Cardiac index and heart rate as prognostic indicators for mortality in septic shock: A retrospective cohort study from the MIMIC-IV database.

Background: Septic shock is a life-threatening condition that can lead to organ dysfunction and death. In the ICU, monitoring of cardiac index (CI) and heart rate (HR) is commonly used to guide management and predict outcomes in septic shock patients. However, there is a lack of research on the association between CI and HR and the risk of mortality in this patient population. Therefore, the aim of this study was to investigate the relationship between different levels of CI and HR and mortality in septic shock patients. Methods: Data analysis was obtained from the MIMIC-IV version 2.0 database. Sepsis and septic shock were primarily defined by sepsis-3, the third international consensus on sepsis and septic shock. CI was computed using cardiac output (CO) and body surface area (BSA). To evaluate the incidence of CI with respect to each endpoint (7-, 14-, 21-, and 28-day mortality), a restricted cubic spline curve function (RCS) was used. The optimal cutoff value for predicted mortality was determined using the Youden index. Analyses of KM curves, cox regression, and logistic regression were conducted separately to determine the relationship between various CI and HR and 28-day mortality. Results: This study included 1498 patients with septic shock. A U-shaped relationship between CI levels and risk of mortality in septic shock was found by RCS analysis (p < 0.001). CI levels within the intermediate range of 1.85-2.8 L/min/m2 were associated with a mortality hazard ratio (HR) < 1. In contrast, low CI (HR = 1.87 95% CI: 1.01-3.49) and high CI (HR = 1.93 95% CI: 1.26-2.97) had a significantly increased risk of mortality. The AUC for heart rate prediction of mortality by Youden index analysis was 0.70 95%CI:0.64-0.76 with a cut-off value of 93.63 bpm. According to the characteristics of HR and CI, patients were divided into six subgroups HR↓+CI intermediate group (n = 772), HR↓+CI↓ group (n = 126), HR↓+CI↑ group (n = 294), HR↑+CI intermediate group (n = 132), HR↑+CI↓ group (n = 24), and HR↑+CI↑ group (n = 150). The KM curves, COX regression, and logistic regression analysis showed that the survival rates the of HR↓+CI intermediate group, HR↓+CI↓ group, and HR↓+CI↑ were higher than the other groups. The risk factors of HR↑+CI intermediate group, HR↑+CI↓, and HR↑+CI↑ with ICU 28-day mortality were HR = 2.91 (95% CI: 1.39-5.97), HR = 3.67 (95% CI: 1.39-11.63), and HR = 5.77 (95% CI: 2.98-11.28), respectively. Conclusion: Our retrospective study shows that monitoring cardiac index and heart rate in patients with septic shock may help predict the organismal response and hemodynamic consequences, as well as the prognosis. Thus, healthcare providers should carefully monitor changes in these parameters in septic shock patients transferred to the ICU for treatment.

Prognostic significance of Naples prognostic score in operable renal cell carcinoma.

Background: Naples prognostic score (NPS), a novel scoring system based on nutritional and inflammatory status, is associated with prognosis in several cancers. This study aimed to evaluate the prognostic significance of preoperative NPS in patients undergoing nephrectomy. Patients and Methods: This study retrospectively analyzed patients with renal cell carcinoma (RCC) who underwent radical or partial nephrectomy between 2010 and 2013. The clinicopathological characteristics of patients stratified by preoperative NPS were compared. Survival analysis was performed using the Kaplan-Meier method and log-rank test. Univariate and multivariate Cox proportional hazards models were used to identify independent prognostic factors. Receiver operating characteristic curves were used to evaluate prediction efficiency. Results: A total of 638 patients with operable RCC were included. The high-NPS group (NPS group 2) was significantly associated with older age (P < 0.001), larger tumor size (P < 0.001), worse pathological T stage (P < 0.001), positive lymph node pathology (P = 0.002), higher tumor grade (P < 0.001), and greater tumor necrosis (P < 0.001). Multivariable analysis demonstrated that the high-NPS subgroup had significantly worse overall survival (OS) [hazard ratio (HR): 2.25, 95% confidence interval (CI): 1.45-3.50, P < 0.001] and progression-free survival (PFS) (HR: 2.26, 95% CI: 1.48-3.44, P < 0.001). Among several preoperative scoring systems, NPS had the strongest discriminatory power for predicting OS and PFS. Conclusion: Preoperative NPS can serve as a simple novel risk stratification tool to optimize the prognosis of patients with operable RCC. Further prospective and large-scale studies are needed to validate our findings.

Expression of glucocorticoid receptor (GR) and clinical significance in adrenocortical carcinoma.

Adrenocortical carcinoma (ACC) is a rare endocrine tumor, and most cases present with hormone excess with poor prognosis. Our research aims to determine the clinical and biological significance of glucocorticoid receptor (GR) expression using large cohorts of ACC patients. Immunohistochemistry was used to assess the expression of GR in 78 ACC cases from the West China Hospital (WCH) cohort. RNA-seq data were retrieved from The Cancer Genome Atlas database (TCGA, n=79). Clinicopathological and follow-up data were obtained from two cohorts. The correlation between the GR gene and tumor immune status was estimated using TIMER and GEPIA2. Kaplan-Meier analysis was performed to identify the prognostic value of GR in ACC. In the WCH cohort, positive nuclear GR staining was identified in 90% of the primary ACC cases. Cortisol-secreting ACCs demonstrated significantly lower GR protein expression than did nonfunctioning tumors (P<0.001). This finding was validated by the mRNA data analysis of the TCGA cohort (P = 0.030). GR expression was found to be positively correlated with the immune cell infiltration level and immune-checkpoint-related gene expression in ACC. Survival comparison and multivariate analysis showed that GR expression is an independent prognostic predictor of disease-free survival and overall survival in ACC patients in both cohorts. Our findings suggest that low GR expression is significantly correlated with excess cortisol, immune signatures and poor survival in ACC patients. We propose that GR signaling may play an important role in ACC behavior and thus may be a therapeutic target, which deserves further research.

N7-Methylguanosine Genes Related Prognostic Biomarker in Hepatocellular Carcinoma.

Background: About 90% of liver cancer-related deaths are caused by hepatocellular carcinoma (HCC). N7-methylguanosine (m7G) modification is associated with the biological process and regulation of various diseases. To the best of our knowledge, its role in the pathogenesis and prognosis of HCC has not been thoroughly investigated. Aim: To identify N7-methylguanosine (m7G) related prognostic biomarkers in HCC. Furthermore, we also studied the association of m7G-related prognostic gene signature with immune infiltration in HCC. Methods: The TCGA datasets were used as a training and GEO dataset "GSE76427" for validation of the results. Statistical analyses were performed using the R statistical software version 4.1.2. Results: Functional enrichment analysis identified some pathogenesis related to HCC. We identified 3 m7G-related genes (CDK1, ANO1, and PDGFRA) as prognostic biomarkers for HCC. A risk score was calculated from these 3 prognostic m7G-related genes which showed the high-risk group had a significantly poorer prognosis than the low-risk group in both training and validation datasets. The 3- and 5-years overall survival was predicted better with the risk score than the ideal model in the entire cohort in the predictive nomogram. Furthermore, immune checkpoint genes like CTLA4, HAVCR2, LAG3, and TIGT were expressed significantly higher in the high-risk group and the chemotherapy sensitivity analysis showed that the high-risk groups were responsive to sorafenib treatment. Conclusion: These 3 m7G genes related signature model can be used as prognostic biomarkers in HCC and a guide for immunotherapy and chemotherapy response. Future clinical study on this biomarker model is required to verify its clinical implications.

Comparison of different surgical methods and strategies for inguinal lymph node dissection in patients with penile cancer.

To compare the clinical feasibility and oncological outcome of different surgical techniques for inguinal lymphadenectomy (ILND) in patients suffering from penile cancer. This study included data from 109 cN0-2 patients diagnosed with penile cancer who received ILND. 80 laparoscopic ILND were performed on 40 patients, while 138 open surgeries were performed on 69 patients. Perioperative complications and prognosis were compared between different surgical techniques. Compared with the open surgery group, the laparoscopy group had a shorter hospital stay (8.88 ± 7.86 days vs. 13.94 ± 10.09 days, P = 0.004), and a lower wound healing delay rate (8.75% vs. 22.46%, P = 0.017), but also had longer drainage time (10.91 ± 9.66 vs. 8.70 ± 4.62, P = 0.002). There were no significant differences in terms of other intraoperative parameters, complications, and survival between open and laparoscopic group. Compared with saphenous vein ligated subgroup, preserved subgroup showed no significant reducing of complication rate. There was no significant difference among complication between different open surgery subgroup. Immediate ILND showed no prognostic advantage over delayed ILND regardless of clinical lymph node status. Compared with open surgery, the minimally invasive ILND technique has similar oncological efficiency and a lower complication rate. Saphenous vein preservation has limited value in reducing complications. Delayed lymphadenectomy might be a more reasonable option for ILND.

Development and validation of pyroptosis-related lncRNAs prediction model for bladder cancer.

Bladder cancer (BLCA) is one of the highly heterogeneous disorders accompanied by a poor prognosis. The present study aimed to construct a model based on pyroptosis-related long-stranded non-coding RNA (lncRNA) to evaluate the potential prognostic application in bladder cancer. The mRNA expression profiles of bladder cancer patients and corresponding clinical data were downloaded from the public database from The Cancer Genome Atlas (TCGA). Pyroptosis-related lncRNAs were identified by utilizing a co-expression network of pyroptosis-related genes and lncRNAs. The lncRNA was further screened by univariate Cox regression analysis. Finally, eight pyroptosis-related lncRNA markers were established using least absolute shrinkage and selection operator (Lasso) regression and multivariate Cox regression analyses. Patients were separated into high- and low-risk groups based on the performance value of the median risk score. Patients in the high-risk group had significantly poorer overall survival (OS) than those in the low-risk group (P<0.001). In multivariate Cox regression analysis, the risk score was an independent predictive factor of OS (HR > 1, P<0.01). The areas under the curve (AUCs) of the 3- and 5-year OS in the receiver operating characteristic (ROC) curve were 0.742 and 0.739, respectively. In conclusion, these eight pyroptosis-related lncRNA and their markers may be potential molecular markers and therapeutic targets for bladder cancer patients.

Prognostic Significance of Prognostic Nutritional Index in Patients with Renal Cell Carcinoma: A Meta-Analysis.

The prognostic nutrition index (PNI), based on the serum lymphocyte counts and albumin levels, has been introduced as a prognostic factor in various cancer. In the present study, we explore the prognostic significance of PNI in patients with renal cell carcinoma (RCC). A literature search of all publications was conducted using the Cochrane library, PubMed and Embase databases from inception to April 2020. A total of 12 studies consisting of 7,391 patients were enrolled in the present study. We found that low pretreatment PNI is significantly correlated to poor survival, including overall survival (OS) (P < 0.001), cancer-specific survival (CSS) (P = 0.002), progression-free survival/recurrence-free survival/disease-free survival (PFS/RFS/DFS) (P < 0.001). The age (P < 0.001), clear cell histology (P = 0.044), T3-T4 (P = 0.049), and Fuhrman grade 3-4 (P = 0.024) were significantly differed in the low and high pretreatment PNI group. In summary, low pretreatment PNI was associated with adverse clinicopathological features in patients with RCC. Besides, low pretreatment PNI was also an unfavorable factor of OS, CSS, and PFS/RFS/DFS in RCC patients, which could serve as an unfavorable factor. More studies with large participants are required to verify our results.Supplemental data for this article is available online at https://doi.org/10.1080/01635581.2021.1931702.

Prognostic Values of Different Clinicopathological Factors and Predictive Models for Penile Carcinoma.

OBJECTIVE: To evaluate the prognostic factors of penile cancer and the utility of prognostic models. METHODS: We analyzed postoperatively collected data of 311 patients diagnosed with penile cancer. Survival analysis (Kaplan-Meier and cox regression methods) was performed on this cohort. The c-index was used to determine the predictive accuracies of potential prognostic factors. The accuracies of four prognostic models were also evaluated, which were AJCC prognostic stage group for three recent editions, and four nomograms constructed by the Surveillance, Epidemiology, and End Results program (SEER). Two novel nomograms using our data were created and AUC of 2-year survival were determined to compare existing and newly established models. RESULTS: Tumor site, T and N stages, nuclear grade and lymph vascular invasion (LVI) significantly influenced prognosis. The 8th T and N stages had better c-indexes than former editions, while no improvement was seen in the 8thAJCC stage group. 6th AJCC+grade nomogram had a higher c-index than other three nomograms (SEER+grade, 6th TNM+grade, and 6th T1-3N0-3+grade nomograms; c-index: 0.831 vs 0.738, 0.792 and 0.781). New nomogram 1 included the 8th T and N stages, tumor site, nuclear grade, and LVI, with a c-index of 0.870. Novel nomogram 2 replaced the T and N stages with the AJCC stage group, which had a lower c-index of 0.855. The order of prediction accuracy of 2-year survival in the old and new models is consistent with the c-index results. CONCLUSION: Tumor site, stages, grade, and LVI play important roles in predicting survival of penile cancer. The 8th stages have better predictive accuracy than former editions. We proposed two models with better predictive accuracy than former models; specifically, nomogram 1 may be a more precise and convenient tool for predicting penile cancer outcomes.

Prognostic factors of non-muscle invasive bladder cancer: a study based on next-generation sequencing.

OBJECTIVE: To investigate the genetic prognostic factors for the recurrence of non-muscle invasive bladder cancer. MATERIALS AND METHODS: The patients underwent transurethral resection of bladder tumor and received bacillus Calmette-Guérin (BCG) or epirubicin. Next-generation sequencing was performed and alterations of genes, pathways, and tumor mutation burden were recorded. Associations between these clinicopathological and genetic variants were estimated, and prognostic factor identified. RESULTS: A total of 58 cases were included in our study, and 46 patients underwent treatment with BCG. FGFR3 was the most frequently altered gene (48%), and more commonly detected in intermediate-risk patients. Univariate Cox analysis demonstrated that 10 genes were significantly correlated with BCG failure, while NEB, FGFR1 and SDHC were independent recurrence predictors. Besides, epigenetic-related gene pathway mutations were negatively correlated with recurrence (hazard ratio: 0.198, P = 0.023). DNA damage response and repair gene alterations were positively correlated with tumor burden, while altered TP53 was most frequent among these genes and significant correlated with high tumor burden. CONCLUSION: BCG instillation significantly reduced the rate of recurrence compared with epirubicin in this population. Potential biomarkers and therapeutic targets were found with the help of next-generation sequencing; correlations between DDR genes alterations and high tumor mutation burden were also demonstrated.

Validation of the Prognostic Value of Preoperative Albumin-to-Alkaline Phosphatase Ratio in Patients with Surgically Treated Non-Metastatic Renal Cell Carcinoma.

PURPOSE: Several studies have revealed that albumin-to-alkaline phosphatase ratio (AAPR) was correlated to the survival of several cancers. To explore the impact of AAPR on the survival of non-metastatic renal cell carcinoma (RCC) patients following nephrectomy, the present study was conducted. PATIENTS AND METHODS: A total of 648 patients were enrolled in the present study. The cut-off value of AAPR was determined based on the receiver-operating characteristic (ROC) analysis. Univariate and multivariate analyses were applied to identify prognostic factors. The discrimination and calibration of models for survival outcomes were evaluated based on the concordance index (C-index), ROC analysis and calibration curve. RESULTS: The low AAPR (≤0.5) was associated with older age (P<0.001), higher T stage (P=0.002), larger tumor size (P=0.014) and tumor necrosis (P=0.003). A high AAPR was significantly correlated to better OS (hazard ratio, HR=0.61; P=0.038) and CSS (HR=0.52; P=0.013) based on multivariate analysis. Integrating AAPR with UISS or SSIGN, the C-indexes of nomogram for OS (UISS: 0.790 vs 0.765; SSIGN: 0.861 vs 0.850) and CSS (UISS: 0.832 vs 0.805; SSIGN: 0.905 vs 0.896) increased. Moreover, the nomogram for OS and CSS was established based on the multivariate analysis. The C-indexes of nomogram for OS and CSS were 0.834 (95% CI 0.794-0.874) and 0.867 (95% CI 0.830-0.904), respectively. CONCLUSION: In conclusion, the high preoperative AAPR was a favorable prognostic factor for surgically treated non-metastatic RCC patients. AAPR also could improve the predictive value of well-established models. The nomogram that incorporates AAPR had a good performance. More prospective studies with a large scale are essential to validate our findings.

Prognostic value of preoperative prognostic nutritional index in patients with renal cell carcinoma after nephrectomy.

PURPOSE: The present study was performed to explore the prognostic value of prognostic nutritional index (PNI) in renal cell carcinoma (RCC) patients following nephrectomy. METHODS: A total of 660 patients were included. PNI was calculated based on the following formula: serum albumin level (g/L) + 0.005 × total lymphocyte count (per mm3). Kaplan-Meier survival curve and the log-rank test were conducted. Univariate analysis and multivariate Cox regression analysis were performed to explore the prognostic factors. RESULTS: The patients in low PNI group were more likely to be older (P < 0.001), have a larger tumor (P < 0.001), higher pathological T stage (P < 0.001), positive lymph node (P = 0.038), distant metastasis (P = 0.005), higher tumor grade (P < 0.001) and tumor necrosis (P < 0.001). Multivariable analysis revealed low preoperative PNI was an independent predictor of overall survival (OS) (P = 0.034) and progression-free survival (PFS) (P = 0.004) for all patients. Besides, low preoperative PNI was also significantly associated with poor OS (P = 0.008), cancer-specific survival (CSS) (P = 0.032) and PFS (P = 0.003) for non-metastatic RCC patients. CONCLUSION: The patients with lower preoperative PNI were associated with adverse factors. Furthermore, the low preoperative PNI was also associated with inferior oncological outcomes in RCC patients who underwent nephrectomy.

Prognostic analysis of postoperative clinically nonmetastatic renal cell carcinoma.

OBJECTIVES: To investigate the survival characteristics of postoperative nonmetastatic renal cell carcinoma (RCC) patients, and the predictive value of a prognostic model. MATERIALS AND METHODS: We retrospectively evaluated data from 1202 postoperative nonmetastatic RCC patients who were treated between 1999 and 2012 at West China Hospital, Sichuan University (Chengdu, China). In addition, we also evaluated data relating to 53 205 cases acquired from the Surveillance, Epidemiology, and End Results (SEER) program. Survival analysis was performed on the cases, and subgroups, using the Kaplan-Meier and Cox regression methods. The concordance index of the Stage Size Grade Necrosis (SSIGN), Leibovich, and the UCLA integrated staging system, scores was determined to evaluate the accuracy of these outcome prediction models. RESULTS: The 5-year overall survival rate for RCC cases in West China Hospital was 87.6%; this was higher than that observed for SEER cases. Survival analysis identified several factors that exerted significant influence over prognosis, including the time of surgery, Eastern Cooperative Oncology Group performance status, tumor stage, size, nuclear differentiation, pathological subtypes, along with necrotic and sarcomatoid differentiation. Moreover tumor stage, size, and nuclear grade were all identified as independent predictors for both our cases and those from the SEER program. Patient groups with advanced RCC, and poorly differentiated RCC subgroups, were both determined to have a poor prognosis. The SSIGN model yielded the best predictive value as a prognostic model, followed by the Leibovich, and UCLA integrated staging system; this was the case for our patients, and for sub-groups with a poor prognosis. CONCLUSION: The prognosis of RCC was mostly influenced by tumor stage, size, and nuclear differentiation. SSIGN may represent the most suitable prognostic model for the Chinese population.

Rates of motorcycle helmet use and reasons for non-use among adults and children in Luang Prabang, Lao People's Democratic Republic.

BACKGROUND: Motorcycles make up 81 % of the total vehicle population and 74 % of road traffic deaths in Lao PDR. Helmets reduce the risk and severity of injuries resulting from motorcycle accidents by 72 %. Although Lao law mandates motorcycle helmet use among drivers and passengers, the prevalence of helmet use in Luang Prabang, Lao PDR is unknown. This project aimed to measure the prevalence of motorcycle helmet use among riders (i.e., drivers and passengers) in Luang Prabang. METHODS: An observational survey in Luang Prabang was conducted in February 2015 to measure the prevalence of motorcycle helmet use among drivers and passengers. Additionally, non-helmet wearing riders were surveyed to identify the reasons for helmet non-use. RESULTS: Of 1632 motorcycle riders observed, only 16.2 % wore helmets. Approximately 29 % of adults wore helmets while less than 1 % of all children wore helmets. When surveyed about attitudes towards helmet use, the majority of adult drivers indicated that they did not like how adult helmets feel or made them look. Additionally, almost half of motorcyclists who did not own child helmets reported that their child was too young to wear a helmet. CONCLUSIONS: Our finding that children wear helmets at significantly lower rates compared to adults is consistent with findings from neighboring countries in Southeast Asia. Results of this study have implications for public health campaigns targeting helmet use, especially among children.