Univariate Cox Proportional Hazards Analyses Research Articles

Elevated mean pulmonary artery pressure in patients with mild-to-moderate mitral stenosis: a useful predictor of worsening renal functions?

Renal dysfunction commonly accompanies the course of cardiac disorders and strongly associates with increased morbidity and mortality. Elevated central venous pressure is related to worsening renal function in patients with heart failure. However, predictors of worsening renal function in mitral stenosis-whose pathophysiologic process is similar to heart failure with regard to right heart dysfunction-are unknown. This study aimed to evaluate whether clinical and echocardiographic parameters might predict worsening renal function in patients with mild-to-moderate mitral stenosis. The current study has a prospective cohort design. Sixty consecutive patients (9 male, 51 female, mean age 50±13 years) with mild-to-moderate mitral stenosis were followed up for 34±13 months (range 1-60) and their renal functions were monitored. Worsening renal function was defined as a decline in glomerular filtration rate of ≥ 20% on follow-up. In order to presence or absence of worsening renal functions, study patients divided into two groups. Statistical analysis was performed using the Chi-square, Independent samples t / Mann-Whitney U tests, univariate and multivariate Cox proportional hazards analyses, receiver operating characteristic (ROC) and Kaplan-Meier curve analyses. Worsening renal function was observed in 14 patients (23%). In univariate analysis, male gender, mean pulmonary artery pressure (mPAP), peak tricuspid regurgitation velocity, systolic pulmonary artery pressure, digitalis and antiplatelet usage, right atrial size, and TEI index were determined to be predictors of worsening renal function. In a multivariate Cox proportional hazards model, mPAP (HR=1.136, 95% CI: 1.058-1.220, p<0.001) and male gender (HR=4.110, 95% CI: 1.812-9.322, p=0.001) were associated with increased risk of worsening renal function during the follow-up period. In ROC curve analysis, the optimal cut-off value of mPAP to predict worsening renal function was measured as more than 21 mmHg, with 78.6% sensitivity and 58.7% specificity (AUC 0.725, 95% CI 0.595-0.838). According to the Kaplan-Meier curve, a significant difference was found between those who had mPAP of >21 mmHg, and those who did not have, in terms of worsening renal function (p=0.006), and the difference between the groups increased after 30 months of follow-up. Elevated mean pulmonary artery pressure at the time of initial evaluation, in patients with mild-to-moderate mitral stenosis, might help to predict worsening renal function.

Prognostic value of high sensitivity troponin T in patients with acutely decompensated heart failure and non-detectable conventional troponin T levels

High-sensitivity troponin Τ (hs-TnΤ) allows the detection of very minor myocardial injury and has emerged as a novel prognostic marker in patients with cardiovascular disease. The aim of the present study was to determine the prognostic utility of hs-TnΤ levels in patients admitted to hospital for acutely decompensated heart failure (ADHF) and non-detectable conventional TnΤ levels. We prospectively enrolled 113 consecutive ADHF patients [77 (68%) men], mean age: 72.7±11.3 years, presented at admission with normal (<0.03 ng/ml) conventional (4th generation) TnΤ levels. Hs-TnΤ levels were measured by relevant commercially available kits and patients were monitored for major adverse events during a median follow-up period of 174 days (94-728 days). In the univariate Cox proportional hazard analysis, hs-TnΤ was significantly related to death (HR=1.002 with 95%: confidence interval (CI) 1.001-1.003, P=0.001). In multivariate analysis, it remained a significant predictor of death after adjustment for age, gender, ejection fraction and creatinine levels (HR=1.003 with 95%: CI 1.001-1.005, P=0.008). hs-TnΤ seems to identify high risk patients hospitalized for ADHF, independently of other classical prognostic biomarkers. Further studies are necessary to confirm the utility of this novel biomarker in risk stratification and management of patients with ADHF.

Predictors of prolonged hospital stay for the treatment of severe neuropsychiatric symptoms in patients with dementia: a cohort study in multiple hospitals

Long hospitalization is often needed to treat severe behavioral and psychological symptoms of dementia (BPSD), which places heavy demands on hospital resources. Consequently, patients with severe BPSD usually wait for a long time to be admitted. There is a need to identify factors related to long hospitalization to better manage resources of a psychiatric hospital. We surveyed 150 consecutive patients hospitalized in the neuropsychiatric units of three hospitals for treatment of BPSD from 11 May 2009 to 30 November 2010. Only patients with reliable relatives were included in the study. We evaluated data of the patients (demographics, cognitive impairment, activities of daily living, causal disease for dementia, dementia severity, and the amount of pension), their primary caregivers (demographics and care burden), and their doctors' years of experience in treating dementia. We followed up to 180 days and assessed the effect of these factors on the length of stay. Of the 150 patients, 104 were discharged within 180 days and 46 were hospitalized for more than 180 days. Average length of stay for patients was 110.4 ± 58.1 days. In both univariate and multivariate Cox proportional hazard analyses, length of stay was longer for patients with smaller pensions and patients whose doctors had fewer years of experience in treating dementia. Length of stay was not found to be associated with any of the other variables. Patients with smaller pensions and whose doctors had less experience in treating dementia tended to require longer hospitalization.

Usefulness of Step Counts to Predict Mortality in Japanese Patients With Heart Failure

The purpose of this study was to determine both an association between mortality and physical activity (PA) objectively measured by accelerometer and cutoff values for PA in Japanese outpatients with heart failure (HF). This prospective observational study comprised 170 HF outpatients (mean age, 65.2 years; 77% men). Peak oxygen uptake (VO2) and the relation between ventilation and carbon dioxide production (VE/VCO2 slope) as indices of exercise capacity were measured during cardiopulmonary exercise testing with a cycle ergometer. PA was assessed by accelerometer-measured average step count (steps) per day for 1 week. Study endpoint was cardiovascular-related death. Over an average follow-up of 1,377.1 (median, 1,335) days, 31 cardiovascular-related deaths occurred. Patients were then divided into survivor (n = 139) and nonsurvivor (n = 31) groups. Brain natriuretic peptide level was significantly different between groups. Peak VO2 and steps were also significantly lower and VE/VCO2 slope higher in the nonsurvivors versus survivors. Univariate Cox proportional hazards analysis showed brain natriuretic peptide, peak VO2, VE/VCO2 slope, and steps to be significant prognostic indicators of survival. Multivariate analysis showed PA of ≤4,889.4 steps/day to be a strong and independent predictor of prognosis (hazard ratio: 2.28, 95% confidence interval: 1.31-6.30; p = 0.008). Kaplan-Meier curves after log-rank test showed significant prognostic difference between PA of ≤4,889.4 and >4,889.4 steps/day in the 2 groups (log-rank: 12.19; p = 0.0005). In conclusion, step count as objectively measured by accelerometer may be a prognostic indicator of mortality in Japanese outpatients with HF.

Preoperative Pulmonary Embolism Does Not Predict Poor Postoperative Outcomes in Patients with Renal Cell Carcinoma and Venous Thrombus

Patients with renal cell carcinoma who present with pulmonary embolism and venous thrombus may not be offered surgery because of presumed poor postoperative outcomes. In this multicenter study we evaluated perioperative mortality, recurrence and cancer specific survival in patients with renal cell carcinoma and venous thrombus diagnosed with preoperative pulmonary embolism. We reviewed consecutive patient records from our 3 tertiary hospitals to identify patients with renal cell carcinoma and venous thrombus treated with surgery from 2000 to 2011. Univariate and multivariate Cox proportional hazards analysis was used to evaluate whether preoperative pulmonary embolism or other clinical variables were associated with postoperative disease recurrence or cancer specific survival. Pulmonary embolism was identified preoperatively in 35 of 782 patients (4.4%) with renal cell carcinoma. Those with pulmonary embolism preoperatively were more likely to have higher level thrombus and higher T stage (p <0.01). No differences were found in other clinical or pathological features between the groups. There was no difference in 90-day mortality in patients diagnosed with pulmonary embolism preoperatively. Of 395 patients without metastasis preoperatively 147 (37.2%) showed metastatic renal cell carcinoma at a median followup of 22 months. There was no difference in the recurrence rate of renal cell carcinoma in patients with pulmonary embolism (p = 0.36). Recurrence in the lung was not more common in patients with vs without pulmonary embolism preoperatively (p = 0.71). Also, preoperative pulmonary embolism was not predictive of worse cancer specific survival (p = 0.58). Preoperative pulmonary embolism is not associated with worse early mortality, recurrence or cancer specific survival in patients with renal cell carcinoma and tumor thrombus.

Red blood cell distribution width as a prognostic marker of mortality in patients on chronic dialysis: a single center, prospective longitudinal study

AimTo determine if red cell distribution width (RDW) is associated with all-cause mortality in patients on chronic dialysis and to evaluate its prognostic value among validated prognostic biomarkers.MethodsThis is a single center, prospective longitudinal study. At the time of inclusion in January 2011, all patients were physically examined and a routine blood analysis was performed. A sera sample was preserved for determination of NT-pro-brain natriuretic peptide (NT-pro-BNP) and eosinophil cationic protein. Carotid intima media thickness (IMT) was also measured. Following one year, all-cause mortality was evaluated.ResultsOf 100 patients, 25 patients died during the follow-up period of one-year. Patients who died had significantly higher median [range] RDW levels (16.7% [14.3-19.5] vs 15.5% [13.2-19.7], P < 0.001. They had significantly higher Eastern Cooperative Oncology Group (ECOG) performance status (4 [2-4] vs 2 [1-4], P < 0.001), increased intima-media thickness (IMT) (0.71 [0.47-1.25] vs 0.63 [0.31-1.55], P = 0.011), increased NT-pro-BNP levels (8300 [1108-35000] vs 4837 [413-35000], P = 0.043), and increased C-reactive protein (CRP) levels (11.6 [1.3-154.2] vs 4.9 [0.4-92.9], P < 0.001). For each 1% point increase in RDW level as a continuous variable, one-year all cause mortality risk was increased by 54% in univariate Cox proportional hazard analysis. In the final model, when RDW was entered as a categorical variable, mortality risk was significantly increased (hazard ratio, 5.15, 95% confidence interval, 2.33 to 11.36) and patients with RDW levels above 15.75% had significantly shorter survival time (Log rank P < 0.001) than others.ConclusionsRDW could be an additive predictor for all-cause mortality in patients on chronic dialysis. Furthermore, RDW combined with sound clinical judgment improves identification of patients who are at increased risk compared to RDW alone.

Abstract WP425: Predictive Value Of Daily Physical Activity And New Onset Of Vascular Events In Patients With Mild Ischemic Stroke.

Introduction: Daily physical inactivity is associated with a substantially increased risk of cardiovascular events. However, the target level of daily physical activity is remained unclear. We aimed to evaluate the impact of physical activity on long-term vascular events in patients with mild ischemic stroke. Methods: We designed prospective observational study and enrolled 142 ischemic stroke patients with modified Rankin Scale 0-1 (mean age: 63.9±9.2). We measured daily step count as a variable of daily physical activity after 6-month from stroke onset. Other clinical characteristics including age, body mass index, blood pressure, blood labo test, carotid echo findings and medications were also assessed. The primary outcome was hospitalization due to stroke recurrence, myocardial infarction, angina pectoris, and peripheral artery disease. Survival curves were calculated by Kaplan-Meier survival analysis, and hazard ratios for recurrence were determined by univariate and multivariate Cox proportional hazards regression models. Results: After 1130.2±372.8 days of follow-up, 29 vascular events (19 stroke recurrence, 10 coronary heart disease) occurred, and the patients were divided into two groups: survival (n=113) and recurrenct (n=29). Daily step counts ( P =0.003) and plaque score ( P &lt;0.001) were significantly lower in the recurrent group than survival group. Univariate and multivariate Cox proportional hazards analysis revealed daily step counts and plaque score to be independent predictors of new vascular events. A daily step counts cutoff value of 6000 steps per day was determined by the analysis of receiver-operating characteristics with sensitivity 69.4% and specificity 79.4%. Kaplan-Meier survival curves after log-rank test showed significantly lower event rate in over 6000 steps group as compared to less than 6000 steps group ( P =0.023). Conclusion: In conclusion, our data indicate that daily physical activity evaluated by step counts may be useful for forecasting prognosis in patients with mild ischemic stroke. Daily step counts of 6000 steps may be a first target level to reduce new vascular events.

Prognostic features and outcomes in primary liver sarcoma.

150 Background: Primary liver sarcoma (PLS) is a rare and aggressive hepatic malignancy. Due to the low incidence of PLS, prognostic factors have not been well characterized. The purpose of our study was to evaluate survival outcomes in primary hepatic sarcomas and determine which factors predict survival. Methods: The Surveillance Epidemiology and End Results registry was used to identify patients with PLS from 1988-2009. Patients were evaluated by standard clinical and pathological indices including: age, gender, race, tumor size, tumor grade, histology, and extent of disease. Treatment related factors included surgery and radiation. Overall survival was assessed by Kaplan-Meier method. Univariate and stepwise multivariate Cox proportional hazards analyses were performed to identify prognostic factors. Results: 541 patients with PLS were identified. The mean age was 52 and most patients were male (55%) and white (75%). The most common histology type was blood vessel tumors (50.1%) followed by soft tissue neoplasms (17.7%) and complex mixed-stromal neoplasms (14.6%). Only 33% of patients underwent surgery and most (93%) did not receive radiation. When assessing outcomes, we observed median overall survival (OS) and cancer specific survival (CSS) of 6 months for the entire cohort. When stratified by treatment type, those who received surgery + radiation had the best survival (MS=97mos, p&lt;.001) compared to those who received either radiation alone (MS=5mos) or no treatment (MS=2mos). Stepwise multivariate analysis showed that age, male gender, tumor size, advanced stage, and no surgery were independent predictors of worse survival, all p-values &lt; .005. Conclusions: Primary liver sarcoma is an aggressive hepatic malignancy with low median OS of 6 months. Patients treated with surgery + radiation had the best outcome with a median survival of 97 months. Independent predictors for decreased survival included age, gender, tumor size, advanced stage, and no surgery.

The clinical significance of S100A10 in pancreatic cancer.

194 Background: S100A10 is a member of the S100 family of proteins containing two EF-hand calcium-binding motifs. They regulate a number of cellular processes such as cell cycle progression and differentiation. The objective of this study is to clarify the clinical significance of S100A10 in patients with pancreatic cancer. Methods: A total of 48 pancreatic adenocarcinoma tissues from patients underwent curative surgery were enrolled. Double 2-mm core tissue microarrays were made from paraffin-embedded pancreatic cancer samples and examined by immunohistochemistry for S100A10 protein. The correlations of expression level and clinicopathological outcome including recurrence free survival (DFS) were analyzed. Results: Expression level of the S100A10 protein in cytoplasm was categorized as overexpressed or others according to the baseline expression level in normal pancreatic duct. Overexpression of S100A10 protein was found in 9 of 48 (16.7%) cases. Statistical analysis revealed that related factor was distant lymph node metastasis. Univariate and multivariate Cox proportional hazard analysis showed S100A10 overexpression was significant independent predictors of DFS in patients with R0/1 resected pancreatic cancer (p=0.003). Although univariate Cox analysis showed overall survival in patient with S100A10 overexpression was significantly shorter (p=0.04), it didn’t show significance in multivariate analysis. Conclusions: S100A10 overexpression is considered to be useful predictor of post-operative recurrences in patients with pancreatic cancer.

Serum p -cresyl sulfate predicts cardiovascular disease and mortality in elderly hemodialysis patients

IntroductionPrevious studies have shown that serum p-cresyl sulfate (PCS) and indoxyl sulfate (IS) were significantly related to clinical outcomes in patients on hemodialysis (HD). However, evidence for the relationship in elderly HD patients remains scarce. We explore whether the two toxins can predict clinical outcomes in elderly HD patients.Material and methodsFifty stable HD patients more than 65 years old were enrolled from a single medical center. Serum total and free PCS, IS levels and biochemistry were measured concurrently. The clinical outcomes including cardiovascular events and all-cause mortality were analyzed after 38-month follow-up.ResultsUnivariate Cox proportional hazard ratio analysis revealed that cardiovascular events were associated with gender (p = 0.02), diabetes (p < 0.01), calcium (p = 0.01), total PCS (p < 0.01), free PCS (p < 0.01) and total IS (p = 0.05). Multivariate analysis showed that diabetes (p = 0.01), total PCS (p = 0.01) and free PCS (p = 0.04) were related to cardiovascular events. For all-cause mortality, only total PCS (p = 0.01) reached significance after adjusting other confounding factors. However, Kaplan-Meier analysis indicated that free PCS (p = 0.02) and total PCS (p < 0.01) were significantly associated with cardiovascular events and total PCS (p = 0.048) was related to all-cause mortality during 38-month follow-up.ConclusionsOur results indicate that total PCS is a valuable marker in predicting cardiovascular event and all-cause mortality in elderly HD patients.

Development and Clinical Validation of a Real-Time PCR Assay for PITX2 DNA Methylation to Predict Prostate-Specific Antigen Recurrence in Prostate Cancer Patients Following Radical Prostatectomy

Prostate cancer is the most common cancer among men. The prospective discrimination of aggressive and clinically insignificant tumors still poses a significant and, as yet, unsolved problem. PITX2 DNA methylation is a strong prognostic biomarker in prostate cancer. Recently, a diagnostic microarray for prostate cancer prognosis based on PITX2 methylation has been developed and validated. Because this microarray requires nonstandard laboratory equipment, its use in a diagnostic setting is limited. This study aimed to develop and validate an alternative quantitative real-time PCR assay for measuring PITX2 methylation that can easily be established in clinical laboratories, thereby facilitating the implementation of this biomarker in clinical practice. A methylation cut-off for patient stratification was established in a training cohort (n = 157) and validated in an independent test set (n = 523) of men treated with radical prostatectomy. In univariate Cox proportional hazards analysis, PITX2 hypermethylation was a significant predictor for biochemical recurrence (P < 0.001, hazard ratio = 2.614). Moreover, PITX2 hypermethylation added significant prognostic information (P = 0.003, hazard ratio = 1.814) to the Gleason score, pathological T stage, prostate-specific antigen, and surgical margins in a multivariate analysis. The clinical performance was particularly high in patients at intermediate risk (Gleason score of 7) and in samples containing high tumor cell content. This assay might aid in risk stratification and support the decision-making process when determining whether a patient might benefit from adjuvant treatment after radical prostatectomy.

Body Weight Loss After Surgery is an Independent Risk Factor for Continuation of S-1 Adjuvant Chemotherapy for Gastric Cancer

Compliance of S-1 adjuvant chemotherapy is not high. The aim of the present study is to clarify risk factors for continuation of S-1 after gastrectomy. This retrospective study selected patients who underwent curative D2 surgery for gastric cancer, were diagnosed with stage 2/3 disease, creatinine clearance more than 60ml/min, and received adjuvant S-1 at our institution between June of 2002 and December of 2011. Time to S-1 treatment failure (TTF) was calculated. A total of 103 patients were selected for the present study. When TTF curve stratified by each clinical factor was compared by the log-rank test, body weight loss (BWL) of 15 % was regarded as a critical point. Both univariate and multivariate Cox proportional hazard analyses demonstrated that BWL was the significant independent risk factor. Moreover, BWL remained a significant factor in both the univariate and multivariate analyses in the subset excluding 8 patients who discontinued S-1 because of recurrence. The 6-month continuation rate was 66.4 % in the patients with BWL<15 and 36.4 % in patients with BWL≥15 % (P = .017). BWL was the most important risk factor for the compliance of adjuvant chemotherapy with S-1 in the patients with stage 2/3 gastric cancer who underwent D2 gastrectomy. To improve drug compliance that leads to survival, it is a key to maintain body weight before starting S-1 adjuvant. Our study emphasizes the requirement for adequate studies of perioperative nutritional intervention in patients who receive gastrectomy for advanced gastric cancer.

8 Years Outcomes of the Dutch Living Donor Kidney Exchange Program

Introduction: In January 2004 the Dutch transplant centers agreed on a protocol for a national Living Donor Kidney Exchange program for ABO blood type incompatible and positive cross match donor-recipient pairs. Here we report the results of that program. Methods: All transplants performed within the Living Donor Kidney Exchange Program between January 2004 and December 2011 were analysed. We collected demographic data of recipients and donors. Univariate and multivariate Cox proportional hazard analyses were performed, including recipient age, donor age and reason for participation in the exchange program. We studied overall survival uncensored and graft survival censored for death in both ABO blood type incompatible and in the positive cross match group. Patients: We enrolled 472 donor-recipient combinations derived from 269 ABO blood type incompatible pairs and 203 positive cross match pairs. At the end we performed 187 kidney transplants (40%) with 83 ABO blood type incompatible and 104 positive cross match pairs. Results: Most of the transplanted recipients (119/187, 64%) had an age difference of less than 5 years with their original incompatible donor. The age differences with their actual donor varied widely, but the number of recipients with a donor > 5 years older was comparable to the number of recipients with a donor > 5 years younger. In the multivariate Cox analysis age as a continuous variable was found to have a significant influence on graft failure. Nevertheless the 5 years uncensored survival (85%) and the graft survival censored for death (89%) were excellent and comparable to the results of direct living donation. No differences were found between the ABO incompatible and the positive cross match group. Conclusion: The Dutch Living Donor Kidney Exchange program has a high transplant rate of 40%, while the 5 years graft survival is excellent.

Completely HLA Mismatched Living Donor Kidneys Have Comparable Results to the Best Matched Deceased Donor Kidneys

Background: HLA mismatches as a categorical variable is known to influence graft survival in deceased donor kidney transplantation. We studied the effect of HLA-A, -B, and -DR mismatches in a population with deceased and living donor kidney transplantations. Methods: All 1821 transplantations performed in our center from 1990 until 2010 were included in the analysis. Univariate and multivariate Cox proportional hazard analyses were performed. Three analyses were performed: HLA mismatches were included as a continuous variable, as a categorical variable (total number of mismatches), and as a binary variable (zero versus non-zero mismatches). Other variables included were year of transplantation, number of previous transplantations, pre-treatment, maximum PRA, current PRA, recipient gender and age, and donor type, gender and age. Results: 941 patients received a deceased donor kidney and 880 a living donor kidney. There were 494 failures, 337 in recipients of deceased donor kidneys and 157 in recipients of living donor kidneys. In multivariate Cox analysis, donor type and age, current PRA, and recipient age were found to have a significant influence on graft failure, censored for death. Number of HLA mismatches had a significant influence in all analyses. There was no interaction between donor type and HLA mismatches. Conclusion: Number of HLA mismatches has a significant influence on death-censored graft survival. This holds true for both deceased and living donor kidney transplantation. However, the risk of death-censored graft failure of a 2-2-2 mismatched living donor kidney is comparable to that of a 0-0-0 mismatched deceased donor kidney (figure 1).[Figure 1]

Single-Center Comparative Oncologic Outcomes of Surgical and Percutaneous Cryoablation for Treatment of Renal Tumors

To compare outcomes between patients undergoing surgical and percutaneous cryoablation for treatment of renal masses and identify prognostic variables that determine survival. We retrospectively evaluated the medical records of 194 patients who underwent cryoablation for renal tumors between 1997 and 2008 at a single large center. Patient demographics, tumor characteristics, perioperative data, and follow-up details were recorded. Univariate and multivariate Cox proportional hazards analysis was performed to identify predictors of overall (OS), cancer-specific (CSS), and recurrence-free survival (RFS). Cryoablation was performed percutaneously (PCA) in 141 patients for 154 tumors, while 53 patients were treated surgically (SCA) using an open or laparoscopic approach for 54 tumors. Mean follow-up was 44.5 months in SCA and 36.1 months in PCA. PCA had a shorter duration of hospital stay (0.7 days vs 3.2 days, P<0.0001). The rate of residual (P=0.38) and recurrent disease (P=0.18) was not significantly different between the two groups. Five-year OS, CSS, and RFS were 78.81%, 100%, and 85.23% for SCA, and 77.71%, 98%, and 95.56% for PCA, respectively; the type of approach was not predictive of OS, CSS, and RFS. SCA and PCA both provide adequate oncologic control for renal masses. Duration of hospital stay was lower in patients undergoing PCA.

High-Resolution CT Findings in Fibrotic Idiopathic Interstitial Pneumonias With Little Honeycombing: Serial Changes and Prognostic Implications

This retrospective study evaluates serial changes of lung abnormalities on high-resolution CT (HRCT) and clarifies prognostic determinants among CT findings in fibrotic idiopathic interstitial pneumonias (IIPs) with little honeycombing. We enrolled 154 patients with a histologic diagnosis of a fibrotic IIP (< 5% honeycombing on CT) who were followed clinically for at least 2 years. One hundred one patients had usual interstitial pneumonia (UIP) and 53 had fibrotic nonspecific interstitial pneumonia (NSIP). On baseline CT, the extent and distribution of lung abnormalities were visually assessed, and serial CT scans were evaluated with a follow-up period of at least 6 months (n = 132). Significant differences were noted in the extent of reticulation and ground-glass opacification (GGO) between the UIP and fibrotic NSIP groups (p < 0.001). On serial scans, honeycombing (5% in UIP and 3% in fibrotic NSIP; p = 0.08) and reticulation (3% in UIP and 8% in fibrotic NSIP; p = 0.03) progressed in extent and GGO (-2% in UIP and -10% in fibrotic NSIP; p = 0.009) decreased in extent. Overall extent of lesions increased in UIP (6%) and decreased in NSIP (-4%) (p = 0.04). On univariate and multivariate Cox proportional hazards analysis, the overall extent of parenchymal abnormalities was a prognostic factor predictive of poor survival duration. Even in cases of fibrotic IIP with little honeycombing, serial CT reveals an increase in the extent of honeycombing and reticulation and a decrease in extent of GGO. Overall extent of lung fibrosis on the baseline CT examination appears predictive of survival in fibrotic IIP with little honeycombing.

Eplerenone and new‐onset diabetes in patients with mild heart failure: results from the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS‐HF)

No studies have examined the effect of mineralocorticoid receptor antagonist therapy on new-onset diabetes. In addition, though the combination of diabetes and chronic heart failure (CHF) carries a poor prognosis, few studies have examined predictors of new-onset diabetes in those with CHF. In patients with symptomatically mild CHF who participated in the placebo-controlled Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure, we examined the effect of the aldosterone antagonist, eplerenone, on physician-diagnosed diabetes using univariate Cox proportional hazard analysis. To identify predictors of new-onset diabetes (measures of glycaemia were not available), data from trial arms were combined and multivariate Cox proportional hazard analyses and receiver operating characteristic curve analyses were conducted. At baseline, the mean age of 1846 initially non-diabetic patients was 69 years and mean left ventricular ejection fraction was 26%. Over 21 months, 69 (3.7%) developed diabetes (33 on eplerenone, 36 on placebo). Eplerenone had no effect on new-onset diabetes [hazard ratio (HR) 0.94, 95% confidence interval (CI) 0.59-1.52] and no effect on the composite of new-onset diabetes or mortality (HR 0.80, 95% CI 0.64-1.01). Independent predictors of new-onset diabetes included digoxin therapy, higher serum alanine aminotransferase, longer duration of heart failure, current or previous smoker, higher waist circumference, lower age, and higher systolic blood pressure with a combined c-statistic of 0.74. Eplerenone had no effect on new-onset diabetes in patients with CHF, but further large-scale studies are required to address this question comprehensively. Commonly recorded parameters provided useful information for predicting new-onset diabetes.

Plasma cell densities and glomerular filtration rates predict renal allograft outcomes following acute rejection

The contribution of T cells and graft-reactive antibodies to acute allograft rejection is widely accepted, but the role of graft-infiltrating B and plasma cells is controversial. We examined 56 consecutive human renal transplant biopsies classified by Banff schema into T-cell-mediated (N = 21), antibody-mediated (N = 18), and mixed (N = 17) acute rejection, using standard immunohistochemistry for CD3, CD20, CD138, and CD45. In a predominantly African-American population (75%), neither Banff classification nor C4d deposition predicted the return to dialysis. Immunohistochemical analysis revealed CD3(+) T cells as the dominant cell type, followed by CD20(+) B cells and CD138(+) plasma cells in all acute rejection types. Using univariate Cox Proportional Hazard analysis, plasma cell density significantly predicted graft failure while B-cell density trended toward significance. Surprisingly T-cell density did not predict graft failure. The estimated glomerular filtration rate (eGFR) at diagnosis of acute rejection also predicted graft failure, while baseline eGFR ≥6 months prior to biopsy did not. Using multivariate analysis, a model including eGFR at biopsy and plasma cell density was most predictive of graft loss. These observations suggest that plasma cells may be a critical mediator and/or an independently sensitive marker of steroid-resistant acute rejection.

Side-by-Side Versus Stent-in-Stent Deployment in Bilateral Endoscopic Metal Stenting for Malignant Hilar Biliary Obstruction

The clinical differences between side-by-side and stent-in-stent deployment using a self-expanding metal stent for hilar malignant obstruction have not been evaluated. The purpose of this study was to compare the clinical features between side-by-side and stent-in-stent deployment. We compared side-by-side and stent-in-stent deployment in 52 consecutive patients with malignant hilar biliary obstruction who underwent endoscopic bilateral drainage using self-expanding metal stent. Side-by-side deployment (SBS group) was performed in 28 patients from 2002 to 2005, and stent-in-stent deployment (SIS group) in 24 patients from 2006 to 2010. Technical success, functional success, complications, stent occlusion and cumulative stent patency in the SBS and SIS groups were evaluated and compared retrospectively. There were no significant inter-group differences in technical success (SBS vs. SIS, 89 vs. 100 %, respectively), functional success (96 vs. 100 %), early complications (11 vs. 4 %), late complications (32 vs. 8 %) or stent occlusion (20 vs. 42 %). The incidence of complications was significantly higher for SBS than for SIS (44 vs. 13 %; p = 0.016). Cumulative stent patency was significantly better for SBS than for SIS (log-rank, p = 0.047). SBS was not associated with significantly longer cumulative stent patency in univariate Cox proportional hazard analysis (HR 0.35; 95 % CI 0.12-1.03; p = 0.056) and multivariate analysis (HR 0.39; 95 % CI 0.13-1.16; p = 0.090). The incidence of complications is higher for side-by-side than stent-in stent deployment in bilateral metal stenting. In terms of cumulative stent patency, side-by-side deployment tends to be more effective than stent-in-stent deployment.

Highly sulfated chondroitin sulfates, a novel class of prognostic biomarkers in ovarian cancer tissue

ObjectiveClinical decision making in ovarian cancer needs new (prognostic) biomarkers. Although the search for biomarkers has traditionally focused on tumor cells, their surrounding contains important information as well. Glycosaminoglycans, heterogeneous polysaccharides which are abundantly present in the stromal compartment, are indicated in several pathological processes including cancer. In this study we investigated a specific glycosaminoglycan motif (4,6-disulfated chondroitin sulfate) for its potential as a prognostic biomarker in ovarian cancer. Methods4,6-Disulfated chondroitin sulfate presence was studied immunohistochemically using the single chain antibody GD3G7 on 148 ovarian tumors including benign and malignant tumors, and tumors with low malignant potential. For comparative purposes p53 and Ki-67 were evaluated. X2 tests, univariate and multivariate Cox proportional hazards analyses were applied for statistical analysis. ResultsThe stroma of malignant tumors showed significantly increased expression of 4,6-disulfated chondroitin sulfate (GD3G7 epitope) compared with benign tumors and tumors with LMP (p-values<0.000 and 0.002, respectively). Expression of GD3G7 in malignant tumors was significantly correlated with serous subtype, high tumor grade, advanced FIGO-stage and high CA-125 levels. In patients with advanced FIGO stage GD3G7 expression was significantly correlated with incomplete debulking and good response to platinum-based chemotherapy. GD3G7 surpassed both p53 and Ki-67 in statistical analysis. Multivariate survival analysis revealed GD3G7 expression as an independent predictor for progression free survival. ConclusionGlycosaminoglycan motifs may form a new class of biomarkers for (ovarian) cancer, as indicated here for the GD3G7 epitope. Expression of GD3G7 may contribute in therapeutic decision making and constitutes a potential biomarker for poor prognosis.