An Invited Commentary "Prognostic effect of the new 5-factor modified frailty index in patients undergoing carotid endarterectomy with regional anesthesia - A prospective cohort study".

Frailty has been studied as a valuable predictor of adverse health events and poor postoperative outcomes in patients undergoing surgery. Thus, the use of simple and adapted indexes to define frailty, like the modified frailty index (Mfi)-11, proved useful in assessing patients undergoing vascular surgery. The role of carotid endarterectomy (CEA) continues to be debated in the age of optimal medical therapy, particularly for patients with limited life expectancy (Rothenberg et al., 2020) [3]. The Risk Analysis Index (RAI) measures frailty, a syndrome of decreased physiologic reserve, which increases vulnerability to adverse outcomes. However, the literature about the applicability of an even more pragmatic index, the modified frailty (mFi) index mFI-5 in vascular patients is scarce, particularly in those submitted to carotid endarterectomy (CEA). This study aimed to validate and estimate the prognostic value of the mFI-5 on the postoperative period and long-term survival of this population (Araújo-Andrade et al., 2020) [1].

Prognostic effect of the new 5-factor modified frailty index in patients undergoing carotid endarterectomy with regional anesthesia - A prospective cohort study.

BACKGROUND: Frailty has been studied as a valuable predictor of adverse health events and poor postoperative outcomes in patients undergoing surgery. Thus, the use of simple and adapted indexes to define frailty, like the modified frailty index (mFI)-11, proved useful in assessing patients undergoing vascular surgery. However, the literature about the applicability of an even more pragmatic index, the modified frailty (mFI) index mFI-5 in vascular patients is scarce, particularly in those submitted to carotid endarterectomy (CEA). This study aimed to validate and estimate the prognostic value of the mFI-5 on the postoperative period and long-term survival of this population. METHODS: From January 2011 to June 2019, 184 patients from a tertiary care referral center who underwent CEA with regional anesthesia for carotid artery stenosis were selected from a previous prospectively mantained cohort database. Clinical adverse events such as stroke, myocardial infarction (MI), acute heart failure (AHF), and all-cause mortality were assessed 30-days post-procedure and in the subsequent long-term surveillance period. mFI-5 was applied to this population to evaluate the impact of frailty on mortality and morbidity. RESULTS: The mFI-5 was significantly associated with increased risk of long-term MI (P < 0.001), AHF (P = 0.043), major adverse cardiovascular events (P = 0.001) and mortality (P < 0.001). Concerning major adverse limb events and stroke survival, mFI-5 did not reveal statistical significance. The mFI-5 was not able to predict 30-day postoperative adverse events. CONCLUSION: The mFI-5 has demonstrated to be a potential index tool capable of easily stratifying patients and predicting outcomes in the long-term and add therapeutic value in the future. The mFI-5 provides a means of rapidly comparing the comorbidity charge between cohorts.

Identification of a novel glycolysis-related gene signature for predicting metastasis and survival in patients with lung adenocarcinoma.

BACKGROUND: Lung cancer (LC) is one of the most lethal and most prevalent malignant tumors, and its incidence and mortality are increasing annually. Lung adenocarcinoma (LUAD) is the most common pathological type of lung cancer. Several biomarkers have been confirmed by data excavation to be related to metastasis, prognosis and survival. However, the moderate predictive effect of a single gene biomarker is not sufficient. Thus, we aimed to identify new gene signatures to better predict the possibility of LUAD. METHODS: Using an mRNA-mining approach, we performed mRNA expression profiling in large LUAD cohorts (n = 522) from The Cancer Genome Atlas (TCGA) database. Gene Set Enrichment Analysis (GSEA) was performed, and connections between genes and glycolysis were found in the Cox proportional regression model. RESULTS: We confirmed a set of nine genes (HMMR, B4GALT1, SLC16A3, ANGPTL4, EXT1, GPC1, RBCK1, SOD1, and AGRN) that were significantly associated with metastasis and overall survival (OS) in the test series. Based on this nine-gene signature, the patients in the test series could be divided into high-risk and low-risk groups. Additionally, multivariate Cox regression analysis revealed that the prognostic power of the nine-gene signature is independent of clinical factors. CONCLUSION: Our study reveals a connection between the nine-gene signature and glycolysis. This research also provides novel insights into the mechanisms underlying glycolysis and offers a novel biomarker of a poor prognosis and metastasis for LUAD patients.

Mediation analysis with a time-to-event outcome: a review of use and reporting in healthcare research.

BACKGROUND: Mediation analysis tests whether the relationship between two variables is explained by a third intermediate variable. We sought to describe the usage and reporting of mediation analysis with time-to-event outcomes in published healthcare research. METHODS: A systematic search of Medline, Embase, and Web of Science was executed in December 2016 to identify applications of mediation analysis to healthcare research involving a clinically relevant time-to-event outcome. We summarized usage over time and reporting of important methodological characteristics. RESULTS: We included 149 primary studies, published from 1997 to 2016. Most studies were published after 2011 (n = 110, 74%), and the annual number of studies nearly doubled in the last year (from n = 21 to n = 40). A traditional approach (causal steps or change in coefficient) was most commonly taken (n = 87, 58%), and the majority of studies (n = 114, 77%) used a Cox Proportional Hazards regression for the outcome. Few studies (n = 52, 35%) mentioned any of the assumptions or limitations fundamental to a causal interpretation of mediation analysis. CONCLUSION: There is increasing use of mediation analysis with time-to-event outcomes. Current usage is limited by reliance on traditional methods and the Cox Proportional Hazards model, as well as low rates of reporting of underlying assumptions. There is a need for formal criteria to aid authors, reviewers, and readers reporting or appraising such studies.

Impact of lymph node ratio on survival in stage III ovarian high-grade serous cancer: a Turkish Gynecologic Oncology Group study.

OBJECTIVE: The purpose of this study was to investigate the prognostic value of lymph node ratio (LNR) in patients with stage III ovarian high-grade serous carcinoma (HGSC). METHODS: A multicenter, retrospective department database review was performed to identify patients with ovarian HGSC at 6 gynecologic oncology centers in Turkey. A total of 229 node-positive women with stage III ovarian HGSC who had undergone maximal or optimal cytoreductive surgery plus systematic lymphadenectomy followed by paclitaxel plus carboplatin combination chemotherapy were included. LNR, defined as the percentage of positive lymph nodes (LNs) to total nodes recovered, was stratified into 3 groups: LNR1 (<10%), LNR2 (10%≤LNR<50%), and LNR3 (≥50%). Kaplan-Meier method was used to generate survival data. Factors predictive of outcome were analyzed using Cox proportional hazards models. RESULTS: Thirty-one women (13.6%) were classified as stage IIIA1, 15 (6.6%) as stage IIIB, and 183 (79.9%) as stage IIIC. The median age at diagnosis was 56 (range, 18-87), and the median duration of follow-up was 36 months (range, 1-120 months). For the entire cohort, the 5-year overall survival (OS) was 52.8%. An increased LNR was associated with a decrease in 5-year OS from 65.1% for LNR1, 42.5% for LNR2, and 25.6% for LNR3, respectively (p<0.001). In multivariate analysis, women with LNR≥0.50 were 2.7 times more likely to die of their tumors (hazard ratio [HR]=2.7; 95% confidence interval [CI]=1.42-5.18; p<0.001). CONCLUSION: LNR seems to be an independent prognostic factor for decreased OS in stage III ovarian HGSC patients.

Impact of lymph node ratio on survival in stage III ovarian high-grade serous cancer: a Turkish Gynecologic Oncology Group study / 부인종양

OBJECTIVE: The purpose of this study was to investigate the prognostic value of lymph node ratio (LNR) in patients with stage III ovarian high-grade serous carcinoma (HGSC). METHODS: A multicenter, retrospective department database review was performed to identify patients with ovarian HGSC at 6 gynecologic oncology centers in Turkey. A total of 229 node-positive women with stage III ovarian HGSC who had undergone maximal or optimal cytoreductive surgery plus systematic lymphadenectomy followed by paclitaxel plus carboplatin combination chemotherapy were included. LNR, defined as the percentage of positive lymph nodes (LNs) to total nodes recovered, was stratified into 3 groups: LNR1 (<10%), LNR2 (10%≤LNR<50%), and LNR3 (≥50%). Kaplan-Meier method was used to generate survival data. Factors predictive of outcome were analyzed using Cox proportional hazards models. RESULTS: Thirty-one women (13.6%) were classified as stage IIIA1, 15 (6.6%) as stage IIIB, and 183 (79.9%) as stage IIIC. The median age at diagnosis was 56 (range, 18–87), and the median duration of follow-up was 36 months (range, 1–120 months). For the entire cohort, the 5-year overall survival (OS) was 52.8%. An increased LNR was associated with a decrease in 5-year OS from 65.1% for LNR1, 42.5% for LNR2, and 25.6% for LNR3, respectively (p<0.001). In multivariate analysis, women with LNR≥0.50 were 2.7 times more likely to die of their tumors (hazard ratio [HR]=2.7; 95% confidence interval [CI]=1.42–5.18; p<0.001). CONCLUSION: LNR seems to be an independent prognostic factor for decreased OS in stage III ovarian HGSC patients.

Thrombospondin-I concentrations behavior in plasma of patients with ovarian cancer.

PURPOSE: To determine whether thrombospondin-1 might be used as a prognostic factor in ovarian cancer patients. METHOD: Ninety-six female subjects hospitalized in years 2011-2014 was included in the study. Transvaginal ultrasound examination was performed in all patients. In 39 cases of suspected ovarian cancer, CT scans were also performed. Each patient had been subjected to collection of a 5-mL blood sample before the laparoscopic procedure. Thrombospondin-1 concentrations were quantified in serum by multiplex fluorescent bead-based immunoassays (Luminex) at the Laboratory of the Department of General Pathology. RESULTS: Statistical analysis performed using the Kaplan-Meier survival curves and log-rank test revealed no statistically significant correlations between the median, 75th percentile and 95th percentile thrombospondin-1 levels with progression-free survival of patients (p= 0.47). In the univariate OS model, median thrombospondin-1 level was a significant variable. Correlation was demonstrated between baseline thrombospondin-1 levels and overall survival of patients (p= 0.04, HR = 0.99). The higher the baseline TSP1 level, the longer the overall survival of patients. CONCLUSION: In our study, we were the first to demonstrate correlation between the levels of thrombospondin-1 and overall survival of patients. Therefore, it appears that thrombospondin-1 may be used as a prognostic factor in ovarian cancer patients.