Serum Neutrophil Research Articles

Interpretable generalized neural additive models for mortality prediction of COVID-19 hospitalized patients in Hamadan, Iran

BackgroundThe high number of COVID-19 deaths is a serious threat to the world. Demographic and clinical biomarkers are significantly associated with the mortality risk of this disease. This study aimed to implement Generalized Neural Additive Model (GNAM) as an interpretable machine learning method to predict the COVID-19 mortality of patients.MethodsThis cohort study included 2181 COVID-19 patients admitted from February 2020 to July 2021 in Sina and Besat hospitals in Hamadan, west of Iran. A total of 22 baseline features including patients' demographic information and clinical biomarkers were collected. Four strategies including removing missing values, mean, K-Nearest Neighbor (KNN), and Multivariate Imputation by Chained Equations (MICE) imputation methods were used to deal with missing data. Firstly, the important features for predicting binary outcome (1: death, 0: recovery) were selected using the Random Forest (RF) method. Also, synthetic minority over-sampling technique (SMOTE) method was used for handling imbalanced data. Next, considering the selected features, the predictive performance of GNAM for predicting mortality outcome was compared with logistic regression, RF, generalized additive model (GAMs), gradient boosting decision tree (GBDT), and deep neural networks (DNNs) classification models. Each model trained on fifty different subsets of a train-test dataset to ensure a model performance. The average accuracy, F1-score and area under the curve (AUC) evaluation indices were used for comparison of the predictive performance of the models.ResultsOut of the 2181 COVID-19 patients, 624 died during hospitalization and 1557 recovered. The missing rate was 3 percent for each patient. The mean age of dead patients (71.17 ± 14.44 years) was statistically significant higher than recovered patients (58.25 ± 16.52 years). Based on RF, 10 features with the highest relative importance were selected as the best influential features; including blood urea nitrogen (BUN), lymphocytes (Lym), age, blood sugar (BS), serum glutamic-oxaloacetic transaminase (SGOT), monocytes (Mono), blood creatinine (CR), neutrophils (NUT), alkaline phosphatase (ALP) and hematocrit (HCT). The results of predictive performance comparisons showed GNAM with the mean accuracy, F1-score, and mean AUC in the test dataset of 0.847, 0.691, and 0.774, respectively, had the best performance. The smooth function graphs learned from the GNAM were descending for the Lym and ascending for the other important features.ConclusionsInterpretable GNAM can perform well in predicting the mortality of COVID-19 patients. Therefore, the use of such a reliable model can help physicians to prioritize some important demographic and clinical biomarkers by identifying the effective features and the type of predictive trend in disease progression.

Clinical value of thyroid related hormones combined with neutrophil to lymphocyte ratio in patients with nonalcoholic fatty liver disease

In sufferers with nonalcoholic fatty liver disease (NAFLD), the differences of thyroid associated hormones and neutrophil to lymphocyte ratio (NLR) in different liver pathological groups have been compared. Patients with NAFLD diagnosed by liver biopsy in our hospital from July 2012 to February 2019 were selected. All subjects were divided into nonalcoholic steatohepatitis (NASH) team and non-NASH group, no/mild fibrosis group (F0-1) and significant fibrosis group (F2-4). The differences of thyroid related hormones and NLR in these groups were in contrast, respectively. For the TSH, we conducted further evaluation based on gender. The TSH and NLR in NASH patients were significantly higher than non-NASH patients, but there was no considerable difference in free triiodothyronine (FT3) and free thyroxine (FT4) between the 2 groups. In the gender-based subgroup analysis, the variations of TSH between the 2 groups were nonetheless statistically significant (P < .05). The TSH and NLR in the significant fibrosis group were higher than these in the non/mild liver fibrosis group, and the differences were statistically significant (P < .05), but there was no large difference in FT3 and FT4 between the 2 groups (P > .05). In addition, in the gender-based subgroup analysis and further multivariable analysis, the variations of TSH between the 2 groups were still statistically significant (P < .05). In this study, we found that serum thyroid stimulating hormone (TSH) and neutrophil to lymphocyte ratio (NLR) were closely associated to the severity of NAFLD, suggesting that this simple available laboratory index may additionally be incorporated into the future noninvasive diagnostic scoring model to predict the incidence of NASH and the degree of fibrosis.

Circulating MicroRNAs and Extracellular Vesicle-Derived MicroRNAs as Predictors of Functional Recovery in Ischemic Stroke Patients: A Systematic Review and Meta-Analysis.

Stroke accounts for the second leading cause of death and a major cause of disability, with limited therapeutic strategy in both the acute and chronic phases. Blood-based biomarkers are intensively researched and widely recognized as useful tools to predict the prognoses of patients confronted with therapeutically limited diseases. We performed a systematic review of the circulating biomarkers in IS patients with prognostic value, with a focus on microRNAs and exosomes as predictive biomarkers of motor and cognitive recovery. We identified 63 studies, totalizing 72 circulating biomarkers with prognostic value in stroke recovery, as follows: 68 miRNAs and exosomal-miRNAs being identified as predictive for motor recovery after stroke, and seven biomarkers being predictive for cognitive recovery. Twelve meta-analyses were performed using effect sizes (random-effects and fixed-effects model). The most significant correlation findings obtained after pooling were with miR-21, miR-29b, miR-125b-5p, miR-126, and miR-335. We identified several miRNAs that were correlated with clinical outcomes of stroke severity and recovery after ischemic stroke, providing predictive information on motor and cognitive recovery. Based on the current state of research, we identified serum miR-9 and neutrophil miR-29b as the most promising biomarkers for in-depth follow-up studies, followed by serum miR-124 and plasma miR-125b.

Role of Serum Endocan Levels in Children with Bacterial and Viral Pneumonia: A Prospective, Case-Control Study.

Introduction and Objective: Endocan has been used as a biomarker in the differential diagnosis of pulmonary diseases in adults. However, there are only a limited number of studies on its use in children. In this context, the objective of this study is to evaluate the relationship between serum endocan levels in children with bacterial and viral pneumonia. Materials and Methods: The population of this prospective case-control study consisted of hospitalized children aged 1 month to 15 years diagnosed with pneumonia between August 2020 and July 2021, whereas the control group consisted of randomly selected healthy children. The demographic and clinical characteristics of all participants were recorded. Participants' endocan levels, white blood cell (WBC) and neutrophil counts, and C-reactive protein (CRP) and procalcitonin (PCT) levels were measured within the scope of the laboratory tests. Results: The study sample consisted of 41 children, of whom 21 had bacterial pneumonia and 20 had viral pneumonia, whereas the control group consisted of 47 healthy children. Serum endocan levels, WBC and neutrophil counts, and PCT and CRP levels were significantly higher in children with bacterial pneumonia than in children with viral pneumonia and healthy children (P < 0.05). Additionally, serum endocan levels were significantly higher in children with viral pneumonia than in healthy children (P < 0.001). The endocan levels in children with bacterial pneumonia were significantly associated with the need for intensive care (P = 0.004) and correlated with the length of hospital stay (LoS) (r = 0.592, P = 0.005). Conclusion: The findings of this study indicated that serum endocan levels can be used in the differential diagnosis of bacterial and viral pneumonias. Additionally, it was found that the need for intensive care and LoS were significantly correlated with endocan levels in children with bacterial pneumonia.

Influence factors of deep venous thromboembolism after knee arthroplasty and significance of changes of serum nets and sVCAM-1 levels

To investigate the relationship between the changes of serum neutrophil extracellular traps (NETs), soluble vascular cell adhesion molecule-1(sVCAM-1) and deep venous thromboembolism after knee arthroplasty. From May 2017 to April 2020, 30 patients with deep venous thromboembolism after knee arthroplasty were retrospectively selected as the observation group, and 60 patients without deep venous thromboembolism after knee arthroplasty in the same period were randomly selected as the control group. The clinical data, serum levels of nets and sVCAM-1 before and 1, 3 and 5 days after operation were compared between the two groups. Logistic regression model was used to analyze the influencing factors of deep venous thromboembolism after knee arthroplasty; Pearson correlation was used to analyze the relationship between serum nets and sVCAM-1 levels;Draw the receiver operating characteristic curve(ROC) to obtain the area under the curve(AUC), and analyze the diagnostic value of serum nets and sVCAM-1 levels for deep vein thromboembolism after knee arthroplasty. There were statistically significant differences between two groups in age, body mass index, and postoperative knee elevation and flexion ratio(P<0.05). The level of serum NETs and sVCAM-1 on the 1st and 3rd day after surgery of the observation group were higher than the control group(P<0.05). Logistic regression analysis showed that age, body mass index, knee flexion position, serum nets and sVCAM-1 levels at 1 and 3 days after operation were all the influencing factors of DVT after knee arthroplasty (P<0.05);Pearson correlation analysis showed that there was a positive correlation between the levels of serum NETs and sVCAM-1 in patients with deep venous thromboembolism after knee arthroplasty 1 and 3 days after operation(P<0.05). The ROC curve of predicting deep venous thromboembolism after knee arthroplasty by serum nets and sVCAM-1 levels at 1 and 3 days after operation was drawn, the results showed that the AUC of serum nets and sVCAM-1 levels at 1 day after operation was higher than that at 3 days after operation, which had a good predictive effect. The influencing factors of deep vein thromboembolism after knee arthroplasty are age, body mass index, postoperative knee elevation and flexion, postoperative serum NETs and sVCAM-1 levels, especially postoperative serum NETs and sVCAM-1 levels. Changes can be used as potential biomarkers for predicting postoperative deep vein thromboembolism, and clinical attention should be paid to it.

Elevated Serum CCL23 Levels at Admission Predict Delayed Cerebral Ischemia and Functional Outcome after Aneurysmal Subarachnoid Hemorrhage

(1) Background: CC chemokine ligand 23 (CCL23) is a chemokine implicated in the inflammatory response following brain damage. The aim of this study is to identify the change in serum CCL23 levels within 24 h after aSAH and whether serum CCL23 levels are associated with initial clinical severity, delayed cerebral ischemia (DCI), and functional outcome in patients with aneurysmal subarachnoid hemorrhage (aSAH). (2) Methods: 102 patients with aSAH and 61 controls were included in this prospective observational study. All clinical data were collected prospectively, and their serum CCL23 levels were measured. Initial clinical severity was reflected by the Hunt-Hess score and mFisher score. Functional outcome was evaluated in terms of the Glasgow Outcome Scale (GOS) score at 6-month follow-up. (3) Results: Patients with aSAH had higher serum CCL23 levels than controls. The temporal profile of serum CCL23 levels and neutrophils count exhibited a sustained increase within 24 h after aSAH. Serum CCL23 levels were related to blood neutrophils count, blood CRP levels, and initial clinical severity. Serum CCL23 level was an independent predictor of DCI and 6-month poor outcome in aSAH patients. (4) Conclusions: Serum CCL23 levels emerged as an independent predictor for DCI and poor outcome in patients with aSAH.

Maternal serum NGAL in the first trimester of pregnancy is a potential biomarker for the prediction of gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) has adverse effects on the health of mothers and their offspring. Currently, no known biomarker has been proven to have sufficient validity for the prediction of GDM in the first trimester of pregnancy. The aim of this study was to investigate the potential relationship between serum neutrophil gelatinase-associated lipocalin (NGAL) levels in the first trimester of pregnancy and later GDM risk and to evaluate the performance of serum NGAL as a biomarker for the prediction of GDM. The study was conducted by recruiting participants at 8-13 weeks of gestation from The First Affiliated Hospital of Chengdu Medical College between January and June 2021; participants were followed up for oral glucose tolerance test (OGTT) screening at 24-28 gestational weeks. We examined the serum NGAL levels of all subjects in the first trimester who met the inclusion and exclusion criteria. Anthropometric, clinical, and laboratory parameters of the study subjects were obtained during the same study period. A logistic regression model was carried out to investigate the potential relationship between serum NGAL levels in the first trimester of pregnancy and later GDM risk. The receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to assess the discrimination and calibration of serum NGAL as a biomarker for the prediction of GDM in the first trimester of pregnancy. Serum NGAL levels in the first trimester of pregnancy were significantly higher in women who later developed GDM than in those who did not develop GDM. Serum NGAL levels in the first trimester of pregnancy were positively associated with an increased risk of GDM after adjustment for potential confounding factors. The risk prediction model for GDM constructed by using serum NGAL levels in the first trimester of pregnancy achieved excellent performance. Maternal serum NGAL in the first trimester of pregnancy is a potential biomarker for the prediction of GDM, which could help guide the clinical practice of antenatal care.

Neutrophil gelatinase-associated lipocalin monitoring reveals persistent subclinical kidney injury following intraarterial administration of iodinated contrast agents

Clinically overt contrast-induced nephropathy (CIN) is one of the most feared complications in patients exposed to iodinated contrast media and has been extensively studied over the years. Meanwhile, the incidence and evolution of subclinical contrast-induced kidney injury remain elusive. With the continuous increase in the number of patients that are repeatedly exposed to contrast media, elucidating these issues is of critical importance. Accordingly, we aimed to evaluate the incidence and the evolution of clinical and subclinical kidney injury in patients exposed to contrast media. A total of 178 patients who underwent elective percutaneous angioplasty procedures were evaluated prospectively. Serum creatinine and neutrophil gelatinase-associated lipocalin (NGAL) levels were evaluated pre-procedurally, 48 h and 1 month after administration of contrast media. The evolution of creatinine and NGAL levels was analyzed at the three time points, and the potential predictors of contrast-induced clinical and subclinical renal injury were evaluated. Clinically overt CIN occurred in 10 (5.6%) patients. Baseline serum creatinine and the volume of contrast media were the only independent predictors of CIN and in all 10 patients creatinine levels returned to baseline by 1 month (p = 0.32). Subclinical contrast-induced kidney injury was much more common, affecting 32 (17.9%) patients, was only predicted by the baseline serum creatinine, and persisted in 53.1% of patients after 1 month. This study showed that whereas clinically overt CIN is rather rare and regressive, subclinical contrast-induced kidney injury is considerably more frequent, affecting almost 18% of patients that receive intraarterial contrast media. More importantly, subclinical kidney injury persisted after 1 month in more than 50% of the initially affected patients, who may thus be at increased risk for further renal impairment, particularly if exposed to nephrotoxic agents or repeated administration of contrast media.

Serum procalcitonin, C-reactive protein, and neutrophil gelatinase-associated lipocalin in early diagnosis of acute kidney injury after upper urinary tract calculi.

To investigate the value of serum procalcitonin(PCT), C-reactive protein(CRP), and neutrophil gelatinase-associated lipocalin(NGAL) in the early diagnosis of acute kidney injury(AKI) after upper urinary tract calculi(UUTC). The clinical data of 86 patients who underwent UUTC surgery in our hospital from March 2020 to April 2021 were analyzed retrospectively(Approval number: 20211205L, Date: 2021-12-21). Patients were divided into an AKI group (AKI≥7 days after the operation) and a Non-AKI group. PCT, CRP, and NGAL concentrations were compared before and two hours after the operation. Multivariate logistic regression analysis was used to identify risk factors affecting the early occurrence of AKI post-operation. The receiver operating characteristic curve evaluated PCT, CRP, and NGAL in the early AKI diagnosis. A total of 86 patients (30 with AKI and 56 with Non-AKI) were included. Kidney injury molecule-1(KIM-1) and urinary microalbumin(mAlb) concentrations were significantly higher in the AKI group (P<0.05). PCT, CRP, and NGAL concentrations were significantly higher two hours after the operation than before the operation (P<0.05). KIM-1 levels and elevated PCT, CRP and NGAL concentrations affected the establishment of AKI after UUTC. The sensitivity of PCT, CRP, and NGAL in evaluating AKI after UUTC were 81.17%, 84.42%, and 79.02%; the specificity was 62.31%, 71.48%, and 73.32%; and the AUC was 0.812, 0.885 and 0.804 respectively. PCT, CRP, and NGAL concentrations in patients with AKI after UUTC were significantly increased two hours after the operation, which can be used for the early diagnosis of AKI after UUTC operation.

Neutrophils Play an Important Role in the Recurrence of Chronic Rhinosinusitis with Nasal Polyps.

Despite the heterogeneity of chronic rhinosinusitis (CRS), a clear link exists between type 2 immunity and the severity of CRS with nasal polyps (CRSwNP). However, recent studies have demonstrated that patients with severe type 2 CRSwNP also display abundant neutrophilic inflammation. Therefore, we investigated the factors associated with the recurrence of CRSwNP following sinus surgery using a machine-learning algorithm. We collected the demographics, clinical variables, and inflammatory profiles of 210 patients with CRSwNP who underwent sinus surgery. After one year, we evaluated whether each patient showed recurrence. Machine-learning methods, such as decision trees, random forests, and support vector machine models, have been used to predict the recurrence of CRSwNP. The results indicated that neutrophil inflammation, such as tissue and serum neutrophils, is an important factor affecting the recurrence of surgical CRSwNP. Specifically, the random forest model showed the highest accuracy in detecting recurrence among the three machine-learning methods, which revealed tissue neutrophilia to be the most important variable in determining surgical outcomes. Therefore, our machine-learning approach suggests that neutrophilic inflammation is increased in patients with difficult-to-treat CRSwNP, and the increased presence of neutrophils in subepithelial regions is closely related to poor surgical outcomes in patients with CRSwNP.

The Systemic Immune-Inflammation Index (SII) Increases the Prognostic Significance of Lymphovascular Invasion in Upper Tract Urothelial Carcinoma After Radical Nephroureterectomy.

Lymphovascular invasion (LVI) and systemic immune-inflammation index (SII) both have been proved to correlate with oncologic outcomes in upper tract urothelial carcinoma (UTUC). We hypothesize that integrating SII with LVI may be an aid for risk-stratification of prognosis. This study aimed to evaluate the prognostic significance of combined SII and LVI in patients with localized UTUC. A retrospective analysis of clinicopathological data of 554 UTUC patients who underwent radical nephroureterectomy (RNU) was conducted. The SII was calculated using the equation (preoperative serum neutrophil*platelet/lymphocyte). Use of Kaplan-Meier analyses and Cox proportional hazards models were to evaluate associations of combining SII and LVI with overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS). Furthermore, receiver operating characteristic (ROC) analysis was applied to estimate predictive ability of combining SII and LVI for oncological outcomes. Positive LVI was significantly associated with advanced stage, high grade, necrosis, lymph node metastasis, and high-level SII. Positive LVI and high-level SII co-existence was significantly associated with unfavorable OS, CSS, and PFS in Kaplan-Meier analyses (all p < 0.001) and was an independent indicator of OS, CSS, and PFS (HR [95% CI]: 3.918 [2.168-7.078], 5.623 [2.679-11.801], 3.377 [2.138-5.334]), respectively) in multivariate analyses. Furthermore, adding LVI and SII to a model that included standard pathologic predictors exhibited a better ability to predict survival in ROC analysis. The integration of SII and LVI was demonstrated to be a potential factor of poor outcomes in patients with localized UTUC. Notably, the combined use of LVI and SII can be a feasible and complementary factor to TNM staging in the prognostic assessment of UTUC patients in clinical practice. The validity of combination of the two markers would be considered in future prospective studies to evaluate its usefulness in staging and application of post-operative chemo or immunotherapy.

Association of Serum Neutrophil Gelatinase-Associated Lipocalin with Childhood Asthma in Benha University Hospitals

Association of Serum Neutrophil Gelatinase-Associated Lipocalin with Childhood Asthma in Benha University Hospitals

Low serum albumin levels and high neutrophil counts are predictive of a poorer prognosis in patients with metastatic breast cancer.

Breast cancer is a severe disease with high incidence and mortality rates in menopausal women. Previous studies have shown that nutritional status and inflammation play a significant role in the development of breast cancer. However, whether serum albumin (ALB) and neutrophils (NE) accelerate the progression of this disease remains unclear. In the present study, a total of 94 cases of newly diagnosed metastatic breast cancer were assessed. For analysis, 26 risk factors including ALB and NE were assessed. Multivariate Cox proportional hazards regression analysis was then used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) after adjusting for continuous and categorical covariates. Compared with the control group, patients with disease progression, low levels of ALB, higher NE, counts, and higher neutrophil to lymphocyte ratio counts were associated with worse overall survival (OS). When these risk factors were fitted into a multivariate regression model, progression [P<0.001, HR=3.03 (1.62-5.66)], NE counts ≥3.370×109 [P=0.004, HR=2.15 (1.27-3.65)] and ALB levels <43.275 g/l [P=0.008, HR=0.47 (0.27-0.82)] remained statistically significant factors for a worse OS. These independently associated risk factors were used to form an OS estimation nomogram. The constructed nomogram demonstrated good accuracy in estimating risk, with a bootstrap-corrected C index of 0.686. We further collected data on 30 patients for external validation and found the nomogram had an accuracy of 83.3%. In conclusion, low serum ALB levels and increased NE counts were predictive of a poorer prognosis in patients with metastatic breast cancer. Nomograms based on the multivariate analysis showed a good predictive ability for estimating the risk of OS.

Could tear be an alternative specimen for SARS-CoV-2 detection?

Abstract Objectives For a definitive diagnosis of COVID-19, respiratory tract samples are evaluated by polymerase chain reaction (PCR). In our study, PCR using a tear sample was used to diagnose COVID-19, and it was questioned whether it was a screening method. Unlike the general practice, Schirmer strips were used instead of a swab for tear sample collection in this study. In addition, the diagnostic values of serum procalcitonin (PCT), C-reactive protein (CRP), and Neutrophil (NEU) count in predicting COVID-19 disease from tears were also questioned. Methods A total of 94 patients who were positive for COVID-19 by PCR test were included in this study. Tear samples were obtained from patients with Schirmer strips, commonly used in eye examination, and studied with the PCR technique. CRP, PCT value, and NEU count were also compared between the positive and negative groups of the PCR. The obtained data were analyzed using the R Studio software, and the results were considered statistically significant for p&lt;0.05. Results Of these patients, 61 (64.9%) tear PCR was negative, and 33 (35.1%) tear PCR was positive. The mean age was 61.72 ± 17.62 years. The patients were divided into two groups: tear PCR positive and negative. There was no significant age difference between these groups. As a result of ROC Analysis; When serum PCT, CRP, and NEU % values were examined in predicting COVID-19 disease from tears, it was seen that CRP (p=0.027) and especially PCT (p=0.003) values of patients with PCR-positive were significantly higher. Conclusions PCR study on tears collected with Schirmer strips is a different and non-invasive method, but it was concluded that the proposed method could not be used as a screening test. In addition, significantly higher serum PCT values were found in patients with COVID-19 positivity in tears (p&lt;0.05).

Predictive and Prognostic Value of Serum Neutrophil Gelatinase-Associated Lipocalin for Contrast-Induced Acute Kidney Injury and Long-Term Clinical Outcomes after Percutaneous Coronary Intervention.

Neutrophil gelatinase-associated lipocalin (NGAL) has been proposed as an early marker for estimating the risk of contrast-induced acute kidney injury (CI-AKI). However, the predictive value of baseline serum NGAL levels for CI-AKI remains unclear. Serum NGAL was measured before percutaneous coronary intervention in 633 patients with coronary artery disease. The primary clinical endpoints were a composite of major adverse cardiac and cerebrovascular events (MACCEs; cardiac death, myocardial infarction, stroke, and any revascularization). The mean follow-up duration was 29.4 months. Ninety-eight (15.5%) patients developed CI-AKI. Compared with patients without CI-AKI, baseline serum NGAL was higher in patients with CI-AKI (149.6 ± 88.8 ng/mL vs. 138.0 ± 98.6 ng/mL, p = 0.0279), although serum creatinine and estimated glomerular filtration rate were not different between groups. Patients in the highest tertile of baseline serum NGAL showed a significantly higher rate of MACCEs (10.5% vs. 3.8%, p = 0.02). Using the first tertile as a reference, the adjusted hazard ratios for MACCEs in patients in the second and third tertiles of NGAL were 2.151 (confidence interval (CI) 0.82 to 5.59, p = 0.116) and 2.725 (CI 1.05 to 7.05, p = 0.039), respectively. Baseline serum NGAL is a reliable marker for predicting CI-AKI, and high serum NGAL levels are associated with a higher incidence rate of long term MACCEs.

Inhibition of the NF-κB pathway and ERK-mediated mitochondrial apoptotic pathway takes part in the mitigative effect of betulinic acid on inflammation and oxidative stress in cyclophosphamide-triggered renal damage of mice

Betulinic acid (BA), an occurring pentacyclic triterpenoid, has various biological activities, such as anti-inflammation and antioxidation. Previous studies found that BA attenuated cyclophosphamide (CYP)-induced intestinal mucosal damage by inhibiting intestinal mucosal barrier dysfunctions and cell apoptosis. However, the effects and regulation mechanisms of BA on CYP-induced renal damage has not been reported in literature. Here, we found that BA pretreatment alleviated the elevation of serum urea level and inhibited the increase in serum neutrophil gelatinase-associated lipocalin level induced by CYP. Meanwhile, BA ameliorated renal tubular epithelial cell edema, and vacuolization of renal cortical tubular and renal glomerulus. Moreover, pretreatment with BA inhibited the mRNA expressions of pro-inflammatory cytokines interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α, and increased mRNA expressions of anti-inflammatory cytokines such as IL-10 and transforming growth factor-β by inactivation nuclear factor kappa-B. Simultaneously, BA decreased the accumulation of reactive oxygen species and malondialdehyde, and lowered the levels of superoxide dismutase and glutathione, while increased the activity of glutathione peroxidase in CYP-induced kidney damage mice. Besides, BA reduced the phosphorylation of extracellular signal-regulated kinases (ERK), inhibited the ratio of Bcl-2/Bax and cell apoptosis in CYP-triggered kidney damage. Furthermore, BA and/or PD98059 (an inhibitor of ERK) regulated mitigation of CYP-elicited renal injury and deactivation of the ERK pathway and mitochondrial apoptotic pathway, indicating that the protective effect of BA on CYP-induced renal damage may be associated with the down-regulation of ERK-mediated mitochondrial apoptotic pathway. Thus, BA could be a candidate agent against chemotherapy drug-induced nephrotoxicity by reducing inflammation and oxidative stress through suppression of ERK-mediated mitochondrial apoptotic pathway.

S1356 Correlation Between Systemic Inflammatory Markers and Evidence of Metastatic Disease in Patients With Hepatocellular Carcinoma

Introduction: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide. A wide variety of scoring systems such as Albumin-Bilirubin (ALBI), Platelet-Album-Bilirubin (PALBI), Monocyte-to-Lymphocyte ratio (MLR), and Neutrophil-Lymphocyte Ratio (NLR) along with tumor characteristics (tumor size, count, and vascular invasion) have been proposed as prognostic indicators. The aim of our study was to determine the correlation, if any between these scoring systems and evidence of metastatic disease at diagnosis in patients with HCC. Methods: A cross-sectional study was conducted at Liver Associates of Texas Hepatology clinics in Houston, Texas. Included were patients diagnosed with HCC between January 2014 and December 2021. Demographic data, chronic liver disease, cirrhosis status, and evidence of metastatic disease at diagnosis were recorded. Laboratory parameters including serum albumin, total bilirubin, platelet count, absolute lymphocyte, neutrophil, and monocyte counts were collected for each patient at the time of diagnosis. The diagnosis of HCC was established by Magnetic Resonance Imaging (MRI). Albumin-Bilirubin (ALBI) score, Platelet-Albumin-Bilirubin (PALBI) score, Monocyte-to-Lymphocyte ratio (MLR), and Neutrophil-to-Lymphocyte ratio (NLR) were calculated by mathematical formulas previously described in the literature. A binomial logistic regression model was performed with the different scores and ratios as independent variables, and evidence of metastatic disease as the dependent variable. A p-value of less than 0.05 was considered significant. (Figure) Results: 231 patients were identified with HCC. The mean age was 69 years old. 72.3% were male. 38.1% white, 21.6% Hispanic, 13.4% African American, 13.4% Asian/Pacific Islander, and 13.4% unspecified ethnicity. Out of the 231, all except one patient had cirrhosis; hepatitis C was the most common cause of cirrhosis (59.7%) followed by NASH (17.7%). 17.3% of the patients had evidence of metastatic disease at diagnosis. Patients with metastatic disease at diagnosis had a higher NLR (OR: 1.64 [1.18 – 2.29], p = 0.003). However, interestingly, patients with metastatic disease at diagnosis had a lower MLR (OR: 0.11 [0.01 – 0.77], p = 0.027). (Table) Conclusion: Our study suggests that patients with metastatic disease at diagnosis had a higher NLR, hence this ratio is a promising non-invasive prognostic parameter for patients with HCC. However, further studies need to be performed to validate our results. Table 1. - Correlation among different steatosis scores and ratios with the evidence of metastatic disease at diagnosis in patients with HCC OR p value 95% CI ALBI score 8.99 0.141 (0.48 – 166.95) PALBI score 0.59 0.219 ( 0.25 – 1.36) MLR 0.11 0.027* (0.01 – 0.77) NLR 1.64 0.003* (1.18 – 2.29) ALBI= Albumin-Bilirubin; PALBI= Platelet-Albumin-Bilirubin; MLR= Monocyte to Lymphocyte Ratio; NLR= Neutrophil to Lymphocyte Ratio; OR= Odds Ratio; * = Statistically significant to the 95% CI; CI = Confidence Interval. Figure 1.: Positive correlation between NLR and metastatic disease in patients with HCC.

Promising Neutrophil-Associated Biomarkers in Lung Diseases of Patients with Antisynthetase Syndrome and Dermatomyositis.

Objectives Antisynthetase syndrome (ASS) and dermatomyositis (DM) are serious autoimmune diseases, with lungs being the most frequently involved organ and sometimes fatal. This study is aimed at clarifying the role of neutrophil-associated biological markers in suggesting ASS and DM-associated respiratory infections and interstitial lung diseases. Methods We carried out a retrospective review of the medical records of 46 cases of ASS and DM diagnosed at the Second Hospital of Zhejiang University College of Medicine, between January 2017 and December 2020. Serum myeloperoxidase (MPO), neutrophil elastase (NE), α1 anti-trypsin (AAT), and interleukin-6 (IL-6) were also detected. Results Gottron's sign is characteristic of dermatomyositis, while polyarthritis is more characteristic of ASS. Pulmonary function is worse in ASS than in DM patients. Patients with ASS and DM had abnormal lymphocyte and neutrophil counts compared to healthy subjects, but not in relation to lung function and rapid progression of interstitial lung disease (RP-ILD). Elevated serum NE, MPO, and IL-6 levels are suggestive of respiratory infections, whereas decreased circulating IL-6 is predictive of RP-ILD. Conclusion Our study identified the neutrophil-associated biomarkers MPO, NE, and IL-6 as promising indicators with different suggestive roles in respiratory infections and interstitial lung diseases in patients with ASS and DM.

Objectively-assessed physical activity and heat stress and the association with kidney function in female harvest workers in Spain

BACKGROUND AND AIM: Physical activity (PA) in hot environments has been associated with kidney damage. In harvest workers, PA has been primarily assessed by questionnaires in males. We aimed to study the association between objectively-measured PA intensity and incidence of acute kidney injury (AKI) over the course of one work shift, in female harvest workers in Spain. METHODS: Ninety women working in greenhouses wore a Zephyr chest harness to measure PA intensity during one regular work shift in June 2020. We determined the mean (PA_mean), standard deviation (PA_sd), and 3-minute-maximum (PA_max, a proxy of peak PA intensity) of PA intensity (vector magnitude units). We estimated heat stress (HS) in greenhouses based on wet bulb globe temperature index (ISO 7243:2017). Serum creatinine and neutrophil gelatinase associated lipocalin (NGAL) levels were measured before and after the work shift. AKI was defined as an increase in post-shift serum creatinine by at least 0.3 mg/dl or at least 1.5 times the pre-shift serum creatinine levels. Additionally, we calculated pre-post-shift differences in NGAL. We used logistic regressions adjusted for age, body mass index, and HS. HS was also assessed as an effect modifier. RESULTS: PA_sd and PA_max seemed to be associated with AKI (OR=1.57 (95%CI=0.82;3.21) and 1.41 (0.71;2.85), respectively), but not PA_mean. There was no interaction between any of the PA variables and HS (p-value LRT&amp;#x3e;0.1). Mean (SD) increase in NGAL levels over the course of a work shift was higher among participants with AKI (27.8 (7.5)) compared to those without AKI (12.2 (2.7)). CONCLUSIONS: Results suggest that large changes and peaks in PA intensity should be avoided to protect renal function of harvest workers. Increased levels of NGAL among those with AKI are indicative of kidney damage among those with increased serum creatinine levels. KEYWORDS: Occupational physical activity, acute kidney injury, ambient heat stress

Bilirubin as a Predictor of Complicated Appendicitis in a District General Hospital: A Retrospective Analysis.

AimsThe objectives of the study were to establish the function of bilirubin as a novel diagnostic tool for predicting complex appendicitis and to compare the impact of other variables such as white blood cell count (WCC), C-reactive protein (CRP), and neutrophil.MethodsThis retrospective, single-center cohort analysis included all patients admitted to Torbay General Hospital in Torquay, United Kingdom, between January 2020 and December 2020 with a clinical diagnosis of acute appendicitis. In addition to serum CRP, WCC, and neutrophil, serum bilirubin and other liver enzymes were obtained from the patients’ blood on admission.ResultsThe quantitative analysis included 174 patients from the group that remained. The large majority of the sample consisted of adults and males (77% and 51.7%, respectively). Overall, 49.4% of participants in the study were diagnosed with complicated appendicitis; 74.7% of adults had complicated appendicitis, with 58.6% being male. In 68.6% of cases, perforated appendicitis was the most prevalent form of complicated appendicitis. Patients with complicated appendicitis had significantly higher WCC, neutrophil, and CRP levels than those with uncomplicated appendicitis (14.15 vs. 12.88, p = 0.016; 11.63 vs. 10.19, p = 0.007; and (89.28 vs. 40.65, p = 0.0001, respectively).. The significantly greater alkaline phosphatase and total serum bilirubin discrepancies were observed in patients with complicated appendicitis. There were statistically significant differences in the means of the patients: (18.46 vs. 10.98, p = 0.0001 and 110.64 vs. 102.24, p = 0.033).ConclusionSerum bilirubin is a crucial diagnostic aid for determining the existence of complicated appendicitis.