scholarly journals Prognostic Significance of NLR About NETosis and Lymphocytes Perturbations in Localized Renal Cell Carcinoma With Tumor Thrombus

2021 ◽  
Vol 11 ◽  
Author(s):  
Bingqing Shang ◽  
Liping Guo ◽  
Rongfang Shen ◽  
Chuanzhen Cao ◽  
Ruiyang Xie ◽  
...  

BackgroundNon-metastatic renal cell carcinoma (RCC) with tumor thrombus showed a greater tendency for developing metastases after surgery. Early identification of patients with high risk of poor prognosis is especially important to explore adjuvant treatment of improving outcomes. Neutrophil-to-lymphocyte ratio (NLR) was a systemic inflammation marker and outcome predictor in RCC, reflecting the chaos in systemic immune status in cancer as myeloid cell expansion and lymphatic cell suppression. Neutrophil extracellular traps (NET) formation (NETosis) is the process of neutrophils generating an extracellular DNA net-like structure. NETosis in tumor was demonstrated to conduce to the subsequent metastases of tumor. However, the role of NLR for systemic immune status and tumor local immune infiltration, especially for neutrophil-associated NETs, in non-metastatic RCC with thrombus remains unclear.Patients and MethodsIn our clinical cohort, we enrolled the clinical, pathologic, and preoperative laboratory parameters of 214 RCC patients with tumor thrombus who were treated surgically. The clinical endpoint was defined as cancer-specific survival (CSS). In our basic research cohort, RNA-seq, TCR-seq, and scRNA-seq data were analyzed. Patients who reached the endpoint as recurrence-free survival (RFS) were defined as the “High-risk” group. Otherwise, they were separated into the “Low-risk” group.ResultsIn the clinical cohort, NLR≥4 was an independent risk factor for 203 localized RCC with tumor thrombus. In the basic research cohort, tumor thrombi were separated into NETosis-thrombi belonging to the “High-risk” group and non-NETosis-thrombi to the “Low-risk” group. NETs induced by tumor-derived G-CSF in tumor thrombus has a mechanistic role in unfavorable prognosis. Besides, NETs-score from single sample GSEA (ssGSEA) algorithm was an independent prognostic factor validated in the TCGA data. Apart from the neutrophils-associated NETosis, systemic immune perturbations of lymphocytes occurred in the “High-risk” group, represented with decreased TCR diversity and increasingly high proportion of CD4-positive effector memory T (Tem) cells, which indirectly represented the state of lymphopenia.ConclusionsOur findings firstly demonstrated that neutrophils-associated NETosis and systemic lymphocytes perturbations were considered as tumor progression in patients of localized RCC with tumor thrombus, which reflected NLR≥4 as an independent risk factor for patients.

2020 ◽  
Vol 9 (7) ◽  
pp. 2057
Author(s):  
Vanja Ristovic ◽  
Sophie de Roock ◽  
Thierry G. Mesana ◽  
Sean van Diepen ◽  
Louise Y. Sun

Background: Despite steady improvements in cardiac surgery-related outcomes, our understanding of the physiologic mechanisms leading to perioperative mortality remains incomplete. Intraoperative hypotension is an important risk factor for mortality after noncardiac surgery but remains relatively unexplored in the context of cardiac surgery. We examined whether the association between intraoperative hypotension and in-hospital mortality varied by patient and procedure characteristics, as defined by the validated Cardiac Anesthesia Risk Evaluation (CARE) mortality risk score. Methods: We conducted a retrospective cohort study of consecutive adult patients who underwent cardiac surgery requiring cardiopulmonary bypass (CPB) from November 2009–March 2015. Those who underwent off-pump, thoracic aorta, transplant and ventricular assist device procedures were excluded. The primary outcome was in-hospital mortality. Hypotension was categorized by mean arterial pressure (MAP) of <55 and between 55–64 mmHg before, during and after CPB. The relationship between hypotension and death was modeled using multivariable logistic regression in the intermediate and high-risk groups. Results: Among 6627 included patients, 131 (2%) died in-hospital. In-hospital mortality in patients with CARE scores of 1, 2, 3, 4 and 5 was 0 (0%), 7 (0.3%), 35 (1.3%), 41 (4.6%) and 48 (13.6%), respectively. In the intermediate-risk group (CARE = 3–4), MAP < 65 mmHg post-CPB was associated with increased odds of death in a dose-dependent fashion (adjusted OR 1.30, 95% CI 1.13–1.49, per 10 min exposure to MAP < 55 mmHg, p = 0.002; adjusted OR 1.18 [1.07–1.30] per 10 min exposure to MAP 55–64 mmHg, p = 0.001). We did not observe an association between hypotension and mortality in the high-risk group (CARE = 5). Conclusions: Post-CPB hypotension is a potentially modifiable risk factor for mortality in intermediate-risk patients. Our findings provide impetus for clinical trials to determine if hemodynamic goal-directed therapies could improve survival in these patients.


2017 ◽  
Vol 58 (1) ◽  
pp. 16-24
Author(s):  
Insook Kim ◽  
Seonae Won ◽  
Mijin Lee ◽  
Won Lee

The aim of this study was to find out the risk factors through analysis of seven medical malpractice judgments related to fall injuries. The risk factors were analysed by using the framework that approaches falls from a systems perspective and comprised people, organisational or environmental factors, with each factor being comprised of subfactors. The risk factors found in each of the seven judgments were aggregated into one framework. The risk factors related to patients (i.e. the people factor) were age, pain, related disease, activities and functional status, urination state, cognitive function impairment, past history of fall, blood transfusion, sleep endoscopy state and uncooperative attitude. The risk factors related to the medical staff and caregivers (i.e. people factor) were observation negligence, no fall prevention activities and negligence in managing high-risk group for fall. Organisational risk factors were a lack of workforce, a lack of training, neglecting the management of the high-risk group, neglecting the management of caregivers and the absence of a fall prevention procedure. Regarding the environment, the risk factors were found to be the emergency room, chairs without a backrest and the examination table. Identifying risk factors is essential for preventing fall accidents, since falls are preventable patient-safety incidents. Falls do not happen as a result of a single risk factor. Therefore, a systems approach is effective to identify risk factors, especially organisational and environmental factors.


PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0257352
Author(s):  
Atsushi Kitazawa ◽  
Shotaro Maeda ◽  
Yoshiharu Fukuda

Background & aims Fatty liver is associated with incident diabetes, and the fatty liver index (FLI) is a surrogate marker for non-alcoholic fatty liver disease (NAFLD). We aimed to determine whether or not FLI was associated with incident diabetes in relation to obesity and prediabetic levels in the general Japanese population. Methods This was a retrospective study using the Japanese health check-up database of one health insurance from FY2015 to FY2018. This study included 28,991 individuals with prediabetes. First, we stratified all participants into two groups: “high-risk,” comprising patients with HbA1c >6.0%, and “standard,” comprising the rest. Subsequently, we divided them into four groups according to FLI (<30 or not) and obesity (BMI <25 kg/m2 or not). Subsequently, the incidence rate of diabetes was compared among the groups after 3 years of follow-up using multiple logistic regression models after adjusting for potential confounders. Results After 3 years of follow-up, 1,547 new cases of diabetes were found, and the cumulative incidence was 2.96% for the standard group and 26.1% for the high-risk group. In non-obese individuals, odds ratios (95% confidence interval) for FLI ≥30 versus FLI <30 were: 1.44 (1.09–1.92) for the standard group and 1.42 (0.99–2.03) for the high-risk group. In the high-risk group, obesity (BMI ≥25 kg/m2) but FLI <30 was not a risk factor for developing diabetes. Conclusion Although high FLI is generally considered to be a risk factor for developing diabetes, obesity might have been a confounding factor. However, the present study showed that high FLI is a risk factor for the development of diabetes, even in non-obese individuals. Our results include suggestion to develop a screening tool to effectively identify people at high risk of developing diabetes from the population (especially non-obese prediabetes) who are apparently at low health risk and are unlikely to be targeted for health guidance.


2021 ◽  
Vol 108 (Supplement_6) ◽  
Author(s):  
J James ◽  
L Drummond ◽  
N Clancy ◽  
S Leung

Abstract Introduction Recurrence rate of surgically treated localised renal cell carcinoma (RCC) is reported to be approximately 20%. There is lack of consensus on the optimal surveillance regimen. We assess the performance of our surveillance protocol based upon prognostic histological factors. We report the outcome of our first cohort to reach 5 years follow up. Method A retrospective analysis was performed of patients who underwent a radical or partial nephrectomy between March 2014 and October 2015. Patients were classified as high, intermediate, or low risk based on pathology; with each group undergoing individualised radiological follow up. Results 80 patients with pathologically confirmed RCC who underwent partial or radical nephrectomy were identified. Recurrence was noted in 24% (n = 19), and a third of those patients (n = 7) died within the 5-year follow-up period. 79% (n = 15) of patients with recurrence were of intermediate or high-risk group. 90% of recurrences were picked up on surveillance scans, 5% due to symptoms related to the recurrence and 5% incidentally. 70% occurred within the first 2 years post-surgery. 92% (n = 6) of those who died had an ASA of 2 or higher. In the whole cohort, total number of deaths was 13. 38% (n = 5) died of RCC, 54% (n = 7) died of other causes and in 8% (n = 1) cause of death of was unclear. Conclusions Our risk stratified surveillance protocol identified 90% of recurrences within the 5-year follow-up. Future refinement of our protocol could include an assessment of performance status which may influence the schedule of radiological surveillance.


2008 ◽  
Vol 102 (10) ◽  
pp. 591-599 ◽  
Author(s):  
Robin Casten ◽  
Barry Rovner

Age-related macular degeneration (AMD) is a major cause of disability in the elderly, substantially degrades the quality of their lives, and is a risk factor for depression. Rates of depression in AMD are substantially greater than those found in the general population of older people, and are on par with those of other chronic and disabling diseases. This article discusses the effect of depression on vision-related disability in patients with AMD, suggests methods for screening for depression, and summarizes interventions for preventing depression in this high-risk group.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Hongyu Li ◽  
Xiliu Zhang ◽  
Chen Yi ◽  
Yi He ◽  
Xun Chen ◽  
...  

Abstract Background The prognosis of oral squamous cell carcinoma (OSCC) patients is difficult to predict or describe due to its high-level heterogeneity and complex aetiologic factors. Ferroptosis is a novel form of iron-dependent cell death that is closely related to tumour growth and progression. This study aims to clarify the predictive value of ferroptosis-related genes (FRGs) on the overall survival(OS) of OSCC patients. Methods The mRNA expression profile of FRGs and clinical information of patients with OSCC were collected from the TCGA database. Candidate differentially expressed ferroptosis-related genes (DE-FRGs) were identified by analysing differences between OSCC and adjacent normal tissues. A gene signature of prognosis-related DE-FRGs was established by univariate Cox analysis and LASSO analysis in the training set. Patients were then divided into high- and low-risk groups according to the cut-off value of risk scores, A nomogram was constructed to quantify the contributions of gene signature and clinical parameters to OS. Then several bioinformatics analyses were used to verify the reliability and accuracy of the model in the validation set. Finally, single-sample gene set enrichment analysis (ssGSEA) was also performed to reveal the underlying differences in immune status between different risk groups. Results A prognostic model was constructed based on 10 ferroptosis-related genes. Patients in high-risk group had a significantly worse OS (p < 0.001). The gene signature was verified as an independent predictor for the OS of OSCC patients (HR > 1, p < 0.001). The receiver operating characteristic curve displayed the favour predictive performance of the risk model. The prediction nomogram successfully quantified each indicator’s contribution to survival and the concordance index and calibration plots showed its superior predictive capacity. Finally, ssGSEA preliminarily indicated that the poor prognosis in the high-risk group might result from the dysregulation of immune status. Conclusion This study established a 10-ferroptosis-releated gene signature and nomogram that can be used to predict the prognosis of OSCC patients, which provides new insight for future anticancer therapies based on potential FRG targets.


Author(s):  
Mei Chen ◽  
Zhenyu Nie ◽  
Yan Li ◽  
Yuanhui Gao ◽  
Xiaohong Wen ◽  
...  

Background: Ferroptosis is closely related to the occurrence and development of cancer. An increasing number of studies have induced ferroptosis as a treatment strategy for cancer. However, the predictive value of ferroptosis-related lncRNAs in bladder cancer (BC) still need to be further elucidated. The purpose of this study was to construct a predictive signature based on ferroptosis-related long noncoding RNAs (lncRNAs) to predict the prognosis of BC patients.Methods: We downloaded RNA-seq data and the corresponding clinical and prognostic data from The Cancer Genome Atlas (TCGA) database and performed univariate and multivariate Cox regression analyses to obtain ferroptosis-related lncRNAs to construct a predictive signature. The Kaplan-Meier method was used to analyze the overall survival (OS) rate of the high-risk and low-risk groups. Gene set enrichment analysis (GSEA) was performed to explore the functional differences between the high- and low-risk groups. Single-sample gene set enrichment analysis (ssGSEA) was used to explore the relationship between the predictive signature and immune status. Finally, the correlation between the predictive signature and the treatment response of BC patients was analyzed.Results: We constructed a signature composed of nine ferroptosis-related lncRNAs (AL031775.1, AL162586.1, AC034236.2, LINC01004, OCIAD1-AS1, AL136084.3, AP003352.1, Z84484.1, AC022150.2). Compared with the low-risk group, the high-risk group had a worse prognosis. The ferroptosis-related lncRNA signature could independently predict the prognosis of patients with BC. Compared with clinicopathological variables, the ferroptosis-related lncRNA signature has a higher diagnostic efficiency, and the area under the receiver operating characteristic curve was 0.707. When patients were stratified according to different clinicopathological variables, the OS of patients in the high-risk group was shorter than that of those in the low-risk group. GSEA showed that tumor- and immune-related pathways were mainly enriched in the high-risk group. ssGSEA showed that the predictive signature was significantly related to the immune status of BC patients. High-risk patients were more sensitive to anti-PD-1/L1 immunotherapy and the conventional chemotherapy drugs sunitinib, paclitaxel, cisplatin, and docetaxel.Conclusion: The predictive signature can independently predict the prognosis of BC patients, provides a basis for the mechanism of ferroptosis-related lncRNAs in BC and provides clinical treatment guidance for patients with BC.


2021 ◽  
Author(s):  
Tuanjie Guo ◽  
Jian Zhang ◽  
Tao Wang ◽  
Zhihao Yuan ◽  
Heting Tang ◽  
...  

Abstract Background: Lactic acid was previously considered a waste product of glycolysis, and has now become a key metabolite for cancer development, maintenance and metastasis. So far, numerous studies have confirmed that tumor lactic acid levels are associated with increased metastasis, tumor recurrence and poor prognosis. However, the prognostic value of lactic acid metabolism and transporter related genes in patients with clear cell renal cell carcinoma has not been explored.Results: We selected lactic acid metabolism and transporter related twenty-one genes for LASSO cox regression analysis in the E-MTAB-1980 cohort, and finally screened three genes (PNKD, SLC16A8, SLC5A8) to construct a clinical prognostic model for patients with clear cell renal cell carcinoma. Based on the prognostic model we constructed, the over survival (hazard ratio = 4.117, 95% CI: 1.810 - 9.362, p < 0.0001) of patients in the high-risk group and the low-risk group in the training set E-MTAB-1980 cohort had significant differences, and similar results (hazard ratio = 1.909, 95% CI: 1.414 - 2.579 p < 0.0001) were also observed in the validation set TGCA cohort. Subsequently, survival prediction was carried out based on the survival prognosis model we constructed. In the E-MTAB-1980 cohort, the area under ROC curve (AUC) of 1-, 3- and 5- years was 0.71, 0.72, and 0.77, respectively. The AUC of 1-, 3- and 5- years in TCGA cohort was 0.65, 0.65, and 0.63, respectively. Using CIBERSORT algorithm to analyze the differences in immune cell infiltration in different risk groups, we found that dendritic cells and CD4+ memory cells in the high-risk group were significantly lower than those in the low-risk group, while Treg cells were higher than in the low-risk group. Finally, through gene enrichment analysis, we found that the signal pathway that is strongly related to the prognostic model is the cell cycle. Conclusions: We constructed a prognostic model using lactic acid metabolism and transporter related genes, which can accurately predict the prognosis of patients. The poor prognosis of the high-risk group may be related to the regulation of cell cycle by lactic acid metabolism.


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