Pulmonary delivery of silver nanoparticles prevents influenza infection by recruiting and activating lymphoid cells.

Silver nanoparticles (AgNPs) are a potential antiviral agent due to their ability to disrupt the viral particle or alter the virus metabolism inside the host cell. In vitro, AgNPs exhibit antiviral activity against the most common human respiratory viruses. However, their capacity to modulate immune responses during respiratory viral infections has yet to be explored. This study demonstrates that administering AgNPs directly into the lungs prior to infection can reduce viral loads and therefore virus-induced cytokines in mice infected with influenza virus or murine pneumonia virus. The prophylactic effect was diminished in mice with depleted lymphoid cells. We showed that AgNPs-treatment resulted in the recruitment and activation of lymphocytes in the lungs, particularly natural killer (NK) cells. Mechanistically, AgNPs enhanced the ability of alveolar macrophages to promote both NK cell migration and IFN-γ production. By contrast, following infection, in mice treated with AgNPs, NK cells exhibited decreased activation, indicating that these nanoparticles can regulate the potentially deleterious activation of these cells. Overall, the data suggest that AgNPs may possess prophylactic antiviral properties by recruiting and controlling the activation of lymphoid cells through interaction with alveolar macrophages.

Can Blood Inflammatory Markers Identify Pregnant Women with Preeclampsia? Still a Controversial Issue.

BACKGROUND: Preeclampsia is a unique vascular disease during pregnancy that generally appears after 20 of weeks gestation or until 6 weeks after delivery. Left undiagnosed, preeclampsia can lead rapidly to death of both mother and fetus. OBJECTIVES: To verify the efficacy of peripheral blood inflammatory markers (BIMs)in diagnosing preeclampsia and compare them with results from other studies. METHODS: Our retrospective case-control study comprised two patient groups. Pregnant women with preeclampsia and pregnant women without preeclampsia were compared for BIMs: neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and mean platelet volume (MPV). The primary endpoint of our research was to assess the predictive power of BIMs for preeclampsia diagnosis. RESULTS: The sample size was calculated based on expected differences of BIMs between the control and study groups. Comparison of quantitative variables was conducted with independent sample t-test or alternatively by Wilcoxon rank sum test. The MPV values were slightly higher in the preeclampsia group, but not statistically significant. NLR and PLR did differentiate between study and control groups. CONCLUSIONS: The diagnostic accuracy of BIMs is unsatisfactory for preeclampsia diagnosis. Discrepancies concerning these values need to be clarified. Further large prospective studies are necessary to validate the potential factor accuracy in preeclampsia diagnosis.

Recipient tissue microenvironment determines developmental path of intestinal innate lymphoid progenitors.

Innate lymphoid cells (ILCs) are critical in maintaining tissue homeostasis, and during infection and inflammation. Here we identify, by using combinatorial reporter mice, a rare ILC progenitor (ILCP) population, resident to the small intestinal lamina propria (siLP) in adult mice. Transfer of siLP-ILCP into recipients generates group 1 ILCs (including ILC1 and NK cells), ILC2s and ILC3s within the intestinal microenvironment, but almost exclusively group 1 ILCs in the liver, lung and spleen. Single cell gene expression analysis and high dimensional spectral cytometry analysis of the siLP-ILCPs and ILC progeny indicate that the phenotype of the group 1 ILC progeny is also influenced by the tissue microenvironment. Thus, a local pool of siLP-ILCP can contribute to pan-ILC generation in the intestinal microenvironment but has more restricted potential in other tissues, with a greater propensity than bone marrow-derived ILCPs to favour ILC1 and ILC3 production. Therefore, ILCP potential is influenced by both tissue of origin and the microenvironment during development. This may provide additional flexibility during the tuning of immune reactions.

Relationship between NLR and penile squamous cell carcinoma: a systematic review and meta-analysis.

OBJECTIVE: We conducted this study to summarize the results of studies reporting the role of NLR (neutrophil to lymphocyte ratio) in PSCC (penile squamous cell carcinoma). METHODS: This meta-analysis was conducted using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) criteria. A systematic search was conducted on PubMed, Scopus, and web of science up to March 10, 2023. Fourteen studies were included in the review. The NOS (Newcastle-Ottawa Scale) was used to determine the quality of the included studies. This meta-analysis was conducted on the studies reporting the relationship between NLR and survival using HR (hazard ratio) and 95% CI (confidence interval). RESULTS: There was a significant association between NLR levels and the prognosis, nodal stage, and anatomical tumor stage of PSCC patients. In the meta-analysis of the association of NLR with survival, NLR level was significantly associated with lower cancer-specific survival (HR = 3.51, 95% CI = 2.07-5.98, p < 0.001) and lower disease-free survival (HR = 2.88, 95% CI = 1.60-5.20, p < 0.001). However, NLR was found to have no association with the stage, grade, location, and size of the tumor. CONCLUSION: NLR has a significant diagnostic and prognostic value in PSCC.

The preoperative scoring system combining neutrophil/lymphocyte ratio and CA19-9 predicts the long-term prognosis of intrahepatic cholangiocarcinoma patients undergoing curative liver resection.

BACKGROUND: This study aims to investigate preoperative prognostic factors available for intrahepatic cholangiocarcinoma (ICC) patients and propose a new preoperative prognostic scoring system for ICC that combines CA19-9 and neutrophil/lymphocyte ratio (NLR). METHODS: In this retrospective analysis, 1728 patients diagnosed with ICC and undergoing curative liver resections were studied. This study employed univariate and multivariate Cox regression to find factors affecting recurrence and overall survival (OS), and furthermore assessed how preoperative models influenced tumor traits and postoperative recurrence. RESULTS: The results of the multivariate Cox regression analysis indicated that two preoperative variables, NLR and Ca19-9, were independent risk factors affecting postoperative recurrence and OS in ICC patients. Based on this data, assigning a score of 0 (NLR ≤ 2.4 and Ca19-9 ≤ 37U/ml) or 1 (NLR > 2.4 and Ca19-9 > 37U/ml) to these two factors, a preoperative prognostic score was derived. According to the scoring model, patients were divided into three groups: 0 points (low-risk group), 1 point (intermediate-risk group), and 2 points (high-risk group). The 5-year recurrence and OS rates for the three groups were 56.6%, 68.2%, 77.8%, and 56.8%, 40.6%, 27.6%, respectively, with all P values < 0.001. Furthermore, high-risk group patients were more prone to early recurrence (early recurrence rates for high-, intermediate-, and low-risk groups were 56.8%, 51.5%, and 37.1%, respectively, P < 0.001) and extrahepatic metastasis (extrahepatic metastasis rates for high-, intermediate-, and low-risk groups were 31.7%, 26.4%, and 15.4%, respectively, P < 0.001). In terms of tumor characteristics, high-risk group patients had larger tumor diameters and were more likely to experience microvascular invasion, lymph node metastasis, and perineural invasion. CONCLUSIONS: The predictive capacity of postoperative recurrence and OS rates in ICC patients is effectively captured by the preoperative scoring system incorporating NLR and CA19-9 levels.

Systemic Immune-Inflammation Indices Could Be Additional Predictive Markers for Cesarean Scar Pregnancy.

PROBLEM: Cesarean scar pregnancy (CSP) is characterized by a gestational sac fully or partially implanted in the scar from a previous cesarean section. Systemic immune-inflammation indices (SIIs) have recently been discussed as additional diagnostic markers in placenta accreta and preeclampsia. CSP shares a similar pathogenesis with these diseases, suggesting that assessing the SIIs and neutrophil-to-lymphocyte ratio (NLR) could enhance additional predictability in diagnosing CSP. METHOD OF STUDY: In this study, we analyzed the complete blood counts between 264 women who were confirmed with CSP by ultrasound and 295 women who underwent elective termination. RESULTS: The mean counts of total white cells and neutrophils were significantly higher, whereas the counts of monocytes, lymphocytes, and platelets were significantly lower in the CSP group compared to the control group (p < 0.001). Additionally, the SII, systemic inflammation response index (SIRI), or NLR was significantly higher in the CSP group compared to the control group (p < 0.0001). Given the limited effect of SII and SIRI on the increased risk of developing CSP, the optimal cut-off value for NLR in predicting CSP was 2.87 (area under the curve [AUC] 0.656, 68% sensitivity). The optimal cut-off value for NLR in predicting type 2 CSP was 2.91 (AUC 0.690, 71% sensitivity). CONCLUSIONS: Although ultrasound or magnetic resonance imaging images are a gold standard for visualizing the gestational sac's location in the diagnosis of CSP, assessing peripheral blood tests is cost-effective, and NLR may provide additional diagnosis value for CSP.

Neutrophil/lymphocyte ratio as a predictor of mortality among aortic dissection patients in the emergency department.

BACKGROUND: Aortic dissection (AD) is a serious cardiovascular condition associated with high mortality rates. The systemic inflammatory response can influence the prognosis of AD, and in this context, the neutrophil-to-lymphocyte ratio (NLR) emerges as a simple and rapid inflammatory biomarker. METHODS: This retrospective cohort study included 103 patients diagnosed with AD and treated in the emergency department between 2018 and 2023. Patient demographics, clinical features, and laboratory results were evaluated. Multivariate logistic regression analysis was performed to adjust for potential confounders such as age, mean systolic blood pressure, oxygen saturation, hemoglobin, lactate values, and the presence of coronary artery disease. The ability of NLR to predict mortality was analyzed using receiver operating characteristic (ROC) analysis. RESULTS: The study population was divided into two groups: non-survivors (68% mortality rate) and survivors (32% survival rate). The non-survivor group had significantly higher NLR values compared to the survivor group (median NLR 7.66 vs. 2.5, p<0.001). Multivariate logistic regression analysis identified NLR as an independent predictor of in-hospital mortality (adjusted odds ratio [OR] 2.33, 95% confidence interval [CI] 1.42-3.82, p<0.001). ROC analysis for NLR demonstrated high discriminative power with an area under the ROC curve (AUROC) of 0.851 (95% CI 0.768-0.914). The determined cut-off point was >5.08 with a sensitivity of 77.14% and specificity of 81.82%. CONCLUSION: The findings indicate that high NLR is strongly associated with increased mortality risk in patients with AD and can be used in emergency clinical settings to predict mortality.

[Predictive value of leukocyte derived markers for postoperative delirium after cardiac valve surgery].

OBJECTIVE: To explore the predictive value of leukocyte derived markers for postoperative delirium (POD) in patients undergoing cardiac valve surgery. METHODS: A prospective cohort study was conducted. The patients who underwent cardiac valve surgery admitted to Beijing Anzhen Hospital of Capital Medical University from October 2021 to March 2023 were enrolled. The demographic, baseline and perioperative data were collected, and the neutrophil to lymphocyte ratio (NLR) and platelet to white blood cell ratio (PWR) were calculated before operation and within 24 hours after operation. Delirium assessment was conducted twice a day for patients within 1-5 days after surgery or discharged within 5 days. According to the evaluation results, the patients were divided into delirium group and non-delirium group. The clinical indexes between the two groups were compared. Multivariate Logistic regression analysis was used to screen the independent risk factors of POD, and the POD predictive model was constructed. The predictive value of POD predictive model was evaluated by receiver operator characteristic curve (ROC curve). RESULTS: A total of 235 patients were enrolled in the analysis, of which 83 patients had POD (35.32%) and 152 patients did not have POD (64.68%). Compared with the non-delirious group, the patients in the delirious group had higher Charlson comorbidity index (CCI) score and lower mini-mental state examination (MMSE) score. In terms of perioperative data, compared with the non-delirium group, the patients in the delirium group had longer operative time, duration of cardiopulmonary bypass, length of intensive care unit (ICU) stay, duration of mechanical ventilation, and postoperative hospital stay, higher incidence of perioperative atrial fibrillation, and lower discharge life score. In terms of leukocyte derived markers, NLR within 24 hours after surgery in both groups were significantly higher than those before surgery, and PWR were significantly lower than those before surgery. The NLR within 24 hours after surgery, PWR difference and NLR difference in the delirium group were significantly higher than those in the non-delirium group. Multivariate Logistic regression analysis showed that CCI score [odds ratio (OR) = 1.394, 95% confidence interval (95%CI) was 1.038-1.872, P = 0.027], perioperative atrial fibrillation (OR = 3.697, 95%CI was 1.711-7.990, P < 0.001), duration of cardiopulmonary bypass (OR = 1.008, 95%CI was 1.002-1.015, P = 0.016), length of ICU stay (OR = 1.006, 95%CI was 1.002-1.010, P = 0.002), NLR difference (OR = 1.029, 95%CI was 1.009-1.050, P = 0.005) and PWR difference (OR = 1.044, 95%CI was 1.009-1.080, P = 0.013) were independently correlated with POD. POD predictive model was constructed by multivariate Logistic regression analysis result: POD predictive model index = -4.970+0.336×CCI score+1.317×perioperative atrial fibrillation+0.009×duration of cardiopulmonary bypass+0.006×length of ICU stay+0.030×NLR difference+0.044×PWR difference. ROC curve analysis showed that the area under the ROC curve (AUC) of NLR difference for predicting POD was 0.659 (95%CI was 0.583-0.735), the optimal critical value was 16.62, the sensitivity was 60.2%, and the specificity was 70.4% (P < 0.05). The AUC of PWR difference for predicting POD was 0.608 (95%CI was 0.528-0.688), the optimal critical value was 25.68, the sensitivity was 51.8%, and the specificity was 75.7% (P < 0.05). The AUC of POD predictive model for predicting POD was 0.805 (95%CI was 0.745-0.865), the optimal critical value was 0.39, the sensitivity was 74.7%, and the specificity was 79.6% (P < 0.05). CONCLUSIONS: The differences of NLR and PWR are independently related to POD, which has potential value in predicting POD after cardiac valve surgery.

Correlation between the Systemic Immunoinflammatory Index and Platelet-Lymphocyte Ratio in Patients with Adenomyosis.

Background: The chronic inflammatory immune response is a significant factor in the pathogenesis of benign gynecological diseases. The systemic immunoinflammatory index (SII) and the platelet-to-lymphocyte ratio (PLR) are commonly available biomarkers of inflammation. However, evidence of the relationship between SII and PLR in patients with adenomyosis is limited. This study aimed to investigate the relationship between SII and PLR in patients with adenomyosis. Methods: This cross-sectional study included 483 patients with adenomyosis who were first diagnosed at our institution between January 2019 and December 2021. Basic patient clinical information and inflammatory factors were collected for univariate analysis, smoothed curve fitting, and multivariate segmented linear regression. Results: The results of the univariate analysis showed a significant positive correlation between PLR levels and SII (P < 0.001). In addition, a nonlinear relationship between PLR and SII was tested using a smoothed curve fit after adjusting for potential confounders. Multiple segmented linear regression models showed a significant relationship between SII and PLR in both SII < 1,326.47 (ß 0.14, 95% CI: 0.12, 0.16; P < 0.0001) and >1,326.47 (ß 0.02, 95% CI: -0.01, 0.05; P = 0.2461). Conclusions: In conclusion, this study showed a nonlinear relationship between SII and PLR in patients with uterine adenomyosis. An increase in serum PLR levels correlates with an increase in SII before SII levels reach an inflection point.

Predictive value of near-term prediction models for severe immune-related adverse events in malignant tumor PD-1 inhibitor therapy.

Immune-related adverse events (irAEs) impact outcomes, with most research focusing on early prediction (baseline data), rather than near-term prediction (one cycle before the occurrence of irAEs and the current cycle). We aimed to explore the near-term predictive value of neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), absolute eosinophil count (AEC) for severe irAEs induced by PD-1 inhibitors. Data were collected from tumor patients treated with PD-1 inhibitors. NLR, PLR, and AEC data were obtained from both the previous and the current cycles of irAEs occurrence. A predictive model was developed using elastic net logistic regression Cutoff values were determined using Youden's Index. The predicted results were compared with actual data using Bayesian survival analysis. A total of 138 patients were included, of whom 47 experienced grade 1-2 irAEs and 18 experienced grade 3-5 irAEs. The predictive model identified optimal α and λ through 10-fold cross-validation. The Shapiro-Wilk test, Kruskal-Wallis test and logistic regression showed that only current cycle data were meaningful. The NLR was statistically significant in predicting irAEs in the previous cycle. Both NLR and AEC were significant predictors of irAEs in the current cycle. The model achieved an area under the ROC curve (AUC) of 0.783, with a sensitivity of 77.8% and a specificity of 80.8%. A probability ≥ 0.1345 predicted severe irAEs. The model comprising NLR, AEC, and sex may predict the irAEs classification in the current cycle, offering a near-term predictive advantage over baseline models and potentially extending the duration of immunotherapy for patients.

Correlation Between Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio with Risk Stratification Indicators and Thrombus Burden in Patients with Moderate-to-High Risk Acute Pulmonary Embolism, and Changes After Treatment.

OBJECTIVE: To investigate the correlation between neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and risk stratification indicators as well as thrombus burden in patients with moderate-to-high risk acute pulmonary embolism (APE), and to assess the changes in these parameters following interventional therapy. METHODS: This study retrospectively included patients with moderate-to-high risk APE who were admitted to the Department of Interventional Vascular Surgery at Putian First Hospital from May 2020 to May 2024. All patients received anticoagulation therapy, pulmonary artery catheter-directed thrombolysis, and/or mechanical thrombectomy. Patients were further divided into subgroup A if they did not present with any of the following conditions at admission: a) acute inflammatory diseases (including lung infections); b) malignant tumors; c) history of trauma or surgery within the past 2 months. Patients with any of the aforementioned conditions were classified as subgroup B. Additionally, 50 healthy individuals were randomly selected as the healthy control group. RESULTS: The NLR and PLR in subgroup A were significantly lower than those in subgroup B (P < .01). Compared with the healthy control group, the NLR in the APE group and subgroup A was significantly higher (P < .001). There were no significant differences in NLR and PLR between the troponin I-negative and troponin I-positive groups (P > .05), or between the N-terminal pro-B-type natriuretic peptide (NT-proBNP)-negative and NT-proBNP-positive groups (P > .05). There were no significant correlations between NLR and PLR with risk stratification indicators and pulmonary artery embolism index (P > .05). Compared with before treatment, NLR, troponin I, NT-proBNP, right ventricular diameter/left ventricular diameter ratio, and pulmonary artery embolism index were significantly reduced after treatment (P < .05), while there was no significant difference in PLR before and after treatment (P > .05). CONCLUSION: Elevated NLR in patients with APE, which decreases after effective treatment, may be used for assessing disease status and treatment efficacy. However, there is no correlation between NLR and risk stratification indicators or thrombus burden. PLR does not demonstrate significant value in assessing APE.

Neutrophil-to-lymphocyte ratio in type 2 diabetes patients combined with Lower Extremity Peripheral Artery Disease.

Objective: This study explored the utility of NLR (neutrophil-to-lymphocyte ratio) as a marker to predict Lower Extremity Peripheral Artery Disease (PAD) in the Chinese population, as well as to assess its consistency and diagnostic value with digital subtraction angiography. Methods: Patients were distributed into three groups according to the angiography in lower limb arterial: group L1, plaque with no stenosis; group L2, plaque with luminal stenosis and group L3, total vascular occlusion. Changes in the neutrophil-to-lymphocyte ratio were documented and compared among groups. Results: Compared to group L1, NLR was significantly increased in L2 (1.76 vs 2.35, p=0.037) and L3 (1.76 vs 3.60, p<0.001), with a gradual decrease in ABI (Ankle-Brachial Index, 1.11 vs 1.02 vs 0.94, p<0.001). Those older patients with higher prevalence of hypertension (p=0.002), obesity (p=0.032), or reduced high-density lipoprotein cholesterol (p=0.020) were more likely to develop PAD; higher glycosylated hemoglobin (p=0.045), low-density lipoprotein cholesterol (p=0.006), and systolic blood pressure (p<0.001) levels led to a greater tendency to suffer stenosis or even occlusion; the probability of severe stenosis (>70%) increased to 2.075 times for every 1 increase in NLR, while it was 46.8% for every 0.1 increase in ABI. The optimal NLR cut-off value to predict severe stenosis in PAD was 2.73. Receiver operating characteristic curve analysis of the inflammatory biomarkers and severe stenosis prediction displayed an area under the curve of 0.81. Conclusion: NLR could serve as a new noninvasive and accurate marker in predicting PAD.

Neutrophil-to-lymphocyte ratio as a predictor of low cardiac output syndrome after open heart surgery in children with congenital heart disease.

Neutrophil-to-lymphocyte ratio (NLR) as a predictor in determining low cardiac output syndrome (LCOS) has not been widely reported. The aim of this study was to explore the role of pre-surgery, 0-, 4-, and 8-hour post-surgery NLR as predictors of LCOS incidence after open heart surgery in children with congenital heart disease (CHD). This study used a prognostic test with a prospective cohort design and was conducted from December 2020 until June 2021 at the cardiac intensive care unit (CICU) of Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia. The subject consisted of children aged one month to 18 years who underwent open heart surgery using a cardiopulmonary bypass (CPB) machine. A receiver operating characteristic curve was applied to identify the predictive performance of NLR for poor outcomes (LCOS incidence). Out of 90 patients included in the study, 25 (27.8%) of them developed LCOS between 3 to 53 hours post-surgery. All NLR values (pre-surgery and 0-, 4-, and 8-hours post-surgery) were associated with the incidence of LCOS. Pre-surgery NLR (cut-off value ≥0.88) had a fair predictive value (area under curve (AUC) 70; 95%CI: 57-83) for predicting LCOS incidence with sensitivity and specificity of 64% and 64.62%, respectively. NLR 0-hour post-surgery (cut-off value ≥4.73) had a good predictive value (AUC 81; 95%CI: 69-94) for predicting LCOS incidence, with 80% sensitivity and 80% specificity. NLR 4- and 8-hours post-surgery had very good predictive values (AUC 97%; 95%CI: 92-100 and 98; 95%CI: 94-100, respectively), with cut-off values ≥6.19 and ≥6.78, had the same 92% sensitivity and the same 96% sensitivity. The presence of LCOS was associated with mortality (odds ratio of 5.11 with 95%CI: 3.09-8.46). This study highlights that pre-surgery, 0-, 4-, and 8-hours post-surgery NLR can be predictors of LCOS after open heart surgery in children with CHD.

Role of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in diagnosing neonatal sepsis.

Clinical manifestations of neonatal sepsis are often unspecified. Therefore, sepsis biomarkers could be used to support diagnosis while waiting for blood culture results, such as the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). The aim of this study was to evaluate the role of NLR and PLR as diagnostic markers in neonatal sepsis. A cross-sectional study was conducted at Haji Adam Malik General Hospital, Medan, Indonesia, from April to October 2019. This study included neonates aged less than 28 days, diagnosed with suspected sepsis, and had no previous history of antibiotics administration. Patients underwent clinical assessment, laboratory examination, and blood culture. Patients were grouped into sepsis and non-sepsis based on the blood culture results. The median hematological examination and the range of NLR and PLR in both the sepsis and non-sepsis groups were subjected to analysis using the Mann-Whitney U test to assess differences. NLR and PLR optimal cut-off values were determined using a receiver operator curve (ROC) with a confidence interval of 95%. A total of 137 neonates were enrolled, of which 49 were classified as sepsis and 89 as non-sepsis based on blood culture results. The optimal cutoff values for NLR and PLR were 2.75 and 11.73. Using those cutoff values, NLR and PLR could predict neonatal sepsis with sensitivities of 52.1% and 47.9%, specificities of 50.6% and 47.2%, area under the curve (AUC) of 0.46 and 0.47, with p=0.525 and p=0.662, respectively. Further investigation is warranted to refine the NLR and PLR utility and enhance diagnostic accuracy in clinical practices.

Predictive biomarkers of preeclampsia severity in a low resource setting: Role of red blood cell indices, NLR, and albumin-to-creatinine ratio.

Preeclampsia (PE), a serious medical condition with substantial maternal and perinatal implications, poses a significant challenge, particularly in high-incidence countries like Indonesia. Red blood cell (RBC) indices, neutrophil-to-lymphocyte ratio (NLR), and microalbuminuria (albumin-to-creatinine ratio (ACR)) may signal systemic inflammation and endothelial dysfunction, recently recognized as potential indicators for diagnosing and predicting disease severity. The aim of this study was to analyze RBC indices, NLR, and ACR changes in women with PE and their potential for predicting disease severity. A cross-sectional study was conducted at multi-center hospitals across Medan, Indonesia, from June 2022 to June 2023. The patients were grouped into PE cases with and without severe features. Demographic characteristics and complications were recorded while blood and urine were tested. The Chi-squared test, Fisher's exact test and Mann-Whitney test were used to determine biomarkers associated with severe PE. A total of 208 PE patients were included in the study (104 patients for each PE with and without severe features). Our data indicated that PE patients with severe features had higher red cell distribution width (18.5% vs 13.7%; p<0.001), NLR (5.66% vs 4.1%; p<0.001), and ACR (755.97 mg/dL vs 468.63 mg/dL; p<0.001) compared to those without severe features. In contrast, the platelet count was lower in severe features than those without (21.9 × 106/µL vs 27.0 × 106/µL; p=0.002). This study highlighted that PE patients with severe features predominantly had higher levels of RDW, NLR, and ACR and lower platelet counts compared to those without severe features. Therefore, basic tests such as complete blood count and urinalysis, which are inexpensive and feasible in primary care settings with limited resources, offer hope as valuable diagnostic biomarkers for pregnant women diagnosed with PE in a low resource setting.

Predictability of Neutrophile to Lymphocyte Ratio and Platelet to Lymphocyte Ratio on the Effectiveness of Immune Checkpoint Inhibitors in Non-small Cell Lung Cancer patients: A Meta-Analysis.

OBJECTIVES: The associations between the neutrophil-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) with the responses of non-small cell lung cancer (NSCLC) patients receiving immune checkpoint inhibitors (ICI) and the NLR/PLR predictive potential were evaluated via meta-analysis. METHODS: A systematic review was conducted using the PubMed, Embase, and The Cochrane Library databases until October 2021. The relationship between NLR/PLR and overall survival (OS) and progression-free survival (PFS) was evaluated using pooled hazard ratios (HR). The relationship between NLR/PLR and overall response rate (ORR) and disease control rate (DCR) was assessed via pooled odds ratios (OR). Heterogeneity between studies, publication bias, subgroup and sensitivity analyses, trim and fill meta-analysis, and the contour-enhanced funnel plot were performed using the R software. RESULTS: A total of 44 (out of 875) studies met the eligibility criteria, providing a sample size of 4597 patients. Patients with a high NLR were statistically significantly associated with worse outcomes, including OS (pooled HR = 2.44; P < 0.001), PFS (pooled HR = 2.06; P < 0.001), DCR (pooled OR = 0.71; P < 0.001), and ORR (pooled OR = 0.33; P < 0.001). Similarly, a high PLR was associated with poorer outcomes in response to ICI drugs, including OS (pooled HR = 2.13; P < 0.001) and PFS (pooled HR = 1.61; P < 0.001). CONCLUSION: High NLR and PLR were associated with a statistically significant reduction in the efficacy of ICI drugs in NSCLC patients. Thereby, it is possible to use NLR and PLR as potential and available biomarkers in the clinical practice to predict the outcome of ICI treatment in NSCLC patients.

Neutrophil-to-lymphocyte ratio as a predictor of all-cause and cardiovascular mortality in coronary heart disease and hypertensive patients: a retrospective cohort study.

Background: To date, no studies have investigated the correlation between the neutrophil-to-lymphocyte ratio (NLR) and the long-term risk of mortality in individuals with both coronary heart disease (CHD) and hypertension. This study aims to evaluate the association between NLR and all-cause and cardiovascular mortality among this patient population. Methods: National Death Index (NDI) and National Health and Nutrition Examination Survey (NHANES 2001-2018) were the data sources. A nonlinear association between the NLR and mortality risk was shown by restricted cubic spline (RCS) analysis. Using a weighted Cox proportional hazards model, we quantitatively evaluated the effect of NLR on mortality risk.The capacity of NLR to forecast survival was assessed by evaluating time-dependent receiver operating characteristic (ROC) curves. A mediating influence analysis was conducted to assess the influence of NLR on mortality through eGFR as a mediator. Results: The study involved a total of 2136 individuals. During the median follow-up interval of 76.0 months, 801 deaths were recorded. The RCS analysis showed NLR and mortality risk to have a nonlinear relationship. Two groups were established based on the participants' NLR levels: a group with high NLR (NLR > 2.65) and a group with low NLR (NLR < 2.65). After adjusting for potential confounding factors, the Cox proportional hazards model revealed that participants with an increased NLR faced a significantly higher risk of cardiovascular mortality. (HR 1.58, 95% CI 1.33-1.82, p < 0.0001) and all-cause mortality (HR 1.46, 95% CI 1.30-1.62, p < 0.0001). An analysis of interactions and data stratification corroborated the validity of our findings. eGFR was identified as a partial mediator in the association between NLR and mortality rates, contributing 12.17% and 9.66% of the variance in all-cause and cardiovascular mortality, respectively. The predictive performance for cardiovascular mortality was quantified using ROC curves, with respective AUC values of 0.67, 0.65, and 0.64 for predictions over 3, 5, and 10 years. The AUC values for all-cause mortality were 0.66, 0.64, and 0.63 for the same time frames. Conclusion: For patients with CHD and hypertension, an elevated NLR serves as an independent prognostic indicator for both all-cause and cardiovascular mortality.

Prognostic value of neutrophil to lymphocyte ratio in patients with advanced pancreatic ductal adenocarcinoma treated with systemic chemotherapy.

OBJECTIVES: Although systemic chemotherapy for pancreatic ductal adenocarcinoma (PDAC) has made progress, ensuring long-term survival remains difficult. There are several reports on the usefulness of neutrophil-to-lymphocyte ratio (NLR) in predicting the prognosis of PDAC, but few reports in systemic chemotherapy. We hereby investigated the usefulness of NLR in systemic chemotherapy for PDAC. MATERIALS AND METHODS: A retrospective study was conducted on patients with advanced PDAC treated with first-line systemic chemotherapy. Cox regression hazards models were performed to analyze the association between baseline patient characteristics and the initial treatment response, and overall survival (OS). RESULTS: A total of 60 patients with PDAC were enrolled. At baseline, there were significant differences in NLR and carbohydrate antigen 19-9 (CA19-9), as well as the selection rate of combination chemotherapy, between patients with partial response or stable disease and those with progressive disease. Univariate and multivariate analysis showed that NLR < 3.10, combination chemotherapy, and CA19-9 < 1011 U/mL were significant and independent predictive factors of the initial treatment response. Meanwhile, NLR < 3.10 and combination chemotherapy were independently associated with longer OS. Moreover, OS was significantly prolonged in patients with NLR < 3.10, regardless of whether combination chemotherapy or monotherapy. Patients with NLR < 3.10 at baseline had a significantly higher conversion rate to third-line chemotherapy and a longer duration of total chemotherapy. CONCLUSIONS: This study suggests that NLR may be a useful marker for predicting the initial treatment response to first-line chemotherapy and the prognosis for patients with advanced PDAC.

Type 1 innate lymphoid cells: a biomarker and therapeutic candidate in sarcoidosis.

Sarcoidosis is an inflammatory disease characterized by immune cell-rich granulomas that form in multiple organs. In this issue of the JCI, Sati and colleagues used scRNA-seq and spatial transcriptomics of skin samples from patients with sarcoidosis and non-sarcoidosis granulomatous disease to identify upregulation of a stromal-immune CXCL12/CXCR4 axis and accumulation of type 1 innate lymphoid cells (ILC1s) in sarcoidosis. The accumulation of ILC1s in skin and blood was specific to patients with sarcoidosis and not observed in other granulomatous diseases. The authors used a mouse model of lung granuloma to show that ILCs contribute to granuloma formation and that blockade of CXCR4 reduced the formation of granulomas, providing a proof of concept that sarcoidosis may be treated by CXCR4 blockade to prevent the progression of disease in patients. These results suggest ILC1s could serve as a diagnostic biomarker in sarcoidosis and a potential therapeutic target.

Single-cell RNA sequencing illuminates the ontogeny, conservation and diversification of cartilaginous and bony fish lymphocytes.

Elucidating cellular architecture and cell-type evolution across species is central to understanding immune system function and susceptibility to disease. Adaptive immunity is a shared trait of the common ancestor of cartilaginous and bony fishes. However, evolutionary features of lymphocytes in these two jawed vertebrates remain unclear. Here, we present a single-cell RNA sequencing atlas of immune cells from cartilaginous (white-spotted bamboo shark) and bony (zebrafish and Chinese tongue sole) fishes. Cross-species comparisons show that the same cell types across different species exhibit similar transcriptional profiles. In the bamboo shark, we identify a phagocytic B cell population expressing several pattern recognition receptors, as well as a T cell sub-cluster co-expressing both T and B cell markers. In contrast to a division by function in the bony fishes, we show close linkage and poor functional specialization among lymphocytes in the cartilaginous fish. Our cross-species single-cell comparison presents a resource for uncovering the origin and evolution of the gnathostome immune system.