [12,22,23] The growing prevalence of MDR infections in pancreatitis is a matter of concern. The paucity of effective antimicrobial therapy for treatment of MDR infections poses a significant challenge. A small proportion of patients developed fungal infections. Patients with fungal infections had a significantly longer median duration of antibiotic use and most of them were admitted in ICU. This highlights the risk of developing fungal infections as a consequence of prolonged antibiotic exposure, which is a known risk factor for fungal infections. [24]

AP can be divided into two phases. In the initial 1-2 weeks, AP triggers a pro-inflammatory response, manifesting as SIRS. After the first 1-2 weeks, there is a shift from this pro-inflammatory state to an anti-inflammatory phase. It is during this second phase that the patient becomes vulnerable to the development of various infectious complications. [10] The current guidelines do not recommend routine antimicrobial prophylaxis in AP. However, our study and the study by Besselink et al highlights that ~ 50% of patients are at risk of infections in the first week of illness. [3] The challenge in the first week of illness is to discriminate fever secondary to sterile inflammation from fever secondary to infections. Cultures take time to become positive, and that wait may contribute to a poor outcome . Routine FNAC of suspected infected necrosis has its own challenges. Therefore, there is a need for surrogate parameters which can discriminate infection from inflammation in the first week of illness. In this study we explored two such parameters, NLR and procalcitonin.

The NLR has been studied in AP patients as a predictor of severity and adverse outcomes. [25-30] In our study, the NLR showed good accuracy in discriminating infections from sterile inflammation, with an AUROC of 0.70. At a cut-off of 6.2, the NLR had 77% sensitivity and 58% specificity for predicting infections. Further NLR >9 exhibited a specificity exceeding 80% in predicting the presence of infections. Given the high specificity associated with an NLR above 9, it would be reasonable to initiate antibiotic treatment promptly after obtaining blood cultures, since the false positive rate of approximately 20% is deemed acceptable. On the other hand, procalcitonin did not appear to be a good discriminant between infection and inflammation in the first week. Our study suggests that NLR could be a useful biomarker in differentiating infections from sterile inflammation in the first week of illness in AP. Analogous to our study, NLR has been employed as a discriminatory tool in patients with COVID-19, to differentiate fever driven by the SIRS from that caused by bacterial infections. [31] Moreover, in a study involving patients on haemodialysis, NLR in conjunction with C-reactive protein (CRP) levels was used to distinguish inflammation of infectious origin from non-infectious aetiology. [32] In another study, NLR was used to predict bacterial infections in patients with acutely decompensated cirrhosis. [4] NLR is a cost and time effective and easy to use daily practice biomarker.

The strength of our study is the large sample size, strict inclusion criteria, comprehensive microbiological data and quantitative analysis of NLR as a predictor of infections. To the best of our knowledge, ours is the first study to examine the ability of NLR in differentiating infections and sterile inflammation in AP.

We acknowledge certain limitations of this study including its single centre study design, and lack of post discharge outcome information.

In conclusion, this study focuses on the early occurrence of infections in AP and provides novel insights on using the NLR to distinguish between infectious and non-infectious fevers in AP. Additionally, it emphasizes the changing microbial profile, which has consequences for choosing antibiotics based on experience. Further multi-centric studies are necessary to confirm the diagnostic accuracy of the NLR and investigate additional biomarkers.

Declaration of personal interest: The authors declare no conflicts of interest regarding this article.

Acknowledgements:

We extend our sincere gratitude to the patients who participated in this study. We also wish to thank our colleagues, the nursing staff, and all allied health professionals who provided invaluable support in our gastroenterology ward and intensive care unit. Their collective efforts and dedication were instrumental in the successful completion of this research.

Funding:

This research received no external funding.

Ethical Approval:

The Institutional Review Board approved the study (IRB Approval Number 15760).

Kylänpää L, Rakonczay Z, O’Reilly DA. The clinical course of acute pancreatitis and the inflammatory mediators that drive it. Int J Inflamm. 2012;2012:360685. doi:10.1155/2012/360685
Chakraborty RK, Burns B. Systemic Inflammatory Response Syndrome. In: StatPearls. StatPearls Publishing; 2024. Accessed May 6, 2024. http://www.ncbi.nlm.nih.gov/books/NBK547669/
Besselink MG, van Santvoort HC, Boermeester MA, et al. Timing and impact of infections in acute pancreatitis. Br J Surg. 2009;96(3):267-273. doi:10.1002/bjs.6447
Janka T, Tornai D, Papp M, Vitális Z. The Value of Neutrophil-to-Lymphocyte Ratio to Identify Bacterial Infection and Predict Short-Term Mortality in Patients with Acutely Decompensated Cirrhosis. Diagnostics. 2023;13(18):2954. doi:10.3390/diagnostics13182954
Procalcitonin as a biomarker of infectious diseases - PubMed. Accessed March 31, 2024. https://pubmed.ncbi.nlm.nih.gov/23682219/
Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: Development and validation. J Chronic Dis. 1987;40(5):373-383. doi:10.1016/0021-9681(87)90171-8
Classification of acute pancreatitis--2012: revision of the Atlanta classification and definitions by international consensus - PubMed. Accessed March 2, 2024. https://pubmed.ncbi.nlm.nih.gov/23100216/
Wu BU, Johannes RS, Sun X, Tabak Y, Conwell DL, Banks PA. The early prediction of mortality in acute pancreatitis: a large population-based study. Gut. 2008;57(12):1698-1703. doi:10.1136/gut.2008.152702
Forsmark CE, Swaroop Vege S, Wilcox CM. Acute Pancreatitis. Campion EW, ed. N Engl J Med. 2016;375(20):1972-1981. doi:10.1056/NEJMra1505202
Zerem E. Treatment of severe acute pancreatitis and its complications. World J Gastroenterol WJG. 2014;20(38):13879-13892. doi:10.3748/wjg.v20.i38.13879
Rao C, Bhasin DK, Rana SS, Gupta R, Gautam V, Singh K. Implications of culture positivity in acute pancreatitis: does the source matter? J Gastroenterol Hepatol. 2013;28(5):887-892. doi:10.1111/jgh.12161
Jain S, Mahapatra SJ, Gupta S, Shalimar, Garg PK. Infected Pancreatic Necrosis due to Multidrug-Resistant Organisms and Persistent Organ failure Predict Mortality in Acute Pancreatitis. Clin Transl Gastroenterol. 2018;9(10):190. doi:10.1038/s41424-018-0056-x
van Baal MC, Bollen TL, Bakker OJ, et al. The role of routine fine-needle aspiration in the diagnosis of infected necrotizing pancreatitis. Surgery. 2014;155(3):442-448. doi:10.1016/j.surg.2013.10.001
CRE Technical Information | CRE | HAI | CDC. Published February 22, 2021. Accessed March 3, 2024. https://www.cdc.gov/hai/organisms/cre/technical-info.html
Ghafourian S, Sadeghifard N, Soheili S, Sekawi Z. Extended Spectrum Beta-lactamases: Definition, Classification and Epidemiology. Curr Issues Mol Biol. 2015;17(1):11-22. doi:10.21775/cimb.017.011
Magiorakos AP, Srinivasan A, Carey RB, et al. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect. 2012;18(3):268-281. doi:10.1111/j.1469-0691.2011.03570.x
Janka T, Tornai D, Papp M, Vitális Z. The Value of Neutrophil-to-Lymphocyte Ratio to Identify Bacterial Infection and Predict Short-Term Mortality in Patients with Acutely Decompensated Cirrhosis. Diagnostics. 2023;13(18):2954. doi:10.3390/diagnostics13182954
Ni T, Wen Y, Zhao B, et al. Characteristics and risk factors for extrapancreatic infection in patients with moderate or severe acute pancreatitis. Heliyon. 2023;9(2):e13131. doi:10.1016/j.heliyon.2023.e13131
Marstrand-Joergensen MR, Bertilsson S, Kalaitzakis E. Extrapancreatic infections are common in acute pancreatitis and they are related to organ failure: a population-based study. Eur J Gastroenterol Hepatol. 2020;32(10):1293. doi:10.1097/MEG.0000000000001847
Bohidar NP, Garg PK, Khanna S, Tandon RK. Incidence, etiology, and impact of Fever in patients with acute pancreatitis. Pancreatol Off J Int Assoc Pancreatol IAP Al. 2003;3(1):9-13. doi:10.1159/000069146
Moka P, Goswami P, Kapil A, Xess I, Sreenivas V, Saraya A. Impact of Antibiotic-Resistant Bacterial and Fungal Infections in Outcome of Acute Pancreatitis. Pancreas. 2018;47(4):489-494. doi:10.1097/MPA.0000000000001019
Wu D, Jia Y, Cai W, et al. Impact of multiple drug-resistant Gram-negative bacterial bacteraemia on infected pancreatic necrosis patients. Front Cell Infect Microbiol. 2022;12. doi:10.3389/fcimb.2022.1044188
Jiang X, Shi JY, Wang XY, Hu Y, Cui YF. The impacts of infectious complications on outcomes in acute pancreatitis: a retrospective study. Mil Med Res. 2020;7(1):38. doi:10.1186/s40779-020-00265-5
Kochhar R, Noor MT, Wig J. Fungal infections in severe acute pancreatitis. J Gastroenterol Hepatol. 2011;26(6):952-959. doi:10.1111/j.1440-1746.2011.06685.x
Azab B, Jaglall N, Atallah JP, et al. Neutrophil-Lymphocyte Ratio as a Predictor of Adverse outcomes of Acute Pancreatitis. Pancreatology. 2011;11(4):445-452. doi:10.1159/000331494
Jeon TJ, Park JY. Clinical significance of the neutrophil-lymphocyte ratio as an early predictive marker for adverse outcomes in patients with acute pancreatitis. World J Gastroenterol. 2017;23(21):3883-3889. doi:10.3748/wjg.v23.i21.3883
Halaseh SA, Kostalas M, Kopec C, et al. Neutrophil-to-Lymphocyte Ratio as an Early Predictor of Complication and Mortality Outcomes in Individuals With Acute Pancreatitis at a UK District General Hospital: A Retrospective Analysis. Cureus. 2022;14(9). doi:10.7759/cureus.29782
Kokulu K, Günaydın YK, Akıllı NB, et al. Relationship between the neutrophil-to-lymphocyte ratio in acute pancreatitis and the severity and systemic complications of the disease. Turk J Gastroenterol. 2018;29(6):684-691. doi:10.5152/tjg.2018.17563
Bhanou NMS, Balachandran G, Jain NB. Neutrophil to lymphocyte ratio (NLR) in acute pancreatitis as an early predictor of severity and outcome. Int Surg J. 2018;5(11):3545-3548. doi:10.18203/2349-2902.isj20184619
Vemparala SV, Bhat AGK, Bhat NK, Hande MH. Neutrophil to Lymphocyte Ratio as an Early Predictive Marker for Adverse Outcomes in Patients with Acute Pancreatitis. J Clin Diagn Res. Published online 2021. doi:10.7860/JCDR/2021/51705.15729
Vélez-Páez JL, Tercero-Martínez W, Jiménez-Alulima G, et al. Neutrophil-to-lymphocyte ratio and mean platelet volume in the diagnosis of bacterial infections in COVID-19 patients. A preliminary analysis from Ecuador. Infez Med. 2021;29(4):530-537. doi:10.53854/liim-2904-5
Beberashvili I, Omar MA, Nizri E, Stav K, Efrati S. Combined use of CRP with neutrophil-to-lymphocyte ratio in differentiating between infectious and noninfectious inflammation in hemodialysis patients. Sci Rep. 2023;13(1):5463. doi:10.1038/s41598-023-32270-8

No competing interests reported.

Supplementarydata.docx

Download PDF

Editorial decision: Revision requested
25 Aug, 2024
Reviews received at journal
25 Aug, 2024
Reviews received at journal
23 Aug, 2024
Reviews received at journal
03 Aug, 2024
Reviewers agreed at journal
28 Jul, 2024
Reviewers agreed at journal
26 Jul, 2024
Reviewers agreed at journal
26 Jul, 2024
Reviewers agreed at journal
24 Jul, 2024
Reviewers agreed at journal
24 Jul, 2024
Reviewers invited by journal
23 Jul, 2024
Editor assigned by journal
15 Jul, 2024
Submission checks completed at journal
11 Jul, 2024
First submitted to journal
10 Jul, 2024

You are reading this latest preprint version

Neutrophil to Lymphocyte Ratio Predicts Infections in First Week of Acute Pancreatitis

Status:

Version 1

Abstract

Background

Aim

Methods

Results

Conclusions

Figures

Introduction

Methods

Data collection and definitions:

Statistical analysis:

Results

Source of infections:

Microbiological profile:

Impact of infections on Serious adverse events (SAE):

Discussion

Declarations

References

Additional Declarations

Supplementary Files

Status:

Version 1