Multivariate Cox Proportional-hazards Regression Analysis Research Articles

Impact of Functional Status on Noncardioembolic Ischemic Stroke Recurrence Within 1 Year: The Korean Stroke Cohort for Functioning and Rehabilitation Study.

Background and PurposeFew studies have investigated the relationship between the specific functional factors potentially associated with functional level and stroke recurrence. We conducted a study of patients with noncardioembolic ischemic stroke (NCIS) to determine the functional factors affecting recurrence within the first year.MethodsIn total, 568 first-ever NCIS patients (age=65.1±17.4 years, mean±SD) were analyzed in a multicenter, prospective cohort study registered from August 2012. Demographic characteristics, past medical history, comorbidities, laboratory data, stroke features in neuroimaging, acute treatments, and medications at discharge were assessed. Functional factors reflecting gross functional impairment, ambulatory function, motor function, activities of daily living, cognition, language ability, swallowing function, mood, and quality of life were comprehensively evaluated in face-to-face assessments using standardized tools at the time of discharge.ResultsThe cumulative incidence of stroke recurrence in NCIS was 6.0% (n=34) at 1 year. The period from admission to discharge was 34.4±7.0 days. The independent predictors of stroke recurrence within 1 year in multivariate Cox proportional-hazards regression analyses were 1) age [per-year hazard ratio (HR)=1.04, 95% confidence interval (CI)=0.97–1.06, p=0.048], 2) Charlson Comorbidity Index higher than 2 (HR=1.72, 95% CI=1.26–2.22, p=0.016), 3) modified Rankin Scale score of 3 or more at discharge (HR=1.56, 95% CI=1.22–1.94, p=0.032), and 4) Functional Ambulation Category of 3 or less at discharge (HR=2.56, 95% CI=1.84–3.31, p=0.008).ConclusionsIn addition to patient age, moderate-to-severe functional impairment requiring the help of others (especially for ambulation) at the time of discharge and the severity of comorbidity were independent predictors of stroke recurrence within 1 year of the first NCIS.

The multi-vessel and diffuse coronary spasm is a risk factor for persistent angina in patients received anti-angina medication.

Coronary artery spasm (CAS) is known to be a risk factor for cardiovascular events. However, there is limited data whether the multi-vessel and diffuse spasm (MVDS) is related to more adverse clinical outcomes compared to the Non-MVDS. The aim of this study is to evaluate the impact of the MVDS on clinical outcomes during a 3-year clinical follow-up period.A total 2797 patients underwent coronary angiography (CAG) with acetylcholine (ACH) provocation test from Nov 2004 to Oct 2010 were enrolled. It is a single-center, observational, prospective, all-comers registry designed to reflect the “real world” practic. The patients were divided into the 3 groups; the negative spasm (NS) group (n = 1188), the Non-MVDS group (n = 1081), and the MVDS group (n = 528). The incidence of major adverse cardiac events (MACE) and recurrent angina was evaluated up to 3 years. To minimize confounding factors, multivariable Cox-proportional hazards regression analysis was performed.In the 3-year clinical follow-up, the incidence of total death, myocardial infarction, de novo percutaneous coronary intervention (PCI), cerebrovascular accident and MACE were similar among the 3 groups. However, recurrent angina occurred more frequently in the MVDS group than in the NS group (hazard ratio [HR], 1.96; 95% confidence interval [CI], 1.27–3.02; P = .002). Recurrence angina between the MVDS group and the Non-MVDS group was not statistically significant (HR, 1.36; 95% CI, 0.91–2.03; P = .129).In this study, although the incidence of major adverse cardiovascular events were not different regardless of spasm type, the MVDS was associated with higher incidence of recurrent chest pain requiring repeat CAG during the 3-year follow-up period, suggesting more intensive optimal medical therapy with close clinical follow up would be necessary for this particular subset of patients.

Oncogene miR-154-5p regulates cellular function and acts as a molecular marker with poor prognosis in renal cell carcinoma

AimsIn adult population, the renal cell carcinoma (RCC) is one of the most common urological malignancies. It is meaningful to research for the molecular markers which are involved in the occurrence and development of RCC. Therefore, we concentrate on illuminating the role of microRNA-154-5p in progression of RCC and explore its prognostic values. Main methodsThe real-time quantitative polymerase chain reaction (RT-qPCR) was applied to determine expression level of miR-154-5p in tissues. Afterwards, the transfected cell lines ACHN and 786-O were used for the CCK-8 assay, MTT assay, wound healing assay, transwell assay and flow cytometric assay to explore the role of miR-154-5p in regulating cellular function. In addition, formalin-fixed paraffin-embedded (FFPE) renal cancer samples were used for detecting the relationship between expression level of miR-154-5p and clinical information. Furthermore, univariate and multivariate Cox proportional-hazards regression analyses, and the Kaplan-Meier survival curves were performed to evaluate the prognostic value of miR-154-5p in RCC. Key findingsThe RT-qPCR indicated that miR-154-5p is up-regulated in RCC pathologic specimens and cell lines. Results of study also demonstrated that upregulation of miR-154-5p reduced cell apoptosis and promoted cell proliferation, viability, migration as well as invasion in RCC cells. The prognosis analyses indicated that the expression level of miR-154-5p is associated with the prognosis of renal cancer, and the overall survival of patients with low expression is longer. SignificanceThe present study revealed that the oncogene miR-154-5p regulates cellular function and acts as a molecular marker with poor prognosis in renal cell carcinoma.

Bleeding risk of cerebral cavernous malformations in patients on β-blocker medication: a cohort study.

Cerebral cavernous malformations (CCMs) are frequently diagnosed vascular malformations of the brain. Although most CCMs are asymptomatic, some can be responsible for intracerebral hemorrhage or seizures. In selected cases, microsurgical resection is the preferred treatment option. Treatment with the unselective β-blocker propranolol has been presumed to stabilize and eventually lead to CCM size regression in a limited number of published case series; however, the underlying mechanism and evidence for this effect remain unclear. The aim of this study was to investigate the risk for CCM-related hemorrhage in patients on long-term β-blocker medication. A single-center database containing data on patients harboring CCMs was retrospectively interrogated for a time period of 35 years. The database included information about hemorrhage and antihypertensive medication. Descriptive and survival analyses were performed, focusing on the risk of hemorrhage at presentation and during follow-up (first or subsequent hemorrhage) in patients on long-term β-blocker medication versus those who were not. Follow-up was censored at the first occurrence of new hemorrhage, surgery, or the last clinical review. For purposes of this analysis, the β-blocker group was divided into the following main subgroups: any β-blocker, β1-selective β-blocker, and any unselective β-blocker. Of 542 CCMs among 408 patients, 81 (14.9%) were under treatment with any β-blocker; 65 (12%) received β1-selective β-blocker, and 16 (3%) received any unselective β-blocker. One hundred thirty-six (25.1%) CCMs presented with hemorrhage at diagnosis. None of the β-blocker groups was associated with a lower risk of hemorrhage at the time of diagnosis in a univariate descriptive analysis (any β-blocker: p = 0.64, β1-selective: p = 0.93, any unselective β-blocker: p = 0.25). Four hundred ninety-six CCMs were followed up after diagnosis and included in the survival analysis, for a total of 1800 lesion-years. Follow-up hemorrhage occurred in 36 (7.3%) CCMs. Neither univariate descriptive nor univariate Cox proportional-hazards regression analysis showed a decreased risk for follow-up hemorrhage under treatment with β-blocker medication (any β-blocker: p = 0.70, HR 1.19, 95% CI 0.49-2.90; β1-selective: p = 0.78, HR 1.15, 95% CI 0.44-3.00; any unselective β-blocker: p = 0.76, HR 1.37, 95% CI 0.19-10.08). Multivariate Cox proportional-hazards regression analysis including brainstem location, hemorrhage at diagnosis, age, and any β-blocker treatment showed no reduced risk for follow-up hemorrhage under any β-blocker treatment (p = 0.53, HR 1.36, 95% CI 0.52-3.56). In this retrospective cohort study, β-blocker medication does not seem to be associated with a decreased risk of CCM-related hemorrhage at presentation or during follow-up.

The platelets-neutrophils to lymphocytes ratio: a new prognostic marker in metastatic colorectal cancer

The cancer micro-environment is recognized as having an increasing importance in cancer progression. Immune cells originating from the peripheral blood are important elements of this environment. Thrombocytosis, neutrophilia and lymphocytopenia have been found to be negative prognostic indicators in many cancers. This study aims to evaluate the potential of the use of a novel hematological marker, the platelet-neutrophil to lymphocyte ratio (PNLR) as a practical, reliable, and inexpensive prognostic tool in metastatic colorectal adenocarcinomas. Charts from 305 patients with colorectal cancer were retrospectively reviewed. Of these, 152 had metastatic disease with complete follow-up data on progression and survival. Data were extracted and stratified by a PNLR cut-off point of 2,000. Baseline parameters of the two groups were evaluated and compared with the χ2 test. Univariate and multivariate Cox proportional-hazards regression analyses were performed on variables of interest. A total of 102 (67.1%) patients had a PNLR of less than 2,000 while the index for 50 (32.9%) patients was 2,000 or higher. Patients with a PNLR above 2,000 had a shorter median progression-free survival (PFS) [6.5 vs. 13.3 months; hazard ratio (HR), 2.05; 95% CI, 1.32-3.19, P=0.001] than in patients with a PNLR below the threshold. Similar results were observed for median overall survival (OS) (9.6 vs. 21.8 months; HR, 2.33; 95% CI, 1.44-3.79, P=0.001). PNLR had a higher predictive HR than Eastern Cooperative Oncology Group (ECOG) performance status (PS). In this retrospective analysis of metastatic colorectal cancer patients, PNLR had prognostic value for both OS and PFS. While other variables held significance for poorer prognosis, PNLR had the highest HR and the highest significance in multivariate analysis for both PFS and OS. Thus, it represents a powerful and objective prognostic tool in the evaluation of metastatic colorectal cancer patients that is readily available and does not require any additional expenses.

Comparison of Hematologic and Other Prognostic Markers in Metastatic Colorectal Cancer

Associations of thrombocytosis, neutrophilia, and lymphopenia with prognosis have been confirmed in many cancers. This study aims at comparing various prognostic indices based on blood counts in metastatic colorectal adenocarcinomas. Records from 152 patients with metastatic colorectal cancer who were treated in our center were reviewed. Demographic and disease characteristics and hematologic parameters data were extracted and patients were stratified according to their scores of several hematologic ratios. Hematologic ratios and parameters considered included the platelet-neutrophil to lymphocyte ratio (PNLR), the platelet to lymphocyte ratio (PLR), the neutrophil to lymphocyte ratio (NLR), the Abnormal Hematological Markers Index (AHMI), and the neutrophil-platelet score (NPS). Optimal cutoffs were defined with the aid of an online tool. Baseline parameters of the two groups derived for each tool were evaluated and compared with the χ2 test. Univariate and multivariate Cox proportional-hazards regression analyses were performed on variables of interest. Progression-Free Survival (PFS) hazard ratios (HR) between the high-risk and low-risk groups derived from the multivariate analyses for each index were as follows: for PNLR 2.0 (95% CI 1.28-3.13), for PLR 1.74 (95% CI 1.13-2.67), for NLR 1.54 (95% CI 1.04-2.29), for AHMI 1.62 (95% CI 1.06-2.46), and for NPS 1.47 (95% CI 1.1-1.96). Overall Survival (OS) hazard ratios (HR) derived from the multivariate analyses for each index were as follows: for PNLR 2.23 (95% CI 1.36-3.66), for PLR 1.68 (95% CI 1.03-2.75), for NLR 1.62 (95% CI 1.06-2.49), for AHMI 1.7 (95% CI 1.07-2.69), and for NPS 1.53 (95% CI 1.11-2.11). Another prognostic index called PRONOPALL, which is based on ECOG PS (0-1 versus 2-3 versus 4), number of metastatic sites (≤ 1 versus ≥ 2), LDH (< 600U/L versus ≥ 600U/L), and albumin (≥ 33g/L versus < 33g/L), had HRs of 1.75 and 2.20 for PFS and OS, respectively, with a cutoff of < 4 versus ≥ 4. This score has a range of 0 to 10 and points are attributed for the presence of each of the four prognostic factors. In this analysis of metastatic colorectal cancer patients, several ratios and other prognostic tools had prognostic value for both OS and PFS. While other variables held significance for poorer prognosis, PNLR had the highest HR and the highest significance in multivariate analysis for both PFS and OS. Thus, it represents a valid prognostic tool in metastatic colorectal cancer among the spectrum of hematologic parameter-constructed tools.

Altered expression of HER-2 and the mismatch repair genes MLH1 and MSH2 predicts the outcome of T1 high-grade bladder cancer.

The identification of factors predicting the outcome of stage T1 high-grade bladder cancer (BC) is a major clinical issue. We performed immunohistochemistry to assess the role of human epidermal growth factor receptor-2 (HER-2) and microsatellite instability (MSI) factors MutL homologue 1 (MLH1) and MutS homologue 2 (MSH2) in predicting recurrence and progression of T1 high-grade BCs having undergone transurethral resection of bladder tumor (TURBT) alone or TURBT + intravesical instillations of bacillus Calmette-Guerin (BCG). HER-2 overexpression was a significant predictor of disease-free survival (DFS) in the overall as well as in the two patients' population; as for progression-free survival (PFS), it was significant in the overall but not in the two patients' population. MLH1 was an independent predictor of PFS only in patients treated with BCG and MSH2 failed to predict DFS and PFS in all populations. Most importantly, the higher the number of altered markers the lowers the DFS and PFS. In multivariate Cox proportional-hazards regression analysis, the number of altered molecular markers and BCG treatment were significant predictors (p = 0.0004 and 0.0283, respectively) of DFS, whereas the number of altered molecular markers was the only significant predictor (p = 0.0054) of PFS. Altered expression of the proto-oncogene HER-2 and the two molecular markers of genetic instability MLH1 and MSH2 predicted T1 high-grade BC outcome with the higher the number of altered markers the lower the DFS and PFS. These findings provide grounds for further testing them in predicting the outcome of this challenging disease.

C-reactive protein-albumin ratio is an independent prognostic predictor of tumor recurrence in stage IIIA-N2 lung adenocarcinoma patients

ObjectiveTo systematically evaluate the prognostic value of nutrition/inflammation-based markers for recurrence-free survival (RFS) in pN2-stage IIIA lung adenocarcinoma patients. Materials and methodsData from 156 patients who had pathologically confirmed pN2-stage IIIA primary lung adenocarcinoma and received complete surgical resection from 2010 to 2014 were retrospectively analyzed. The data for Glasgow prognostic score (GPS), modified GPS (mGPS), high-sensitivity mGPS, C-reactive protein/albumin ratio (CAR), neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, and prognostic nutritional index were analyzed. Univariate and multivariate Cox proportional-hazards regression analyses were used to identify the prognostic factors associated with RFS. ResultsThe optimal cutoff value for the CAR was set at 0.6. A significant correlation was found between the CAR and RFS (P=0.001) by univariate analysis. Multivariate analysis between RFS and the factors selected from univariate analysis showed that ECOG performance status, pneumonectomy, multi-level N2, and high CAR were independent predictors of RFS. ConclusionThe CAR was the best prognostic marker to predict tumor recurrence in pN2-stage IIIA lung adenocarcinoma patients among the 7 nutrition/inflammation-based markers. The preoperative CAR may identify patients with a high risk of postoperative tumor recurrence.

Risk Factors for Lateral Neck Recurrence of N0/N1a Papillary Thyroid Cancer.

Current guidelines advocate no prophylactic dissection of the lateral neck compartment for papillary thyroid carcinoma (PTC) without clinical evidence of lateral neck metastasis (cN1b). However, lateral neck recurrence can affect patient treatment outcomes and quality of life. Therefore, this study examined the risk factors for lateral neck recurrence after the definitive treatment of PTC without cN1b. The study enrolled 1928 consecutive patients who underwent total thyroidectomy between 2006 and 2012 for PTC without cN1b. Logistic regression analysis was used to identify the relationship of clinicopathologic factors with lateral neck recurrence. Uni- and multivariate Cox-proportional hazards regression analyses were used to identify factors predictive of lateral neck recurrence-free survival (LRFS). During a median follow-up period of 94 months (range, 24-133 months), lateral neck recurrence occurred in 47 patients (2.4%). Binary logistic regression showed that tumor size (>2cm), multifocality, clinical central neck metastasis (cN1a), number of positive lymph nodes (LNs, >5), and LN ratio (>0.5) were significantly associated with lateral neck recurrence (P<0.05). Multivariate analyses showed that multifocality (hazards ratio [HR], 2.338; 95% confidence interval [CI], 1.126-4.858; P=0.023), cN1a (HR, 5.301; 95% CI, 2.416-11.630; P<0.001), LN ratio (HR, 2.628; 95% CI, 1.228-5.626; P=0.013), extranodal extension (HR, 2.570; 95% CI, 1.063-6.213; P=0.036), and MACIS (distant metastasis, patient age, completeness of resection, local invasion and tumour size) score (HR, 2.513; 95% CI, 1.211-5.216; P=0.013) were independent factors for LRFS. Lateral neck recurrence after thyroidectomy is predicted by the clinicopathologic factors of multifocality, cN1a, LN ratio, extranodal extension, and MACIS score in N0/N1a PTC patients.

Increased C4 and decreased C3 levels are associated with a poor prognosis in patients with immunoglobulin A nephropathy: a retrospective study

BackgroundAn association between serum complement levels and poor renal prognosis in patients with immunoglobulin A nephropathy (IgAN) remains controversial.MethodsWe conducted a retrospective study examining the relationship between serum complement levels and prognosis in patients with IgAN. Between 2009 and 2013, patients with biopsy-confirmed IgAN were identified from the Second Affiliated Hospital of Wenzhou Medical College, China, and various parameters were documented during follow-up until 2015. The definition of the primary endpoint was a decrease of estimated glomerular filtration rate (eGFR) more than 30% from their baseline levels.ResultsA total of 403 patients (55.3% female, average 33.7 months of follow-up) were identified and enrolled, with the primary endpoint occurring in 39 (9.8%) patients. Among the patients selected, 202 (50.1%) received corticosteroid treatment alone or in combination with another immunosuppressant (GS group), while others did not receive immunosuppressive treatment (non-GS group). The incidence of the primary endpoint was slightly lower in the GS group compared to the non-GS group (7.0% versus 12.6%, p = 0.06). Multivariate Cox proportional-hazard regression analyses, adjusting for age, systolic and diastolic blood pressure, 24-h urine protein, and immunosuppressive therapy, showed that serum complement 4 (C4) levels (hazard ratio [HR] 2.4, 95% confidence interval [CI] 1.6-3.8, p < 0.001) and serum complement 3 (C3) levels (HR 0.6, 95% CI 0.2-0.6, p < 0.001) were significantly associated with a poor prognosis among patients with IgAN.ConclusionsWe demonstrated that an increase in serum C4, as well as a decrease in C3, was an important outcome determinant for patients with IgAN. Testing serum C3 and C4 levels might assist in predicting renal outcomes among these patients.

Impact of postoperative complications on readmission and long-term survival in patients following surgery for colorectal cancer.

It is well known that specific postoperative complications such as stroke influence readmissions and overall survival (OS) after surgery for colorectal cancer (CRC). Whether overall hospital morbidity is associated with increased risk of readmission and poorer long-term survival is unknown. New tools are available to accurately quantify overall morbidity, such as the comprehensive complication index (CCI). The aim is to evaluate the impact of complications on readmission and overall survival (OS) in patients operated for colorectal cancer. Postoperative complications of patients undergoing surgery for CRC were assessed over a 5-year period using the Clavien-Dindo classification, and overall morbidity was assessed by using the CCI. Individual scores were analyzed regarding their association with readmission and OS by using the multivariate logistic and Cox proportional-hazards regression analysis, respectively. Two hundred eighty-four patients were operated for CRC, of which 22 (8%) were readmitted. One hundred five patients (37%) developed at least one postoperative complication during the hospital stay. While single complications or the use of severe complication only (grade ≥IIIb) was not associated with readmission, overall morbidity (CCI) predicted readmission (OR 1.02 (95% CI 1.0-1.04), p=0.044). Similarly, morbidity assessed by the CCI had a significant negative predictive value on OS, e.g., patients with a CCI of 20 were 22% more likely to die within a 5-year follow-up, when compared to patients with a CCI of 10 (p=0.022). Overall combined morbidity as assessed by the CCI leads to more frequent readmission, and is associated with poorer long-term survival after surgery for CRC.

Variant histology as a significant predictor of survival after radical nephroureterectomy in patients with upper urinary tract urothelial carcinoma

ObjectivesTo investigate the effect of variant histology (VH) on survival after radical nephroureterectomy in patients with upper urinary tract urothelial carcinoma (UTUC) and the effect of adjuvant chemotherapy on the survival of patients with UTUC with VH. Materials and methodsA total of 452 patients who underwent radical nephroureterectomy for UTUC without neoadjuvant chemotherapy in our institution between 1991 and 2012 were retrospectively analyzed. We performed a comparative analysis between pure UTUC and UTUC with VH groups. The Kaplan-Meier method was used to calculate survival estimates for cancer-specific survival (CSS) and overall survival (OS), and log-rank test was used to conduct comparisons between the groups. Univariate and multivariate Cox-proportional hazard regression analyses were performed to evaluate significant variables associated with CSS and OS. ResultsUTUC with VH was present in 41 (9.1%) patients. UTUC with VH showed aggressive clinicopathological features in comparison with pure UTUC. The Kaplan-Meier curves showed significantly decreased 5-year CSS and OS (both, P<0.001) in UTUC with VH group. Multivariate analysis revealed that VH was an independent predictor of CSS (P<0.001) and OS (P<0.002). The Kaplan-Meier curves also showed significantly decreased 5-year CSS and OS in UTUC with the VH group compared to the pure UTUC group in patients who received adjuvant chemotherapy. ConclusionsWe found that UTUC with VH harbored aggressive biologic features, and VH was an independent prognostic factor for CSS and OS on both univariate and multivariate analyses. In addition, UTUC with VH group had poorer survival outcomes than pure UTUC group in patients who received adjuvant chemotherapy. Consequently, adjuvant treatment modalities other than adjuvant chemotherapy should be considered in this group.

Human epidermal growth factor receptor 2 expression is more important than Bacillus Calmette Guerin treatment in predicting the outcome of T1G3 bladder cancer.

In the present study we tested the role of Human Epidermal Growth Factor Receptor-2 (HER-2) expression, as assayed by immunohistochemistry, in predicting recurrence and progression in 67 patients with T1G3 BC having undergone transurethral resection of bladder tumor (TURBT) alone (33) or TURBT + Bacillus Calmette Guerin (BCG) instillations (34). All patients had a negative restaging TURBT within 4 months after the first TURBT. At median follow-up of 75.7 months, the overall disease-free and progression-free rates were 35.8% and 73.0%, respectively. Univariate Kaplan-Meier survival analysis showed that traditional prognostic factors (sex, tumor number/size/recurrence) failed to predict disease-free and progression free survival (DFS, PFS). BCG treatment was a significant predictor of DFS (p=0.0231) but not of PFS (p=0.6901). HER-2 overexpression was a significant predictor of DFS (p=0.0013) and PFS (p=0.0322) in the overall patients population, but failed to predict PFS when patients were stratified for treatment (BCG: p=0.1290; no BCG: p=0.1696) probably due to the limited number of events. Multivariate Cox proportional-hazards regression analysis confirmed that BCG treatment was a significant predictor of DFS (p=0.012) but not of PFS (p=0.924), whereas HER-2 overexpression was a significant predictor of DFS (p=0.001) and PFS (p=0.041). These findings suggest that HER-2 status performs better than “traditional” prognostic factors as well as of BCG treatment in predicting the outcome of T1G3 BC, thus providing grounds for further testing this marker and possibly incorporating it in a panel of molecular markers that could reliably predict the behavior of this challenging disease.

Comparative evaluation of copeptin and NT-proBNP in patients with severe acute decompensated heart failure, and prediction of adverse events in a 90-day follow-up period: A prospective clinical observation trial.

The present study compared the prognostic value of a marker, the C-terminal section of the arginine vasopressin prohormone (copeptin), with N-terminal B-type natriuretic peptide (NT-proBNP) in patients with severe acute decompensated heart failure. A prospective, observational cohort study was conducted in a tertiary care hospital and enrolled 129 patients with severe acute decompensated heart failure. Clinicians were blinded to investigational markers except NT-proBNP, and the study participants were followed up for 90 days. The end-point was a composite of cardiovascular death or re-hospitalization due to decompensated heart failure. Of the 129 patients enrolled, 47 reached the end-point and 82 were in a stable condition during follow-up. Receiver operating characteristic curve analysis revealed that the areas under curve for the prediction of adverse events within 90 days were similar for copeptin [0.602±0.052; 95% confidence interval (CI), 0.499-0.705], NT-proBNP (0.659±0.048; 95% CI, 0.565-0.753) and their combination (0.670±0.050; 95% CI, 0.573-0.767). Kaplan-Meier survival analysis showed that the predictive value of NT-proBNP regarding the probability of survival was superior compared with that of copeptin (log-rank test for trend, P=0.001 vs. 0.040). Furthermore, multivariate Cox proportional-hazards regression analysis revealed that increased NT-proBNP and copeptin plasma concentrations were significant independent predictors of adverse events. The present study provided evidence that copeptin has similar predictive properties compared with NT-proBNP regarding adverse events within 90-days in patients with severe acute decompensated heart failure, but that copeptin may not provide superior 90-day prediction compared to NT-proBNP.

Association between Periodontal disease and Prostate cancer: Results of a 12-year Longitudinal Cohort Study in South Korea.

The incidence of prostate cancer (PC) accompanying periodontal disease (PD) is anticipated to increase due to population aging. The aim of this study was to determine the association between PD and PC using data in the National Health Insurance Service-Health Examinee Cohort (NHIS-HEC). A random stratified sample of 187,934 South Koreans was collected from the NHIS database from 2002 to 2013. We assessed the relationship between PD and PC while adjusting for potential confounding factors (sex, age, household income, insurance status, residence area, hypertension, diabetes mellitus, cerebral infarction, angina pectoris, myocardial infarction, smoking status, alcohol intake, and regular exercise). The overall incidence of PC with PD among those aged 40 years and older was 0.28% (n = 531). In the multivariate Cox proportional-hazard regression analysis with adjustment for confounding factors, PD was associated with a 14% higher risk of PC (HR = 1.14, 95% CI = 1.01-1.31, P = 0.042). The findings of this study suggest that PD is significantly and positively associated with PC. Further studies are required to identify the mechanisms underlying the links between PD and PC.

Significance of the Extent of Resection in Modern Neurosurgical Practice of World Health Organization Grade I Meningiomas

Since the prognostic importance of radical resection was introduced in 1957, the neurosurgery practice has undergone several technologic advancements. The aim of this study was to evaluate whether the prognostic value of the extent of resection is still relevant in modern neurosurgical practice. Over a 10-year period, all patients with histologic-confirmed World Health Organization grade I meningiomas and who underwent meningioma surgery were retrospectively analyzed. Survival analyses were performed using Kaplan-Meier analysis and univariate and multivariate Cox proportional-hazards regression analyses. There were 113 patients included in this study. A better Simpson grade was associated with recurrence-free survival (RFS) 5, 10, and 15 years after surgery (P<0.001). Comparing Simpson grade I with Simpson grades III and IV, 13.1 and 36.6 times higher hazard ratios were revealed with respect to RFS, respectively. A 7.5 times higher hazard ratio was revealed when comparing Simpson grades II and IV. Additional survival analyses were performed within specific locations and groups with low and high mitotic indices, demonstrating that the extent of resection can add additional information about RFS. Simpson grade remains a highly significant predictor of RFS in meningioma-resected patients in modern neurosurgical practice. Extent of resection should therefore be emphasized when predicting prognosis and considering postoperative treatment and frequency of radiologic follow-up after surgery.

An Admission-to-Discharge BNP Increase Is a Predictor of Six-Month All-Cause Death in ADHF Patients: Inferences from Multivariate Analysis Including Admission BNP and Various Clinical Measures of Congestion.

Background: According to some authors, a single isolated measurement of serum B-type natriuretic peptide (BNP) executed on hospital admission would not be a sufficiently accurate method to predict the outcome of patients with acute decompensated heart failure (ADHF). Aims: To verify this assumption, a retrospective study was conducted on patients hospitalized for ADHF. Our main objective was to ascertain whether there was any difference in midterm mortality among patients with increasing BNP at discharge as compared with those with decreasing BNP at discharge. Methods: Medical records were examined so as to make a partition of the ADHF patient population into two groups, the former characterized by a rise in BNP during hospitalization, and the latter exhibiting a decrease in BNP in the measurement taken at hospital discharge. Results: 177 patients were enrolled in a retrospective study. Among them, 53 patients (30%) had increased BNP at the time of discharge, whereas 124 (70%) showed decreases in serum BNP during their hospital stay. The group with patients who exhibited BNP increases at the time of discharge had a higher degree of congestion evident in the higher frequency of persistent jugular venous distention and persistent orthopnea at discharge. Moreover, patients with increased BNP at the time of discharge had a lower reduction in inferior vena cava maximum diameter (1.58 ± 2.2 mm vs. 6.32 ± 1.82 mm; p (one-way ANOVA) = 0.001). In contrast, there was no significant difference in weight loss when patients with increased BNP at discharge were compared with those with no such increase. A total of 14 patients (7.9%) died during the six-month follow-up period. Multivariable Cox proportional-hazards regression analysis revealed that a BNP increase at the time of discharge was an independent predictor of six-month all-cause mortality after adjustment for persistent jugular venous distention, persistent orthopnea, reduction in inferior vena cava maximum diameter at discharge, weight loss, serum urea, systolic blood pressure at admission, and BNP at admission (hazard ratio = 30.5424; 95% CI: 1.7409–535.8294, p = 0.0199). Conclusions: Among patients with a history of ADHF, more elevated BNP levels at the time of discharge from the hospital compared with those detected at admission identify a patient subset with a higher grade of congestion and higher six-month mortality.

Effects of Hyponatremia Normalization on the Short-Term Mortality and Rehospitalizations in Patients with Recent Acute Decompensated Heart Failure: A Retrospective Study.

Background: Several studies have shown that hyponatremia is associated with increased risk of rehospitalization and death in patients with heart failure. In these studies, chronic heart failure (CHF) patients with persistent hyponatremia were compared only with CHF patients with a normal sodium level at hospital admission. Aims: In the present retrospective study, conducted in a cohort of patients with recent acute decompensated heart failure (ADHF), all with hyponatremia ascertained at the time of hospital admission, we aimed to evaluate the effect of the normalization of serum sodium on the composite endpoint of short-term rehospitalization and mortality. Methods: A retrospective study centered on medical records of patients hospitalized for ADHF in the period April 2013 to April 2016 was performed. Data regarding serum sodium measurements had to be collected from medical records of cardiology wards of two hospitals, and were then processed for statistical analysis. As an inclusion criterion for enrollment, patients had to be suffering from heart failure that had required at least one hospitalization. Moreover, they had to be suffering from a state of hyponatremia (serum sodium < 135 mEq/L) at admission on the occasion of the index hospitalization. Patients with hyponatremia at admission were divided into two groups, one comprising patients with hyponatremia that persisted at the time of discharge (persistent hyponatremia) and a second including patients who had achieved normalization of their serum sodium levels (serum Na+ ≥ 135 mEq/L) during hospitalization until discharge. For both groups, the risk of mortality and rehospitalization during a 30-day follow-up was assessed. Results: One hundred and sixty CHF patients with various degrees of functional impairment were enrolled in the study. Among them, 56 (35%) had persistent hyponatremia over the course of hospitalization. At multivariable Cox proportional-hazards regression analysis, the risk of having a 30-day unplanned readmission or death was significantly higher in patients with persistent hyponatremia compared to those who exhibited a sodium level normalized at discharge (adjusted hazard ratio = 3.0743; 95% CI: 1.3981–6.7601; p = 0.0054). Among the other variables included in the Cox regression model, the number of admissions in the last 12 months (p < 0.0001), the length of stay of the index admission (p = 0.0015) and the New York Heart Association (NYHA) class III at discharge (p = 0.0022) were also identified as risk factors associated with the composite endpoint of 30-day unplanned readmission or death. Conclusions: In the present retrospective study, the risk of 30-day rehospitalization or death was significantly higher in patients with recent ADHF and persistent hyponatremia in comparison with ADHF patients who had had their serum sodium normalized during the hospital stay. This association seemed to be independent of the heart failure severity.

The predictive value of arterial stiffness on major adverse cardiovascular events in individuals with mildly impaired renal function.

ObjectivesDespite growing evidence that arterial stiffness has important predictive value for cardiovascular disease in patients with advanced stages of chronic kidney disease, the predictive significance of arterial stiffness in individuals with mildly impaired renal function has not been established. The aim of this study was to evaluate the predictive value of arterial stiffness on cardiovascular disease in this specific population.Materials and methodsWe analyzed measurements of arterial stiffness (carotid–femoral pulse-wave velocity [cf-PWV]) and the incidence of major adverse cardiovascular events (MACEs) in 1,499 subjects from a 4.8-year longitudinal study.ResultsA multivariate Cox proportional-hazard regression analysis showed that in individuals with normal renal function (estimated glomerular filtration rate [eGFR] ≥90 mL/min/1.73 m2), the baseline cf-PWV was not associated with occurrence of MACEs (hazard ratio 1.398, 95% confidence interval 0.748–2.613; P=0.293). In individuals with mildly impaired renal function (eGFR <90 mL/min/1.73 m2), a higher baseline cf-PWV level was associated with a higher risk of MACEs (hazard ratio 2.334, 95% confidence interval 1.082–5.036; P=0.031).ConclusionArterial stiffness is a moderate and independent predictive factor for MACEs in individuals with mildly impaired renal function (eGFR <90 mL/min/1.73 m2).

Abstract 4751: Genetic subtype-specific prognostic significance of genetic alterations in lower-grade gliomas

Abstract BACKGROUND: Lower-grade gliomas (WHO grade II and III gliomas) are usually slowly progressive but rarely curable brain caners, for which optimal therapy is still controversial. Recently, we have delineated a comprehensive picture of genetic alterations in lower-grade gliomas and revealed that they could be clearly classified into three genetic subtypes characterized by distinct genetic and clinical features: IDH1/2 mutated tumors with 1p/19q co-deletion (Type−I), IDH1/2 mutated tumors without 1p/19q co-deletion (Type−II) and IDH1/2 wild-type tumors (Type−III). Median survival of each genetic subtype is 16.4, 7.77, and 2.12 years in Type−I, −II, and −III tumors, respectively. Given a higher layer of inter-tumor heterogeneity inferred from the presence of additional genetic lesions on each subtype, there still remains a possibility that within each subtype, we could find one or more subgroups showing distinct biological behaviors and clinical outcomes. In the current study, we analyzed a large data set of patients with lower-grade gliomas fully genotyped for major genetic lesions to determine the prognostic significance of additional genetic alterations.. METHODS: We analyzed genetic alterations detected by exome and/or targeted sequencing as well as SNP-array karyotyping obtained from clinically well-annotated 724 patients aged ≥18 years with supratentorial lower-grade gliomas from the Japan and The Cancer Genome Atlas (TCGA) cohorts. We performed univariate and multivariate Cox hazard proportional analyses for overall survival; multivariate models incorporated age at the time of surgery (≥60 vs. &amp;lt;60 years old), WHO grade (grade II vs. III), and extent of resection (gross total resection vs. partial resection or biopsy) with stratification of cohorts (Japan or TCGA) and were performed with stepwise selection of variables based on the Akaike information criterion. RESULTS: In the multivariate Cox proportional-hazards regression analysis, we revealed that several genetic alterations have subtype-specific prognostic significance: NOTCH1 mutation in Type-I [hazard ratio (HR) = 2.57, 95% confidence interval (CI) = 1.40-4.70], high-level focal amplification of CDK4 [HR = 9.40, 95% CI = 3.08-28.7], PIK3R1 mutation [HR = 8.13, 95% CI = 2.70-24.52], and loss of chromosome 9p [HR = 1.98, 95% CI = 1.16-3.38] in Type-II, and loss of chromosome 10 [HR = 2.26, 95% CI = 1.28-3.97] in Type-III tumors. In Type-III tumors, WHO grade [HR = 5.79, 95% CI = 2.79-12.0] showed a much higher prognostic value than other prognostic factors. Most of these genetic alterations are components of three major signaling pathways or copy number variations frequently affected in glioblastomas, suggesting a close link of disease progression to glioblastoma pathophysiology. CONCLUSIONS: Subtype-specific genetic lesions can be used to further stratify patients in each genetic subtype for overall survival to improve management of lower-grade gliomas. Citation Format: Kosuke Aoki, Hiromichi Suzuki, Hideo Nakamura, Keitaro Matsuo, Kazuya Motomura, Fumiharu Ohka, Masahiro Mizoguchi, Yasutomo Momii, Yasuhiro Muragaki, Satoru Miyano, Toshihiko Wakabayashi, Atsushi Natsume, Seishi Ogawa. Genetic subtype-specific prognostic significance of genetic alterations in lower-grade gliomas. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4751.