Clinical study of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in hypertriglyceridemia-induced acute pancreatitis and acute biliary pancreatitis with persistent organ failure.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are novel inflammatory indicators that can be used to predict the severity and prognosis of various diseases. We categorize acute pancreatitis by etiology into acute biliary pancreatitis (ABP) and hypertriglyceridemia-induced acute pancreatitis (HTGP). AIM: To investigate the clinical significance of NLR and PLR in assessing persistent organ failure (POF) in HTGP and ABP. METHODS: A total of 1450 patients diagnosed with acute pancreatitis (AP) for the first time at Shanxi Bethune Hospital between January 2012 and January 2023 were enrolled. The patients were categorized into two groups according to the etiology of AP: ABP in 530 patients and HTGP in 241 patients. We collected and compared the clinical data of the patients, including NLR, PLR, and AP prognostic scoring systems, within 48 h of hospital admission. RESULTS: The NLR (9.1 vs 6.9, P < 0.001) and PLR (203.1 vs 160.5, P < 0.001) were significantly higher in the ABP group than in the HTGP group. In the HTGP group, both NLR and PLR were significantly increased in patients with severe AP and those with a SOFA score ≥ 3. Likewise, in the ABP group, NLR and PLR were significantly elevated in patients with severe AP, modified computed tomography severity index score ≥ 4, Japanese Severity Score ≥ 3, and modified Marshall score ≥ 2. Moreover, NLR and PLR showed predictive value for the development of POF in both the ABP and HTGP groups. CONCLUSION: NLR and PLR vary between ABP and HTGP, are strongly associated with AP prognostic scoring systems, and have predictive potential for the occurrence of POF in both ABP and HTGP.

Application of neutrophil-lymphocyte ratio and red blood cell distribution width in diabetes mellitus complicated with heart failure.

BACKGROUND: Accumulating clinical evidence has shown that diabetes mellitus (DM) is a serious risk factor for cardiovascular disorders and an important factor for adverse cardiovascular events. AIM: To explore the value of the combined determination of the neutrophil-lymphocyte ratio (NLR) and red blood cell distribution width (RDW) in the early diagnosis and prognosis evaluation of DM complicated with heart failure (HF). METHODS: We retrospectively analyzed clinical data on 65 patients with type 2 DM (T2DM) complicated with HF (research group, Res) and 60 concurrent patients with uncomplicated T2DM (control group, Con) diagnosed at Zhejiang Provincial People's Hospital between January 2019 and December 2021. The NLR and RDW values were determined and comparatively analyzed, and their levels in T2DM + HF patients with different cardiac function grades were recorded. The receiver operating characteristic (ROC) curves were plotted to determine the NLR and RDW values (alone and in combination) for the early diagnosis of HF. The correlation between NLR and RDW with the presence or absence of cardiac events was also investigated. RESULTS: Higher NLR and RDW levels were identified in the Res vs the Con groups (P < 0.05). The NLR and RDW increased gradually and synchronously with the deterioration of cardiac function in the Res group, with marked differences in their levels among patients with grade II, III, and IV HF (P < 0.05). ROC curve analysis revealed that NLR combined with RDW detection had an area under the curve of 0.915, a sensitivity of 76.9%, and a specificity of 100% for the early diagnosis of HF. Furthermore, HF patients with cardiac events showed higher NLR and RDW values compared with HF patients without cardiac events. CONCLUSION: NLR and RDW were useful laboratory indicators for the early diagnosis of DM complicated with HF, and their joint detection was beneficial for improving diagnostic efficiency. Additionally, NLR and RDW values were directly proportional to patient outcomes.

Postoperative neutrophil-to-lymphocyte ratio predicts malignant cerebral edema following endovascular treatment for acute ischemic stroke.

Background and purpose: Malignant cerebral edema (MCE) is one of serious complications with high mortality following endovascular treatment (EVT) for acute ischemic stroke (AIS) with large vessel occlusion. We aimed to investigate the relationship between postoperative neutrophil-to-lymphocyte ratio (NLR) and MCE after EVT. Methods: The clinical and imaging data of 175 patients with AIS of anterior circulation after EVT were studied. Admission and postoperative NLR were determined. The presence of MCE was evaluated on the computed tomography performed 24 h following EVT. The clinical outcomes were measured using the modified Rankin Scale (mRS) at 90-day after onset. Univariate and multivariate regression analyses were used to analyze the relationship between postoperative NLR and MCE. Optimal cutoff values of postoperative NLR to predict MCE were defined using receiver operating characteristic analysis. Results: MCE was observed in 24% of the patients who underwent EVT and was associated with a lower rate of favorable clinical outcomes at 90-day. Multivariate logistic regression analysis demonstrated that baseline Alberta Stroke Program Early CT Score (ASPECT) score (OR = 0.614, 95% CI 0.502-0.750, p = 0.001), serum glucose (OR = 1.181, 95% CI 1.015-1.374, p = 0.031), and postoperative NLR (OR = 1.043, 95% CI 1.002-1.086, p = 0.041) were independently associated with MCE following EVT for AIS with large vessel occlusion. Postoperative NLR had an area under the receiver operating characteristic curve of 0.743 for prediction MCE, and the optimal cutoff value was 6.15, with a sensitivity and specificity of 86.8% and 55%. Conclusion: Elevated postoperative NLR is independently associated with malignant brain edema following EVT for AIS with large vessel occlusion, and may serve as an early predictive indicator for MCE after EVT.

The association between the neutrophil-to-lymphocyte ratio and type 2 diabetes mellitus: a cross-sectional study.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a prevalent chronic disease often accompanied by low-grade inflammation. Recently, the neutrophil-to-lymphocyte ratio (NLR) has garnered researchers' interest as an emerging inflammation biomarker. This study aimed to comprehensively explore the relationship between NLR and T2DM using the National Health and Nutrition Examination Survey (NHANES) database. METHOD: We employed a cross-sectional study design to analyze data from five NHANES cycles from 2007 to 2016, excluding individuals with incomplete data. This study utilized a weighted logistic regression model, subgroup analyses, and restricted cubic spline (RCS) analysis to assess the potential relationship between NLR and T2DM. RESULTS: A total of 9903 participants were eligible for the analysis, of which 1280 were diagnosed with T2DM. The T2DM group exhibited significantly higher NLR levels than the non-T2DM group. After adjusting for potential confounders, elevated NLR levels were associated with an increased risk of developing T2DM, indicated by an odds ratio (OR) of 1.14, 95% CI: (1.05,1.24), P = 0.003. The results of the subgroup analyses revealed a significant interaction effect between NLR and T2DM concerning race and hypertension (P for interaction < 0.05). In contrast, no significant interactions were found for age, sex, education level, body mass index (BMI), smoking status, recreational activities, and alcohol drinker (P for interaction > 0.05). RCS analysis showed a significant non-linear relationship between NLR and T2DM, with an inflection point at 2.27 (all P for non-linearity < 0.05). CONCLUSION: Our study indicates that an elevated neutrophil-to-lymphocyte ratio is associated with a higher risk of T2DM.

Mechanistic insights into Lipocalin-2 in ischemic stroke and hemorrhagic brain injury: Integrating animal and clinical studies.

Brain injuries, including strokes and traumatic brain injuries (TBI), are a major global health concern, contributing significantly to both mortality and long-term disability. Recent research has identified lipocalin-2 (LCN2), a glycoprotein secreted by various brain cells, as a key factor in influencing brain injury outcomes. Evidence from animal and clinical studies firmly establishes the pivotal role of LCN2 in driving the inflammatory responses triggered by damage to brain tissue. Furthermore, increased LCN2 promotes cellular differentiation, blood-brain barrier breakdown, and decreases cell viability. Interventions with LCN2 inhibitors attenuated brain injury through a reduction in the inflammation process and enhanced cellular viability. Potential mechanisms of LCN2 involve several pathways including the Janus kinase-2 (JAK2)-signal transducers and the transcription-3 (STAT3) signaling, hypoxia-inducible factor 1-alpha (HIF-1α)-LCN2-vascular endothelial growth factor alpha (VEGFα), and the PKR-like ER kinase (PERK) pathways. LCN2 itself interacts with diverse inflammatory cytokines in TBI and intracranial hemorrhage (ICH), resulting in disruption of the blood-brain barrier, increased programmed cell death, and an imbalance in iron homeostasis. Clinical studies have also shown that increased LCN2 level can act as a prognostic biomarker of outcomes following brain injuries. Therefore, this review aims to comprehensively evaluate the role and underlying mechanisms of LCN2 in brain injuries, including stroke and TBI, and explore potential therapeutic interventions targeting LCN2 in these conditions.

Dynamic change of neutrophil-to-lymphocyte ratio and its predictive value of prognosis in acute ischemic stroke.

OBJECTIVE: The present research aimed to explore the dynamic change of the neutrophil-to-lymphocyte ratio (NLR) and its relationship with functional outcome following an acute ischemic stroke (AIS), whether receiving intravenous thrombolysis (IVT) or not. METHODS: We retrospectively analyzed data that were prospectively acquired from patients with AIS treated with IVT or not. For patients receiving IVT, the NLR was based on a blood test performed prior to IVT (d0) and at different time points after disease onset (d1, d3, d7). In addition, in the non-IVT group, the NLR was obtained at different time points after disease onset (d1, d3, d7). Follow-ups were performed 3 months after onset via telephone. In addition, a good outcome was defined as a modified Rankin scale (mRS) ≤1; a poor outcome means 2 ≤ mRS ≤ 6. RESULTS: A total of 204 AIS patients were included in this study. The NLR presented a dynamic change as it increased to its peak at day 1 and gradually declined to its baseline at day 7, no matter whether patients were receiving IVT or not. Patients with poor outcomes have a higher NLR at various time points. The results of multivariate logistic regression analysis demonstrated that the National Institutes of Health Stroke Scale (NIHSS), NLR d1, NLR d3, and NLR d7 were independently associated with functional outcomes. The area under the receiver operating characteristic curve of NLR in predicting outcomes was as follows: NLR d3 demonstrated robust predictive power within the IVT therapy cohort, whereas NLR d7 was predictive in the non-IVT cohort. However, the most potent predictor emerged as the combination of NIHSS and NLR. CONCLUSION: NLR has the potential to predicate diagnosis for AIS, especially when combined with the NIHSS score.

Limited impact of traumatic brain injury on the post-traumatic inflammatory cellular response.

PURPOSE: Trauma triggers a systemic inflammatory cellular response due to tissue damage, potentially leading to a secondary immune deficiency. Trauma severity is quantified by the Injury Severity Score (ISS). Severe Traumatic Brain Injury (TBI) is associated with high ISSs due to high lethality, despite limited tissue damage. Therefore, ISS might overestimate the post-traumatic inflammatory cellular response. This study investigated the effect of TBI on the occurrence of different systemic neutrophil phenotypes as alternative read-out for systemic inflammation. METHODS: A single-center retrospective cohort study was conducted at a level-1 trauma center. Patients aged ≥ 18 years, admitted between 01-03-2021-01-11-2022 and providing a diagnostic blood sample were included. Four groups were created: isolated TBI, isolated non-TBI, multitrauma TBI and multitrauma non-TBI. Primary outcome was occurrence of different neutrophil phenotypes determined by automated flow cytometry. Secondary outcome was infectious complications. RESULTS: In total, 404 patients were included. TBI and non-TBI patients demonstrated similar occurrences of different neutrophil phenotypes. However, isolated TBI patients had higher ISSs than their isolated non-TBI controls who suffered similar post-traumatic inflammatory cellular responses. Regardless of the type of injury, patients exhibiting higher systemic inflammation had a high infection risk. CONCLUSION: When TBI is involved, ISS tends to be higher compared to similar patients in the absence of TBI. However, TBI patients did not demonstrate an increased inflammatory cellular response compared to non-TBI patients. Therefore, TBI does not add much to the inflammatory cellular response in trauma patients. The degree of the inflammatory response was related to the incidence of infectious complications.

A synbiotic mixture of Bifidobacterium breve M16-V, oligosaccharides and pectin, enhances Short Chain Fatty Acid production and improves lung health in a preclinical model for pulmonary neutrophilia.

Introduction: Pulmonary neutrophilia is a hallmark of numerous airway diseases including Chronic Obstructive Pulmonary Disease (COPD), Neutrophilic asthma, Acute Lung Injury (ALI), Acute Respiratory Distress Syndrome (ARDS) and COVID-19. The aim of the current study was to investigate the effect of dietary interventions on lung health in context of pulmonary neutrophilia. Methods: Male BALB/cByJ mice received 7 intra-nasal doses of either a vehicle or lipopolysaccharides (LPS). To study the effect of nutritional interventions they received 16 intra-gastric doses of either a vehicle (PBS) or the following supplements (1) probiotic Bifidobacterium breve (B. breve) M16-V; (2) a prebiotic fiber mixture of short-chain galacto-oligosaccharides, long-chain fructo-oligosaccharides, and low-viscosity pectin in a 9:1:2 ratio (scGOS/lcFOS/lvPectin); and (3) A synbiotic combination B. breve M16-V and scGOS/lcFOS/lvPectin. Parameters for lung health included lung function, lung morphology and lung inflammation. Parameters for systemic immunomodulation included levels of fecal short chain fatty acids and regulatory T cells. Results: The synbiotic supplement protected against the LPS induced decline in lung function (35% improved lung resistance at baseline p = 0.0002 and 25% at peak challenge, p = 0.0002), provided a significant relief from pulmonary neutrophilia (40.7% less neutrophils, p < 0.01) and improved the pulmonary neutrophil-to-lymphocyte ratio (NLR) by 55.3% (p = 0.0033). Supplements did not impact lung morphology in this specific experiment. LPS applied to the upper airways induced less fecal SCFAs production compared to mice that received PBS. The production of acetic acid between day -5 and day 16 was increased in all unchallenged mice (PBS-PBS p = 0.0003; PBS-Pro p < 0.0001; PBS-Pre, p = 0.0045; PBS-Syn, p = 0.0005) which upon LPS challenge was only observed in mice that received the synbiotic mixture of B. breve M16-V and GOS:FOS:lvPectin (p = 0.0003). A moderate correlation was found for butyric acid and lung function parameters and a weak correlation was found between acetic acid, butyric acid and propionic acid concentrations and NLR. Conclusion: This study suggests bidirectional gut lung cross-talk in a mouse model for pulmonary neutrophilia. Neutrophilic lung inflammation coexisted with attenuated levels of fecal SCFA. The beneficial effects of the synbiotic mixture of B. breve M16-V and GOS:FOS:lvPectin on lung health associated with enhanced levels of SCFAs.

Sterile Endocarditis and Splenic Infarct: A Rare Masquerading Presentation of Granulomatosis With Polyangiitis in a Patient With Pulmonary Aspergillosis.

Granulomatosis with polyangiitis (GPA) is a rare multisystem disease characterized by vasculitis affecting small vessels, resulting in the formation of necrotising granulomata, primarily affecting the lungs, the upper respiratory tract, and kidneys. Almost all patients have upper and lower respiratory involvement; up to 85% of patients with GPA develop kidney disease within two years of diagnosis. Cutaneous, neurological, and ocular manifestations are also seen with varying frequencies. However, cardiac manifestations of the disease are rare and scarcely reported in the literature. Here, we report a case of a 65-year-old female with an initial diagnosis of pulmonary aspergillosis based on the presence of septate hyphae branching at acute angles on lung biopsy and elevated serum galactomannan, who, over the following months, developed a multitude of issues such as myocardial infarction, sterile endocarditis, splenic infarction, and heart block, as well as the challenges faced in establishing a diagnosis and managing its complications.

Neutrophil-to-Lymphocyte Ratio and Procalcitonin in Sepsis Patients: Do They Have Any Prognostic Significance?

INTRODUCTION: Biomarkers like white blood cells, C-reactive protein, procalcitonin, and interleukin-1 are used in patients with sepsis for early diagnosis, differentiating various infections, making decisions to start antibiotics and evaluate their response, and to prognosticate morbidity and mortality. Despite the availability of these biomarkers, the prognosis of patients with sepsis in the ICU remains poor. Hence, this study was carried out to test the efficacy of procalcitonin and neutrophil-to-lymphocyte ratio (NLR) to prognosticate mortality and morbidity in terms of incidence of organ dysfunction and length of ICU stay in sepsis patients. METHODS: In this prospective observational study, we measured NLR and procalcitonin at days one, three, and seven of sepsis patients and divided them into four groups: low NLR and high procalcitonin (LNHP), high NLR and high procalcitonin (HNHP), high NLR and low procalcitonin (HNLP), and low NLR and low procalcitonin (LNLP). Mortality at 28 days was noted as the primary outcome. RESULTS: Out of 85 patients included in the study, five were lost to follow-up. Although no statistically significant difference was found in the primary outcome between all four groups, regression analysis showed that rising NLR and procalcitonin values were associated with a significant increase in mortality. CONCLUSION: Serial values of NLR and procalcitonin are more important in predicting severity in comparison to a single value at presentation and can be used as a prognostic marker in sepsis patients.

Association of Delta Neutrophil Index with the 30-day Mortality in Adult Cardiac Surgical Patients.

Purpose: This study aimed to assess the predictive accuracy of 30-day mortality with delta neutrophil index (DNI) in adult cardiac surgical patients. Methods: This study enrolled patients who underwent cardiac surgery under general anesthesia between March 2016 and May 2022 at a tertiary hospital in the Republic of Korea. DNI was measured preoperatively, on postoperative arrival to the surgical intensive care unit (ICU), and 12, 24, 48, and 72 h postoperatively. Receiver operating characteristic (ROC) analysis was employed to identify the prediction accuracy of DNI. An area under ROC curve (AUROC) ≥0.700 was defined as satisfactory predictive accuracy. An optimal cutoff point for the DNI value to maximize predictive accuracy was revealed in the ROC curve, where [sensitivity + specificity] was maximum. Results: This study included a total of 843 patients in the final analyses. The mean age of the study population was 66.9±12.2 years and 38.4% of them were female patients. The overall 30-day mortality rate was 5.2%. Surgery involving the thoracic aorta, history of prior cardiac surgery, or emergency surgery were associated with a higher mortality rate. The DNI showed satisfactory predictive accuracy at 24 h, 48 h, and 72 h postoperatively, with AUROC of 0.729, 0.711, and 0.755, respectively. The optimal cutoff points of DNI at each time point were 3.2, 3.8, and 2.3, respectively. Conclusions: Postoperative DNI is a good predictor of 30-day mortality after cardiac surgery and has the benefit of no additional financial costs or time.

The role of severity and duration of inflammation and hematological parameters on the outcome of subacute thyroiditis.

Background: The role of severity and duration of inflammatory findings on the development of persistent hypothyroidism and anemia has not been clarified in subacute thyroiditis (SAT). Methods: Demographic data and laboratory parameters of patients with SAT were analyzed retrospectively. Results: Permanent hypothyroidism was observed in 28.1% of patients. Baseline elevated erythrocyte sedimentation rate as defined >74.5 mm/h was found to be associated with permanent hypothyroidism, but the duration of inflammation was not different between the recovered and hypothyroid patients. Baseline hemoglobin values improved without specific therapy in 3.5 months. Conclusion: The initial severity but not the duration of inflammation increases the risk for the development of permanent thyroid dysfunction, and anemia improves with the resolution of inflammation.

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Monocyte-to-lymphocyte ratio in the early second trimester is a predictor of gestational diabetes mellitus.

OBJECTIVE: To evaluate neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), neutrophil-to-monocyte ratio (NMR), and other hemogram-derived inflammatory parameters measured in the early second trimester and their association with the risk of gestational diabetes mellitus (GDM). METHODS: This case-control study was conducted with 105 women with GDM and 205 healthy pregnant women, matched for maternal age at a 1:2 ratio with the cases at two regional maternity hospitals between January 2021 and August 2022. The inflammatory blood cell indices were tested in the early second trimester, and the patient's characteristics and the course of the pregnancy were analyzed. Logistic regression was used to determine the association between hematological parameters and the risk of GDM. Data were analyzed using SPSS, version 25.0 (SPSS, Chicago, IL). RESULTS: The final analysis included 310 pregnant women. The GDM group showed a higher pre-pregnancy BMI compared to the healthy controls (p < .01). There was no difference in NMR, PLR, and NLR between the groups (p = .63, .54, and .39, respectively). GDM was only positively associated with MLR (p = .02). After adjusting for potential confounding risk factors including maternal age, parity, and BMI, the multivariate regression analysis showed a higher level of MLR, with a cutoff point of 0.312, was independently associated with the risk of GDM (OR = 2.15, 95%CI 1.51-4.31, p = .03). However, ROC analysis showed that the AUC value of MLR was poor (0.670). CONCLUSIONS: We found that MLR, an inflammatory combined index derived from whole blood counts, may potentially serve as a predictor of GDM in the early second trimester.

In Fanconi Anemia, impaired accumulation of bone marrow neutrophils during emergency granulopoiesis induces hematopoietic stem cell stress.

Fanconi Anemia (FA) is an inherited disorder of DNA-repair due to mutation in one of 20+ interrelated genes that repair intra-strand DNA crosslinks and rescue collapsed or stalled replication forks. The most common hematologic abnormality in FA is anemia, but progression to bone marrow failure (BMF), clonal hematopoiesis, or acute myeloid leukemia (AML) may also occur. In prior studies, we found that Fanconi DNA-repair is required for successful emergency granulopoiesis; the process for rapid neutrophil production during the innate immune response. Specifically, Fancc-/- mice did not develop neutrophilia in response to emergency granulopoiesis stimuli, but instead exhibited apoptosis of bone marrow hematopoietic stem cells (HSCs) and differentiating neutrophils. Repeated emergency granulopoiesis challenges induced BMF in most Fancc-/- mice, with AML in survivors. In contrast, we found equivalent neutrophilia during emergency granulopoiesis in Fancc-/-Tp53+/- mice and wild type (WT) mice, without BMF. Since termination of emergency granulopoiesis is triggered by accumulation of bone marrow neutrophils, we hypothesize neutrophilia protects Fancc-/-Tp53+/- bone marrow from the stress of a sustained inflammation that is experienced by Fancc-/- mice. In the current work, we found that blocking neutrophil accumulation during emergency granulopoiesis led to BMF in Fancc-/-Tp53+/- mice, consistent with this hypothesis. Blocking neutrophilia during emergency granulopoiesis in Fancc-/-Tp53+/- mice (but not WT) impaired cell cycle checkpoint activity, also found in Fancc-/- mice. Mechanisms for loss of cell cycle checkpoints during infections challenges may define molecular markers of FA progression, or suggest therapeutic targets for bone marrow protection in this disorder.

Mesenchymal stem cell-derived extracellular vesicles accelerate diabetic wound healing by inhibiting NET-induced ferroptosis of endothelial cells.

Impaired angiogenesis is a major factor contributing to delayed wound healing in diabetes. Dysfunctional mitochondria promote the formation of neutrophil extracellular traps (NETs), obstructing angiogenesis during wound healing. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have shown promise in promoting tissue repair and regeneration in diabetes; however, the precise pathways involved in this process remain unclear. In this study, NET-induced ferroptosis of endothelial cells (ECs) and angiogenesis were assessed in diabetic wound samples from both patients and animal models. In vitro and in vivo experiments were performed to examine the regulatory mechanisms of NETs in ECs using specific inhibitors and gene-knockout mice. MSC-EVs encapsulating dysfunctional mitochondria were used to trigger mitochondrial fusion and restore mitochondrial function in neutrophils to suppress NET formation. Angiogenesis in wound tissue was evaluated using color laser Doppler imaging and vascular density analysis. Wound healing was evaluated via macroscopic analysis and histological evaluation of the epithelial gap. NET-induced ferroptosis of ECs was validated as a crucial factor contributing to the impairment of angiogenesis in diabetic wounds. Mechanistically, NETs regulated ferroptosis by suppressing the PI3K/AKT pathway. Furthermore, MSC-EVs transferred functional mitochondria to neutrophils in wound tissue, triggered mitochondrial fusion, and restored mitochondrial function, thereby reducing NET formation. These results suggest that inhibiting NET formation and EC ferroptosis or activating the PI3K/AKT pathway can remarkably improve wound healing. In conclusion, this study reveals a novel NET-mediated pathway involved in wound healing in diabetes and suggests an effective therapeutic strategy for accelerating wound healing.

Evaluating Cardiovascular Risks: The Platelet Lymphocyte Ratio and the Neutrophil Lymphocyte Ratio As High-Risk Heart Score Predictors in Non-ST Elevation Myocardial Infarction (NSTEMI) and Unstable Angina Patients.

Introduction Acute coronary syndromes (ACS), encompassing non-ST elevation myocardial infarction (NSTEMI) and unstable angina (UA), present significant challenges in risk assessment and management, particularly in resource-constrained environments like India. The burden of cardiovascular diseases in such regions necessitates cost-effective and readily accessible tools for risk stratification. Previous research has emphasized the role of inflammatory markers in coronary artery disease (CAD), prompting investigations into simple and affordable biomarkers for risk assessment. Platelet lymphocyte ratio (PLR) and neutrophil lymphocyte ratio (NLR) have emerged as potential biomarkers for thrombotic activity in cardiac illnesses, offering simplicity, accessibility, and cost-effectiveness in risk assessment making them particularly valuable in resource-poor settings like India, where advanced diagnostic tools may be limited. Objective This study aims to evaluate the effectiveness of PLR and NLR as predictors of high-risk HEART (history, ECG, age, risk factors, and troponin) scores in patients with NSTEMI and UA. Methods A prospective cross-sectional study was conducted at the Saveetha Medical College and Hospitals in Chennai, India, from March 2021 to September 2022. The study included 288 adults diagnosed with NSTEMI or UA, aged 18 years and above. The inclusion criteria comprised patients with confirmed diagnoses of NSTEMI or UA based on clinical symptoms, electrocardiographic findings, and cardiac biomarker elevation. The exclusion criteria encompassed patients with active infections, acute traumatic injuries, end-stage renal disease, malignant neoplasms, and ST-elevation myocardial infarction (STEMI). In addition to the HEART score, PLR, and NLR were computed to assess the prognosis of patients admitted to the Saveetha Medical College and Hospitals. Results The statistical analysis revealed significant correlations between PLR, NLR, and HEART score risk categories. The Pearson's correlation coefficient indicated strong associations between PLR/NLR values and HEART score risk groups, suggesting their potential as predictive markers for adverse clinical outcomes. Additionally, analysis of variance (ANOVA) demonstrated significant differences in PLR/NLR values across different HEART score risk categories, further highlighting their relevance in risk stratification. The effect sizes for these correlations were moderate to large, indicating clinically meaningful associations between PLR/NLR and cardiovascular risk. Conclusion In cases of NSTEMI and UA, PLR and NLR show potential as simple and inexpensive indicators of high-risk patients. By leveraging these inexpensive biomarkers, healthcare providers can enhance risk assessment and prognostication in patients presenting with ACS, facilitating timely interventions and tailored management strategies.

Morphological Changes of Peri-Coronary Adipose Tissue Together with Elevated NLR in Acute Myocardial Infarction Patients in-Hospital.

Background: Inflammation triggers atherosclerotic plaque rupture, leading to acute myocardial infarction (AMI). Following AMI, peri-coronary adipose tissue (PCAT) undergoes a transition from lipid-rich to hydrophilic characteristics due to vascular inflammation. This study investigates PCAT changes and neutrophil-to-lymphocyte ratio levels during AMI. Patients and Methods: 60 AMI patients undergoing coronary computed tomography angiography and angiography (Jan 2020-Jun 2022) were studied 60 age, gender, BMI-matched stable angina, and 60 non-coronary artery disease patients were included. Siemens VB20.0 measured PCAT-volume and fat attenuation index (FAI). Neutrophil-to-lymphocyte ratio levels were calculated by peripheral blood tests. Results: The PCAT volume and PCAT-FAI gradually increased across the control, stable angina, and AMI groups, with a corresponding gradual rise in NLR. NLR exhibited weak positive correlation with PCAT-FAI (r=0.35) and PCAT-volume (r=0.24). Multivariable logistic regression identified increased PCAT-volume, PCAT-FAI and neutrophil-to-lymphocyte ratio as possible independent AMI risk factors. No significant PCAT-volume difference was observed between infarct-related artery (IRA) and non-IRA for all three coronary arteries. Only PCAT-FAI around IRA-LAD was higher than non-IRA-LAD (-74.84±6.93 HU vs -79.04±8.68 HU). PCAT-FAI around culprit vessels in AMI was higher than corresponding lesion related vessel in SA. PCAT-volume around narrowed non-IRA in AMI was higher than that of corresponding LRV in SA. PCAT-FAI of narrowed non-IRA-LADs and non-IRA-LCXs in AMI were elevated compared to LADs (-78.46±8.56HU vs -83.13±8.34 HU) and LCXs (-73.83±10.63 HU vs -81.38±7.88 HU) of lesion related vessel in stable angina. Conclusion: We found an association between AMI and inflammation in the coronary perivascular adipose tissue and systemic inflammatory response.

Predictive ability of complete blood count, mean platelet ratio, mean platelet volume, and neutrophil/lymphocyte ratio for severe pneumonia among RT-PCR or radiologically proven COVID-19 patients.

Background: Immuno-inflammatory markers related to white blood cells, and platelets are shown to be associated with COVID-19 infection, and considered to be independent markers for clinical outcomes and mortality. The present study aimed to study the predictive value of these hematologic parameters in progression of COVID-19 to severe pneumonia. Methods: This was an analytical cross-sectional study conducted among RT-PCR or radiologically proven COVID-19 patients in a tertiary care hospital in Rajasthan. Semi-structured questionnaire was used to collect the epidemiological information of the patients with COVID-19. Complete blood count and other laboratory parameters were also studied among the patients. Results: Mean age of participants in the study was 52 years, with about 70% being males. Cough and breathlessness were the most common symptoms among the patients. It was found that the parameters related to white blood cells were significantly different between patients with COVID-19 infection and severe pneumonia (except absolute monocyte count). NLR was significantly higher among those with severe pneumonia. In the univariate analysis, age (OR - 1.02), NLR (OR - 1.16), and albumin (OR - 0.45) were found to be significant predictors of progression to severe pneumonia. In the final model, adjusted for confounders, only NLR and albumin levels significantly predicted progression to severe pneumonia among COVID-19 patients. Conclusion: The study consolidates the predictive ability of NLR for severe pneumonia. It is an important finding, as health facilities with limited access to laboratory investigations can rely on simple markers in routine practice to predict the progression of COVID-19 infection to severe pneumonia.

Reciprocal Interaction with Neutrophils Facilitates Cutaneous Accumulation of Liposomes.

Liposomes are versatile drug delivery systems in clinical use for cancer and many other diseases. Unfortunately, PEGylated liposomal doxorubicin (sLip/DOX) exhibits serious dose-limiting cutaneous toxicities, which are closely related to the extravascular accumulation of sLip/DOX in the dermis. No clinical interventions have been proposed for cutaneous toxicities due to the elusive transport pathways. Herein, we showed that the reciprocal interaction between liposomes and neutrophils played pivotal roles in liposome extravasation into the dermis. Neutrophils captured liposomes via the complement receptor 3 (CD11b/CD18) recognizing the fragment of complement component C3 (iC3b) deposited on the liposomal surface. Uptake of liposomes also activated neutrophils to induce CD11b upregulation and enhanced the ability of neutrophils to migrate outside the capillaries. Furthermore, inhibition of complement activation either by CRIg-L-FH (a C3b/iC3b targeted complement inhibitor) or blocking the phosphate negative charge in mPEG-DSPE could significantly reduce liposome uptake by neutrophils and alleviate the cutaneous accumulation of liposomes. These results validated the liposome extravasation pathway mediated by neutrophils and provided potential solutions to the devastating cutaneous toxicities occurring during sLip/DOX treatment.

Prognostic Value of the 18F-FDG PET/CT and Haematological Parameters in Head and Neck Cancer.

INTRODUCTION: Fluorine 18-fluoro-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) is commonly used for the staging of head and neck cancer. This study aimed to evaluate the correlation between 18F-FDG PET/CT, haematological parameters and prognosis in patients with advanced head and neck cancer. METHODS: This was a single-institutional retrospective study of 83 patients with advanced head and neck squamous cell carcinoma (HNSCC) who underwent 18F-FDG PET/CT imaging before initial treatment between 2014 and 2018. 18F-FDG PET/CT after treatment was performed in 57 patients. The prognostic parameters of the pre- and post-treatment maximum standardised uptake value (SUVmax), metabolic tumour volume (MTV), total lesion glycolysis (TLG) of primary tumours and haematological parameters were analysed to evaluate the association between overall survival (OS) and progression-free survival (PFS). RESULTS: Pre-MTV, pre-TLG and post-SUVmax were significantly associated with poor OS and PFS (p < 0.05). Haematological parameters, including pretreatment neutrophil/lymphocyte ratio and C-reactive protein/albumin ratio, were associated with 18F-FDG PET/CT parameters. In multivariate analysis, post-SUVmax was an independent prognostic factor for OS and PFS. CONCLUSION: A correlation between PET/CT metabolic and haematological parameters was observed. The volume and intensity of 18F-FDG uptake region, in addition to haematological parameters, are feasible markers for predicting the progression of HNSCC in daily practice. Further, post-SUVmax could be an independent parameter for predicting poor survival.