Multivariate Cox Proportional-hazards Regression Analysis Research Articles

Prognostic Significance of HbA1c Level in Asian Patients with Prediabetes and Coronary Artery Disease

Background: Measuring glycosylated hemoglobin (HbA1c) is a simple way to assess patients with prediabetes or diabetes mellitus. It has been shown that HbA1c level predicts prognosis in patients with coronary artery disease (CAD) and the incidence of diabetes mellitus. However, the prognostic significance of HbA1c level in Asian patients with prediabetes and CAD is not yet clear. Our study aimed to determine the relationship between HbA1c level and major adverse cardiovascular events (MACE) in patients with prediabetes and CAD. Methods: We enrolled 1367 patients with prediabetes and CAD in the final analysis, and grouped them according to the HbA1c level. Primary end points included nonfatal myocardial infarction, hospitalization for unstable angina, and ischemia-driven revascularization. Cox proportional-hazards regression analysis was used to determine the relationship between HbA1c level and MACE after our accounting for confounding factors. Results: A total of 1367 patients (age 58.8 ± 10.3 years; 71.6% men) were included. During 43 months of follow-up, 197 patients experienced at least one primary end point event. Multivariate Cox proportional-hazards regression analysis showed in comparison of HbA1c levels that the hazard ratio for primary end points was 4.110, with a 95% confidence interval of 2.097–6.011 (P<0.001). Conclusions: HbA1c level positively correlated with MACE, demonstrating it is a valuable indicator for independently predicting MACE in Asian patients with prediabetes and CAD.

Cerebral Microbleed Burden in Ischemic Stroke Patients on Aspirin: Prospective Cohort of Intracranial Hemorrhage.

Objective: This investigation aimed at studying the prevalence of cerebral microbleeds (CMBs), including risk factors and the correlation of CMBs to ischemic stroke (IS) patient end results.Methods: Four hundred and fifty-nine acute IS cases were recruited between April 2014 and December 2016. Cerebral microbleeds were analyzed using susceptibility-weighted imaging (SWI) brain MRI scan. The enrolled patients with acute IS were followed up for 12–24 months, with a median follow-up time of 19 months. The follow-up endpoint events including recurrent ischemic stroke (RIS), intracranial hemorrhage (ICH), transient ischemic attack (TIA), mortality, and cardiovascular events. The associations between vascular risk factors and CMBs in IS patients were analyzed using univariate and multivariate logistic regression analysis. Cox regression model was employed for evaluating CMB impact on clinical outcome.Results: Among 459 enrolled patients, 187 (40.7%) had CMBs and 272 (59.2%) had no CMB. In comparison with patients with no CMBs, age was higher and hypertension was more frequent in patients with CMBs. Multivariate logistic regression analyses revealed age and hypertension were independently associated with the presence of CMBs. Among the patient cohort, 450 cases completed the follow-up. During the follow-up period, 22 (4.9%) of patients developed ICH, 12 (2.7%) developed TIA, 68 (15.1%) developed RIS, cardiovascular events occurred in 20 (4.44%), and 13 (2.89%) cases were mortalities. Compared with patients without CMBs, IS patients with CMBs have an increased prevalence of ICH (p < 0.05). However, no statistically valid variations regarding other outcome incidences between both groups was identified (p > 0.05). The incidence of ICH was elevated in tandem with elevations in number of CMBs. Following adjusting for age, multivariate Cox proportional-hazards regression analysis revealed that CMBs ≥10 were independent predictors of ICH in acute IS patients.Conclusion: Age and hypertension are independently associated with the presence of CMBs. Intracranial hemorrhage incidence rate was increased with the number of CMBs, and the number of CMBs ≥10 were independent predictors of ICH in acute stroke patients.

Association between high systolic blood pressure and objective hearing impairment among Japanese adults: a facility-based retrospective cohort study.

This retrospective longitudinal study examined the association between systolic blood pressure and hearing impairment among 13,187 Japanese individuals (men, 46.5%) aged 20-59 years. The systolic blood pressure of participants was categorized as <120, 120-129, 130-139, 140-149, 150-159, and ≥160 mmHg. Using pure-tone audiometry, hearing impairment at 1 and 4 kHz was defined as hearing thresholds in either ear >30 and >40 dB, respectively. We performed multivariable Cox proportional-hazards regression analysis to examine the association using two multiple-imputation methods (fully conditional specification and Markov chain Monte Carlo). There were 695 and 774 hearing-impairment cases at 1 and 4 kHz, respectively, during ~77,000 person-years of follow-up. Compared with the <120 mmHg group, the hazard ratios (95% confidence intervals) of hearing impairment for the 120-129, 130-139, 140-149, 150-159, and ≥160 mmHg groups after adjustment for age, sex, body mass index, high serum glucose, current smoking, and other potential confounders were 1.35 (1.12-1.63), 1.45 (1.13-1.86), 1.07 (0.73-1.58), 1.91 (1.18-3.07), and 1.81 (1.01-3.25), respectively, at 1 kHz using the first imputation method; 1.36 (1.13-1.63), 1.48 (1.17-1.86), 1.09 (0.76-1.58), 1.99 (1.29-3.06), and 1.92 (1.08-3.41), respectively, at 1 kHz using the second imputation method; 1.04 (0.86-1.24), 1.14 (0.91-1.43), 1.13 (0.83-1.54), 1.45 (0.96-2.19), and 1.35 (0.82-2.23), respectively, at 4 kHz using the first imputation method; and 1.03 (0.86-1.24), 1.17 (0.95-1.44), 1.15 (0.87-1.53), 1.54 (1.06-2.24), and 1.44 (0.88-2.35), respectively, at 4 kHz using the second imputation method. In conclusion, higher systolic blood pressure was associated with hearing impairment at 1 kHz. No clear association was observed at 4 kHz.

The utility of geriatric nutritional risk index to predict outcomes in chronic limb-threatening ischemia.

To assess geriatric nutritional risk index (GNRI) in patients with chronic limb-threatening ischemia (CLTI). The prevalence of CLTI continues to rise, with major amputation and mortality remaining prominent. Frailty is a vital risk factor for adverse outcomes in cardiovascular care. The GNRI is a nutrition-based surrogate for frailty that has been utilized in Southeast Asia to predict adverse events in CLTI. It has not yet been evaluated in a primarily Western population, nor in the context of wound healing. Between 8August 2017 and April 2019, we identified patients undergoing endovascular interventions for CLTI at our institution, categorized into low GNRI (≤ 94, frail) versus normal GNRI (> 94, reference). We analyzed the risks of major adverse limb events (MALE), its individual components [mortality, major amputation, and target vessel revascularization (TVR)], amputation free survival (AFS), and wound healing using Kaplan-Meier and multivariate cox-proportional hazard regression analyses. A total of 255 patients were included in the analysis, with follow up of 14 ± 9.1months. Lower GNRI was associated with higher cumulative event rates for MALE (71.0% vs. 43.3%, p< 0.001), mortality (34.3% vs. 15.2%, p< 0.001), major amputation (31.2% vs. 15.8%, p= 0.002), and freedom from AFS (56.0% vs. 28.2%, p< 0.001). There was a trend toward lower TVR and higher wound healing with higher GNRI score. Our single-center, retrospective evaluation of GNRI (as a surrogate for frailty) correlated with increased risks of MALE, mortality, and major amputation. Future directions should focus not only on the recognition of these patients, but risk-factor modification to optimize long-term outcomes.

Prognostic Significance of Preoperative Tumor Markers in Pseudomyxoma Peritonei from Low-Grade Appendiceal Mucinous Neoplasm: a Study from the US HIPEC Collaborative

BackgroundTumor markers are commonly utilized in the diagnostic evaluation, treatment decision making, and surveillance of appendiceal tumors. In this study, we aimed to determine the prognostic significance of elevated preoperative tumor markers in patients with pseudomyxoma peritonei secondary to low-grade appendiceal mucinous neoplasm who underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. MethodsUsing a multi-institutional database, eligible patients with measured preoperative tumor markers [carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA 19-9), or cancer antigen 125 (CA-125)] were identified. Univariate and multivariate Cox-proportional hazards regression analysis assessed relationships between normal and elevated serum tumor markers with progression-free and overall survival in the context of multiple clinicopathologic variables. ResultszTwo hundred and sixty-four patients met criteria. CEA was the most commonly measured tumor marker (97%). Patients who had any elevated tumor marker had a higher peritoneal carcinomatosis index (PCI) as compared to those with normal range markers. Elevated CEA and CA 19-9 levels were individually associated with longer inpatient length of stay, requirement for intraoperative transfusion, and incomplete cytoreduction. Utilization of neoadjuvant chemotherapy, increased PCI score, elevated CA 19-9 (p = 0.007), and CA-125 levels (p = 0.01) were predictive of decreased progression-free survival on univariate analysis. However, in a multivariate model, only elevated PCI was a statistically significant predictor of progression-free survival. ConclusionElevated preoperative tumor markers indicate a higher burden of disease but are not independently associated with survival in this retrospective multi-institutional cohort. Further prospective studies are needed to clarify the utility of these markers in this patient population.

Prognostic factors for overall survival in patients with clear cell metastatic renal cell carcinoma: Model development and external validation with Memorial Sloan Kettering Cancer Center model and the international metastatic renal cell carcinoma database consortium model.

To develop a new prognostic model for the overall survival of patients with clear cell metastatic renal cell carcinoma (mRCC) using Korean Renal Cancer Study Group (KRoCS) database and compared it with 2 renowned prognostic models: the Memorial Sloan Kettering Cancer Center (MSKCC) and the international metastatic renal cell carcinoma database consortium (IMDC) models.Data of 790 patients diagnosed with mRCC and receiving targeted therapy as their first-line treatment were pooled to this study. Data from 4 hospitals (n = 619) were used to develop the new model and those from other 5 hospitals (n = 171) were used for external validation. After detecting prognostic factors in multivariable Cox proportional-hazards regression analysis, patients were classified into 3 risk groups, favorable (0), intermediate (1–2), and poor (3 and more) by the number of prognostic factors.Seven variables such as more than 2 metastasis sites, no prior nephrectomy, Eastern Cooperative Oncology Group performance status ≥2, low hemoglobin, high serum corrected calcium, high neutrophil, high serum alkaline phosphatase were identified as prognostic factors for poor overall survival. Also, risk groups were categorized into 3 groups; median overall survival was 61.1 months in favorable, 26.5 months in intermediate, and 6.8 months in poor group. KRoCS ranked the first in all 3 statistical parameters including akaike information criterion (AIC), concordance index and generalized R2 among other prognostic models.We developed the KRoCS model and validated it externally with demonstrating its superiority over MSKCC and IMDC models. The KRoCS model can provide useful information for counseling patients with clear cell mRCC regarding life-expectancy.

Long-term outcomes of peripheral arterial disease patients with significant coronary artery disease undergoing percutaneous coronary intervention.

Patients with peripheral arterial disease (PAD) have known to a high risk of cardiac mortality. However, the effectiveness of the routine evaluation of coronary arteries such as routine coronary angiography (CAG) in PAD patients receiving percutaneous transluminal angioplasty (PTA) is unclear. A total of 765 consecutive PAD patients underwent successful PTA and 674 patients (88.1%) underwent routine CAG. Coronary artery disease (CAD) was defined as angiographic stenosis ≥70%. Patients were divided into three groups; 1) routine CAG and a presence of CAD (n = 413 patients), 2) routine CAG and no CAD group (n = 261 patients), and 3) no CAG group (n = 91 patients). To adjust for any potential confounders that could cause bias, multivariable Cox-proportional hazards regression and propensity score matching (PSM) analysis was performed. Clinical outcomes were evaluated by Kaplan-Meier curved analysis at 5-year follow-up. In this study, the 5-year survival rate of patients with PAD who underwent PTA was 88.5%. Survival rates were similar among the CAD group, the no CAD group, and the no CAG group, respectively (87.7% vs. 90.4% vs. 86.8% P = 0.241). After PSM analysis between the CAD group and the no CAD group, during the 5-year clinical follow-up, there were no differences in the incidence of death, myocardial infarction, strokes, peripheral revascularization, or target extremity surgeries between the two groups except for repeat PCI, which was higher in the CAD group than the non-CAD group (9.3% vs. 0.8%, P<0.001). PAD patients with CAD were expected to have very poor long-term survival, but they are shown no different long-term prognosis such as mortality compared to PAD patients without CAD. These PAD patients with CAD had received PCI and/or optimal medication treatment after the CAG. Therefore a strategy of routine CAG and subsequent PCI, if required, appears to be a reasonable strategy for mortality risk reduction of PAD patients. Our results highlight the importance for evaluation for CAD in patients with PAD.

Survival time to first antenatal care visit and its predictors among women in Ethiopia.

BackgroundFirst-trimester pregnancy stage is the fastest developmental period of the fetus, in which all organs become well developed and need special care. Yet, many women make their first antenatal visit with the pregnancy already compromised due to fetomaternal complications. This study aimed to fill this dearth using the 2016 national representative data set to augment early antenatal care visits in Ethiopia.MethodsA cross-sectional study design using the 2016 Ethiopia Demographic and Health Survey (EDHS) data set. Kaplan-Meir estimate was used to explain the median survival time of the timing of the first ANC visit. Multivariate Cox-proportional hazard regression analysis was performed to identify the factors related to the timing of the first ANC visit. Adjusted hazard ratios (AHR) with a 95% Confidence interval (CI) plus a p-value of < 0.05 were considered to declare a statistically significant association.ResultsData for 4666 study participants who had ANC follow-up history during pregnancy were included in the study and analyzed. The overall median survival time in this study was seven months. The timing of the first ANC visit was shorter by 2.5 times (AHR: 2.5; 95% CI: 2.34–3.68), 4.3 times (AHR: 4.3; 95% CI: 2.2–7.66), 4.8 times (AHR: 4.8, 95% CI: 4.56–10.8) among women who attended primary, secondary, and higher education as compared with non-educated one. Similarly, women who were residing in urban areas had 3.6 times (AHR: 3.6; 95% CI: 2.7–4.32) shorter timing of first ANC visit than rural residents. Furthermore, the timing of the first visit among the richest women was 3.2 times (AHR: 3.2; 95% CI: 2.5–9.65) shorter than the poorest women.ConclusionThe median survival time of the first ANC visit was seven months. The timing of the first ANC was longer among younger, poorer women, those who had no access to media, who considered distances as a big challenge to reach a health facility and, those with no education. Therefore, health care providers and community health workers should provide health education to create community awareness regarding the timing of the first ANC visit.

Introduction of rectosigmoid colectomy improves survival outcomes in early-stage ovarian cancer patients.

To investigate whether rectosigmoid colectomy can improve the prognosis of patients with early-stage ovarian cancer when the ovarian tumor adheres to the rectum. We retrospectively studied 210 consecutive patients with stage I/II ovarian cancer treated between 2000 and 2016. The surgical strategy differed between the periods 2000-2007 and 2008-2016 with respect to adhesion between the ovarian tumor and rectum. In the former period, ovarian tumor was exfoliated from the rectum. Only when the residual tumor was apparently observed on the rectal surface after salpingo-oophorectomy with hysterectomy, it was subsequently removed by colorectal surgeons performing rectosigmoid colectomy. In the latter period, the ovarian tumor was resected en bloc with the rectum by performing rectosigmoid colectomy. We compared the progression-free survival (PFS) between the two treatment periods. Rectosigmoid colectomy was performed more frequently in the latter period than in the former period (43 patients, 31% vs. 6 patients, 8%, p < 0.001). There was no significant difference in complete resection rate between the two periods (97% in the former period, 99% in the latter period, p = 0.278). However, the 5-year PFS rate was significantly higher in the latter period than in the former period (86.0% vs. 74.4%, log-rank test, p = 0.034). Multivariate Cox proportional-hazards regression analysis indicated that disease stage (hazard ratio [HR], 2.87, 95% confidence interval [CI] 1.14-7.34) and treatment period (HR 0.32, 95% CI 0.14-0.73) were independent risk factors for recurrence. Rectosigmoid colectomy could improve the prognosis of patients with early-stage ovarian cancer when the ovarian tumor adheres to the rectum.

Periodontitis and the outcome of atrial fibrillation ablation: Porphyromonas gingivalis is related to atrial fibrillation recurrence.

Inflammation is one of the main causes of atrial fibrillation (AF) recurrence after ablation. Porphyromonas gingivalis is a key periodontal pathogen in the oral-systemic disease connection and serum immunoglobulin G (IgG) antibody titers against P. gingivalis reflect the clinical status of periodontitis. This study aimed to investigate the relationship between late recurrence of AF after radiofrequency catheter ablation (RFCA) and serum IgG antibody titers against P. gingivalis. A total of 596 AF patients (mean age, 64.9 ± 10.0 years; 69% male; 61% paroxysmal AF) who underwent a first session of RFCA were enrolled. Patients were carefully examined for late recurrence during a mean follow-up period of 17.1 ± 14.5 months. Serum IgG antibody titers against P. gingivalis (types I-IV) were measured using enzyme-linked immunosorbent assay. The results of serum antibody titers were divided into a high-value and a low-value group. Among the five P. gingivalis subtypes, serum antibody titer against P. gingivalis type IV was associated with late recurrence (odds ratio, 1.937; 95% confidence interval [CI], 1.301-2.884; p = .002). Multivariate Cox proportional-hazards regression analysis revealed that high-value serum antibody titer against P. gingivalis type IV independently predicted late recurrence (paroxysmal AF: adjusted hazard ratio [HR], 1.569; 95% CI, 1.010-2.427; p = .04; non-paroxysmal AF: adjusted HR, 1.909; 95% CI, 1.213-3.005; p = .004). Periodontitis was related to the late recurrence of AF after RFCA. P. gingivalis type IV may be pathogenic for AF recurrence after RFCA.

PETCO2 gradient: a novel prognostic parameter in cardiopulmonary exercise testing

Abstract Background Previous parameters such as peak VO2, VE/VCO2 slope and OUES have been described to be prognostic in heart failure (HF). The aim of this study was to identify further prognostic factors of cardiopulmonary exercise testing (CPET) in HF patients. Methods A retrospective analysis of HF patients who underwent CPET from January to November 2019 in a single centre was performed. PETCO2 gradient was defined by the difference between final PETCO2 and baseline PETCO2. HF events were defined as decompensated HF requiring hospital admission or IV diuretics, or decompensated HF resulting in death. Results A total of 64 HF patients were assessed by CPET, HF events occurred in 8 (12.5%) patients. Baseline characteristics are shown in table 1. Patients having HF events had a negative PETCO2 gradient while patients not having events showed a positive PETCO2 gradient (−1.5 [IQR −4.8, 2.3] vs 3 [IQR 1, 5] mmHg; p=0.004). A multivariate Cox proportional-hazards regression analysis revealed that PETCO2 gradient was an independent predictor of HF events (HR 0.74, 95% CI [0.61–0.89]; p=0.002). Kaplan-Meier curves showed a significantly higher incidence of HF events in patients having negative gradients, p=0.002 (figure 1). Conclusion PETCO2 gradient was demonstrated to be a prognostic parameter of CPET in HF patients in our study. Patients having negative gradients had worse outcomes by having more HF events. Time to first event, decompensated heart Funding Acknowledgement Type of funding source: None

Ventricular stroke work indices to predict mortality after successful percutaneous edge-to-edge-repair for severe mitral valve regurgitation

Abstract Background Several studies identified predictors of worse clinical outcome despite successful transcatheter mitral valve repair (TMVR). The capability of invasively measured left and right ventricular stroke work indices (LVSWi, RVSWi) to predict mortality after successful TMVR is unclear. Purpose To assess the impact of LVSWi and RVSWi on mortality in patients with chronic heart failure (CHF) and severe mitral regurgitation (MR) undergoing TMVR. Methods Consecutive patients (pts.) with CHF (LV ejection fraction ≤50% from any cause) and severe MR who underwent successful TMVR (MR≤2+ at discharge) were included and followed prospectively. Primary endpoint was defined as all-cause mortality during a median follow-up period of 16±9 months. LVSWi was calculated as: Stroke volume index × (mean arterial pressure − postcapillary wedge pressure) × 0.0136 = g/m–1/m2. RVSWi was calculated as: Stroke volume index × (mean pulmonary artery pressure − right atrial pressure) × 0.0136 = g/m–1/m2. Receiver operator characteristic (ROC) analysis was used to determine discriminative capacity of LVSWi and RVSWi. Kaplan-Meier estimate was used for survival analysis. A multivariable Cox proportional-hazards regression analysis was performed to identify independent risk factors for all-cause mortality. Results 140 patients (median age 74±9.9 years, 67.9% male) at high operative risk (LogEuro-SCORE 34.6±14.1%) were enrolled. Mean LVSWi and RVSWi were 22.3±10.7 g/m–1/m2 and 8.9±4.1 g/m–1/m2, respectively. 46 pts. died (33.1%). Pts. who died presented higher LogEuro-SCORE (27.8±16.6% vs. 20.1±13.7%; p=0.001), higher levels of NT-proBNP (12121±10602 ng/l vs. 6745±10820 ng/l; p=0.001), higher levels of creatinine (1.8±0.8 mg/dl vs. 1.4±0.8 mg/dl; p&amp;lt;0.001), lower LVSWi (18.9±8.1 g/m–1/m2 vs. 24.0±11.4 g/m–1/m2; p=0.01) and RVSWi (7.8±3.2 g/m–1/m2 vs. 9.4±4.4 g/m–1/m2; p=0.037), respectively. ROC curve analysis revealed that optimal sensitivity and specificity were achieved using a threshold of 24.8 g/m–1/m2 for LVSWi (sensitivity 80.4%, specificity 40.2%, area under the curve (AUC) 0.71 [0.60–0.81]; p=0.001) and 8.3 g/m–1/m2 for RVSWi (sensitivity 67.4%, specificity 57.0%, AUC 0.67 [0.56–0.78]; p=0.006), respectively. At long-term follow-up, a significantly lower survival rate was observed in pts. with LVSWi ≤24.8 g/m–1/m2 (20.0% vs. 39.4%; log-rank p=0.038) and in pts. with RVSWi ≤8.3 g/m–1/m2 (22.1% vs. 43.7%; log-rank p=0.026), respectively. In Cox regression analysis a LVSWi of ≤24.8 g/m–1/m2 and a RVSWi of ≤8.3 g/m–1/m2 were independent predictors for all-cause mortality (hazard ratio (HR) 2.83; 95% confidence interval (CI) 1.1 to 7.6; p=0.04; HR 2.52; 95% CI 1.04 to 6.1; p=0.041). Conclusions LVSWi and RVSWi are associated with mortality among pts. with CHF undergoing successful TMVR for severe MR. A LVSWi cut-off value of &amp;gt;24g/m–1/m2 and a RVSWi cut-off value of &amp;lt;8g/m–1/m2 seem to predict mortality independent of other clinical and echocardiographic factors. Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): Hospital Links der Weser, Bremen, Germany

Simple cardiovascular risk stratification using anthropometric measures instead of serum cholesterol. The MORGAM Prospective Cohort Project

Abstract Background Body composition predicts cardiovascular outcomes, but it is uncertain whether anthropometric measures can replace the more expensive serum total cholesterol for cardiovascular risk stratification in low resource settings. Purpose The purpose of the study was to compare the additive prognostic ability of serum total cholesterol with that of body mass index (BMI), waist/hip ratio (WHR), and estimated fat mass (EFM, calculated using a validated prediction equation), individually and combined. Methods We used data from the MORGAM (MONICA, Risk, Genetics, Archiving, and Monograph) Prospective Cohort Project, an international pooling of cardiovascular cohorts, to determine the relationship between anthropometric measures, serum cholesterol, and cardiovascular events, using multivariable Cox proportional-hazards regression analysis. We further investigated the ability of these measures to enhance prognostication beyond a simpler prediction model, consisting of age, sex, smoking status, systolic blood pressures, and country, using comparison of area under the receiver operating characteristics curve (AUCROC) derived from binary logistic regression models. The primary endpoint was major adverse cardiovascular events (MACE), defined as a composite of death from coronary heart disease, myocardial infarction, or stroke. Results The study population consisted of 52,188 apparently healthy subjects (56.3% men) aged 47±12 years ranging from 20 to 84, derived from 37 European cohorts, with baseline between 1982–2002 all followed for 10 years during which MACE occurred in 2465 (4.7%) subjects. All anthropometric measures (BMI: hazard ratio (HR) 1.04 [95% confidence interval (CI): 1.03–1.05] per kg/m2; WHR: HR 7.5 [4.0–14.0] per unit; EFM: HR 1.02 [1.01–1.02] per kg) as well as serum total cholesterol (HR 1.20 [1.16–1.24] per mmol/l) were significantly associated with MACE (P&amp;lt;0.001 for all), independently of age, sex, smoking status, systolic blood pressures, and country. The addition of serum cholesterol significantly improved the predictive ability of the simple model (AUCROC 0.818 vs. 0.814, P&amp;lt;0.001), as did the combination of WHR, BMI, and EFM (AUCROC 0.817 vs. 0.814, P=0.004). When assessed individually, BMI (AUCROC 0.816 vs. 0.814, P=0.004) and WHR (AUCROC 0.815 vs. 0.814, P=0.02) improved model performance, while EFM narrowly missed significance (AUCROC 0.815 vs. 0.814, P=0.06). There was no significant difference in the predictive ability of a model including serum cholesterol versus that including all three anthropometric measures (AUCROC 0.818 vs. 0.817, P=0.13). The figure shows the pertinent areas under the ROC curve in predicting MACE. Conclusion In this large population-based cohort study, the addition of a combination of anthropometric measures, i.e. BMI, WHR, and EFM, raised the predictive ability of a simple prognostic model comparable to that obtained by the addition of serum total cholesterol. Figure 1 Funding Acknowledgement Type of funding source: None

Gustave Roussy Immune Score based on a three-category risk assessment scale serves as a novel and effective prognostic indicator for surgically resectable early-stage non-small-cell lung cancer: A propensity score matching retrospective cohort study

BackgroundsThe Gustave Roussy Immune score (GRIm-Score) emerges as a novel prognostic scoring system for patient selection in phase I trials testing targeted immunotherapy for advanced-stage cancer. We tried to assess potential prognostic roles of preoperative GRIm-Score in patients undergoing video-assisted thoracoscopic surgery (VATS) lobectomy for stage I-II non-small-cell lung cancer (NSCLC) by propensity score-matching (PSM) analysis. MethodsThis PSM-based analysis was performed on our single-center prospectively-maintained database between January 2014 and October 2015. A Kaplan-Meier survival analysis using the log-rank test was used to distinguish differences in both overall survival (OS) and disease-free survival (DFS) between the patients stratified by preoperative GRIm-Score. Multivariable Cox-proportional hazards regression analysis and PSM analysis were both carried out to determine the final independent prognostic parameters. ResultsThere were 405 patients with surgically resectable stage I-II NSCLC included. Both OS and DFS were significantly shortened along with each number increase in the GRIm-Score group, showing a step-wise fashion. Such strong correlations between preoperative GRIm-Score estimated by a modified 3-category risk scale and survival outcomes still remained validated after PSM analysis. In addition, this GRIm-Score held the superior discriminatory power for predicting both OS and DFS to the other peripheral blood biomarkers. Multivariable analyses on the entire cohort and the PSM cohort demonstrated that GRIm-Score based on a 3-category risk assessment scale could be independently predictive of both OS and DFS. ConclusionsThe GRIm-Score tool can also serve as an effective and noninvasive marker to optimize prognostic prediction for surgically resectable stage I-II NSCLC.

A Predictive Model for Super-Response to Cardiac Resynchronization Therapy: The QQ-LAE Score.

Objectives It is important to identify super-responders who can derive most benefits from cardiac resynchronization therapy (CRT). We aimed to establish a scoring model that can be used for predicting super-response to CRT. Methods We retrospectively reviewed 387 CRT patients. Multivariate logistic regression analysis was performed to identify predictors for super-response (defined as an absolute increase in left ventricular ejection fraction of ≥15% at 6-month follow-up) and to create a score model. Multivariate Cox proportional-hazard regression analysis was conducted to assess associations with the long-term endpoint (defined as cardiac death/heart transplant, heart failure (HF) hospitalization, or all-cause death) across the score categories at follow-up. Results Among 387 patients, 109 (28.2%) met super-response. In multivariable analysis, 5 independent predictors (QQ-LAE) were identified: prior no fragmented QRS (odds ratio (OR) = 3.10 (1.39, 6.94)), QRS duration ≥170 ms (OR = 2.37 (1.35, 4.12)), left bundle branch block (OR = 2.57 (1.04, 6.37)), left atrial diameter <45 mm (OR = 3.27 (1.81, 5.89)), and left ventricular end-diastolic dimension <75 mm (OR = 4.11 (1.99, 8.48)). One point was attributed to each predictor, and three score categories were identified. The proportion of super-response after 6-month CRT implantation in patients with scores 0–3, 4, and 5 was 14.6%, 40.3%, and 64.1%, respectively (P < 0.001). Patients with score 5 had an 88% reduction in the risk of cardiac death/heart transplant (P=0.042), a 71% reduction in the risk of HF hospitalization (P=0.048), and an 89% reduction in the risk of all-cause mortality (P=0.028) compared to patients with scores 0–3. Conclusions The QQ-LAE score can be used for prediction of super-response to CRT and selection of most suitable patients in clinical practices.

Low Geriatric Nutritional Risk Index as a Poor Prognostic Marker for Second-Line Pembrolizumab Treatment in Patients with Metastatic Urothelial Carcinoma: A Retrospective Multicenter Analysis

Background: We evaluated the prognostic efficacy of the Geriatric Nutritional Risk Index (GNRI) in second-line pembrolizumab (PEM) therapy for patients with metastatic urothelial carcinoma (mUC). Patients and Methods: From January 2018 to October 2019, 52 mUC patients, treated previously with platinum-based chemotherapy, underwent second-line PEM therapy. Peripheral blood parameters were measured at the start of treatment: serum neutrophil-to-lymphocyte ratio (NLR), serum albumin, serum C-reactive protein (CRP), and body height and weight. PEM was intravenously administered (200 mg every 3 weeks). The patients were organized into two groups based on their GNRI (<92 [low GNRI] and ≥92 [high GNRI]), and the data were retrospectively analyzed. Adverse events (AEs) were evaluated and imaging studies assessed for all patients. Analyses of survival and recurrence were performed using Kaplan-Meier curves. Potential prognostic factors affecting cancer-specific survival (CSS) were assessed by univariate and multivariate Cox regression analyses. Results: patients’ baseline characteristics, except for their BMI and objective response rate, did not significantly differ between the two groups. The median total number of cycles of PEM therapy was significantly higher for the high-GNRI group (n [range]: 6 [2–20] vs. 3 [1–6]). The median CSS with second-line PEM therapy was 3.6 months (95% confidence interval [CI]: 2.5–6.1) and 11.8 months (95% CI: 6.2–NA) in the low-GNRI and the high-GNRI group (p < 0.01), respectively. Significant differences in CSS between the low- and high-CRP or -NRL groups were not found. Multivariate Cox proportional-hazards regression analysis revealed that a poor Eastern Cooperative Oncology Group performance status, visceral metastasis, and a low GNRI were significant prognostic factors for short CSS (95% CI: 1.62–6.10, HR: 3.14; 95% CI: 1.13–8.11, HR: 3.03; 95% CI: 1.32–8.02, HR: 3.25, respectively). Of the AEs, fatigue showed a significantly higher incidence in the low-GNRI group. Conclusions: For mUC patients receiving second-line PEM therapy, the GNRI is a useful predictive biomarker for survival outcome.

Naples Prognostic Score as a novel prognostic prediction tool in video-assisted thoracoscopic surgery for early-stage lung cancer: a propensity score matching study.

The Naples Prognostic Score (NPS) emerges as a novel prognostic scoring system in surgical oncology. We aim to assess the prognostic significance of preoperative NPS in patients undergoing completely video-assisted thoracoscopic surgery (VATS) lobectomy for early-stage non-small cell lung cancer (NSCLC) by propensity score matching (PSM) analysis. The present study was conducted on our single-center prospectively maintained database between January 2014 and December 2015. A Kaplan-Meier survival analysis using the log-rank test was used to distinguish differences in both overall survival (OS) and disease-free survival (DFS) between the patients stratified by preoperative NPS. Finally, multivariable Cox-proportional hazards regression analysis and PSM analysis were carried out to determine the independent prognostic factors for both OS and DFS. There were 457 patients with operable primary stage I-II NSCLC included. Per 1-point increase in NPS was found to be significantly associated with unfavorable OS and DFS of NSCLC. Both OS and DFS were significantly shortened along with each number increase in the NPS group, showing a step-wise fashion. Such strong correlations between preoperative NPS and survival outcomes still remained validated after PSM analysis. In addition, NPS held the best discriminatory power for predicting both OS and DFS when compared to the other peripheral biomarkers. Multivariable analyses on the entire cohort and the PSM cohort demonstrated that preoperative NPS could be an independent prognostic indicator for both OS and DFS. The NPS scoring system can serve as a novel risk stratification tool to refine prognostic prediction after VATS lobectomy for surgically resected NSCLC.

Left Atrial Structure and Function Predictors of New-Onset Atrial Fibrillation in Patients with Chagas Disease

Atrial fibrillation (AF) carries ominous consequences in patients with Chagas disease. The aim of this study was to determine whether left atrial (LA) volume and function assessed using three-dimensional echocardiographic (3DE) imaging and two-dimensional speckle-tracking echocardiographic deformation analysis of strain (ε) could predict new-onset AF in patients with Chagas disease. A total of 392 adult patients with chronic Chagas disease (59% women; mean age, 53±11years) who underwent echocardiography were consecutively enrolled in this prospective longitudinal study. Echocardiographic evaluation included two-dimensional (2D) Doppler echocardiography, with evaluation of left ventricular systolic and diastolic function, LA size, and LA and left ventricular function on 3DE and ε analyses. Multivariate Cox proportional-hazards regression analysis models adjusting for age, sex, hypertension, presence of a pacemaker, and 2D Doppler echocardiographic parameters were used to test if the variables of interest had independent prognostic value for AF prediction. Patients with Chagas disease were followed for 5.6±2.7years. Among these, 139 (35.5%) had the indeterminate form, 224 (57.1%) had the cardiac form, five (1.3%) had the digestive form, and 24 (6.1%) had the cardiodigestive form. The study end point of AF occurred in 45 patients. Total LA emptying fraction (hazard ratio, 0.93; 95% CI, 0.89-0.98; P=.002), passive LA emptying fraction (HR, 0.95; 95% CI, 0.91-0.99; P=.02), and peak negative global LA ε (HR, 1.22; 95% CI, 1.05-1.41; P=.01) were predictors of new-onset AF independent of clinical and 2D Doppler echocardiographic parameters. LA function assessed on 3DE and ε analyses predicts new-onset AF in patients with Chagas disease independent of clinical and 2D Doppler echocardiographic indexes.

Prognostic value of CHADS2 and CHA2DS2-VASc scores for post-discharge outcomes in patients with acute coronary syndrome undergoing percutaneous coronary intervention.

The CHADS2 and CHA2DS2-VASc scores were initially developed to assess the risk of stroke or systemic embolism in patients with atrial fibrillation (AF). Recently, these two scoring systems have been demonstrated to predict long- and short-term cardiovascular (CV) outcomes in many patient cohorts. However, to the best of our knowledge, their prognostic value has not been fully elucidated in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). This study aimed to investigate the association of CHADS2 and CHA2DS2-VASc scores with CV outcomes in such patients.We included a total of 915 ACS patients undergoing PCI in this study. CHADS2 and CHA2DS2-VASc scores were calculated from data collected before discharge. The primary endpoint was defined as a composite of major adverse CV events (MACE) including overall death, nonfatal stroke, nonfatal myocardial infarction (MI) and unplanned repeat revascularization. We assessed MACE's relationship to CHADS2 and CHA2DS2-VASc scores using Cox proportional-hazard regression analyses.Mean follow-up duration was 918 days. MACE occurred in 167 (18.3%) patients. A higher CHADS2 score was associated with reduced event-free survival (EFS) from MACE (logrank test, P = .007) with differences potentiated if stratified by CHA2DS2-VASc score (logrank test, P < .001). Univariate analysis showed that both CHADS2 and CHA2DS2-VASc scores were good predictors of MACE. In the multivariate Cox proportional-hazard regression analysis, CHA2DS2-VASc score (hazard ratio [HR], 1.15; 95% confidence interval [CI] 1.04–1.27; P = .007) remained a useful predictor of MACE; however, CHADS2 score was no longer associated with increased risk of MACE. C-statistics for CHA2DS2-VASc score, GRACE (Global Registry of Acute Coronary Events) hospital discharge risk score (GRACE Score) and SYNTAX (Synergy between PCI with TAXUS and Cardiac Surgery) Score II (SS II) in predicting MACE were 0.614, 0.598, and 0.609, respectively.CHA2DS2-VASc score was an independent and significant predictor of MACE in ACS patients undergoing PCI, and its discriminatory performance was not inferior to those of GRACE Score and SS II.

Prognostic Implications of Immune-Related Genes' (IRGs) Signature Models in Cervical Cancer and Endometrial Cancer.

Cervical cancer and endometrial cancer remain serious threats to women’s health. Even though some patients can be treated with surgery plus chemoradiotherapy as a conventional option, the overall efficacy is deemed unsatisfactory. As such, the development for new treatment approaches is truly necessary. In recent years, immunotherapy has been widely used in clinical practice and it is an area of great interest that researchers are keeping attention on. However, a thorough immune-related genes (IRGs) study for cervical cancer and endometrial cancer is still lacking. We therefore aim to make a comprehensive evaluation of IRGs through bioinformatics and large databases, and also investigate the relationship between the two types of cancer. We reviewed the transcriptome RNAs of IRGs and clinical data based on the TCGA database. Survival-associated IRGs in cervical/endometrial cancer were identified using univariable and multivariable Cox proportional-hazard regression analysis for developing an IRG signature model to evaluate the risk of patients. In the end, this model was validated based on the enrichment analyses through GO, KEGG, and GSEA pathways, Kaplan-Meier survival curve, ROC curves, and immune cell infiltration. Our results showed that out of 25/23 survival-associated IRGs for cervical/endometrial cancer, 13/12 warranted further examination by multivariate Cox proportional-hazard regression analysis and were selected to develop an IRGs signature model. As a result, enrichment analyses for high-risk groups indicated main enriched pathways were associated with tumor development and progression, and statistical differences were found between high-risk and low-risk groups as shown by Kaplan-Meier survival curve. This model could be used as an independent measure for risk assessment and was considered relevant to immune cell infiltration, but it had nothing to do with clinicopathological characteristics. In summary, based on comprehensive analysis, we obtained the IRGs signature model in cervical cancer (LTA, TFRC, TYK2, DLL4, CSK, JUND, NFATC4, SBDS, FLT1, IL17RD, IL3RA, SDC1, PLAU) and endometrial cancer (LTA, PSMC4, KAL1, TNF, SBDS, HDGF, LTB, HTR3E, NR2F1, NR3C1, PGR, CBLC), which can effectively evaluate the prognosis and risk of patients and provide justification in immunology for further researches.