Comparison of Neutrophil Lymphocyte Ratio combined SOFA versus APACHE IV in assessing the Prognosis of Sepsis Patients admitted to Medical Intensive Care Unit

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Accurate prognostic tools are essential for guiding patient management. This study aims to compare the effectiveness of Neutrophil–Lymphocyte Ratio with Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation IV (APACHE IV) in predicting sepsis outcomes. A prospective cross-sectional design will enrol septic MICU patients, collecting baseline data and scoring systems. Patient outcomes, including mortality and length of MICU stay, will be analyzed using correlation and ROC curve analyses. This study addresses the current gap in direct comparisons of these tools. Results The results of this study are anticipated to reveal significant correlations between the Neutrophil Lymphocyte Ratio combined with SOFA and APACHE IV scores and patient outcomes. Specifically, we expected to observe strong associations between the combined scoring system and mortality rates, length of MICU stay, and the need for organ support. Furthermore, we anticipate that the Neutrophil Lymphocyte Ratio combined with SOFA will demonstrate higher predictive accuracy than APACHE IV to assess prognosis in sepsis patients admitted to the MICU. Conclusion Based on the results obtained from this prospective cross-sectional study, we can draw conclusions regarding the comparative effectiveness of NLR (Neutrophil Lymphocyte Ratio) combined with SOFA and APACHE IV in assessing the prognosis of sepsis in the MICU. We anticipate that the combined scoring system will provide a more accurate prognostic assessment and enable healthcare professionals to make well-informed choices regarding patient care and the distribution of resources. These findings will contribute to building evidence on sepsis and may have implications for improving patient outcomes in the MICU setting. 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F1000Research 2024, 13 :403 ( https://doi.org/10.12688/f1000research.143930.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. Close Copy Citation Details Export Export Citation Sciwheel EndNote Ref. Manager Bibtex ProCite Sente EXPORT Select a format first Track Share ▬ ✚ Study Protocol Comparison of Neutrophil Lymphocyte Ratio combined SOFA versus APACHE IV in assessing the Prognosis of Sepsis Patients admitted to Medical Intensive Care Unit [version 1; peer review: 2 approved with reservations] Venkat Reddy https://orcid.org/0009-0009-7102-2702 1 , Sunil Kumar 1 Venkat Reddy https://orcid.org/0009-0009-7102-2702 1 , Sunil Kumar 1 PUBLISHED 26 Apr 2024 Author details Author details 1 Department of Medicine, Datta Meghe Institute of Higher Education and Research, Wardha, Maharashtra, 442001, India Venkat Reddy Roles: Conceptualization, Data Curation, Formal Analysis, Funding Acquisition, Investigation, Methodology, Project Administration, Resources, Software, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Sunil Kumar Roles: Data Curation, Supervision, Validation, Visualization, Writing – Review & Editing OPEN PEER REVIEW DETAILS REVIEWER STATUS This article is included in the Datta Meghe Institute of Higher Education and Research collection. Abstract Background Sepsis poses a significant threat in the Medical Intensive Care Unit (MICU), with high morbidity and mortality rates. Accurate prognostic tools are essential for guiding patient management. This study aims to compare the effectiveness of Neutrophil–Lymphocyte Ratio with Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation IV (APACHE IV) in predicting sepsis outcomes. A prospective cross-sectional design will enrol septic MICU patients, collecting baseline data and scoring systems. Patient outcomes, including mortality and length of MICU stay, will be analyzed using correlation and ROC curve analyses. This study addresses the current gap in direct comparisons of these tools. Results The results of this study are anticipated to reveal significant correlations between the Neutrophil Lymphocyte Ratio combined with SOFA and APACHE IV scores and patient outcomes. Specifically, we expected to observe strong associations between the combined scoring system and mortality rates, length of MICU stay, and the need for organ support. Furthermore, we anticipate that the Neutrophil Lymphocyte Ratio combined with SOFA will demonstrate higher predictive accuracy than APACHE IV to assess prognosis in sepsis patients admitted to the MICU. Conclusion Based on the results obtained from this prospective cross-sectional study, we can draw conclusions regarding the comparative effectiveness of NLR (Neutrophil Lymphocyte Ratio) combined with SOFA and APACHE IV in assessing the prognosis of sepsis in the MICU. We anticipate that the combined scoring system will provide a more accurate prognostic assessment and enable healthcare professionals to make well-informed choices regarding patient care and the distribution of resources. These findings will contribute to building evidence on sepsis and may have implications for improving patient outcomes in the MICU setting. READ ALL READ LESS Keywords Neutrophil Lymphocyte Ratio, SOFA, APACHE IV, critical ill patient, sepsis Corresponding Author(s) Venkat Reddy ( [email protected] ) Close Corresponding author: Venkat Reddy Competing interests: No competing interests were disclosed. Grant information: The author(s) declared that no grants were involved in supporting this work. Copyright: © 2024 Reddy V and Kumar S. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. How to cite: Reddy V and Kumar S. Comparison of Neutrophil Lymphocyte Ratio combined SOFA versus APACHE IV in assessing the Prognosis of Sepsis Patients admitted to Medical Intensive Care Unit [version 1; peer review: 2 approved with reservations] . F1000Research 2024, 13 :403 ( https://doi.org/10.12688/f1000research.143930.1 ) First published: 26 Apr 2024, 13 :403 ( https://doi.org/10.12688/f1000research.143930.1 ) Latest published: 26 Apr 2024, 13 :403 ( https://doi.org/10.12688/f1000research.143930.1 ) Introduction Sepsis, a potentially fatal illness, is a severe organic malfunction caused by an uncontrolled response to infection in the body. If ignored, it can develop into septic shock, which is characterized by serious metabolic and circulatory problems and is often fatal. 1 Inflammation and immunological response are crucial factors in many chronic illnesses. An indicator of the balance between two components of the defense mechanism, including acute and chronic inflammation (expressed by means of neutrophil count) and adaptive immunity (expressed by means of lymphocyte count), is (theeutrophil-to-lymphocyte ratio NLR, a biomarker found in the blood (peripheral). NLR, an inflammatory biomarker computed by dividing the total count of neutrophils by the total count of lymphocytes, is a marker of systemic inflammation. This measure does not increase the price of standard full blood count testing routinely conducted in hospital settings. NLR has been studied as a prognostic indicator in various conditions, including sepsis, community-acquired pneumonia, and various forms of cancer. 2 NLR is a widely utilized marker to assess the severity of bacterial infection and to predict the prognosis of patients with tumor pneumonia. 3 NLR serves as a straightforward parameter for evaluating an individual’s inflammatory status and has demonstrated its utility in predicting the mortality of significant cardiac diseases, as well as being a robust prognostic factor for various cancer types. 4 , 5 The SOFA is a straightforward and objective scoring system that assesses the severity and number of multi-organ dysfunctions across six organ systems: respiratory, liver, urology, cardiovascular, coagulation, and neurological. This score gauges dysfunction in individual organs or provides an overall assessment of organ dysfunction. 6 A higher SOFA score indicates a greater likelihood of mortality. Aim • To Compare Neutrophil Lymphocyte Ratio combined with SOFA versus APACHE (Acute Physiology And Chronic Health Evaluation) IV in assessing the Prognosis of Sepsis Patients admitted to the Medical Intensive Care Unit. Objectives • To estimate the combined SOFA and Neutophil Lymphocyte Ratio score in sepsis patients • To estimate APACHE IV Score in sepsis patients • To compare the neutrophil lymphocyte ratio combined sofa with APACHE IV in predicting outcomes in terms of mortality, ICU (Intensive Care Unit) stay, and mechanical ventilation in patientswith sepsis Methods Research design: Prospective, Cross sectional study. Setting: All patients visiting the Department of General Medicine (Acharya VinobhaBhave Rural Hospital, Datta Meghe Institute of Medical Sciences, Sawangi (Meghe), Wardha) who met the criteria for sepsis. After obtaining written informed consent, all patients who satisfied the inclusion and exclusion criteria were included in the study. Duration for study: 2022 to 2024. Inclusion criteria: • Patients older than 18 years of age • The patient satisfied diagnosis and diagnostic criteria of sepsis on the SOFA, and their survival time after admission is ≥24 hours. The following exclusion criteria must be met: • Patients with an emergency room survival time of fewer than twenty-four hours; Cardiac or Respiratory Arrest • Pregnancy; • Immune system disorders; • Malignant tumors; and • Haematological disorders. Variables Outcomes: 1. Mortality (within a specified time frame): The primary outcome measure indicated whether the patient died within a specified time period. 2. Length of MICU stay - The duration will be measured in hours or days. 3. Requirement for organ support: The need for specific interventions or therapies to support organ function, such as mechanical ventilation or vasopressors. Exposures: 1. Neutrophil Lymphocyte Ratio - A calculated by dividing the neutrophil count by the lymphocyte count from a patient’s blood sample, reflecting the balance between anti-inflammatory neutrophils and pro-inflammatory lymphocytes. 2. SOFA score: A scoring system that evaluates the degree of organ malfunction in six major organ systems: circulatory, neurological, hepatic, renal, respiratory, and coagulation. 3. APACHE IV score: A comprehensive scoring system that evaluates the severity of acute conditions, incorporating physiological parameters, chronic illness, and age. Predictors: 1. Comorbidities: pre-existing illnesses that could affect the patient’s prognosis, such as diabetes, hypertension, or chronic kidney disease. 2. Source of infection: The primary site or origin of the infection causing sepsis (e.g., respiratory, urinary, and abdominal). 3. Microbiological culture results: Laboratory results identifying the specific causative organism responsible for the infection. 4. Laboratory parameters: Results of blood tests, including white blood cell count and lactate levels, may indicate the severity of infection and organ dysfunction. Potential confounders: 1. Presence of septic shock: The occurrence of sepsis-induced circulatory and cellular/metabolic abnormalities results in a higher risk of mortality. 2. Severity of illness: The overall severity and complexity of the patient’s acute illness, which may affect prognosis. 3. Use of specific treatments or interventions: The administration of specific therapies or interventions such as antibiotics or fluid resuscitation can influence patient outcomes. Effect modifiers: 1. Age: Patient age may modify the relationship between exposure and outcomes. 2. Sex: The biological sex of the patient may interact with exposure to influence outcomes. 3. Presence of comorbidities: Pre-existing medical conditions may modify the effects of exposure on outcomes. 4. Source of infection: The specific site or origin of the infection may interact with the exposure to affect outcomes. 5. Specific type of organ dysfunction: The presence of specific organ dysfunction may modify the effects of exposure on outcomes. Data sources/measurement Collection of Blood Sample To begin the blood collection process, the skin above the median cubital vein was prepared by applying spirit to the cubital fossa area. Additionally, a tourniquet was placed proximal to the fossa. Subsequently, a sterile venipuncture needle, the standard in its design, was used to collect the blood. blood was drawn into a bulb containing potassium ethylenediamine tetra acetate for sample collection and complete blood cell count analysis. Importantly, blood sample analysis was carried out within a 15-minute timeframe from the time of collection. Confidentiality The collected data will be kept confidential. The data were coded and entered into a password-protected digital form. The names and other personal details of the patients will not be revealed. Procedure Blood samples will be taken under strict aseptic precautions. Measurement of Blood Pressure According to the guidelines set forth by the American Heart Association (AHA), readings of 130 mmHg or higher for systolic blood pressure (SBP) or 80 mmHg or higher for diastolic blood pressure (DBP) are indicative of elevated blood pressure. The blood pressure of each patient was measured according to the protocol recommended by the AHA. Clinical examination A comprehensive clinical examination will be conducted and all observed findings will be recorded. A thorough patient history and examinations will be performed. Relevant historical information, including smoking and alcohol consumption as well as medication use, will be documented. We will also assess any pre-existing medical conditions in the patients, inquiring about a history of hypertension, diabetes, malignancy, and chronic kidney and liver disease. Physical examination will include pulse rate, blood pressure, Glassgow coma scale score, and complete blood count. SOFA The SOFA score, referred to as the sepsis-related organ failure assessment score previously, is employed to monitor an individual’s condition during their ICU stay. It is used to assess the degree of organ function or rate of organ failure in a person ( Table 1 ) Table 1. Shows SOFA score. 7 Organ system 0 1 2 3 4 Respiratory (PaO 2 /FiO 2 ) >400 ≤400 ≤300 ≤200 ≤100 Renal Creatinine (μmol/L) <106 106-168 169-300 301-433 Urine output 433 Urine output <200ml/day Hepatic Bilirubin (μmol/L) 203 Cardiovascular Hypotension No Hypotension MAP 5 or epinephrine ≤0.1 or norepinephrine ≤0.1 μg/kg/min Dopamine >15 or epinephrine >0.1 or norepinephrine >0.1μg/kg/min Haematological Platelet count (x10 3 /mm 3 ) >150 ≤150 ≤100 ≤50 ≤20 Neurological Glasgow Coma Scale score 15 13-14 10-12 6-9 <6 . APACHE IV The parameters for assessment include: 1. Age (years) 2. Body Temperature (°C) 3. Mean Arterial Pressure (MAP, mmHg) 4. Heart Rate (HR, beats per minute) 5. Respiratory Rate (RR, breaths per minute) 6. Mechanical Ventilation (Yes/No) 7. Fraction of Inspired Oxygen (FiO 2 , %) 8. Partial Pressure of Oxygen (pO 2 , mmHg) 9. Partial Pressure of Carbon Dioxide (pCO 2 , mmHg) 10. Arterial pH 11. Sodium (Na+, mEq/L) 12. Urine Output (mL per 24 hours) 13. Creatinine (mg/dL) 14. Urea (mEq/L) 15. Blood Sugar Level (BSL, mg/dL) 16. Albumin (g/L) 17. Bilirubin (mg/dL) 18. Hematocrit (Ht, %) 19. White Blood Cell Count (x1000/mm3) 20. Glasgow Coma Scale (GCS) with subcomponents: - Eye Response - Verbal Response - Motor Response 21. Chronic Health Conditions: - Chronic Renal Failure (CRF) or hemodialysis (HD) - Cirrhosis - Hepatic Failure - Metastatic Carcinoma - Lymphoma - Leukemia or Myeloma - Immunosuppression - Acquired Immunodeficiency Syndrome (AIDS) Statistical analysis Continuous variables will be expressed as mean ± Standard Deviation and compared across groups using unpaired t-test or ANOVA. Categorical variables will be expressed as the number and percentage of patients and compared across groups. All the data will be entered in Microsoft Excel 2013, and the statistical software R studio Version 4.3.1 will be used for the analysis. An alpha level of 5% will be considered, that is, if any p-value is less than 0.05, it will be considered significant. Means between two different groups will be assessed using an unpaired t-test. Correlations will be done using Spearman’s or Pearson’s correlations. Bias 1. Selection Bias: Non-random or non-representative participant selection. 2. Information Bias: Errors or inconsistencies in measurement or data recording. 3. Confounding Bias: Distortion of association due to an extraneous variable. 4. Reporting Bias: Publication bias favoring significant or positive results. 5. Observer Bias: Biased interpretation or reporting by researchers or clinicians. 6. Lead-time Bias: Differences in outcome assessment timing affecting results. Sample size Applying Krejcie and Morgan Formula for the estimation of the sample size (1) n = χ 2 ∗ N ∗ P ∗ ( 1 − P ) c 2 ∗ ( N − 1 ) + χ 2 ∗ P ∗ ( 1 − P ) where χ 2 is the chisquare tabulated value for 1 Degree of Freedom at 95% confidence interval N is the total number of patients P is the 50% proportion c is the Error of Margin at 5% Substituting the appropriate values for the statistical estimation in equation 1 leads to n = 3.84 ∗ 600 ∗ 0.5 ∗ ( 1 − 0.5 ) 0.05 2 ∗ ( 600 − 1 ) + 3.84 ∗ 0.5 ∗ ( 1 − 0.5 ) = 234.38 n = DEFF ∗ N ∗ P ∗ ( 1 − P ) / ( d / Z 1 − α / 2 ) 2 ∗ ( N − 1 ) + P ∗ ( 1 − P ) Expected outcome This study aimed to assess the prognosis of sepsis patients in the MICU by comparing the neutrophil-lymphocyte ratio combined with the SOFA score versus the APACHE IV score. The expected outcomes included a comparative analysis of the predictive performance of these scoring systems in predicting mortality, length of MICU stay, and requirement for organ support. Additionally, the association between Neutrophil Lymphocyte Ratio, SOFA score, APACHE IV score, and outcomes will be examined. This study will evaluate the accuracy and discriminatory power of the scoring systems, identify potential effect modifiers, and explore the clinical implications of using these tools in assessing sepsis prognosis. These findings will contribute to the understanding of prognostic assessment in sepsis and may have implications for patient management and decision-making in the MICU. Dissemination The study will be distributed in index journal. Discussion A critical clinical state known as sepsis is characterised by dysregulated response of host to infections & frequently develops as consequence of severe infection. 8 Cardinal symptoms of inflammation, such as vasodilation, leukocyte buildup, and increased vascular permeability, are part of this response and can manifest in tissues far from the infection site. High death rates are associated with sepsis, especially in patients who require treatment in the ICU. Early and precise diagnosis is essential to improve the prognosis of patients with sepsis. 9 In critically ill patients, sepsis diagnosis is a formidable challenge, necessitating a multifaceted approach. In addition to obtaining a comprehensive medical history and conducting thorough physical examination, laboratory markers of infection and inflammation are vital components of the diagnostic process. These markers include White Blood Cell (WBC), C-reactive protein (CRP), procalcitonin (PCT), neutrophil, and lymphocyte counts. Among these indicators, neutrophil-to-lymphocyte ratio (NLR) has emerged as a valuable biomarker for sepsis diagnosis. NLR is a straightforward and cost-effective parameter derived from complete blood count (CBC). It offers insights into the balance between neutrophils, which are indicative of inflammation, and lymphocytes, which reflects the immune response. Significantly, in sepsis, a higher NLR is associated with a worse outcome. The natural reaction of the immune system to infection and other stressful situations is an increase in neutrophil counts and a decrease in lymphocyte counts. While lymphocyte numbers decrease when activated cells travel to inflammatory tissues and incur greater apoptosis, neutrophil counts increase as a result of reduced apoptosis and rapid mobilization of neutrophils from the bone marrow. 8 The neutrophil-lymphocyte count ratio (NLCR), first described in 2001, is a simple, quick, and economical metric for evaluating stress and inflammation in critically ill patients. Zahorec et al. conducted a prospective study. involving ninty patients in the ICU, revealing that NLR had the capability to forecast the severity and future outcomes in patients with sepsis. 10 Recent research has demonstrated the predictive utility of NLCR in patients presenting to the Emergency Department (ED) with suspected bacteremia, as well as its correlation with the short- and long-term outcomes of patients in critical conditions. 11 Heffernan et al. observed that trauma patients and those meeting the criteria for systemic inflammatory response syndrome (SIRS) exhibited a concurrent condition characterized by both low lymphocyte counts and high neutrophil counts. 12 In contrast, Bermejo-Martín et al. found a link between reduced circulating neutrophil counts and an increased risk of mortality. 13 This raises the possibility that sepsis patients with low circulating neutrophil counts may find it difficult to generate a potent innate immune response. Furthermore, sepsis syndrome may cause neutrophils to adhere to the vascular endothelium more strongly, which would lower the number of circulating neutrophils. Endothelial injury is a common consequence of sepsis. 12 The SOFA scoring system is a widely utilized tool for gauging the severity of organ dysfunction in critically ill patients, including those with sepsis. The SOFA examines the condition in six distinct organ systems: cardiovascular, neurological, hepatic, renal, respiratory, and coagulation. Each system was assigned a score ranging from zero, representing normal function, to four, denoting severe dysfunction or failure). A score of 3 or 4 in any particular system indicated a high likelihood of organ failure within that specific system. The SOFA assigns a numerical value to each system, providing healthcare providers with a measurable indicator of dysfunction across various organs. 13 In a study conducted by Shimoyama et al., it was noted that SOFA scores were correlated with higher estimated risk levels than NLR. Furthermore, this study disclosed that the likelihood of mortality increased by 13 % %with every increase of 1 unit in the SOFA scores. This phenomenon can be explained by the fact that SOFA scores are confined to a limited numerical range between 0 and 20, whereas the NLR lacks an upper numerical limit, permitting a wider spectrum of values. 13 , 14 Both NLR and platelet-to-lymphocyte ratio (PLR) were identified as straightforward, cost-efficient, and expeditious indicators of mortality when juxtaposed with more intricate scoring systems, such as APACHE II and SOFA scores. The amalgamation of these biomarkers, such as SOFA scores and NLR, has the potential to increase the accuracy of mortality predictions. This unified approach capitalizes on the strengths of both systems and offers a more comprehensive evaluation of a patient’s condition. Consequently, the integration of SOFA scores and NLR can empower healthcare providers to make better informed decisions regarding the prognosis and treatment of critically ill patients, particularly those with sepsis in the intensive care unit (ICU). 13 Notably, when measuring the neutrophil-to-lymphocyte ratio (NLR) upon admission to the Intensive Care Unit (ICU), researchers have found associations with both short-term and long-term mortality in critically ill adult patients. This suggests that NLR could serve as a valuable indicator of the inflammatory response in critically ill adults. In the context of sepsis management in the ICU, the NLR and NLCR can serve as valuable tools for risk stratification and prognostication. These biomarkers provide clinicians with additional insights into patients’ inflammatory and immune responses, helping to guide early intervention and treatment decisions. The APACHE IV is an enhanced and modernized model designed to forecast the mortality rate of groups of critically ill patients, while the previously revised equation is used to predict mortality rates in hospitals following coronary artery bypass graft (CABG) surgery. The APACHE IV is a scoring system and predictive model utilized in medical settings to assess the severity of illness and predict the risk of mortality. 15 It includes the following components: 1. Acute Physiology Score (APS): This component assesses the physiological status of a patient upon admission to the ICU. It considers vital signs, laboratory values, and other clinical parameters to measure the severity of an acute illness. 2. Age: The patient’s age is a factor in the APACHE IV model, as older age can be associated with increased mortality risk. 3. Chronic Health Points (CHP): This component considers a patient’s pre-existing health conditions and comorbidities. It assigns points based on the presence and severity of chronic illness. 4. Glasgow Coma Scale (GCS): The patient’s degree of consciousness and neurological function are evaluated using the GCS. 5. Admission Source: This component considers where the patient was admitted, such as the emergency department, operating room, or other locations within the hospital. 6. Admission Type: It categorizes the patient’s admission as either scheduled (elective) or unscheduled (emergency). 7. Diagnostic Category: This component classifies the patient into one of several diagnostic categories, which helps to group patients with similar conditions for risk prediction. 8. Chronic Health Conditions: APACHE IV includes specific chronic health conditions and comorbidities as risk factors. 9. Organ Support: It considers whether the patient requires mechanical ventilation, renal replacement therapy, or other forms of organ support. 10. Surgical Status: APACHE IV accounts for surgical patients and their post-operative status, including elective or emergency surgery. These components were used to calculate the predicted risk of mortality for each ICU patient. The APACHE IV score provides valuable information for clinicians and researchers to assess illness severity and make informed decisions regarding patient care. It is a widely used tool in critical care medicine for risk stratification and quality improvement. Keep in mind that The specific details and components of the APACHE IV may evolve over time as new versions or updates are developed. 15 This study aimed to assess the combined SOFA and NLR scores as predictors of outcomes in patients with sepsis and to estimate the APACHE IV Score for the same patient population. This study aimed to compare the predictive capabilities of the combined NLR-SOFA score with the APACHE IV score in terms of mortality risk, length of stay in the intensive care unit (ICU), and need for mechanical ventilation among sepsis patients. This analysis aimed to provide valuable insights into the effectiveness of these scoring systems in guiding clinical decisions and improving patient care for individuals with sepsis. Written consent will be taken from all the participants in the study. Ethical committee: Datta Meghe Institute of Medical Sciences (Deemed to be University) IEC NO- DMIMS (DU)/IEC/2022/1091 aprooved on 27/06/2022. Study status: Not yet started. Data availability No data are associated with this article. Acknowledgement All authors mentioned for the study have contributed equally to the study design, data curation, data availability, conceptuality, writing, and drafting. References 1. Evans L, Rhodes A, Alhazzani W, et al. : Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. Intensive Care Med. 2021; 47 (11): 1181–1247. PubMed Abstract | Publisher Full Text | Free Full Text 2. de Jager CP , Wever PC, Gemen EF, et al. : The neutrophil-lymphocyte count ratio in patients with community-acquired pneumonia. PLoS One. 2012; 7 (10): e46561. PubMed Abstract | Publisher Full Text | Free Full Text 3. Berhane M, Melku M, Amsalu A, et al. : The Role of Neutrophil to Lymphocyte Count Ratio in the Differential Diagnosis of Pulmonary Tuberculosis and Bacterial Community-Acquired Pneumonia: a Cross-Sectional Study at Ayder and Mekelle Hospitals, Ethiopia. Clin. Lab. 2019; 65 (4). PubMed Abstract | Publisher Full Text 4. Azab B, Chainani V, Shah N, et al. : Neutrophil–Lymphocyte Ratio as a Predictor of Major Adverse Cardiac Events Among Diabetic Population: A 4-Year Follow-Up Study. Angiology. 2013; 64 (6): 456–465. PubMed Abstract | Publisher Full Text 5. Tomita M, Shimizu T, Ayabe T, et al. : Preoperative neutrophil to lymphocyte ratio as a prognostic predictor after curative resection for non-small cell lung cancer. Anticancer Res. 2011; 31 (9): 2995–2998. PubMed Abstract 6. Vincent JL, Moreno R, Takala J, et al. : The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med. 1996; 22 (7): 707–710. PubMed Abstract | Publisher Full Text 7. Williams L, Gannon J: Use of the SOFA Score in Pandemic Influenza — A Prospective Study. J. Intensive Care Soc. 2009; 10 (3): 179–182. Publisher Full Text 8. Westerdijk K, Simons KS, Zegers M, et al. : The value of the neutrophil-lymphocyte count ratio in the diagnosis of sepsis in patients admitted to the Intensive Care Unit: A retrospective cohort study. PLoS One. 2019; 14 (2): e0212861. PubMed Abstract | Publisher Full Text | Free Full Text 9. Annane D, Bellissant E, Cavaillon JM: Septic shock. Lancet. 2005; 365 (9453): 63–78. Epub 2005/01/11. Publisher Full Text 10. Zahorec R: Ratio of neutrophil to lymphocyte counts--rapid and simple parameter of systemic inflammation and stress in critically ill. Bratisl. Lek. Listy. 2001; 102 (1): 5–14. English, Slovak. PubMed Abstract 11. Salciccioli JD, Marshall DC, Pimentel MA, et al. : The association between the neutrophil-to-lymphocyte ratio and mortality in critical illness: an observational cohort study. Crit. Care. 2015; 19 : 13. Epub 2015/01/20. PubMed Abstract | Publisher Full Text | Free Full Text 12. Heffernan DS, Monaghan SF, Thakkar RK, et al. : Failure to normalize lymphopenia following trauma is associated with increased mortality, independent of the leukocytosis pattern. Crit. Care. 2012 Jan; 16 (1): R12. PubMed Abstract | Publisher Full Text | Free Full Text 13. Altas OF, Kizilkaya M: The effects of neutrophil-lymphocyte ratio, platelet-lymphocyte ratio and prognostic markers in determining the mortality in patients diagnosed with pneumonia in intensive care. Medeni. Med. J. 2021; 36 (2): 130–137. PubMed Abstract | Publisher Full Text | Free Full Text 14. Shimoyama Y, Umegaki O, Agui T, et al. : Neutrophil to lymphocyte ratio and platelet to lymphocyte ratio are superior to other inflammation-based prognostic scores in predicting the mortality of patients with gastrointestinal perforation. JA Clin. Rep. 2017; 3 (1): 49. PubMed Abstract | Publisher Full Text | Free Full Text 15. Zimmerman JE, Kramer AA, McNair DS, et al. : Acute Physiology and Chronic Health Evaluation (APACHE) IV: Hospital mortality assessment for today’s critically ill patients. Crit. Care Med. 2006; 34 (5): 1297–1310. PubMed Abstract | Publisher Full Text Comments on this article Comments (0) Version 1 VERSION 1 PUBLISHED 26 Apr 2024 ADD YOUR COMMENT Comment Author details Author details 1 Department of Medicine, Datta Meghe Institute of Higher Education and Research, Wardha, Maharashtra, 442001, India Venkat Reddy Roles: Conceptualization, Data Curation, Formal Analysis, Funding Acquisition, Investigation, Methodology, Project Administration, Resources, Software, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Sunil Kumar Roles: Data Curation, Supervision, Validation, Visualization, Writing – Review & Editing Competing interests No competing interests were disclosed. Grant information The author(s) declared that no grants were involved in supporting this work. Article Versions (1) version 1 Published: 26 Apr 2024, 13:403 https://doi.org/10.12688/f1000research.143930.1 Copyright © 2024 Reddy V and Kumar S. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Download Export To Sciwheel Bibtex EndNote ProCite Ref. Manager (RIS) Sente metrics Views Downloads F1000Research - - PubMed Central info_outline Data from PMC are received and updated monthly. - - Citations open_in_new 0 open_in_new 0 open_in_new SEE MORE DETAILS CITE how to cite this article Reddy V and Kumar S. Comparison of Neutrophil Lymphocyte Ratio combined SOFA versus APACHE IV in assessing the Prognosis of Sepsis Patients admitted to Medical Intensive Care Unit [version 1; peer review: 2 approved with reservations] . F1000Research 2024, 13 :403 ( https://doi.org/10.12688/f1000research.143930.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS track receive updates on this article Track an article to receive email alerts on any updates to this article. TRACK THIS ARTICLE Share Open Peer Review Current Reviewer Status: ? Key to Reviewer Statuses VIEW HIDE Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Version 1 VERSION 1 PUBLISHED 26 Apr 2024 Views 0 Cite How to cite this report: Landoni G. Reviewer Report For: Comparison of Neutrophil Lymphocyte Ratio combined SOFA versus APACHE IV in assessing the Prognosis of Sepsis Patients admitted to Medical Intensive Care Unit [version 1; peer review: 2 approved with reservations] . F1000Research 2024, 13 :403 ( https://doi.org/10.5256/f1000research.157657.r422549 ) The direct URL for this report is: https://f1000research.com/articles/13-403/v1#referee-response-422549 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 22 Oct 2025 Giovanni Landoni , IRCCS San Raffaele Scientific Institute, Milan, Italy Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.157657.r422549 Thank you for the opportunity to review this manuscript. Authors describe the protocol for a prospective observational study aimed at comparing NLR+SOFA vs APACHE IV for septic patients’ prognosis in the medical ICU. The topic is of great importance, ... Continue reading READ ALL Thank you for the opportunity to review this manuscript. Authors describe the protocol for a prospective observational study aimed at comparing NLR+SOFA vs APACHE IV for septic patients’ prognosis in the medical ICU. The topic is of great importance, since sepsis still represents a life-threatening condition with high mortality rates. This study could provide insights on the use of different scoring systems in guiding clinical decisions, adding a valuable parameter such as NLR without increasing the costs – and the workload – in the ICU. Please find below some comments that might improve the manuscript: Please revise the text for grammar and typographical errors (e.g., “theeutrophil”, “Glassgow” coma scale, 13% %, ninty, “Neutrophil Lymphocyte Ratio - A calculated”). Consider providing more context to the use of NLR in other medical conditions apart from sepsis, focusing on other non-infectious medical conditions which might affect NLR. You might find these articles useful for this purpose: DOI: 10.22514/sv.2025.006, DOI: 10.22514/sv.2024.122 Please provide a detailed description of the specific criteria used for sepsis definition and provide references. Consider describing how you will handle the presence of septic shock, which was listed among the potential confounders. This will increase transparency and provide strength to study results. Please adjust the layout of the exclusion criteria section. Please specify outcome assessment timepoint for mortality to increase transparency and strengthen the results. Please provide details about SOFA score calculation, SOFA assessment timepoints, management of competing risks and handling of missing data. Since the SOFA score is one of the pillars of this cross-sectional study, the detailed description of all these aspects will provide transparency and will strengthen study design and results. You might find this article useful for this purpose: (refer to 1) Please specify the exact number of patients planned to conduct the study. Consider also specifying if any additional patients are planned in case of loss to follow up and/or dropouts. Please describe and contextualize NLCR, its relation and differences with NLR to improve clarity and readability. Please clarify the use of the past tense throughout the manuscript, which contradicts the current study status “not yet started”. Please consider revising the text. Is the rationale for, and objectives of, the study clearly described? Yes Is the study design appropriate for the research question? Yes Are sufficient details of the methods provided to allow replication by others? Partly Are the datasets clearly presented in a useable and accessible format? Not applicable References 1. Marmiere M, D’Amico F, Monti G, Landoni G: Mastering the Sequential Organ Failure Assessment Score: Critical Choices of Score Statistic, Timing, Imputations, and Competing Risk Handling in Major Trials—A Systematic Review. Critical Care Medicine . 2025; 53 (5): e1116-e1124 Publisher Full Text Competing Interests: No competing interests were disclosed. Reviewer Expertise: Critical care, hemodynamics, ventilation I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Landoni G. Reviewer Report For: Comparison of Neutrophil Lymphocyte Ratio combined SOFA versus APACHE IV in assessing the Prognosis of Sepsis Patients admitted to Medical Intensive Care Unit [version 1; peer review: 2 approved with reservations] . F1000Research 2024, 13 :403 ( https://doi.org/10.5256/f1000research.157657.r422549 ) The direct URL for this report is: https://f1000research.com/articles/13-403/v1#referee-response-422549 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Sivayoham N. Reviewer Report For: Comparison of Neutrophil Lymphocyte Ratio combined SOFA versus APACHE IV in assessing the Prognosis of Sepsis Patients admitted to Medical Intensive Care Unit [version 1; peer review: 2 approved with reservations] . F1000Research 2024, 13 :403 ( https://doi.org/10.5256/f1000research.157657.r301706 ) The direct URL for this report is: https://f1000research.com/articles/13-403/v1#referee-response-301706 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 22 Jul 2024 Narani Sivayoham , , St George’s University Hospitals NHS Foundation Trust, London, UK Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.157657.r301706 Thank you for inviting me to review the manuscript, ‘Comparison of neutrophil lymphocyte ratio combined SOFA versus APACHE IV in assessing the prognosis of sepsis patients admitted to Medical Intensive Care Unit’. In this prospective cross-sectional study, the authors plan ... Continue reading READ ALL Thank you for inviting me to review the manuscript, ‘Comparison of neutrophil lymphocyte ratio combined SOFA versus APACHE IV in assessing the prognosis of sepsis patients admitted to Medical Intensive Care Unit’. In this prospective cross-sectional study, the authors plan to compare the prognostic performance of the SOFA score combined with the neutrophil lymphocyte ratio with that of the APACHE IV score. The purpose of this study as I understand it is to improve the SOFA score by adding the neutrophil lymphocyte ratio and study its prognostic performance to a much more complex scoring system, the APACHE IV score. This is all the more important as it uses routinely available parameters. Whilst the purpose of the study is commendable, there are some areas in this study protocol that need clarification. My comments are as follows: The title of the protocol implies that the population studied are those patients admitted to a medical intensive care unit. However, under methods, the authors state that the setting is, ‘all patients visiting the department of general medicine’. Please clarify the study population. The authors have described how blood will be drawn in this prospective cross-sectional study. Will the patients provide informed consent? The authors state that patients will be included if they meet the sepsis criteria. Which criteria are these? If it is the Sepsis-3 criteria, will they be collecting baseline blood results? What is meant by immune system disorders’ and ‘haematological disorders’? Outcomes—The authors have not specified the time period in which they will measure the primary outcome. This needs to be specified. The authors state that the blood sample analysis will take place within 15 minutes of collection. How will this be monitored? What will happen to samples that are not processed within 15 minutes? There are long lists of predictors, potential confounders and effect modifiers. How will they collect data on this? Will they be controlling for these? It is not clear why the definition of elevated blood pressure is included in the protocol. Please explain. The protocol lists several biases. However, it does not mention any systems in place to mitigate these biases. Thank you for providing a sample size calculation. Is the P=50% proportion the expected mortality rate? If so, how was this arrived at? Statistical tests- Please provide the statistical tests that will be used to compare the NLR combined SOFA score with the APACHE IV score What test will determine if the NLR combined SOFA score has higher predictive accuracy than the APACHE IV score? The manuscript could be streamlined. The descriptions of the different scoring systems are replicated throughout. The tense in which the protocol is written is not consistent. For example on page 5, under ‘confidentiality’, the following is stated: ‘The collected data will be kept confidential. The data were coded…..’ Is the rationale for, and objectives of, the study clearly described? Yes Is the study design appropriate for the research question? Partly Are sufficient details of the methods provided to allow replication by others? Partly Are the datasets clearly presented in a useable and accessible format? Not applicable Competing Interests: No competing interests were disclosed. Reviewer Expertise: Scoring systems in sepsis I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Sivayoham N. Reviewer Report For: Comparison of Neutrophil Lymphocyte Ratio combined SOFA versus APACHE IV in assessing the Prognosis of Sepsis Patients admitted to Medical Intensive Care Unit [version 1; peer review: 2 approved with reservations] . F1000Research 2024, 13 :403 ( https://doi.org/10.5256/f1000research.157657.r301706 ) The direct URL for this report is: https://f1000research.com/articles/13-403/v1#referee-response-301706 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Comments on this article Comments (0) Version 1 VERSION 1 PUBLISHED 26 Apr 2024 ADD YOUR COMMENT Comment keyboard_arrow_left keyboard_arrow_right Open Peer Review Reviewer Status info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Reviewer Reports Invited Reviewers 1 2 Version 1 26 Apr 24 read read Narani Sivayoham , , St George’s University Hospitals NHS Foundation Trust, London, UK Giovanni Landoni , IRCCS San Raffaele Scientific Institute, Milan, Italy Comments on this article All Comments (0) Add a comment Sign up for content alerts Sign Up You are now signed up to receive this alert Browse by related subjects keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Landoni G. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 22 Oct 2025 | for Version 1 Giovanni Landoni , IRCCS San Raffaele Scientific Institute, Milan, Italy 0 Views copyright © 2025 Landoni G. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Thank you for the opportunity to review this manuscript. Authors describe the protocol for a prospective observational study aimed at comparing NLR+SOFA vs APACHE IV for septic patients’ prognosis in the medical ICU. The topic is of great importance, since sepsis still represents a life-threatening condition with high mortality rates. This study could provide insights on the use of different scoring systems in guiding clinical decisions, adding a valuable parameter such as NLR without increasing the costs – and the workload – in the ICU. Please find below some comments that might improve the manuscript: Please revise the text for grammar and typographical errors (e.g., “theeutrophil”, “Glassgow” coma scale, 13% %, ninty, “Neutrophil Lymphocyte Ratio - A calculated”). Consider providing more context to the use of NLR in other medical conditions apart from sepsis, focusing on other non-infectious medical conditions which might affect NLR. You might find these articles useful for this purpose: DOI: 10.22514/sv.2025.006, DOI: 10.22514/sv.2024.122 Please provide a detailed description of the specific criteria used for sepsis definition and provide references. Consider describing how you will handle the presence of septic shock, which was listed among the potential confounders. This will increase transparency and provide strength to study results. Please adjust the layout of the exclusion criteria section. Please specify outcome assessment timepoint for mortality to increase transparency and strengthen the results. Please provide details about SOFA score calculation, SOFA assessment timepoints, management of competing risks and handling of missing data. Since the SOFA score is one of the pillars of this cross-sectional study, the detailed description of all these aspects will provide transparency and will strengthen study design and results. You might find this article useful for this purpose: (refer to 1) Please specify the exact number of patients planned to conduct the study. Consider also specifying if any additional patients are planned in case of loss to follow up and/or dropouts. Please describe and contextualize NLCR, its relation and differences with NLR to improve clarity and readability. Please clarify the use of the past tense throughout the manuscript, which contradicts the current study status “not yet started”. Please consider revising the text. Is the rationale for, and objectives of, the study clearly described? Yes Is the study design appropriate for the research question? Yes Are sufficient details of the methods provided to allow replication by others? Partly Are the datasets clearly presented in a useable and accessible format? Not applicable References 1. Marmiere M, D’Amico F, Monti G, Landoni G: Mastering the Sequential Organ Failure Assessment Score: Critical Choices of Score Statistic, Timing, Imputations, and Competing Risk Handling in Major Trials—A Systematic Review. Critical Care Medicine . 2025; 53 (5): e1116-e1124 Publisher Full Text Competing Interests No competing interests were disclosed. Reviewer Expertise Critical care, hemodynamics, ventilation I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (0) Landoni G. Peer Review Report For: Comparison of Neutrophil Lymphocyte Ratio combined SOFA versus APACHE IV in assessing the Prognosis of Sepsis Patients admitted to Medical Intensive Care Unit [version 1; peer review: 2 approved with reservations] . F1000Research 2024, 13 :403 ( https://doi.org/10.5256/f1000research.157657.r422549) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/13-403/v1#referee-response-422549 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2024 Sivayoham N. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 22 Jul 2024 | for Version 1 Narani Sivayoham , , St George’s University Hospitals NHS Foundation Trust, London, UK 0 Views copyright © 2024 Sivayoham N. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Thank you for inviting me to review the manuscript, ‘Comparison of neutrophil lymphocyte ratio combined SOFA versus APACHE IV in assessing the prognosis of sepsis patients admitted to Medical Intensive Care Unit’. In this prospective cross-sectional study, the authors plan to compare the prognostic performance of the SOFA score combined with the neutrophil lymphocyte ratio with that of the APACHE IV score. The purpose of this study as I understand it is to improve the SOFA score by adding the neutrophil lymphocyte ratio and study its prognostic performance to a much more complex scoring system, the APACHE IV score. This is all the more important as it uses routinely available parameters. Whilst the purpose of the study is commendable, there are some areas in this study protocol that need clarification. My comments are as follows: The title of the protocol implies that the population studied are those patients admitted to a medical intensive care unit. However, under methods, the authors state that the setting is, ‘all patients visiting the department of general medicine’. Please clarify the study population. The authors have described how blood will be drawn in this prospective cross-sectional study. Will the patients provide informed consent? The authors state that patients will be included if they meet the sepsis criteria. Which criteria are these? If it is the Sepsis-3 criteria, will they be collecting baseline blood results? What is meant by immune system disorders’ and ‘haematological disorders’? Outcomes—The authors have not specified the time period in which they will measure the primary outcome. This needs to be specified. The authors state that the blood sample analysis will take place within 15 minutes of collection. How will this be monitored? What will happen to samples that are not processed within 15 minutes? There are long lists of predictors, potential confounders and effect modifiers. How will they collect data on this? Will they be controlling for these? It is not clear why the definition of elevated blood pressure is included in the protocol. Please explain. The protocol lists several biases. However, it does not mention any systems in place to mitigate these biases. Thank you for providing a sample size calculation. Is the P=50% proportion the expected mortality rate? If so, how was this arrived at? Statistical tests- Please provide the statistical tests that will be used to compare the NLR combined SOFA score with the APACHE IV score What test will determine if the NLR combined SOFA score has higher predictive accuracy than the APACHE IV score? The manuscript could be streamlined. The descriptions of the different scoring systems are replicated throughout. The tense in which the protocol is written is not consistent. For example on page 5, under ‘confidentiality’, the following is stated: ‘The collected data will be kept confidential. The data were coded…..’ Is the rationale for, and objectives of, the study clearly described? Yes Is the study design appropriate for the research question? Partly Are sufficient details of the methods provided to allow replication by others? Partly Are the datasets clearly presented in a useable and accessible format? Not applicable Competing Interests No competing interests were disclosed. Reviewer Expertise Scoring systems in sepsis I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (0) Sivayoham N. Peer Review Report For: Comparison of Neutrophil Lymphocyte Ratio combined SOFA versus APACHE IV in assessing the Prognosis of Sepsis Patients admitted to Medical Intensive Care Unit [version 1; peer review: 2 approved with reservations] . F1000Research 2024, 13 :403 ( https://doi.org/10.5256/f1000research.157657.r301706) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. 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