OBJECTIVE: Cardiac autonomic neuropathy (CAN) is one of the most serious complications of diabetes. This study aimed to analyze the correlation between neutrophil-to-lymphocyte ratio (NLR) and CAN in patients with type 2 diabetes (T2D) using 24-hour Holter ECG and to assess the relationship between NLR and severity of diabetic peripheral neuropathy (DPN).
METHODS:  This cross-sectional study included 90 T2D patients with DPN confirmed by nerve conduction study (NCS). A 24-hour Holter ECG was done to detect the decrease in heart rate variability (HRV). Laboratory parameters, including fasting blood glucose, creatinine, cholesterol, triglyceride, and glycosylated hemoglobin (HbA1c) levels, as well as CBC, neutrophils, lymphocytes, NLR, and platelet-to-lymphocyte ratio (PLR), were calculated accordingly. An albumin-to-creatinine ratio (ACR) test was done and the estimated glomerular filtration rate (eGFR) was calculated. Chronic kidney disease was diagnosed by the presence of albuminuria (≥30 mg/g creatinine) and/or eGFR less than 60.
RESULTS: Based on the 24-hour Holter ECG, 25 patients out of 90 (27.7%) had CAN. On comparing both the CAN and non-CAN groups, the CAN group had higher HbA1C (p = 0.005), higher NLR (p = 0.014), and higher neutrophils (p = 0.10). Also, PLR was higher in the CAN group than in the non-CAN group, but this was not statistically significant (p = 0.180). Receiver operator characteristic curve analysis revealed that NLR with a cutoff of 1.7 succeeded in detecting patients with CAN.
CONCLUSIONS: NLR can be used as an inexpensive and accessible marker to detect patients with diabetes at risk for developing CAN.

UNASSIGNED: In locally advanced rectal cancers (LARC), tumour node metastasis (TNM) staging is far from optimal. The authors aimed to investigate the value of previously described circulating biomarkers as predictors of prognosis.
UNASSIGNED: Retrospective analysis of 245 LARC patients diagnosed between January 2010 and December 2022, who underwent neoadjuvant chemoradiotherapy and surgery at two centres. A Cox regression and Kaplan-Meier analysis were performed.
UNASSIGNED: Post-treatment platelet-to-lymphocyte ratio (PLR) predicted pathological complete response. The neutrophil-to-lymphocyte ratio (NLR) in two timepoints of the treatment significantly predicted overall survival, whereas the platelet-neutrophil (PN) index significantly predicted disease-free survival. In pathological stage II, the PN index predicted patients with a higher risk of disease-free survival.
UNASSIGNED: Blood parameters might allow the definition of subgroups of risk beyond TNM for the application of different therapeutic strategies.

BACKGROUND: Recent studies have highlighted the prognostic value of easily accessible inflammatory markers, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) for predicting severe outcomes in patients affected by Coronavirus disease 2019 (COVID-19). Our study validates NLR and PLR cut-off values from a prior cohort at IRCCS Policlinico San Matteo (OSM) of Pavia, Italy, across two new cohorts from different hospitals. This aims to enhance the generalizability of these prognostic indicators.
METHODS: In this retrospective cohort study, conducted at Milan\'s Ospedale Luigi Sacco (OLS) and IRCCS Ospedale Maggiore Policlinico (OMP) hospitals, we assess the predictive capacity of NLR and PLR for three main outcomes-non-invasive ventilation (NIV) or continuous positive airway pressure (CPAP) usage, invasive ventilation (IV), and death-in patients with COVID-19 at admission. For each outcome, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were computed separately for male and female cohorts. Distinct NLR and PLR cut-off values were used for men (7.00, 7.29, 7.00 for NLR; 239.22, 248.00, 250.39 for PLR) and women (6.36, 7.00, 6.28 for NLR; 233.00, 246.45, 241.54 for PLR), retrieved from the first cohort at OSM.
RESULTS: A total of 3599 patients were included in our study, 1842 from OLS and 1757 from OMP. OLS and OMP sensitivity values for both NLR and PLR (NLR: 24-67%, PLR: 40-64%) were inferior to specificity values (NLR: 64-76%, PLR: 55-72%). Additionally, PPVs generally remained lower (< 63%), while NPVs consistently surpassed 68% for PLR and 72% for NLR. Finally, both PLR and NLR exhibited consistently higher NPVs for more severe outcomes (> 82%) compared to NPVs for CPAP/NIV.
CONCLUSIONS: Consistent findings across diverse patient populations validate the reliability and applicability of NLR and PLR cut-off values. High NPVs emphasize their role in identifying individuals less likely to experience severe outcomes. These markers not only aid in risk stratification but also guide resource allocation in emergencies or limited-resource situations.

Schizophrenia is a severe mental disorder that may involve inflammation. Inflammatory indices, such as the neutrophil to lymphocyte ratio (NLR), the monocyte to lymphocyte ratio (MLR), the platelet to lymphocyte ratio (PLR), and the systemic inflammation index (SII), are simple and inexpensive measures of inflammation that have been associated with various diseases. However, few studies have compared these indices and their relationships with clinical symptoms in schizophrenia. We conducted a cross-sectional study of 121 schizophrenia patients (101 males, 20 females). We measured the blood-based inflammatory indices (NLR, MLR, PLR, and SII) and assessed the clinical symptoms of schizophrenia using the Positive and Negative Syndrome Scale (PANSS). Statistical analyses were performed to examine the correlations and effects of the inflammatory indices on PANSS scores. We found that NLR, MLR, PLR, and SII were positively correlated with PANSS total score, PANSS positive score, PANSS negative score, and general psychopathology score (adjusted P < 0.02 for all correlations). Subgroup analysis showed that correlations between inflammatory indices and the clinical scores differed by gender. In males, all inflammatory indices were positively correlated with all clinical scores. On the other hand, in females, only NLR and SII were positively correlated with all clinical scores. After adjusting for confounders, we also found that NLR was a predictor of PANSS total score (β = 23, adjusted P < 0.02), PANSS positive score (β = 2.6, adjusted P = 0.03), PANSS negative score (β = 6.8, adjusted P < 0.02), and PANSS general psychopathology score (β = 13.6, adjusted P < 0.02), while SII was only a predictor for PANSS total score (β = -0.00003, adjusted P = 0.01) and general psychopathology scores (β = -0.00002, adjusted P < 0.02). These findings suggest that inflammation is involved in the pathophysiology and clinical manifestations of schizophrenia, and that blood-based inflammatory indices may serve as screening tools or indicators for the inflammatory status and severity of symptoms of schizophrenia patients.

UNASSIGNED: Peripheral blood inflammation indices, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII), have become research hotspots in the diagnosis, treatment, and prognosis prediction of breast cancer, whereas existing research findings remain controversial.
UNASSIGNED: Data pertaining to 1808 breast cancer patients were collected retrospectively to analyze the predictive value of NLR/PLR/SII for breast cancer clinicopathological characteristics, chemotherapy response, and relapse. 1489, 258, and 53 eligible breast cancer patients entered into the three analyses, respectively. Logistic regression analyses were used to assess the correlation between these indices and poor response to chemotherapy. A predictive scoring model was established to predict chemotherapeutic responses based upon the odds ratio values of significant variables identified in logistic regression analyses.
UNASSIGNED: Higher pretherapeutic NLR/PLR/SII values were significantly correlated with higher tumor stage, triple-negative breast cancer, premenopausal status, and younger age. Logistic regression analyses indicated that pretherapeutic high SII (as a continuous variable or with a cut-off value of 586.40) and HER2-negative status were independent predictors of poor response to neoadjuvant chemotherapy. A first-in-class SII-based predictive scoring model well distinguished patients who might not benefit from neoadjuvant chemotherapy, with an area under the curve of 0.751. In HR-positive cancers, SII was more strongly associated with clinicopathological features and chemotherapy response. In addition, a receiver operating characteristic curve analysis indicated that the specificity of follow-up SII in identifying cancer relapse was greater than 98.0% at a cut-off value of 900.
UNASSIGNED: As a predictor of breast cancer, especially in the HR-positive subtype, SII may eclipse NLR/PLR. SII-high patients are more likely to have a worse chemotherapy response and a higher risk of recurrence.

BACKGROUND: This study aimed to investigate pain management, functional recovery, and stress response expressed by the neutrophile-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) after the popliteal artery and posterior knee capsule infiltration (iPACK) block combined with adductor canal block (ACB) in total knee arthroplasty (TKA).
METHODS: This was a prospective, double-blinded, randomised, controlled trial in a tertiary referral hospital. Three hundred and sixty-six patients were randomly allocated into the sham block group and iPACK combined with the ACB group. The primary outcome was postoperative pain scores. The secondary outcomes were opioid consumption, functional recovery expressed by a range of motion, and quadriceps strength. Also, the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were calculated.
RESULTS: There were significant differences between the sham block and iPACK + ACB group in pain scores p < 0.0001 at all time points. Therefore, there was a significant difference in opioid consumption (p < 0.0001) and functional recovery (p < 0.0001). Also, NLR and PLR levels 12 h (p < 0.0001) and 24 h (24 h) after surgery (p < 0.0001) were much lower in the iPACK + ACB group.
CONCLUSIONS: After total knee arthroplasty, the iPACK combined with ACB block group improved pain management, functional recovery, and stress response. Therefore, we strongly recommend this technique as a part of a multimodal analgesia protocol in knee surgery.

UNASSIGNED: We aimed to assess the effects of pretreatment neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios on the response to neoadjuvant chemotherapy and survival rates in patients with extremity osteosarcoma.
UNASSIGNED: Patients with high-grade osteosarcoma admitted to oncologic centers affiliated with Iran University of Medical Sciences, Tehran, Iran from 2015 to 2021 were evaluated retrospectively to assess the impact of complete blood count-related parameters on the pathologic response after neoadjuvant chemotherapy. Then, patients were followed up prospectively to evaluate the survival rates. All patients received at least three cycles of cisplatin/doxorubicin regimen, preoperatively. In this study, the cut-off values for high neutrophil-to-lymphocyte and high platelet-to-lymphocyte ratio were considered 3.28 and 128, respectively.
UNASSIGNED: One hundred eighty-six patients were enrolled. Patients with high neutrophil-to-lymphocyte ratio and high platelet-to-lymphocyte ratio had a significantly lower overall survival rates (20.7 [95% CI 18-23.5] month vs. 34.6 [95% CI 33.2-36], p = 0.003 and 21.9 [95% CI 20.2-23.6] month versus 35.3 [95% CI 33.9-36.7], p = 0.002; respectively). Moreover, disease-free survival of patients with high platelet-to-lymphocyte ratio was worse than patients with low platelet-to-lymphocyte ratio (20.4 [95% CI 18.4-22.4] month vs. 32.7 [95% CI 30.8-34.7], p = 0.02).
UNASSIGNED: Our study showed that neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios at the baseline can predict the survival of patients with high-grade osteosarcoma.

MicroRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally regulate gene expression and different immune-related pathways. There is a great interest in identifying miRNAs involved in immune cell development and function to elucidate the biological mechanisms underlying the immune system, its regulation, and disease. In this study, we aimed to investigate the association of circulating miRNAs with blood cell compositions and blood-based immune markers. Circulating levels of 2083 miRNAs were measured by RNA-sequencing in plasma samples of 1999 participants from the population-based Rotterdam Study collected between 2002 and 2005. Full blood count measurements were performed for absolute granulocyte, platelet, lymphocyte, monocyte, white, and red blood cell counts. Multivariate analyses were performed to test the association of miRNAs with blood cell compositions and immune markers. We evaluated the overlap between predicted target genes of candidate miRNAs associated with immune markers and genes determining the blood immune response markers. First, principal component regression analysis showed that plasma levels of circulating miRNAs were significantly associated with red blood cell, granulocyte, and lymphocyte counts. Second, the cross-sectional analysis identified 210 miRNAs significantly associated (P < 2.82 × 10-5) with neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index. Further genetic look-ups showed that target genes of seven identified miRNAs (miR-1233-3p, miR-149-3p, miR-150-5p, miR-342-3p, miR-34b-3p, miR-4644, and miR-7106-5p) were also previously linked to NLR and PLR markers. Collectively, our study suggests several circulating miRNAs that regulate the innate and adaptive immune systems, providing insight into the pathogenesis of miRNAs in immune-related diseases and paving the way for future clinical applications.

OBJECTIVE: The current study aimed to delineate the relationship between furin and chronic inflammation while cervical intraepithelial neoplasia progresses to cancer.
METHODS: This cross-sectional study included 81 women who required colposcopic examinations. The study groups were formed based on pathological results: Group I included women with cervical intraepithelial neoplasia (CIN) I (n = 30); Group II included women with CIN II-III (n = 28); and Group III included women with cervical cancer (CC) (n = 23). Furin, ki-67, and p16 levels were evaluated based on immunostaining intensity. The inflammatory indices were calculated in parallel with the literature from routine blood samples retrieved within one week before the procedure.
RESULTS: Furin expression gradually increased from CIN I to CIN II-III and from CIN II-III to CC, respectively (p < 0.001, p = 0.005). NLR, MLR, PLR, and SII were significantly higher in the CC group (p < 0.001). ROC curve analysis unveiled that NLR, MLR, PLR, and SII predicted the presence of CC with a cutoff value of 2.39 for NLR (sensitivity: 91.3%, specificity: 63.8%, AUROC: 0.79, p < 0.001); a cutoff value of 0.27 for MLR (sensitivity: 78.3%, specificity: 72.4%, AUROC: 0.77, p = 0.009); a cutoff value of 123 for PLR (sensitivity: 100%, specificity: 41.4%, AUROC: 0.70, p = 0.04); and a cutoff value of 747 for SII (sensitivity: 69.6%, specificity: 90.7%, AUROC: 0.71, p = 0.014).
CONCLUSIONS: Furin expression increased gradually in parallel with the severity of cervical intraepithelial neoplasia. The inflammatory indices were higher in the presence of CC and denoted a good discrimination ability for predicting cervical cancer.

UNASSIGNED: The mechanism of sudden sensorineural hearing loss (SSNHL) remains incompletely understood, but immune cell infiltration has been identified as a crucial component in the sickness. The patients with SSNHL may benefit from investigating markers related to inflammation.
UNASSIGNED: From April 2022 to 2023, 80 patients who were diagnosed with SSNHL in the Department of Otolaryngology at Yangzhou University\'s Clinical Medical College were enrolled in the SSNHL group. And patients were separated into effective and ineffective groups based on the degree to which their hearing had recovered prior to discharge. As the control group, 80 healthy volunteers were chosen from hospital\'s physical examination center. Neutrophils, lymphocytes, platelets, and white blood cells were counted. Additionally, quantified and statistically examined were the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune inflammation index (SII). The risk variables for prognosis were identified using logistic regression models, and the prediction accuracy of the model was calculated using the receiver operating characteristic (ROC) curves.
UNASSIGNED: The SSNHL group had higher levels of white blood cells, neutrophils, platelets, NLR, PLR, and SII than the control group. While the PLR lacked statistical significance, the NLR and SII of the patients in the ineffective group were noticeably higher than those in the effective group.
UNASSIGNED: Patients with SSNHL exhibit inflammatory immune responses. Patients with SSNHL can have their prognosis determined by the simple peripheral blood indicators NLR and SII, particularly SII, which is significant for predicting prognosis and directing treatment.