Association of pretreatment neutrophil-to-lymphocyte ratio with clinical outcomes in cancer immunotherapy: An evidence synthesis from 30 meta-analyses.

BACKGROUND: The Neutrophil-to-lymphocyte ratio (NLR) holds relevance in cancer immunotherapy outcomes, yet its validation remains limited. Thus, we conducted an umbrella review to comprehensively assess the association between pretreatment NLR and immunotherapy outcomes, along with evaluating their credibility and strength. METHODS: Electronic databases, including PubMed, Web of Science, Embase, Scopus, and Cochrane, were systematically searched for eligible systematic reviews and meta-analyses. Quality assessment and evidence grading utilized AMSTAR, GRADE, and additional classification criteria, following PRISMA and PRIOR guidelines. RESULTS: Thirty unique meta-analyses were included, with 24 associations (80%) exhibiting statistical significance. Notably, associations between pretreatment NLR and the prognosis of renal cell carcinoma, hepatocellular carcinoma, melanoma, and non-small cell lung cancer garnered highly suggestive or convincing evidence grading. CONCLUSIONS: Elevated pretreatment NLR correlates with poor outcomes in cancer immunotherapy, suggesting its potential as a biomarker for identifying appropriate treatment populations and predicting clinical outcomes. Nevertheless, further validation through prospective cohort studies is warranted.

Prognostic Value of the Glasgow Prognostic Score in Non-Small Cell Lung Cancer Patients Receiving Immunotherapy: A Meta-Analysis.

BACKGROUND: The Glasgow Prognostic Score (GPS) has proven to be a good biomarker for lung cancer prognosis. However, its usefulness in lung cancer patients receiving checkpoint inhibitor immunotherapy remains controversial. Therefore, we performed a meta-analysis to explore the prognostic value of the GPS in non-small cell lung cancer patients receiving immunotherapy. METHODS: PubMed, Web of Science, Scopus, and Embase were systematically searched for relevant studies up to May 31, 2023, and hazard ratios (HRs) with 95% confidence intervals (95% CIs) were merged to investigate the prognostic value of the GPS for overall survival (OS) and progression-free survival (PFS). RESULTS: Seven studies comprising 833 patients were included in the primary analysis, and the pooled results indicated that a higher baseline GPS was associated with poorer OS and PFS in non-small cell lung cancer patients treated with immune checkpoint inhibitors (ICIs) (OS: HR = 1.95, 95% CI: 1.47-2.58, p < 0.01; PFS: HR = 1.63, 95% CI: 1.26-2.11, p < 0.01). These findings were robust after subgroup and sensitivity analyses. CONCLUSIONS: The GPS can serve as a biomarker in non-small cell lung cancer patients receiving immunotherapy with significant prognostic value; however, these findings require more prospective evidence for validation.

Association between pretreatment C-reactive protein level and survival in non-small cell lung cancer patients treated with immune checkpoint inhibitors: A meta-analysis.

BACKGROUND: Current evidence suggests that C-reactive protein (CRP) levels may affect cancer prognosis. However, the effect of CRP has not been validated in immunotherapy recipients with non-small cell lung cancer (NSCLC). Therefore, we performed a meta-analysis to explore the prognostic value of CRP level in patients with NSCLC treated with immune checkpoint inhibitors. METHODS: PubMed, Web of Science, Embase, and Scopus databases were systematically retrieved for eligible publications, and hazard ratios (HRs) with corresponding 95% confidence intervals (95%CIs) were extracted and merged to evaluate the correlation between pretreatment CRP levels and overall survival (OS) and progression-free survival (PFS). Subgroup and sensitivity analyses were conducted to confirm these findings. RESULTS: Thirty-five cohorts consisting of 4698 patients were included in the primary analysis. Pooled results demonstrated that a higher pretreatment CRP level is associated with worse OS and PFS (OS: HR = 1.13, 95 %CI:1.09-1.18; PFS: HR = 1.16, 95 %CI:1.10-1.22). These findings remained robust after further statistical analyses. CONCLUSION: Pretreatment CRP level could be a promising biomarker for NSCLC immunotherapy. However, prospective studies are required to validate these findings.

Risk of second primary lung cancer in patients with thyroid cancer: a meta-analysis based on big population studies.

BACKGROUND: Previous studies have revealed that the number of cancer survivors developing a second primary malignancy is increasing, especially among thyroid cancer patients, and lung cancer is still the main cause of cancer death. Therefore, we aimed to investigate the risk of second primary lung cancer (SPLC) in patients with thyroid cancer. METHODS: We searched the PubMed, Web of Science, Embase, and Scopus databases up to November 24, 2021, for relevant research and merged the standardized incidence ratios (SIRs) and 95% confidence intervals (95% CIs) to evaluate the risk of developing SPLC in patients with thyroid cancer. RESULTS: Fourteen studies involving 1,480,816 cases were included in our meta-analysis. The pooled result demonstrated that thyroid cancer patients may have a higher risk of SPLC than the general population (SIR = 1.21, 95% CI: 1.07-1.36, P  < 0.01, I2  = 81%, P  < 0.01). Subgroup analysis stratified by sex indicated that female patients may have a markedly higher risk of SPLC than male patients (SIR = 1.65, 95% CI: 1.40-1.94, P  < 0.01, I2  = 75%, P  < 0.01). CONCLUSIONS: Thyroid cancer patients are more likely to develop SPLC than the general population, especially women. However, other risk factors must be investigated, and more prospective studies are needed to confirm our results. REGISTRATION: International Prospective Register of Systematic Reviews: No. CRD42021285399.

Alanine Aminotransferase and Bilirubin Dynamic Evolution Pattern as a Novel Model for the Prediction of Acute Liver Failure in Drug-Induced Liver Injury.

Aims: To develop, optimize, and validate a novel model using alanine aminotransferase (ALT) and total bilirubin (TB) dynamic evolution patterns in predicting acute liver failure (ALF) in drug-induced liver injury (DILI) patients. Methods: The demographics, clinical data, liver biopsy, and outcomes of DILI patients were collected from two hospitals. According to the dynamic evolution of ALT and TB after DILI onset, the enrolled patients were divided into ALT-mono-peak, TB-mono-peak, double-overlap-peak, and double-separate-peak (DSP) patterns and compared. Logistic regression was used to develop this predictive model in both discovery and validation cohorts. Results: The proportion of ALF was significantly higher in patients with the DSP pattern than in the ALT-mono-peak pattern and DOP pattern (10.0 vs. 0.0% vs. 1.8%,p < 0.05). The area under receiver operating characteristic curve (AUROC) of the DSP pattern model was 0.720 (95% CI: 0.682-0.756) in the discovery cohort and 0.828 (95% CI: 0.788-0.864) in the validation cohort in predicting ALF, being further improved by combining with international normalized ratio (INR) and alkaline phosphatase (ALP) (AUROC in the discovery cohort: 0.899; validation cohort: 0.958). Histopathologically, patients with the DSP pattern exhibited a predominantly cholestatic hepatitis pattern (75.0%, p < 0.05) with a higher degree of necrosis (29.2%, p = 0.084). Conclusion: DILI patients with the DSP pattern are more likely to progress to ALF. The predictive potency of the model for ALF can be improved by incorporating INR and ALP. This novel model allows for better identification of high-risk DILI patients, enabling timely measures to be instituted for better outcome.

Explainable Machine Learning Model to Prediction EGFR Mutation in Lung Cancer.

Objectives: The aim of this study is to determine whether the clinical features including blood markers can establish an explainable machine learning model to predict epidermal growth factor receptor (EGFR) mutation in lung cancer. Methods: We retrospectively analyzed 7,413 patients with lung adenocarcinoma (LA) diagnosed by gene sequencing in West China Hospital of the Sichuan University from April 2015 to June 2019. The machine learning algorithms (MLAs) included logistic regression (LR), random forest (RF), LightGBM, support vector machine (SVM), multi-layer perceptron (MLP), extreme gradient boosting (XGBoost), and decision tree (DT). Demographic characteristics, personal history, and blood markers were taken into. The area under the receiver operating characteristic curve (AUC) and SHapley Additive exPlanation (SHAP) value were used to explain the prediction models. Results: Of the 7,413 patients with LA (47.6%), 3,527 were identified with EGFR mutation; RF achieved greatest performance in predicting EGFR mutation AUC [0.771, 95% confidence interval (CI): 0.770, 0.772], which was like XGBoost with AUC (0.740, 95% CI: 0.739, 0.741). The five most influential features were smoking consumption, sex, cholesterol, age, and albumin globulin ratio. The SHAP summary and dependence plot have been used to explain the affection of the 12 features to this model and how a single feature influences the output, respectively. Conclusion: We established EGFR mutation prediction models by MLAs and revealed that the RF was preferred, AUC (0.771, 95% CI: 0.770, 0.772), which was better than the traditional models. Therefore, the artificial intelligence-based MLA predicting model may become a practical tool to guide in diagnosis and therapy of LA.

Prognostic value of the platelet-to-lymphocyte ratio in lung cancer patients receiving immunotherapy: A systematic review and meta-analysis.

BACKGROUND: Current studies have revealed that the platelet to lymphocyte ratio (PLR) may lead to a poor prognosis in lung cancer patients receiving immunotherapy. We conducted a meta-analysis to explore the prognostic value of PLR in lung cancer patients receiving immunotherapy. METHODS: We retrieved potential studies from the PubMed, Web of Science, Embase, and Scopus databases up to June 2021 and merged the hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) to evaluate the association between PLR and overall survival (OS) or progression-free survival. RESULTS: Fourteen studies involving 1761 patients were included in our meta-analysis. The results indicated that an elevated level of pretreatment PLR was associated with poorer OS and PFS in lung cancer patients receiving immunotherapy (OS: HR = 1.88, 95% CI: 1.37-2.58; PFS: HR = HR = 1.40, 95% CI: 1.11-1.76). The association remained consistent after subgroup analysis and was robust even after sensitivity analysis. CONCLUSIONS: PLR may be a prognostic factor of lung cancer patients receiving immunotherapy, which can lead to worse survival outcomes. However, further studies are necessary for evidence in clinical application.

Monoterpenoid indole alkaloids with potential neuroprotective activities from the stems and leaves of Melodinus cochinchinensis.

A chemical study on the stems and leaves of Melodinus cochinchinensis resulted in the isolation and identification of a new monoterpenoid indole alkaloid, melodicochine A (1), together with seven known monoterpenoid indole alkaloids (2-8). The chemical structure of 1 was elucidated on the basis of extensive spectral data analyses and the known compounds were identified by comparing their experimental spectral data with the reported data in the literature. All isolated indole alkaloids were evaluated for their neuroprotective effects against 6-hydroxydopamine induced cell death in human neuroblastoma SH-SY5Y cells in vitro. Monoterpenoid indole alkaloids 1-8 exhibited notable neuroprotective effects with EC50 values in range of 0.72 ± 0.06 to 17.89 ± 0.16 µM.[Formula: see text].

Impact of concomitant idiopathic pulmonary fibrosis on prognosis in lung cancer patients: A meta-analysis.

BACKGROUND: Current studies showed that idiopathic pulmonary fibrosis (IPF) may lead to a poor prognosis of lung cancer. We conducted a meta-analysis to explore the impact of concomitant IPF in lung cancer and its prognostic value. METHODS: We searched the databases of PubMed, Web of Science, Embase up to Feb 10th, 2021 for relevant researches and merged the hazard ratios (HRs) and 95% confidence intervals (CIs) to evaluate the association between concomitant IPF and overall survival (OS) in patients with lung cancer. RESULTS: Twelve studies involving 58424 patients were included in our meta-analysis. The results indicated that concomitant IPF was correlated with poor prognosis of lung cancer patients (HR = 1.99, 95%CI, 1.59-2.51). The association remained consistent after subgroup analysis and meta-regression stratified by study region, sample size, tumor histology, and therapy. In addition, our results were robust even after sensitivity analysis. CONCLUSIONS: Concomitant IPF may be a prognostic factor of lung cancer, which can lead to poor survival. However, further studies were necessary for evidence in clinical application.

Prognostic Value of the Geriatric Nutritional Risk Index in Non-Small Cell Lung Cancer Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: Novel evidence showed that the Geriatric Nutritional Risk Index (GNRI) may lead to poor prognosis of human cancers. Therefore, we conducted a meta-analysis to explore the impact of GNRI in lung cancer and its prognostic value. METHODS: We searched the databases of PubMed, Web of Science, Embase, Scopus, and Cochrane Library up to July 2021 for relevant research and merged the hazard ratios (HRs) and 95% confidence intervals (CIs) to evaluate the association between GNRI and overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS) in patients with lung cancer. RESULTS: Eight studies involving 2,399 patients were included in our primary meta-analysis. The results indicated that lower level of GNRI was associated with poorer OS, RFS, and CSS of lung cancer patients (OS: HR = 1.99, 95% CI: 1.68-2.35, p < 0.0001; RFS: HR = 2.34, 95% CI: 1.11-4.95, p = 0.0258; CSS: HR = 2.45, 95% CI: 1.43-4.18, p = 0.0011). The association was robust after subgroup analysis and sensitivity analysis. CONCLUSIONS: GNRI may be a prognostic factor of lung cancer, which can lead to poorer survival. However, more prospective studies are necessary to confirm the results. SYSTEMATIC REVIEW REGISTRATION: International Prospective Register of Systematic Reviews (PROSPERO), identifier CRD42021269574.

Removal of pharmaceuticals and personal care products (PPCPs) and environmental estrogens (EEs) from water using positively charged hollow fiber nanofiltration membrane.

Nanofiltration (NF) membranes show great potential for advanced water treatment, especially for trace organic pollutant removal. The removal efficiency of pharmaceuticals and personal care products (PPCPs) and environmental estrogenic hormones (EEHs) by positively charged hollow fiber NF membranes (PEI-NF) were evaluated. The separation properties were evaluated by changing the operating pressure, temperature, ionic strength, and cation species. A relationship between the physicochemical characteristics of the pharmaceuticals and the NF membrane retention behavior was established. The results showed that the rejection rates of the PEI-NF membrane for the selected PPCPs and EEHs ranged from 81 to ~ 91.26%. For positively (negatively) charged pharmaceutical molecules, the electrostatic repulsion (attraction) effect and steric hindrance were the dominant rejection mechanisms of the PEI-NF membrane. For neutral pharmaceutical molecules, in addition to the size sieving effect, the hydration-induced size increase of hydrophilic substances improved the rejection rates. Both the molecular structure and diffusion coefficient of pharmaceutical molecules influenced their rejection by the PEI-NF membrane to a certain extent. Moreover, the PEI-NF membrane showed a high removal effect for PPCPs and EEHs in water samples from actual tap water plants.

A High Serum Level of Taurocholic Acid Is Correlated With the Severity and Resolution of Drug-induced Liver Injury.

BACKGROUND & AIMS: Alterations in the serum levels of bile acids are associated with drug-induced liver injury (DILI). We investigated the association between serum levels of bile acids and the severity and outcome of DILI, along with the potential role of variants in the ATP binding cassette subfamily B member 11 (ABCB11) gene and expression of its product, ABCB11 (also called BSEP). METHODS: We performed this prospective study of 95 patients (median age, 53 years; 73.7% female) with DILI from August 2018 through August 2019. Patients were matched for age, gender, and body mass index with healthy individuals (n = 100; healthy controls) and patients with chronic hepatitis B (n = 105; CHB controls). We collected demographic and biochemical data at baseline and 1 week, 1 month, 3 months, and 6 months after DILI onset and at the time of biochemical recovery, liver failure or liver transplantation. Serum levels of bile acids were measured using high-performance liquid-chromatography tandem mass-spectrometry. All 27 exons of ABCB11 were sequenced and expression of BSEP was analyzed by immunohistochemistry in liver biopsy specimens. RESULTS: Levels of 30 of the 37 bile acids analyzed differed significantly between patients with DILI and healthy controls. Changes in levels of taurocholic acid (TCA), glycocholic acid, taurochenodeoxycholate, and glycochenodeoxycholate associated with the increased levels of bilirubin and greater severity of DILI, and were also associated with CHB. Cox regression analysis showed that only change in the levels of TCA independently associated with biochemical resolution of DILI. Combination of TCA level (≥ 1955.41 nmol/L), patient age, and DILI severity was associated with abnormal blood biochemistry at 6 months after DILI onset (area under the curve, 0.81; 95% confidence interval, 0.71-0.88; sensitivity, 0.69; specificity, 0.81). ABCB11 missense variants were not associated with differences in the serum bile acid profiles, DILI severity, or clinical resolution. However, lower levels of BSEP in bile canaliculi in liver biopsies were associated with altered serum levels of bile acids. CONCLUSIONS: In this prospective study performed in Chinese patients, we found that the serum levels of TCA were associated with the severity and clinical resolution of DILI. Reduced protein expression of BSEP in liver tissue, rather than variants of the ABCB11 gene were associated with altered serum levels of bile acids.

Clinicopathological features of Bu Gu Zhi-induced liver injury, a long-term follow-up cohort study.

BACKGROUND & AIMS: Bu Gu Zhi (BGZ) is a Chinese herb consumed mainly for osteoporosis treatment. Only small case series of BGZ-induced liver injury (BGZILI) have been reported. We describe the clinicopathological features and clinical course of BGZILI. METHODS: Patients diagnosed with drug-induced liver injury (DILI) at Beijing Friendship Hospital from 2005 to 2017 were reviewed. Clinical and follow-up data were analysed. RESULTS: Of the 547 DILI patients, 40 cases (7.3%) were attributed to BGZILI. About 34/40 (85.0%) patients were females with a median age of 63 (range, 54-70) years. The median latency period was 45 (range, 29-90) days. Patients commonly presented with loss of appetite (57.5%), dark urine (57.5%) and fatigue (55.0%). The median level of alanine aminotransferase and aspartate aminotransferase at BGZILI onset was 673.5 and 423.0 U/L respectively. Total bilirubin (TB) and direct bilirubin (DB) were 59.0 and 39.4 µmol/L respectively. The biochemical liver injury pattern was hepatocellular (92.5%), cholestatic (5.0%) and mixed (2.5%). They were categorized into 'mild' (N = 23, 57.5%), 'moderate' (6, 15.0%) or 'severe' (11, 27.5%) according to severity assessment by DILI network. The main histological injury pattern in 9/40 patients with liver biopsy was acute hepatitis with/without cholestasis. Median duration of follow-up was 26.3 months with recovery in 37 patients within 6 months. No patients died or required transplantation. CONCLUSIONS: BGZ-induced liver injury manifested more often as a hepatocellular injury pattern with mild to moderate hepatocellular damage. Most patients recovered after cessation of BGZ within 6 months, and none developed end-stage liver disease or died.

Histologic pattern is better correlated with clinical outcomes than biochemical classification in patients with drug-induced liver injury.

Histologically, drug-induced liver injury could be classified into acute hepatitis, chronic hepatitis, acute cholestasis, chronic cholestasis, and cholestatic hepatitis. The correlation between these histologic patterns and long-term clinical outcomes has not been well established. Therefore, we conducted a retrospective cohort study to investigate the association of histologic patterns and long-term clinical outcomes defined as biochemical normalization, persistent abnormal liver biochemistry or death at designated time points. In this study, biochemical classification was determined by R-values; histologic injury pattern was determined by morphological features. Predictive ability of clinical outcomes by these two classifications was assessed using Receiver Operating Characteristic Curves. Logistic regression was performed to identify histologic factors associated with outcomes. Totally, 88 patients with drug-induced liver injury were included for final analysis. Biochemical and histologic classification were consistent in 50 (57%) cases. 53 (60%) cases showed biochemical normalization within 6 months, and a further 11 (13%), 16 (18%), and 6 (7%) cases within 1, 2, and 3 years, respectively. Compared with biochemical classification, histologic injury pattern had better predictive ability for abnormal biochemistry at 6 months (Areas under Receiver Operating Characteristic Curves 0.92 versus 0.60, P < 0.001) and 1 year (Areas under Receiver Operating Characteristic Curves 0.94 versus 0.69, P < 0.001). Interlobular bile duct loss in >25% portal areas was independently associated with abnormal biochemistry at 6 months, 1 year, and 2 years. In conclusion, histologic injury pattern is better correlated with clinical outcome at 6 months and 1 year than biochemical classification. Moderate bile duct loss is an important histologic feature associated with persistent biochemical abnormality at 6 months, 1 year, and 2 years.

Clinicopathological features of He Shou Wu-induced liver injury: This ancient anti-aging therapy is not liver-friendly.

BACKGROUND & AIMS: Polygonum Multiflorum Thumb (PMT), an ancient anti-aging Chinese herb known traditionally as He Shou Wu, has side effects of liver toxicity. To determine the main clinical and pathological characteristics of liver toxicity induced by PMT and the clinical course after its cessation. METHODS: Data of patients, diagnosed as drug-induced liver injury and hospitalised in Beijing Friendship Hospital from August 2005 to August 2017, were retrospectively reviewed. Clinical, pathological data and outcome after cessation of He Shou Wu were obtained and analysed. Kruskal-Wallis and Chi-square (χ2 ) tests were performed. RESULTS: Twenty-nine patients with He Shou Wu-induced liver injury were enrolled. The median age was 53 years (range 15-74) and 75.9% (22/29) were women. The most common symptom was jaundice (79.3%, 23/29). Of nine patients with liver biopsies, six showed acute cholestatic hepatitis, two acute, and one chronic hepatocellular injury pattern. The latency, liver chemistries and outcomes were comparable between pure He Shou Wu (5 patients) and its compounds (24 patients). Twenty-five of 29 patients (86.2%) had normal serum alanine aminotransferase levels after 45 days (range: 10-138 days) and total bilirubin of 46 days (range: 0-551 days). One patient was rechallenged with He Shou Wu and two developed autoimmune features. One patient died of liver failure and three had chronic persistent liver injury. CONCLUSIONS: The main clinicopathological injury pattern of He Shou Wu-induced liver injury is moderate to severe hepatitis with or without cholestasis. Most patients recover completely; however, chronic disease and death do occur.

Separation of chlorogenic acid from honeysuckle crude extracts by macroporous resins.

Chlorogenic acid, one of the most bioactive compounds rich in the Chinese medicinal herb honeysuckle, is a natural antioxidant and serves as anti-inflammatory, anti-tumor, anti-mutagenic and anti-carcinogenic agent. An efficient preparative separation process of chlorogenic acid from honeysuckle crude extracts has been developed in the present study. HPD-850 resin offers the best adsorption capacity, and adsorption and desorption ratios for chlorogenic acid among the nine macroporous resins tested, and its adsorption rate at 25 degrees C fit best to the Langmuir isotherm. The adsorption capacity of HPD-850 resin was found to depend strongly on the pH value of the initial adsorption solution. The dynamic adsorption and desorption experiments have been carried out on a HPD-850 resin packed column to optimize the separation process of chlorogenic acid from honeysuckle crude extracts. After one run treatment with HPD-850 resin, the chlorogenic acid content in the final product was increased 4.46-fold from 11.2% to 50.0%, with a recovery yield of 87.9%. The preparative separation of chlorogenic acid can be easily and efficiently achieved via adsorption and desorption on HPD-850 resin, and the method developed will provide a potential approach for large-scale separation and purification of chlorogenic acid for its wide pharmaceutical use.

Radiation degradation of Congo Red in aqueous solution.

Radiation-induced degradation of Congo Red (an azo dye) in aqueous solution was studied both with steady-state radiolysis and time-resolve techniques of pulse radiolysis and laser flash photolysis. Decomposition and mineralization of Congo Red by gamma-rays was investigated with the changes of absorption spectra, degradation efficiency, TOC removal and pH changes of the solutions in different irradiation systems. The main radiolytic products resulting from steady-state radiolysis of Congo Red were examined by HPLC and LC-MS. Complete degradation of Congo Red was observed at different absorbed doses under diverse irradiation condition. The TOC removal of the solutions saturated with O2 or N2O reached 76% and 86% at the absorbed dose of 11.9 kGy, respectively. Pulse radiolysis and laser flash photolysis experiments were carried out to study the reaction of Congo Red with e(aq)- and ()OH. The reaction rate constants were determined.