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Older age at anterior cruciate ligament reconstruction associates with a lower systemic inflammation response index after surgery
⁎Corresponding author: Tyler Barker. tyler.barker@osumc.edu
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Received: ,
Accepted: ,
This article was originally published by Reed Elsevier India Pvt. Ltd. and was migrated to Scientific Scholar after the change of Publisher.
Abstract
Abstract
The purpose of this study was to investigate the association of age at anterior cruciate ligament reconstruction (ACLR) with systemic indices of the immune system and inflammation after surgery.
This study consisted of a retrospective, cohort design. Patients (male and female, ≥18 years) that underwent ACLR at a single academic institution and with complete blood cell (CBC) count data obtained ≥ 1-year after surgery were included. Patients with a documented diagnosis of knee osteoarthritis (OA) before ACLR were excluded, while those with a documented diagnosis of knee OA after ACLR were included in this study. The systemic inflammation response index (SIRI), systemic immune-inflammatory index (SII), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) were calculated from the CBC data. Patients (n = 198) were separated into groups based on age at ACLR: (1) 18–29 y (n = 96), (2) 30–39 y (n = 50), or (3) ≥40 y (n = 52).
Subject characteristics (patient sex, height, body mass, and body mass index), follow-up interval, time from ACLR to CBC assessment, and concomitant procedures performed at ACLR were not significantly different between age groups. The PLR, NLR, MLR, and SII were not significantly different between groups, while the SIRI was significantly lower in the 30–39 (p < 0.01) and ≥40 y (p < 0.01) groups compared to the 18–29 y group. An older age at ACLR (i.e., 30–39 y and ≥40 y) was associated with an increased occurrence (11.5 and 12 %, respectively) of a knee OA diagnosis following surgery compared to that in the younger age group (18–29 y, 1.0 %; p = 0.04).
We conclude that an older age at ACLR associated with a lower systemic inflammatory response index at a minimum of 1-year following surger.
Level III.
Keywords
Anterior cruciate ligament
Knee osteoarthritis
Systemic inflammation response index
Systemic immune-inflammatory index
Neutrophil-to-lymphocyte ratio
Platelet-to-lymphocyte ratio
And monocyte-to-lymphocyte ratio
1 Introduction
An anterior cruciate ligament (ACL) tear is one of the most common knee injuries. ACL reconstruction (ACLR) is a safe and successful procedure to restore joint kinematics and proprioception following an ACL tear. Despite the high success rate of ACLR, post-operative impairments (e.g., quadriceps weakness and atrophy) and accelerated knee osteoarthritis (OA) continue to hinder rehabilitation efforts, strain the healthcare system, and impair patients’ quality of life. Among others, older age at ACLR is associated with a higher prevalence of medial chondral injury, increased degradation of articular cartilage and urinary biomarkers of collagen proteolysis, and an increased risk of developing knee OA.1–9
Aging deleteriously impacts the innate and adaptive immunity responses, thereby increasing vulnerability to pathogens and prevalence of chronic, low-grade inflammation. Systemic indices of the immune system and inflammation are elevated with aging,10,11 and emerging research demonstrates the clinical utility, reliability, and validity of systemic indices of the immune system and inflammation that are easily calculated from the differentials of a complete blood cell count (CBC).12,13 Composed of lymphocytes, monocytes, and neutrophils, the systemic inflammatory response index (SIRI) is a theoretical indicator of chronic inflammation14,15 and a potential diagnostic and prognostic biomarker in cancer, stroke, and inflammatory disease.16,17 The systemic immune-inflammation index (SII), consisting of platelets, neutrophils, and lymphocytes, is a suggestive indicator of the local immune response, systemic inflammation,18–20 and predictive of poor outcomes in acute kidney injury, heart failure, acute ischemic stroke, diabetes, spinal metastasis, and various cancers.21–25 An increase in the SIRI, SII, and other immune system and inflammatory indices have been found to associate with poor outcomes following surgery and with various diseases, including OA.10,20,25–32
Altered immune responses and inflammation are key regulators to the onset and progression of various chronic diseases, and despite the widespread appreciation of advancing age associating with immune system dysfunction and inflammation, it is surprisingly unknown if systemic indices of the immune system and inflammation after surgery associate with age at ACLR. Therefore, the purpose of this study was to investigate the association of age at ACLR with systemic indices of the immune system and inflammation after surgery. We hypothesized that an older age at ACLR associates with an increase in systemic indices of the immune system and inflammation after surgery.
2 Materials and methods
2.1 Study design and subjects
This retrospective study included patients (male and female, ≥18 y) who underwent arthroscopic ACLR between August 2009 and December 2021 at a single academic institution (The Ohio State University Wexner Medical Center, Columbus, OH) with a minimum 1-year follow-up. The last date of data review and extraction from the electronic medical records was June 1st, 2023. This study was approved with a consent waiver by the Institutional Review Board at The Ohio State University Wexner Medical Center (Columbus, OH).
Patients were initially identified using the International Classification of Diseases (ICD) 9th and 10th Revision and Current Procedural Terminology (CPT) codes. The initial query included patients that underwent ACLR (CPT code: 29888). Potential patients were subsequently screened for a documented diagnosis of knee OA (ICD 9 code: 715.96 or ICD 10 code: M17) in their medical records. Patients with a documented diagnosis of knee OA before ACLR were excluded, while those with a documented diagnosis of knee OA after ACLR were included in this study. Patients were then screened for available CBC with differential data obtained after ACLR. To minimize the transient impact of ACLR on systemic indices of the immune system and inflammation, patients with cell count data in their electronic medical records ≥ 1-year following ACLR were included. All data were identified and extracted from electronic medical records and time aligned to the dates of ACLR, diagnosis of knee OA (when applicable), and CBC with differential assessment.
The initial study criteria identified 431 patients that underwent ACLR and with CBC results obtained after surgery. However, some patients were subsequently excluded due to outlying neutrophil counts (above or below 1.5 x interquartile range [IQR]; n = 8), a documented diagnosis of knee OA before the first available CBC following ACLR (n = 22), or the first available CBC was obtained within 1 year after ACLR (n = 203). The final analysis included 198 patients that underwent ACLR with their first available CBC obtained ≥1 year after surgery and before a documented knee OA diagnosis (when applicable).
Patients were then separated into groups based on age at ACLR: (1) 18–29, (2) 30–39, or (3) ≥40 y. Additional procedures performed on the meniscus (CPT codes: 29880, 29881, 29882, and 29883), articular cartilage (CPT code: 29877), other ligaments (CPT code: 27427), patella (CPT codes: 27520, 27524, and 27562), and proximal tibia (CPT code: 27530) at ACLR were extracted from the electronic medical records database and documented for each patient.
2.2 Blood cell counts and systemic indices of inflammation
Blood cell counts were analyzed using an automated hematology analyzer (Sysmex XN 9000, Kobe, Japan) at The Ohio State University Wexner Medical Center central laboratory (Columbus, OH) and ordered as a standard of care separate from the routine care of ACLR. The first available CBC 1-year after ACLR (and before OA diagnosis when applicable) was used in this study. To characterize the systemic immune and inflammatory responses, SIRI (neutrophil x monocyte/lymphocyte counts), SII (platelet x neutrophil/lymphocyte absolute counts), neutrophil-to-lymphocyte ratio (NLR; neutrophil/lymphocyte absolute counts), platelet-to-lymphocyte ratio (PLR; platelet/lymphocyte absolute counts), and monocyte-to-lymphocyte ratio (MLR; monocyte/lymphocyte absolute counts) were calculated from the cell count data.
2.3 Statistical analysis
Data were checked for normality with a Shapiro-Wilk test before statistical analysis. Group (e.g., age) differences were assessed with separate one-way analysis of variance (ANOVA) tests followed by a Bonferroni correction for multiple pairwise comparisons or with a Kruskal-Wallis one-way ANOVA followed by a Dwass-Steel-Chritchlow-Fligner test for pairwise comparisons when appropriate. Separate Chi-Square tests were performed to analyze the associations between categorical variables. Sex and BMI were used as covariates. Non-normally distributed data were rank transformed prior to assessing the association between variables using a Pearson Product Moment Linear correlation analysis. Significance was set at p < 0.05. All statistical analyses were performed with SYSTAT (version 13.1, Chicago, IL).
3 Results
3.1 Subject characteristics
The final analysis consisted of 198 patients (median [IQR]: age, 30.3 [16.6] y; body mass index (BMI): 26.5 [7.6] kg/m2; time from ACLR to CBC, 2.44 [2.56] y; follow-up, 6.55 [5.92] y) that underwent ACLR. Subject characteristics (patient sex, height, weight, and BMI) were not significantly different between age groups (Table 1). As expected, age was significantly different between groups. Concomitant procedures performed at ACLR, time from ACLR to CBC assessment, and follow-up interval were not significantly different between age groups.
| Age groups at ACLR | ||||
| 18-29 y | 30-39 y | ≥40 y | p-value | |
| n (f/m) rowhead | 96 (45/51) | 50 (29/21) | 52 (24/28) | 0.38∗ |
| Age at ACLR, y | 23.8 (6.9) | 33.1 (4.8)a | 47.5 (10.6)ab | <0.01 |
| Height, m | 1.74 (0.13) | 1.74 (0.15) | 1.70 (0.13) | 0.78 |
| Body mass, kg | 77.1 (23.4) | 83.1 (28.3) | 83.8 (19.7) | 0.47 |
| Body mass index (BMI), kg/m2 | 25.4 (7.1) | 27.2 (9.3) | 27.4 (7.8) | 0.22 |
| Additional procedures at ACLR, n (%) | 0.23 | |||
| no | 24 (25.0) | 17 (34.0) | 10 (19.2) | |
| yes | 72 (75.0) | 33 (66.0) | 42 (80.8) | |
| ACLR to CBC, y | 2.49 (2.67) | 2.90 (2.56) | 2.36 (2.43) | 0.72 |
| Follow-up, y | 6.55 (5.74) | 6.73 (5.86) | 6.33 (6.57) | 0.72 |
| Post-ACLR OA diagnosis, n (%) | 0.01 | |||
| no | 95 (99.0) | 44 (88.0) | 46 (88.5) | |
| yes | 1 (1.0) | 6 (12.0) | 6 (11.5) | |
Although this study was not designed to assess the association between age at ACLR and a knee OA diagnosis following ACLR, a secondary analysis was performed and briefly included here. Consistent with previous research, older age at ACLR (i.e., 30–39 y and ≥40 y) associated with an increased occurrence (11.5 and 12.0 %, respectively) of a knee OA diagnosis following surgery compared to that in the younger age group (18–29 y, 1.0 %; seeTable 1).
3.2 Blood cell counts
White blood cell (WBC), red bed blood cell (RBC), platelet, neutrophil, and lymphocyte counts were not significantly different between groups (Table 2). However, monocytes were significantly lower in the 30–39 and ≥ 40 y groups compared to the 18–29 y group.
| Age groups at ACLR | ||||
| 18-29 y | 30-39 y | ≥40 y | p-value | |
| WBC (K/μL) | 7.75 (3.80) | 7.06 (2.99) | 6.71 (2.71) | 0.06 |
| RBC (M/μL) | 4.83 (0.72) | 4.63 (0.80) | 4.80 (0.98) | 0.39 |
| Platelets (K/μL) | 237 (80) | 232 (79) | 247 (97) | 0.30 |
| Neutrophils (K/μL) | 4.86 (3.36) | 4.22 (3.05) | 4.09 (1.88) | 0.06 |
| Lymphocytes (K/μL) | 1.91 (0.91) | 1.87 (0.75) | 1.77 (0.99) | 0.92 |
| Monocytes (K/μL) | 0.60 (0.24) | 0.53 (0.20)a | 0.52 (0.27)a | 0.04 |
3.3 Systemic indices of the immune system and inflammation
Systemic indices of the immune system and inflammation were not significantly different with and without concomitant procedures performed at ACLR (Table 3). The PLR, NLR, MLR, and SII were not significantly different between groups (Fig. 1). In contrast, the SIRI was significantly lower in the 30–39 and ≥ 40 y groups compared to the 18–29 y group. SIRI was not correlated with the time interval from ACLR to CBC assessment (Table 4). Conversely, the SII was significantly correlated with time from ACLR to CBC assessment, suggesting an increase in the SII with time (i.e., ≥ 1-year) after ACLR.
| Additional procedures at ACLR | |||
| No | Yes | p-value | |
| PLR | 116 (53) | 129 (65) | 0.73 |
| NLR | 2.53 (1.61) | 2.05 (1.65) | 0.33 |
| MLR | 0.31 (0.20) | 0.29 (0.14) | 0.28 |
| SII | 526 (292) | 558 (424) | 0.77 |
| SIRI | 1.24 (1.46) | 1.21 (1.14) | 0.50 |
| Age (y) at ACLR | Time (d) from ACLR to CBC | |||
| r | p-value | r | p-value | |
| PLR | −0.02 | 0.82 | 0.11 | 0.14 |
| NLR | −0.11 | 0.14 | 0.13 | 0.08 |
| MLR | −0.09 | 0.22 | 0.03 | 0.67 |
| SIRI | −0.11 | 0.11 | 0.09 | 0.20 |
| SII | −0.11 | 0.14 | 0.15 | 0.03 |
4 Discussion
The major finding of the present investigation was an older age at ACLR associated with a lower SIRI and a greater occurrence of a knee OA diagnosis after surgery. Importantly, the SIRI was not correlated with the time interval from ACLR to CBC assessment and was not significantly elevated in those who underwent concomitant procedures at ACLR. Overall, these data suggest a lower systemic index of inflammation in a patient population susceptible to knee OA following an ACL injury and reconstruction.
Traumatic knee injuries mediate the development of knee OA at a younger age compared to that associated with idiopathic or primary knee OA,33 and older age at ACLR is associated with an accelerated onset of knee OA.1,4 In contrast to our hypothesis, this study found a lower SIRI after surgery in patients who were older at the time of ACLR, plausibly suggesting a lower systemic inflammatory response in patients with an increased predisposition to developing a chronic, degenerative disease in the knee following trauma. Somewhat contrasting with this finding, previous data indicates an elevated SIRI with increased age10,11 and knee OA.12,34 In theory, these contrasting results could relate to differences in patient characteristics. For example, this study consisted of relatively younger patients with an increased risk of developing knee OA following ligamentous trauma compared to previous research that included older participants with signs and symptoms of primary knee OA. Additionally, SIRI and other systemic indices of the immune system and inflammation were assessed in the absence of, or in some situations, prior to a knee OA diagnosis, whereas previous research examined SIRI in subjects with an existing disease diagnosis.12,34 Based on these differences, it is feasible that patients at risk for a faster and earlier onset of knee OA following ligamentous trauma possess different immune and inflammatory profiles in the circulation than participants with existing or primary knee OA.
Along with other systemic indices of the immune system and inflammation, the SII has been found to associate with an increased risk of OA.13,34 In a large sample size study that excluded post-traumatic joint OA, Zhang and colleagues13 provided evidence linking an increase in the SII with hip, hand, and knee OA. The association of SII with OA was strengthened after excluding participants with extreme exposure values and with propensity score matching.13 Potentially magnifying this association, patients with an elevated SII and with OA are at an increased risk of all-cause and cardiovascular-related mortality.10 Nonetheless, in the present study, the SII values were not significantly different between age groups. However, the SII correlated with the time from ACLR to the CBC assessment, indicating an increase in the systemic inflammation-immune index with time (≥1 year) after ACLR. The sensitivity and specificity of the SII to diagnosis or predict knee OA, other diseases, complications, or outcomes after ACLR warrants additional examination.
The MLR is another immune system and inflammation index increased in the circulation with knee OA.11 In synovial fluid, a higher MLR has been recently identified to predict a worse treatment response (i.e., residual pain symptoms >3 on a visual analog scale) after intra-articular corticosteroid injections in patients with knee OA.35 Despite the localized findings from synovial fluid, the peripheral blood MLR was not significantly different between responders and non-responders, and the peripheral blood MLR did not predict the treatment response to intra-articular corticosteroid injections.35 In this investigation, an older age at ACLR was not associated with a perturbed MLR after surgery. Although this reports identifies the MLR following ACLR between cohorts (i.e., younger vs older) with different rates of developing knee OA after surgery,36–38 it is unknown if MLR alterations in the circulation predict treatment responses and outcomes following an ACL tear and surgery.
Prior data illustrates a lower circulating monocyte count in knee OA (i.e., Kellgren-Lawrence ≥2) compared to healthy controls.32 Incorporating a bidirectional two-sample Mendelian randomization approach to investigate the causality between circulating immune cells and different sites of OA, Xu and colleagues39 eloquently demonstrated an association between decreased monocyte counts and knee OA. Here, we extend those results by providing data illustrating an older age at ACLR associated with a lower monocyte count ≥ 1-year after surgery. The peripheral decrease of immune cells with aging could be related to the increased recruitment to the knee joint following ACLR.
In addition to those discussed above, there are other limitations to this study that require discussion. This study consisted of patients that underwent ACLR and lacked non-ACLR participants or healthy controls for comparison. Along these lines, cell counts are a common clinical chemistry but not commonly performed as a routine standard of care following ACLR without a suspected underlying condition, illness, or disease. Thus, it is plausible that other factors were guiding the clinical decision process of ordering cell counts in this cohort, and therefore, the results herein might not be generalizable to a wider ACLR patient population. Examples of suspected or known underlying conditions include but not limited to medical history (e.g., autoimmune disease, inflammatory arthritis, and tobacco use), post-operative complications, and chronic disease(s). Somewhat consistent with this limitation, is the lack of longitudinal CBC data obtained prior to and following ACLR. Next, groups were established based on the age at ACLR. Based on the literature of a knee OA diagnosis or degenerative changes found after ACLR, patients were separated into 30–39 y and ≥40 y groups.2,5,6,40 As a comparator to the older age groups and to reflect those potentially less likely to show early signs and symptoms of knee OA following ACLR, the younger age group was set at 18–29 y5, 6. Despite this reasoning for delineating age groups, it is unknown if utilizing younger or older ages or different age groupings at ACLR for group comparisons facilitates different results. Finally, graft type, fixation technique, and concurrent examination of comorbidities, such as hypertension and diabetes, were not included in this study and should be considered in future research.
5 Conclusions
An ACL tear and reconstruction alter the immune system and inflammatory components that regulate physiological and pathophysiological processes in health, disease, and wellness. Based on the findings of the present study, we conclude that an older age at ACLR associated with a lower systemic inflammatory response index at 1-year and beyond following surgery. Future research identifying the role of immune cells and systemic indices of the immune system and inflammation on outcomes following ACLR is warranted.
CRediT authorship contribution statement
Sonu Bae: Conceptualization, Data curation, Methodology, Formal analysis, Investigation, Methodology, Project administration, Supervision, Writing – original draft, Writing – review & editing. Christopher C. Kaeding: Conceptualization, Writing – review & editing. David C. Flanigan: Conceptualization, Writing – review & editing. Tyler Barker: Conceptualization, Data curation, Methodology, Formal analysis, Investigation, Methodology, Project administration, Supervision, Visualization, Writing – original draft, Writing – review & editing.
Guardian/patients consent
Not applicable.
Ethical statement
This study complies with the Declaration of Helsinki and was approved with a consent waiver by the Institutional Review Board at The Ohio State University Wexner Medical Center (Columbus, OH USA).
Funding statement
No funding
References
- Time from ACL injury to reconstruction and the prevalence of additional intra-articular pathology: is patient age an important factor? Knee Surg Sports Traumatol Arthrosc. 2013;21:2029-2034.
- [Google Scholar]
- High rates of osteoarthritis develop after anterior cruciate ligament surgery: an analysis of 4108 patients. Am J Sports Med. 2018;46:2011-2019.
- [Google Scholar]
- Predictors of osteoarthritis development at a median 25 Years after anterior cruciate ligament reconstruction using a patellar tendon autograft. Am J Sports Med. 2022;50:1195-1204.
- [Google Scholar]
- Predictors of radiographic osteoarthritis 2 to 3 Years after anterior cruciate ligament reconstruction: data from the MOON on-site nested cohort. Orthop J Sports Med. 2019;7
- [Google Scholar]
- Factors involved in the development of osteoarthritis after anterior cruciate ligament surgery. Am J Sports Med. 2010;38:455-463.
- [Google Scholar]
- Post-traumatic osteoarthritis diagnosed within 5 years following ACL reconstruction. Knee Surg Sports Traumatol Arthrosc. 2020;28:790-796.
- [Google Scholar]
- The long-term consequence of anterior cruciate ligament and meniscus injuries: osteoarthritis. Am J Sports Med. 2007;35:1756-1769.
- [Google Scholar]
- Patients aged 50 Years and older have greater complication rates after anterior cruciate ligament reconstruction: a large database study. Arthrosc Sports Med Rehabil. 2021;3:e1827-e1834.
- [Google Scholar]
- Deep venous thrombosis and pulmonary embolism after anterior cruciate ligament reconstruction: incidence, outcome, and risk factors. Bone Joint Lett J. 2019;101-b:34-40.
- [Google Scholar]
- Systemic inflammatory biomarkers are novel predictors of all-cause and cardiovascular mortality in individuals with osteoarthritis: a prospective cohort study using data from the NHANES. BMC Public Health. 2024;24:1586.
- [Google Scholar]
- Diagnostic value of the blood monocyte-lymphocyte ratio in knee osteoarthritis. J Int Med Res. 2019;47:4413-4421.
- [Google Scholar]
- Systemic inflammation response index as an emerging biomarker in osteoarthritis patients: a bibliometric and large sample retrospective investigation. Clin Exp Rheumatol. 2024;42:92-103.
- [Google Scholar]
- Association of peripheral inflammatory indicators with osteoarthritis risk. Osteoarthr Cartil Open. 2024;6
- [Google Scholar]
- Investigation of the associations of novel inflammatory biomarkers-systemic inflammatory index (SII) and systemic inflammatory response index (SIRI)-With the severity of coronary artery disease and acute coronary syndrome occurrence. Int J Mol Sci. 2022;23
- [Google Scholar]
- The association between systemic inflammation markers and the prevalence of hypertension. BMC Cardiovasc Disord. 2023;23:615.
- [Google Scholar]
- Prognostic value of the systemic inflammation response index in human malignancy: a meta-analysis. Medicine (Baltim). 2020;99
- [Google Scholar]
- The association between serum vitamin D concentration and new inflammatory biomarkers-systemic inflammatory index (SII) and systemic inflammatory response (SIRI)-In patients with ischemic heart disease. Nutrients. 2022;14
- [Google Scholar]
- Association between systemic immunity-inflammation index and hyperlipidemia: a population-based study from the nhanes (2015-2020) Nutrients. 2023;15
- [Google Scholar]
- Neutrophil-to-lymphocyte ratio as a prognostic biomarker for men with metastatic castration-resistant prostate cancer receiving first-line chemotherapy: data from two randomized phase III trials. Ann Oncol. 2015;26:743-749.
- [Google Scholar]
- Systemic immune-inflammation index predicting chemoradiation resistance and poor outcome in patients with stage III non-small cell lung cancer. J Transl Med. 2017;15:221.
- [Google Scholar]
- Association between systemic immune-inflammation index and systemic inflammation response index and outcomes of acute ischemic stroke: a systematic review and meta-analysis. Ann Indian Acad Neurol. 2023;26:655-662.
- [Google Scholar]
- The prognostic role of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and systemic immune-inflammation index on short- and long-term outcome following surgery for spinal metastases. J Neurosurg Spine. 2024;40:475-484.
- [Google Scholar]
- Systemic immune-inflammation index predicted overall survival and radiosensitivity in advanced non-small-cell lung cancer. Future Oncol. 2020;16:103-115.
- [Google Scholar]
- The association of systemic inflammatory biomarkers with non-alcoholic fatty liver disease: a large population-based cross-sectional study. Prev Med Rep. 2024;37
- [Google Scholar]
- Could systemic inflammatory index predict diabetic kidney injury in type 2 diabetes mellitus? Diagnostics. 2023;13
- [Google Scholar]
- Is there a link between the neutrophil-to-lymphocyte ratio and venous thromboembolic events after knee arthroplasty? A pilot study. J Orthop Traumatol. 2016;17:163-168.
- [Google Scholar]
- An elevated neutrophil-to-lymphocyte ratio associates with weight loss and cachexia in cancer. Sci Rep. 2020;10:7535.
- [Google Scholar]
- Neutrophil lymphocyte ratio significantly improves the Framingham risk score in prediction of coronary heart disease mortality: insights from the National Health and Nutrition Examination Survey-III. Int J Cardiol. 2014;171:390-397.
- [Google Scholar]
- Prognostic value of neutrophil to lymphocyte ratio in patients with acute pulmonary embolism: a restrospective study. Heart Lung Circ. 2014;23:56-62.
- [Google Scholar]
- Neutrophil lymphocyte ratio as a measure of systemic inflammation in prevalent chronic diseases in Asian population. Int Arch Med. 2012;5:2.
- [Google Scholar]
- Is blood neutrophil-lymphocyte ratio an independent predictor of knee osteoarthritis severity? Clin Rheumatol. 2016;35:1579-1583.
- [Google Scholar]
- The relationship of platelet to lymphocyte ratio and neutrophil to monocyte ratio to radiographic grades of knee osteoarthritis. Z Rheumatol. 2018;77:533-537.
- [Google Scholar]
- Joint injury causes knee osteoarthritis in young adults. Curr Opin Rheumatol. 2005;17:195-200.
- [Google Scholar]
- Association between the immune-inflammation indicators and osteoarthritis - nhanes 1999-2018. Osteoarthritis & Cartilage, Open. 2025;7:1-9.
- [Google Scholar]
- Synovial fluid monocyte-to-lymphocyte ratio in knee osteoarthritis patients predicts patient response to conservative treatment: a retrospective cohort study. BMC Muscoskelet Disord. 2024;25:379.
- [Google Scholar]
- Optiknee 2022: consensus recommendations to optimise knee health after traumatic knee injury to prevent osteoarthritis. Br J Sports Med. 2022;56:1393-1405.
- [Google Scholar]
- Long-term quality of life, work limitation, physical activity, economic cost and disease burden following ACL and meniscal injury: a systematic review and meta-analysis for the OPTIKNEE consensus. Br J Sports Med. 2022;56:1465-1474.
- [Google Scholar]
- Post-traumatic osteoarthritis: the worst associated injuries and differences in patients' profile when compared with primary osteoarthritis. BMC Muscoskelet Disord. 2023;24:568.
- [Google Scholar]
- Causal associations between circulating immune cells and osteoarthritis: a bidirectional mendelian randomization study. Int Immunopharmacol. 2024;142
- [Google Scholar]
- Anterior cruciate ligament reconstruction in patients over the age of 50 years: 2- to 8-year follow-up. Knee Surg Sports Traumatol Arthrosc. 2003;11:204-211.
- [Google Scholar]