Multivariate Cox Survival Analysis Research Articles

A novel four‑snoRNA signature for predicting the survival of patients with uveal melanoma.

Uveal melanoma (UM), the predominant histological subtype of intraocular malignant tumors in adults, often results in high rates of mortality; effective prognostic signatures used to predict the survival of patients with UM are limited. Small nucleolar RNAs (snoRNAs) are emerging as important regulators in the processes of carcinogenesis and tumor progression, but knowledge of their application as prognostic markers in UM is limited. In the present study, the expression profiles of snoRNAs in UM were determined; a total of 60 snoRNAs were notably associated with the overall survival of patients with UM via univariate Cox survival analysis. Subsequently, a prognostic signature based on four snoRNAs was proposed, which retained their prognostic significance determined by a multivariate Cox survival analysis. The formula is as follows: ACA17 * (‑1.602) + ACA45 * 0.803 + HBII‑276 * 0.603 + SNORD12 * 1.348. Furthermore, the results of insilico analysis indicated that perturbation of the phototransduction, GABAergic synapse and amphetamine addiction pathways may be the potential molecular mechanisms underlying the poor prognosis of patients with UM. Collectively, the present study proposed a potential prognostic signature for patients with UM and the prospective mechanisms at the genome‑wide level were determined.

High Expression of CCDC34 Is Associated with Poor Survival in Cervical Cancer Patients.

BackgroundThe present study explored the expression of coiled-coil domain-containing 34 (CCDC34) in cervical cancer (CC) and its prognostic value.Material/MethodsGEPIA and Oncomine cancer databases were mined to predict the CCDC34 differential expression level between a CC group and a normal group. Immunohistochemistry was performed to examine the CCDC34 expression in 67 CC and corresponding adjacent tissues. CD31 and vascular endothelial growth factor (VEGF) were stained to reflect tumor angiogenesis in 67 CC tissues. Kaplan-Meier univariate and Cox multivariate survival analysis were done to evaluate the correlation between CCDC34 expression and prognosis of CC patients.ResultsBoth GEPIA and Oncomine cancer databases mining results revealed that CCDC34 was more highly expressed in the CC group than in the normal group (all P<0.05). Our immunochemical staining data showed that CCDC34 expression was dramatically higher in CC than in adjacent normal tissues (71.6 vs. 20.9%; P<0.001). High expression of CCDC34 was strongly associated with histological grade (P=0.022), lymph node metastasis (P=0.044), and FIGO stage (P=0.002). Furthermore, patients with CCDC34-positive expression had much more MVD than those with CCDC34-negative expression (P<0.001). Kaplan-Meier survival analysis showed that CCDC34-positive expression was associated with worse overall survival (OS) (P=0.004) and disease-free survival (DFS) (P=0.005). Additionally, Cox multivariate analysis revealed that CCDC34 was an independent unfavorable prognostic parameter of DFS and OS (P=0.040 and 0.039, respectively).ConclusionsHigh expression of CCDC34 is an independent unfavorable prognostic parameter for OS and DFS of CC patients, which was strongly associated with tumor angiogenesis.

Effectiveness of home based intervention program in reducing mortality of hip fracture patients: A non-randomized controlled trial

PurposeThe study was done to investigate whether a postoperative intervention program is effective in reducing mortality and improving mobility in two comparative hip fracture patients over one year postoperatively. MethodsA non-randomized controlled trial study with an intervention group of hip fracture patients and historical control group with 12 months follow up.One hundred twenty four admitted hip fracture patients to the Trauma Unit of Assiut University Hospitals, aged 50 years and older were included from 1st July to 31st December 2014. They were divided into 64 and 60 patients as intervention and control groups respectively. Weight, height and bone mineral density were measured and baseline characteristics were taken. The intervention was a postoperative care program in the form of education sessions with an explanatory leaflet on discharge for nutrition and physical exercise program at home. Follow up phone calls were done at 3 months, 6 months and one year postoperatively by one assessor. Physical mobility was assessed by 24 items Western Ontario And McMaster Universities Osteoarthritis Index (WOMAC). ResultsMortality was significantly higher in the control group, WOMAC score was significantly better among intervention group through follow up. By multivariate Cox survival analysis, advancing age, no intervention, osteoporosis, postoperative complications, chest infections and heart attacks were significant predictors for mortality. ConclusionA significant improvement in mobility and reduction of mortality was achieved by application of a postoperative care program that could be incorporated into the hip fracture patients' care pathway.

Prognostic significance of combined preoperative platelet-to-lymphocyte ratio and lymphocyte-to-monocyte ratio in patients undergoing surgery with stage IB non-small-cell lung cancer.

BackgroundResearch indicates that the presence of a systemic inflammatory response plays an important role in predicting survival in patients with cancer. The aim of this study was to investigate the prognostic value of preoperative neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), prognostic nutritional index, and the combination of preoperative LMR and PLR (LMR-PLR) in predicting the survival of patients with stage IB non-small-cell lung cancer (NSCLC).Materials and methodsWe retrospectively analyzed clinical data of 577 patients with stage IB NSCLC who underwent pneumonectomy from January 1999 to December 2009. Univariate and multivariate Cox survival analyses were used to evaluate the prognostic indicators, including LMR-PLR. The cutoff values for LMR and PLR were defined by the receiver operating characteristic (ROC) curve analysis. According to the ROC curve, the recommended cutoff values of LMR and PLR were 3.16 and 81.07, respectively. We divided the patients into three groups according to their LMR and PLR status and defined them with different scores. Patients with both high LMR (>3.16) and low PLR (≤81.07) were given a score of 2, whereas those with one or neither were scored 1 or 0, respectively. Survival curves were plotted using the Kaplan–Meier method and compared with the log-rank test. Cox proportional hazards analyses were used to identify the factors associated with overall survival (OS).ResultsThe median follow-up time was 93.77 months. The allocation of the LMR-PLR score was as follows: LMR-PLR = 0, 193 (33.4%) patients; LMR-PLR = 1, 308 (53.4%) patients; and LMR-PLR = 2, 76 (13.2%) patients. After multivariate analysis, our results showed that LMR-PLR was an independent prognostic indicator for OS (P=0.001). The 10-year OS rates were 70.0%, 60.4%, and 49.5% for LMR-PLR =2, LMR-PLR =1, and LMR-PLR =0, respectively (P<0.001).ConclusionThis study demonstrated that preoperative LMR and PLR are simple, readily available, and low-cost biomarkers. Preoperative LMR-PLR score can be used as a valuable prognostic marker for long-term survival in stage IB NSCLC patients who underwent surgery.

A novel prognostic signature of seven genes for the prediction in patients with thymoma

PurposeA thymoma is a tumor arising from the epithelium of the thymus, mostly occurring in the anterior mediastinum. The incidence of this disease is low and research progress in this field is slow. Consequently, there is an urgent need to investigate the correlation between molecular regulation and the prediction of survival and prognosis in patients with thymoma.MethodsWe collected thymoma datasets from The Cancer Genome Atlas (TCGA). Differentially expressed genes (DEGs) of TCGA datasets were then determined using R software. A gene signature was obtained by screening prognostic DEGs from the TCGA datasets using univariate and multivariate Cox survival analysis. The summation of the weighted expression levels was calculated as a risk score, which could then be used to predict the survival rate and prognosis of patients with thymoma. The validity of this model was verified by the analysis of receiver operating characteristic (ROC) curves and area under the curve (AUC).ResultsIn total, 297 DEGs were identified from the integrated results of TCGA datasets. A seven-gene signature, along with a regression model of prognostic risk, was obtained by Cox survival analysis. The expression levels of the seven genes were then weighted and summed to calculate the risk score for each sample. Patients were effectively divided into high- and low-risk groups using the median risk score (P < 0.05). ROC analysis showed that this Cox regression model was effective in predicting the prognosis of patients with thymus tumors (AUC = 0.983, P < 0.05).ConclusionFor the first time, we identified an effective seven-gene signature in patients with thymic tumors. In the future, the risk and prognosis of patients can be preliminarily assessed using this model, although further testing is required to improve rigor.

Epilepsy is not statistically associated with systemic sclerosis but significantly impacts on mortality: A real-world epidemiological survey-based study.

Little is known about the relationship between epilepsy and SSc. Our study included 2431 SSc patients and 12,710 age- and sex-matched controls. In 209 controls (1.6%) and 66 SSc patients (2.7%), epilepsy diagnosis was made (not significant). In the multivariate logistic regression analysis, higher age (OR 1.01 [95% CI 1.00-1.02], p=0.0207) was associated with an increased risk of epilepsy, whereas high vs low socioeconomic status (SES) (OR=0.62 [95% CI 0.42-0.92], p=0.0189) was associated with a low risk of epilepsy. In the Cox multivariate survival analysis, higher age (HR=1.06 [95% CI 1.06-1.07], p<0.0001), epilepsy (HR=2.28 [95% CI 1.77-2.94], p<0.0001) and SSc (HR=2.37 [95% CI 2.07-2.71], p<0.0001) were independent risk factors for all-cause mortality. In contrast, BMI >30kg/m2vs BMI <20kg/m2 (HR=0.69 [95% CI 0.59-0.81, p<0.0001]), female gender (HR=0.73 [95% CI 0.65-0.83], p<0.0001) and high SES (HR=0.72 [95% CI 0.63-0.82], p<0.0001) were protective factors for mortality. SSc-related autoantibodies were not associated with the risk of epilepsy. In conclusion, whilst epilepsy and SSc are not significantly associated, epilepsy is a predictor of mortality in SSc patients.

Characteristics and longer-term outcomes of paravalvular leak after aortic and mitral valve surgery

BackgroundParavalvular leak (PVL) is often seen after aortic (AV) and mitral valve (MV) surgery, either due to infection or valve dehiscence. We sought to describe predictors of longer-term outcomes in patients who developed PVL after AV and MV surgery and were considered eligible for reoperative cardiac surgery (RCS). MethodsWe studied 495 such patients (65 ± 14 years, 65% men, 47% with MV PVL) who presented at our center between January 2003 and December 2011. Patients with severe mitral/aortic stenosis, patients with less than mild PVL, and those with prohibitive risk precluding RCS were excluded. Society of Thoracic Surgeons (STS) score was calculated. Primary endpoint was mortality. ResultsAt baseline, mean STS score and left ventricular ejection fraction were 5.8 ± 4% and 52 ± 12%, respectively. In total, 105 (21%) had infective PVL and 72% had moderate or greater PVL. At a median of 8 days, 351 (71%) patients underwent RCS to repair PVL (3% in-hospital postoperative mortality), and at 6.6 ± 4 years, 230 (47%) patients died. On multivariable Cox survival analysis, greater STS score (hazard ratio or HR 1.35), mitral versus aortic PVL (HR 1.66), infectious etiology (HR 2.05), and greater right ventricular systolic pressure (HR 1.09) were associated with greater longer-term mortality, whereas surgery (HR 0.58) was associated with improved longer-term survival (all P < .05). ConclusionsPatients who develop mild or greater PVL after AV/MV surgery have a high rate of longer-term mortality, despite excellent perioperative outcomes. Greater STS score, right ventricular systolic pressure, infectious etiology, and MV (vs AV) involvement were all independently associated with long-term mortality, whereas RCS for PVL closure was associated with improved longer-term survival.

Chemoembolisation with polyvinyl alcohol for advanced hepatocellular carcinoma with portal vein tumour thrombosis and arterioportal shunts: efficacy and prognostic factors

To evaluate the efficacy and to identify prognostic factors of polyvinyl alcohol (PVA) chemoembolisation for treating advanced hepatocellular carcinoma (HCC) with portal vein (PV) tumour thrombosis (PVTT) and arterioportal shunts. The clinical data of 145 advanced HCC patients with PVTT and arterioportal shunts were collected. The patients were divided into two groups: group A, with main PV invasion, (n=56) and group B, with PV branch invasion, (n=89). Based on arterioportal shunt types, different particle sizes of PVA were used for chemoembolisation. The overall survival (OS), time to progression (TTP), and postoperative complications were analysed retrospectively. The median OS of all patients was 10.1 months. The median OS of group A and group B was 8.2 and 12.5 months, respectively (χ2=6.03, p=0.01). The overall 6-, 12-, and 18-month survival rates of groups A and B were 63.8%, 24.9%, and 6.3%, and 78.1%, 55.2%, and 23.7%, respectively. After embolisation, there were two cases of acute liver failure and three cases of upper gastrointestinal bleeding. Cox multivariate survival analysis revealed that main PVTT (HR [hazard ratio]=1.75, p=0.01), Child-Pugh B class (HR=1.99, p=0.003) and tumour burden ≥50% (HR=3.25, p<0.001) were independent risk factors. A dose of oxaliplatin >100 mg (HR=0.48, p<0.001) was an independent protection factor. Treatment of advanced HCC with PVTT and arterioportal shunts by PVA chemoembolisation is safe and effective. The patients achieved a better prognosis with the dose of oxaliplatin >100 mg, while main PVTT, Child-Pugh B class, and tumour burden ≥50% were poor prognostic indicators.

Alzheimer's Disease in Systemic Sclerosis Patients: A Nationwide Population-Based Cohort Study.

Neurological features are often overlooked in systemic sclerosis (SSc) patients and little is known about the link between dementia and SSc. We sought to investigate whether an association exists between Alzheimer's disease (AD) and SSc, as well as assess the impact of a dual diagnosis on mortality rates, by performing an extensive data analysis on a large subject sample. We utilized the medical database of the Clalit-Health-Services in a case-control study. Patients with SSc were compared with age- and sex-matched controls with regard to the prevalence of AD and its impact on their mortality. Our study included 2,431 SSc patients and 12,377 age- and sex-matched controls. The mean age of the study population was 63.32±18.06 years and the female to male ratio was 4.5:1. 134 (5.5%) cases had AD as a co-morbidity in comparison with 749 (5.9%) of the controls. The mortality rate was 12.5% among controls and 26.2% among SSc cases. On the Cox multivariate survival analysis, diagnosis of SSc and AD demonstrated significant HRs (2.35 (95% CI 2.05-2.69, p < 0.0001) and 2.19 (95% CI 1.94-2.48, p < 0.0001), respectively). SSc patients with AD had a relative risk of death of 2.35 (95% CI: 1.44-3.83) in comparison with SSc patients without AD. AD is a predictor of death in SSc and therefore preemptive screening may be warranted. Further studies are needed to evaluate whether improvements in the medical regimen for SSc may lead to a reduction in AD development and possibly to increased survival as well.

Predictors of mortality for preterm infants with intraventricular hemorrhage: a population-based study.

The goal of this longitudinal, population-level study was to examine factors affecting mortality in preterm infants with intraventricular hemorrhage (IVH). The study examined patients who were born at 36weeks estimated gestational age (EGA) or less with a diagnosis of IVH between the years 2005 and 2014 using data from the New York and Nebraska State Inpatient Databases. Potential predictors for mortality were investigated with multivariable survival analysis. The cohort included 7437 preterm infants with IVH. All-cause inpatient mortality occurred in 746 (10.0%). The majority of deaths were in infants born at less than 25weeks EGA (378 or 50.7%) and with birthweight less than 750g (459 or 61.5%). Mortality was highest for children with grade IV IVH (306/848 or 36.1%), followed by grades III (203/955 or 21.3%), II (103/1328 or 7.8%), and I (134/4306 or 3.1%). Hydrocephalus was diagnosed within 6months in 627 (8.4%) patients, with cerebrospinal fluid shunts required in 237 (3.2%). Shunts were eventually revised in 122 (51.5% of shunts), and 43 (18.1%) had infections. Multivariable Cox survival analyses found male sex (HR 1.3 [95% CI 1.1-1.5]), Asian race (HR 1.5 [1.1-2.2]), lower EGA (HR 9.9 [6.3-15.5] for < 25weeks), higher IVH grade (HR 6.1 [4.9-7.6] for grade IV), gastrostomy (HR 4.0 [2.0-7.7]), tracheostomy (HR 3.5 [1.7-7.1]), and shunt infection (HR 3.2 [1.0-9.9]) to be independently associated with increased mortality risk. This database is the first of its kind assembled for population-based investigations of long-term neurosurgical outcomes in preterm infants with IVH.

Clinicopathological significance of chemokine receptor (CCR1, CCR3, CCR4, CCR5, CCR7 and CXCR4) expression in head and neck squamous cell carcinomas.

Head and neck squamous cell carcinoma shows high prevalence of lymph node metastasis at diagnosis, and despite the advances in treatment, the overall 5-year survival is still under 50%. Chemokine receptors have a role in the development and progression of cancer, but their effect in head and neck carcinoma remains poorly characterised. This study aimed to assess the prognostic value of CCR1, CCR3, CCR4, CCR5, CCR7 and CXCR4 in head and neck squamous cell carcinomas. Immunohistochemical expression of chemokine receptors was evaluated in a retrospective cohort of 76 cases of head and neck squamous cell carcinoma. Clinicopathological associations were analysed using the chi-square test, survival curves were analysed according to the Kaplan-Meier method, and the Cox proportional hazard model was applied for multivariate survival analysis. The chemokine receptors were highly expressed in primary carcinomas, except for CCR1 and CCR3. Significant associations were detected, including the associations between CCR5 expression and lymph node metastasis (N stage, P = .03), advanced clinical stage (P = .003), poor differentiation of tumours (P = .05) and recurrence (P = .01). The high expression of CCR5 was also associated with shortened disease-free survival (HR: 2.85, 95% CI: 1.09-8.14, P = .05), but the association did not withstand the Cox multivariate survival analysis. At univariate analysis, high expression of CCR7 was associated with disease-free survival and low levels of CXCR4 were significantly associated with both disease-specific and disease-free survival. These findings show that chemokine receptors may have an important role in head and neck squamous cell carcinoma progression, regional lymph node metastasis and recurrence.

CARDIOVASCULAR PROGNOSTIC FACTORS IN PREDIABETIC PATIENTS WITHIN A HYPERTENSIVE POPULATION

Objective: Prediabetes is a major risk for development of type 2 diabetes, but it is unclear whether it increases the risk for cardiovascular disease (CVD). Our aim was to determine whether prediabetic patients was a a higher risk of CVD than non-prediabetic patients in our hypertensive population. Design and method: We conducted a longitudinal, retrospective research with patients attended at a Hypertension Unit. Prediabetes was defined according to American Diabetes Association (ADA) criteria. Our primary outcome was a composite of non-fatal coronary disease, non-fatal stroke, heart failure and cardiovascular (CV) death. We fitted survival analysis using a Cox proportional hazard regression model to estimate the survival and time-to-event rates in prediabetic patients compared to non-prediabetic ones. Results: We selected 1,652 patients, 713 (43%) with prediabetes (table 1). We encoded 13 cases of coronary disease, 26 strokes, 5 cases of heart failure and 27 CV deaths in the prediabetes cohort, and 16 cases of coronary disease, 18 strokes, 14 cases of heart failure and 14 CV deaths in the non-prediabetic group. The risk of developing a CV event was higher in the prediabetic patients (HR = 1.61, 95% CI 1.01- 2.54, p = 0.04), as shown in Figure 1. In a multivariate Cox survival analysis, age and cystatin C were the most relevant prognostic factors within the potential studied predictors (table 2). Conclusions: Prediabetes was associated with a higher risk of CV event in prediabetic patients than non-prediabetic individuals from our hypertensive population. Cystatin C, along with age, was a major prognostic factor for CV risk, and can be useful in the risk asessment in prediabetic, hypertensive patients.

Predictors of survival after intramedullary nail fixation of completed or impending pathologic femur fractures from metastatic disease

BackgroundSurgical decision-making can be challenging when treating patients with osseous metastases. Numerous factors, including expected duration of survival, must be considered to ensure optimal operative stabilization of the affected bone. However, life expectancy of patients with metastatic carcinoma is often difficult to estimate. The goal of our study was to assess the associations of various clinical and demographic factors with survival time after intramedullary nail fixation of impending or completed pathologic femur fractures. MethodsOne hundred thirty-eight consecutive patients treated with intramedullary nail fixation for impending or completed pathologic femur fractures between 2005 and 2017 were included in this study. Factors related to patient survival were assessed with Cox multivariate survival analysis. For all analyses, p < 0.05 was considered significant. ResultsThe median overall postoperative survival time was 8.4 months. Lower hemoglobin concentration (p = 0.001), lower albumin concentration (p = 0.002), and having a group 2 primary cancer (p = 0.001) were associated with shorter survival on multivariate analysis. When considering the subgroup of 88 prophylactically stabilized patients, lower hemoglobin concentration (p = 0.005), lower albumin concentration (p = 0.015), and having a group 2 primary cancer (p = 0.037) were predictive of shorter survival. ConclusionSeveral factors are associated with shorter survival after intramedullary nail fixation of pathologic femur fractures. These factors should be considered by orthopedic surgeons when educating patients and determining appropriate treatment.

Overexpression of Kin of IRRE-Like Protein 1 (KIRREL) in Gastric Cancer and Its Clinical Prognostic Significance.

BackgroundThe aim of this study was to examine the expression level of IRRE-like protein 1 (KIRREL) in gastric cancer (GC) and to explore its prognostic significance.Material/MethodsBioinformatics methods were used to predict the differential expression levels of KIRREL mRNA in GC and normal gastric tissues by mining cancer-related databases (TCGA and Oncomine). Immunohistochemistry was done to verify the KIRREL protein expression levels in 71 cases of GC tissues combined with matched normal tissues. The relationship between clinicopathologic parameters and KIRREL differential expression levels in GC was investigated by the chi-square test. Kaplan-Meier univariate and Cox multivariate survival analyses were performed to explore the prognostic significance of KIRREL expression in GC patients.ResultsTCGA and GEO data analyses showed that KIRREL mRNA expression level was remarkably higher in GC than that in normal gastric tissues (both P<0.05). KIRREL mRNA levels were dramatically increased from stage I to stage IV (P=0.037). Immunohistochemical results showed that the high positive rate of KIRREL staining in GC was 61.97% (44/71). Moreover, GC patients with KIRREL mRNA or protein high levels had significantly shorter overall survival times than those with KIRREL mRNA or low protein levels (All P<0.05). Additionally, Cox multivariate survival analysis revealed that KIRREL differential expression levels (low vs. high) were the only independent parameter predicting the prognosis of GC patients (P=0.000).ConclusionsKIRREL was overexpressed in GC and the overexpression of KIRREL could serve as an independent predictor of poor prognosis in GC patients.

Analysis of the high incidence of acute kidney injury associated with acute-on-chronic liver failure

To investigate the incidence, risk, and prognostic factors of acute kidney injury (AKI) in acute-on-chronic liver failure (ACLF) patients. A total of 188 patients were prospectively included and divided into AKI and non-AKI groups. Patients were followed at 1, 3, 7, 14, 28, 60, and 90days after the onset of AKI. Significant risk factors were screened by univariate and Cox multivariate survival analyses to confirm the independent risk factors for 30- or 90-day mortality and the 90-day renal function recovery rate. A total of 98 AKI cases (52.1%, [95% CI 44.9-59.3%]) occurred and the risk factors for AKI development in ACLF patients were age > 50years (p = 0.009) and albumin (Alb) levels < 32g/L (p = 0.007). The 30- and 90-day mortalities were significantly higher in the AKI than in the non-AKI group (79.6 vs 41.1%, 82.7 vs 56.7%, p < 0.05). AKI highest staging occurring within < 4days of its onset and spontaneous peritonitis as well as MELD scores > 27 were independent risk factors for 30- and 90-day mortalities of ACLF AKI patients. AKI stage 3 and age > 52years were independent risk factors for non-renal function recovery in ACLF patients with AKI. ACLF patients had a high incidence of AKI, which correlated with 30- and 90-day mortalities.

Treatment of Isolated Peritoneal Recurrences in Patients with Colorectal Peritoneal Metastases Previously Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

Colorectal peritoneal carcinomatosis (PC) is preferably treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Peritoneal recurrence of disease after treatment can occur without distant metastases, with a variety of treatment options. This study aimed to evaluate the management of isolated peritoneal recurrence after primary CRS-HIPEC. In two tertiary referral centers, all patients who underwent CRS-HIPEC for colorectal PC between 2004 and 2015 and who developed isolated peritoneal recurrences were retrospectively evaluated. Location, treatment of peritoneal recurrences, and curative or palliative treatment intent were reported, and univariable and multivariable Cox regression analysis and survival analyses were performed. Of 414 patients treated with CRS-HIPEC for colorectal PC, 106 patients (26%) developed isolated peritoneal recurrence. Forty-three patients (41%) were treated with curative intent and 63 (59%) were treated with palliative intent. Median overall survival (OS) in the patients treated with curative intent was 24.7months (interquartile range [IQR] 12.1-61.7), compared with 7.6months (IQR 2.5-15.9) in those treated with palliative intent (p < 0.001). In the patients treated with curative CRS (n = 17) and curative second CRS-HIPEC (n = 15), median OS was 51.7months (IQR 14.4-NA) and 29.0months (IQR 18.1-63.0), respectively (p = 0.620). The latter group had a significantly higher region count (median 1 vs. 3; p < 0.001). Postoperative complications and hospital stay did not significantly differ between first and second CRS-HIPEC. After CRS-HIPEC for colorectal cancer, approximately one of four patients will develop isolated peritoneal recurrences. A substantial amount of these patients can be safely treated with curative intent yielding long-term survival.

High Expression of Retinoic Acid Induced 14 (RAI14) in Gastric Cancer and Its Prognostic Value.

BackgroundTo explore the expression level of retinoic acid induced 14 (RAI14) in gastric cancer (GC) patients and its potentially clinical prognostic value.Material/MethodsInitially, The Cancer Genome Atlas (TCGA) and Oncomine databases were mined to examine the differential expression levels and clinical prognostic significance of RAI14 mRNA in GC patients. Subsequently, 68 cases of GC and paired adjacent normal tissues were collected retrospectively, and the expression level of RAI14 protein was detected by immunohistochemical staining. In addition, Kaplan-Meier univariate and Cox multivariate survival analyses were used to verify the correlation between RAI14 expression and clinicopathological parameters in GC patients and its clinical prognostic significance.ResultsTCGA and GEO (from Oncomine database) data mining results found that RAI14 mRNA level was remarkably higher in GC than normal gastric tissues (All P<0.05). Besides, immunohistochemical results detected that RAI14 protein level in GC was dramatically higher (P=0.004) compared to that in the matched normal tissues. Moreover, TCGA database and Kaplan-Meier Plotter mining results showed that compared to those with RAI14 low mRNA expression levels, GC patients with RAI14 high mRNA expression levels had remarkably lower time of both overall survival and disease-free survival (All P<0.05). Additionally, based on the immunohistochemical results, Kaplan-Meier univariate and Cox multivariate survival analyses indicated that high expression of RAI14 was the only independent predictor of unfavorable prognosis in patients with gastric cancer (P=0.000).ConclusionsRAI14 was highly expressed in GC, and the high expression of RAI14 could be an independent predictor of poor prognosis in GC patients.

Outcomes in Asymptomatic Severe Aortic Stenosis With Preserved Ejection Fraction Undergoing Rest and Treadmill Stress Echocardiography.

BackgroundIn asymptomatic patients with severe aortic stenosis and preserved left ventricular ejection fraction, we sought to assess the incremental prognostic value of resting valvuloarterial impedence (Zva) and left ventricular global longitudinal strain (LV‐GLS) to treadmill stress echocardiography.Methods and ResultsWe studied 504 such patients (66±12 years, 78% men, 32% with coronary artery disease who underwent treadmill stress echocardiography between 2001 and 2012. Clinical and exercise variables (% of age‐sex predicted metabolic equivalents [%AGP‐METs]) were recorded. Resting Zva ([systolic arterial pressure+mean aortic valve gradient]/[LV‐stroke volume index]) and LV‐GLS (measured offline using Velocity Vector Imaging, Siemens) were obtained from the baseline resting echocardiogram. Death was the primary outcome. There were no major adverse cardiac events during treadmill stress echocardiography. Indexed aortic valve area, Zva, and LV‐GLS were 0.46±0.1 cm2/m2, 4.5±0.9 mm Hg/mL per m2 and −16±4%, respectively; only 50% achieved >100% AGP‐METs. Sixty‐four percent underwent aortic valve replacement. Death occurred in 164 (33%) patients over 8.9±3.6 years (2 within 30 days of aortic valve replacement). On multivariable Cox survival analysis, higher Society of Thoracic Surgeons score (hazard ratio or HR 1.06), lower % AGP‐METS (HR 1.16), higher Zva (HR 1.25) and lower LV‐GLS (HR 1.12) were associated with higher longer‐term mortality, while aortic valve replacement (HR 0.45) was associated with improved survival (all P<0.01). Sequential addition of ZVa and LV‐GLS to clinical model (Society of Thoracic Surgeons score and %AGP‐METs) increased the c‐statistic from 0.65 to 0.69 and 0.75, respectively, both P<0.001); findings were similar in the subgroup of patients who underwent aortic valve replacement.ConclusionsIn asymptomatic patients with severe aortic stenosis undergoing treadmill stress echocardiography, LV‐GLS and ZVa offer incremental prognostic value.

Novel Echocardiographic Parameters in Patients With Aortic Stenosis and Preserved Left Ventricular Systolic Function Undergoing Surgical Aortic Valve Replacement

We sought to study the incremental prognostic impact of baseline valvuloarterial impedance (Zva) and left ventricular global longitudinal strain (LV-GLS) in patients with severe aortic stenosis and preserved left ventricular ejection fraction (LVEF) treated with surgical aortic valve replacement (AVR). We included 961 consecutive patients (68 ± 13 years; 63% men) with severe aortic stenosis (indexed aortic valve area <0.6 cm2) and LVEF >50% who underwent surgical AVR at our institution between January 2007 and December 2008. The analysis is based on derivation (n = 637) and validation (n = 324) subgroups. Society of Thoracic Surgeons (STS) score was calculated. Zva (systolic arterial pressure + mean aortic valve gradient)/left ventricular stroke volume index and LV-GLS (measured offline using Velocity Vector Imaging; Siemens Medical Solutions, Mountain View, California) were calculated. The primary outcome was death. Median Zva and LV-GLS were 4.5 mmHg × ml-1 × m2 and -14.5%, respectively. AVR was performed at a median of 34 days from initial evaluation (isolated AVR in 46%, bioprosthetic AVR in 93%). At 7.5 ± 3 years, 320 patients died (33%; 30 days/in-hospital death in 0.5%). In the derivation subgroup, on multivariate Cox survival analysis, higher STS score (hazard ratio [HR] 1.06), higher Zva (HR 1.13), and worse LV-GLS (HR 1.07) were independently associated with long-term survival (all p <0.01). When Zva and LV-GLS were sequentially added to STS score, the c-statistic improved from 0.63 [0.55 to 0.77] to 0.70 [0.60 to 0.81] and 0.78 [0.69 to 0.83], respectively, all p <0.001). Findings were confirmed in the validation subgroup. In conclusion, in patients with severe aortic stenosis and preserved LVEF treated with surgical AVR, baseline Zva and LV-GLS provide improved risk stratification with synergistic prognostic value.

RETRACTED ARTICLE: CircHIPK3 promotes colorectal cancer growth and metastasis by sponging miR-7

Mounting evidences indicate that circular RNAs (circRNAs) have a vital role in human diseases, especially cancers. More recently, circHIPK3, a particularly abundant circRNA, was proposed to be involved in tumorigenesis. However, its role in colorectal cancer (CRC) has not been explored. In this study, we found circHIPK3 was significantly upregulated in CRC tissues and cell lines, at least in part, due to c-Myb overexpression and positively correlated with metastasis and advanced clinical stage. Moreover, Cox multivariate survival analysis showed that high-level expression of circHIPK3 was an independent prognostic factor of poor overall survival (OS) in CRC (hazard ratio [HR] = 2.75, 95% confidence interval [CI] 1.74–6.51, p = 0.009). Functionally, knockdown of circHIPK3 markedly inhibited CRC cells proliferation, migration, invasion, and induced apoptosis in vitro and suppressed CRC growth and metastasis in vivo. Mechanistically, by using biotinylated-circHIPK3 probe to perform RNA pull-down assay in CRC cells, we identified miR-7 was the only one microRNA that was abundantly pulled down by circHIPK3 in both HCT116 and HT29 cells and these interactions were also confirmed by biotinylated miR-7 pull-down and dual-luciferase reporter assays. Overexpression of miR-7 mimicked the effect of circHIPK3 knockdown on CRC cells proliferation, migration, invasion, and apoptosis. Furthermore, ectopic expression of circHIPK3 effectively reversed miR-7-induced attenuation of malignant phenotypes of CRC cells by increasing the expression levels of miR-7 targeting proto-oncogenes (FAK, IGF1R, EGFR, YY1). Remarkably, the combination of circHIPK3 silencing and miR-7 overexpression gave a better effect on tumor suppression both in vitro and in vivo than did circHIPK3 knockdown or miR-7 overexpression alone. Taken together, our data indicate that circHIPK3 may have considerable potential as a prognostic biomarker in CRC, and support the notion that therapeutic targeting of the c-Myb/circHIPK3/miR-7 axis may be a promising treatment approach for CRC patients.