Independent Predictor Of Worse Outcome Research Articles

Central blood pressure (BP) is an independent predictor of worse outcome in young to middle age subjects screened for stage I hypertension

Central blood pressure (BP) is an independent predictor of worse outcome in young to middle age subjects screened for stage I hypertension

Higher Rates of AML Transformation and Poor Risk Cytogenetics in Patients with Low Average Albumin Levels Confers Poor Prognosis in Myelodysplastic Syndromes,

Abstract 3832Myelodysplastic syndromes (MDS) represent a heterogeneous group of clonal disorders characterized by reduced hematopoiesis and progression to leukemia. Albumin is a prognostic biomarker in many malignant and non-malignant conditions, including multiple myeloma, chronic inflammation and aging. Recently, one study (Yepez, M, ASH 2010, abst #4001) showed that hypoalbuminemia was an independent prognostic factor in MDS. However, serum albumin levels can vary with time and be influenced by nutrition, age and presence of other comorbidities which are prevalent in MDS. To have an accurate assessment, we took the average serum albumin level of MDS patients over a period of 6 months. We hypothesize low average albumin will confer worse outcomes We conducted a retrospective analysis of 237 MDS patients seen in Cleveland Clinic between 1999 and 2009 (RARS= 30, RCMD=25, RAEB1/2=61, 5q- syndrome= 4, CMML1/2=39, MDS/MPN-U=32, RARS-T=30, RCUD=26). A total of 194 patients were included since average albumin was able to be calculated. The median age is 66 (20–92) years. Median follow-up time is 15 months (0–81 months). Clinical information including age, SNP-A karyotyping results, hemoglobin and serum albumin at time of diagnosis, average serum albumin level over 6 months, absolute neutrophil count, platelet counts, bone marrow blasts, and metaphase cytogenetic results were obtained.Patients were divided based on IPSS into lower and higher risk disease. We analyzed a total of 123 patients in the lower risk and 71 patients in the higher risk group. Further, we subdivided patients into lower albumin level (<3.5) or higher (3.5 or greater) based on the average albumin over 6 months. The median overall survival (OS) of the cohort is 15 months. Categorical variables were analyzed using Fisher’s exact test. The Cox-proportional hazards model was used to assess univariate and multivariate analyses for OS and progression free survival (PFS); factors assessed included age (≥60 vs. <60 years), disease grouping (MDS and MDS/MPN vs sAML), BM blasts (≥5 vs. <5 %), Hgb level (≥10 vs. <10 g/dL), metaphase cytogenetics (MC) risk groups using IPSS criteria (good, intermediate, poor), presence or absence of new SNP lesions and average albumin level. Each variable was retained in the multivariate model regardless of its statistical significance. Only variables with p<.05 in multivariate analysis were considered significant. Similar to the study by Yepez M et al, we also found that serum albumin level at the time of original diagnosis is prognostic in MDS and related disorders. Patients with low albumin levels at diagnosis (<3.5) have a worse OS compared to those with high albumin levels (6 vs 16 mos, p=.005). However, this was possible with a dichotomized albumin level. More importantly, we also found that the lower average serum albumin level [OS (8 vs 30 mos, p=.0001) and PFS (5 vs 20 mos, p=<.0001)] over 6 months can also be prognostic in MDS but not in MDS/MPN and sAML. Patients with low average albumin have poorer survival compared to patients with high albumin (OS: 6 vs 23 months, p=<.0001; PFS: 5 vs 15 months, p= <.0001). The same statistically significant findings were observed in patients stratified to lower (OS: 9 vs 37 mos, p=.001; PFS: 5 vs 24 mos, p=<.0001) or higher (5 vs 13 mos, p=.03) risk MDS by IPSS. Multivariate analysis showed that low average albumin level is an independent predictor of poor outcomes in MDS (OS: HR=2.12 CI:1.53–2.99, p=<.0001; PFS: HR=1.91 CI:1.31–2.76, p=.0009). Similarly, previously validated poor prognostic factors in MDS remained significant (Age ≥60 [HR:1.87, p=.0003], sAML disease grouping [HR:2.08, p=.0001], Hgb <10 g/dl [HR:1.42, p=.009], BM blasts [HR:1.44, p=.03], Poor risk cytogenetics [HR:2.22, p=.004], and presence of new SNP lesions [HR:1.59, p=.0008]. To identify factors that may result in worse outcomes in low average albumin patients, we assessed treatment response differences between patients which were not significant between low and high albumin levels. However AML transformation [(42/92 (45%) vs 111/150 (74%), p.002] and cytogenetics [Poor vs Good/Intermediate (21/43 (49%) vs 55/185 (30%), p=.02)] correlated with lower average albumin levels. In conclusion, low average serum albumin levels are an independent predictor of worse outcomes in MDS. Moreover, these data suggest that low average serum albumin is associated with poor risk karyotype and with progression to AML. Disclosures:No relevant conflicts of interest to declare.

Second induction with high-dose cytarabine and mitoxantrone: different impact on pediatric AML patients with t(8;21) and with inv(16)

AbstractPatients with core binding factor acute myeloid leukemia (CBF-AML) benefit from more intensive chemotherapy, but whether both the t(8;21) and inv(16)/t (16;16) subtypes requires intensification remained to be determined. In the 2 successive studies (AML-BFM-1998 and AML-BFM-2004), 220 CBF-AML patients were treated using the same chemotherapy backbone, whereby reinduction with high-dose cytarabine and mitoxantrone (HAM) was scheduled for these cohorts only in study AML-BFM-1998 but not in AML-BFM-2004 against the background to minimize overtreatment. Five-year overall survival (OS) and event-free survival (EFS) were significantly higher and the cumulative incidence of relapse (CIR) lower in t(8;21) patients treated with HAM (n = 78) compared with without HAM (n = 53): OS 92% ± 3% versus 80% ± 6%, plogrank0.047, EFS 84% ± 4% versus 59% ± 7%, plogrank0.001, and CIR 14% ± 4% versus 34% ± 7%, p(gray)0.006. These differences were not seen for inv(16) (n = 43 and 46, respectively): OS 93% ± 4% versus 94% ± 4%, EFS 75% ± 7% versus 71% ± 9% and CIR 15% ± 6% versus 23% ± 8% (not significant). The subtype t(8;21), but not inv(16), was an independent predictor of worse outcome without HAM reinduction. Based on our data, a 5-year OS of > 90% can be expected for CBF-AML, when stratifying t(8;21), but not inv(16), patients to high-risk chemotherapy, including HAM reinduction.

Selected Abstracts

Abstract Objective Damage-control laparotomy, initially developed for trauma patients, has expanded into the general surgery arena. Little evidence exists regarding the utility of damage-control celiotomy (DCCT) in elderly nontrauma patients. Our objective was to review the management and outcomes of DCCT in elderly patients with intra-abdominal catastrophes. Methods Retrospective chart review from 1998 to 2008 identified cases of DCCT. Demographics, comorbidities, surgical techniques, morbidity, long-term disposition, and mortality were analyzed. Results From 210 patients with emergency surgeries, 88 (42%) patients with DCCT were identified, 33 (38%) were greater than 65 years old and 55 (63%) were ≤65 years old. The average APACHE IV score for the elderly was 84 ± 2 versus 68 ± 2 for the younger group ( p Conclusions Age is not an independent predictor of worse outcomes in patients managed by the DCCT technique after intra-abdominal catastrophes. This management technique should be considered for elderly patients who require DCCT.

Do Concomitant Cranium and Axis Injuries Predict Worse Outcome? A Trauma Database Quantitative Analysis

We performed a trauma database analysis to identify the effect of concomitant cranial injuries on outcome in patients with fractures of the axis. We identified patients with axis fractures over a 14-year period. A binary outcome measure was used. Univariate and multiple logistic regression analysis were performed. There were 259 cases with axis fractures. Closed head injury was noted in 57% and skull base trauma in 14%. Death occurred in 17 cases (6%). Seventy-two percent had good outcome. Presence of abnormal computed tomography head findings, skull base fractures, and visceral injury was significantly associated with poor outcome. Skull base injury in association with fractures of the axis is a significant independent predictor of worse outcomes, irrespective of the severity of the head injury. We propose that presence of concomitant cranial and upper vertebral injuries require careful evaluation in view of the associated poor prognosis.

Relative Merits of Left Ventricular Dyssynchrony, Left Ventricular Lead Position, and Myocardial Scar to Predict Long-Term Survival of Ischemic Heart Failure Patients Undergoing Cardiac Resynchronization Therapy

The relative merits of left ventricular (LV) dyssynchrony, LV lead position, and myocardial scar to predict long-term outcome after cardiac resynchronization therapy remain unknown and were evaluated in the present study. In 397 ischemic heart failure patients, 2-dimensional speckle tracking imaging was performed, with comprehensive assessment of LV radial dyssynchrony, identification of the segment with latest mechanical activation, and detection of myocardial scar in the segment where the LV lead was positioned. For LV dyssynchrony, a cutoff value of 130 milliseconds was used. Segments with <16.5% radial strain in the region of the LV pacing lead were considered to have extensive myocardial scar (>50% transmurality, validated in a subgroup with contrast-enhanced magnetic resonance imaging). The LV lead position was derived from chest x-ray. Long-term follow-up included all-cause mortality and hospitalizations for heart failure. Mean baseline LV radial dyssynchrony was 133±98 milliseconds. In 271 patients (68%), the LV lead was placed at the latest activated segment (concordant LV lead position), and the mean value of peak radial strain at the targeted segment was 18.9±12.6%. Larger LV radial dyssynchrony at baseline was an independent predictor of superior long-term survival (hazard ratio, 0.995; P=0.001), whereas a discordant LV lead position (hazard ratio, 2.086; P=0.001) and myocardial scar in the segment targeted by the LV lead (hazard ratio, 2.913; P<0.001) were independent predictors of worse outcome. Addition of these 3 parameters yielded incremental prognostic value over the combination of clinical parameters. Baseline LV radial dyssynchrony, discordant LV lead position, and myocardial scar in the region of the LV pacing lead were independent determinants of long-term prognosis in ischemic heart failure patients treated with cardiac resynchronization therapy. Larger baseline LV dyssynchrony predicted superior long-term survival, whereas discordant LV lead position and myocardial scar predicted worse outcome.

Outcomes of damage-control celiotomy in elderly nontrauma patients with intra-abdominal catastrophes

Objective Damage-control laparotomy, initially developed for trauma patients, has expanded into the general surgery arena. Little evidence exists regarding the utility of damage-control celiotomy (DCCT) in elderly nontrauma patients. Our objective was to review the management and outcomes of DCCT in elderly patients with intra-abdominal catastrophes. Methods Retrospective chart review from 1998 to 2008 identified cases of DCCT. Demographics, comorbidities, surgical techniques, morbidity, long-term disposition, and mortality were analyzed. Results From 210 patients with emergency surgeries, 88 (42%) patients with DCCT were identified, 33 (38%) were greater than 65 years old and 55 (63%) were ≤65 years old. The average APACHE IV score for the elderly was 84 ± 2 versus 68 ± 2 for the younger group ( p < .001). Elderly patients had significantly higher comorbidites with respect to cardiovascular, pulmonary, and renal disease. When comparing the 2 groups, there were no significant differences in-hospital or intensive care unit lengths of stay or ventilator days. There were also no significant differences in complications and disposition. Using Cox proportional hazards analysis, age was not an independent predictor of 30-day mortality. Conclusions Age is not an independent predictor of worse outcomes in patients managed by the DCCT technique after intra-abdominal catastrophes. This management technique should be considered for elderly patients who require DCCT.

Weight Approximation in Stroke Before Thrombolysis

Because of the narrow therapeutic range for thrombolysis in stroke, accurate weight-based dosing is essential for efficacy and safety. Stroke patients are frequently incapable to communicate their correct body weight (BW). Thus, dosing is often based on BW estimation, which may lead to dosing errors. The aim of our study was to evaluate availability of BW information, accuracy of estimations, and final dosing of Alteplase (tissue plasminogen activator [tPA]) in a routine clinical setting. A total of 109 consecutive intravenous thrombolysis patients were prospectively included in the study. Recruitment concluded with 100 complete data sets. Before therapy, BW was estimated independently by 2 physicians, 2 emergency nurses, and a neuroradiological technical assistant. Patients were weighed, and anthropometric measurements for BW approximation were taken. Dosing errors were assessed. Clinical outcome was evaluated at 90 days. Of 109 patients, 55 (50.5%) were unable to provide information on their BW. Of those, 11 (20%) were accompanied by relatives able to give BW information. For all patients, estimation errors rates ranged from 20.8% (patient's own estimation) up to 38.2% (treating physician) and 42.2% (emergency nurse). Finally, 29 patients received an Alteplase dosage diverging >10% from the optimal dose. Twelve were under- and 17 overdosed. Underdosage was an independent predictor for worse outcome in multivariate analysis. Our study shows that reliable BW data are missing for a majority of intravenous thrombolysis patients. Measuring BW before administering Alteplase remains challenging. Given dosing errors in one-third of patients and the observed impact on outcome, standardized weighing before thrombolysis should be considered. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01006434.

Prior Aspirin Use and Outcomes in Acute Coronary Syndromes

The purpose of this study was to determine whether patients taking aspirin before an acute coronary syndrome (ACS) are at higher risk of recurrent events or mortality. Controversy exists whether prior aspirin use is an independent predictor of worse outcomes in patients who experience an ACS. We evaluated 66,443 ACS patients from a merged database of previous Thrombolysis in Myocardial Infarction trials. We evaluated the differences in ACS type, total mortality, and the composite end point of death, myocardial infarction (MI), recurrent ischemia, or stroke between prior aspirin and nonprior aspirin users. We used multivariate analysis to control for differences in baseline characteristics. Prior aspirin users (n = 17,839) were older (63 years vs. 59 years) and had more coronary risk factors and evidence of coronary artery disease (MI, angina, prior intervention) than nonprior aspirin users (n = 48,604) (all p < 0.0001). Prior aspirin use was associated with less severe types of ACS at presentation (e.g., unstable angina > non-ST-segment elevation MI > ST-segment elevation MI) than their nonaspirin user counterparts (p < 0.0001). After multivariate analysis, there was no difference in total mortality between prior aspirin users and nonaspirin users at day 30 (odds ratio [OR]: 1.01; 95% confidence interval [CI]: 0.90 to 1.13) or by the last follow-up visit (mean 328 days) (hazard ratio: 1.03; 95% CI: 0.95 to 1.11). Prior aspirin use was modestly associated with recurrent MI (OR: 1.26; 95% CI: 1.12 to 1.43) and the composite end point (OR: 1.16; 95% CI: 1.08 to 1.24). Prior aspirin use was associated with more comorbidities and coronary disease and a higher risk of recurrent MI, but not mortality. As such, it should best be considered a marker of a patient population at high risk for recurrent adverse events after ACS.

High RASSF1A promoter methylation levels are predictive of poor prognosis in fine-needle aspirate washings of breast cancer lesions

Previously, we reported that the accuracy of cytological diagnosis of breast lesions could be augmented through the quantitative assessment of DNA methylation of fine-needle aspirate (FNA) washings. Herein, we aimed at the evaluation of the prognostic value of quantitative promoter methylation at three gene loci (APC, CCND2, and RASSF1A) in a large series of FNA washings from breast lesions. Methylation levels of three gene promoters were assessed by quantitative methylation-specific PCR in bisulfite-modified DNA from 211 FNA washings, comprising 178 carcinomas and 33 benign lesions, both histopathologically confirmed. Receiver operator characteristic (ROC) curve analysis was used to determine the diagnostic performance of the gene panel in distinguishing cancer from non-cancerous lesions. Relevant clinicopathologic data and time to progression and/or death from breast cancer were correlated with methylation findings. Log-rank test and Cox-regression model identified independent predictors of prognosis. APC, CCND2, and RASSF1A methylation levels differed significantly between malignant and benign lesions. ROC curve analysis confirmed the diagnostic performance of the gene panel. In univariate analysis, stage was significantly associated with overall, disease-specific and disease-free survival, whereas tumor grade was associated with disease-specific and disease-free survival. Remarkably, RASSF1A methylation was significantly and independently associated with worse disease-free survival in the final multivariate analysis. We confirmed that quantitative gene promoter methylation augments the diagnostic performance of cytopathology. Importantly, and in addition to standard clinicopathologic parameters, RASSF1A high-methylation levels are independent predictors of worse outcome in breast cancer. Thus, epigenetic biomarkers provide valuable tools for breast cancer patient management.

Intermittent claudication as a predictor of outcome in patients with ischaemic systolic heart failure: analysis of the Controlled Rosuvastatin Multinational Trial in Heart Failure trial (CORONA)

To examine the relationship between baseline intermittent claudication and outcomes in patients enrolled in the Controlled Rosuvastatin Multinational Trial in Heart Failure trial (CORONA). Intermittent claudication is an independent predictor of worse outcome in coronary heart disease, but its prognostic importance in heart failure (HF) is unknown. Patients aged >or=60 years with NYHA class II-IV, low ejection fraction HF of ischaemic aetiology were enrolled in CORONA. Rosuvastatin did not reduce the primary outcome or all-cause mortality. To determine whether intermittent claudication was an independent predictor of clinical outcomes, a three-step multivariable model was built: (i) demographic/clinical variables, (ii) biochemical measures added, (iii) high-sensitivity C-reactive protein and N-terminal pro B-type natriuretic-peptide added. Of the 5011 patients, 637 (12.7%) had intermittent claudication at baseline. Patients with intermittent claudication were more likely to be male (83 vs. 75%), be a current smoker (19 vs. 9%), and have diabetes mellitus (36 vs. 29%) relative to those without intermittent claudication. Over a median 33-month follow-up, 2168 patients died or were hospitalized for HF. Patients with intermittent claudication had an increased risk of death (any cause) (adjusted hazard ratio 1.36, 95% CI 1.19-1.56, P < 0.0001), death from worsening HF (1.35, 1.03-1.77, P = 0.028), sudden death (1.24, 1.00-1.54, P = 0.05), and risk of non-fatal or fatal myocardial infarction (time to first event 1.67, 1.24-2.27, P < 0.001). In the full multivariable model, intermittent claudication remained an independent predictor of most outcomes evaluated. Intermittent claudication is a relatively common symptom in ischaemic HF and an independent predictor of worse outcome. NCT00206310-http://clinicaltrials.gov/ct2/show/NCT00206310?term=corona&rank=2.

Prognostic significance of CD20 expression in adults with de novo precursor B-lineage acute lymphoblastic leukemia

AbstractImmunophenotypic classification of acute lymphoblastic leukemia (ALL) has well-recognized prognostic implications. The significance of CD20 expression has been evaluated in childhood precursor B-lineage ALL with conflicting results. We retrospectively analyzed the influence of CD20 expression on outcome in 253 adults with de novo precursor B-lineage ALL treated with either conventional (VAD/CVAD) or intensive (hyper-CVAD) frontline chemotherapy regimens in the pre-rituximab era. Overall, CD20 positivity of at least 20% was associated with lower 3-year rates of complete remission duration (CRD; 20% vs 55%, P < .001) and overall survival (OS; 27% vs 40%, p = .03). In the CD20 negative subset, the 3-year rates for CRD (58% vs 42%, p = .04) and OS (60% vs 28%, P < .001) were superior for hyper-CVAD compared with VAD/CVAD; rates were particularly favorable for the CD20 negative younger age group (68% and 85%, respectively). In contrast, 3-year CRD and OS rates were uniformly poor for the CD20-positive group regardless of therapy (27% or less). Multivariate analysis for event-free survival identified older age, leukocyte count higher than 30 × 109/L, presence of Philadelphia chromosome, high systemic risk classification, and CD20 positivity as independent predictors of worse outcome. In conclusion, CD20 expression in de novo adult precursor B-lineage ALL appears to be associated with a poor prognosis. Incorporation of monoclonal antibodies directed against CD20 into frontline chemotherapy regimens warrants investigation.

Pediatric Intestinal Foregut and Small Bowel Solid Tumors: A Review of 105 Cases

The outcomes of pediatric intestinal foregut and small bowel solid tumors have never been studied on a population scale. The Surveillance, Epidemiology, and End Results database (1973-2005) was queried for all patients under 20 y of age. A total of 105 cases of pediatric intestinal foregut and small bowel solid tumors were identified. Tumors occurred in the esophagus (8.6%), stomach (61%), and small bowel (30.5%). The most common histologies include sarcoma (43.8%), which consisted mostly of gastrointestinal stromal tumors (GIST), carcinoma (41.0%), which consisted mostly of adenocarcinomas, and neuroendocrine tumors (NET) (10.5%). Most tumors were poorly differentiated and presented with advanced disease. The overall median survival time was 207 mo. Gastric solid tumors had significantly worse 5- and 10-y survival compared with their small bowel counterparts, though this difference disappeared in those who received surgical resection. Patients with carcinoma had significantly worse survival compared with those with sarcoma or NET, regardless of site and surgical intervention. Univariate analysis identified race, differentiation, stage, and surgery as significant predictors of survival. Multivariate analysis revealed that African American race, advanced stage of disease, carcinoma histology, and failure to undergo surgical extirpation were all independent predictors of worse outcome. In patients with carcinoma, failure to undergo radiotherapy was also a predictor of worse outcome. Surgery is associated with a significantly improved survival for pediatric patients with solid tumors of the intestinal foregut and small bowel. Radiotherapy appears to be an important adjuvant therapy for patients with carcinoma.

Simple intravenous fluid regimens to control fever in hospitalized stroke patients: A theoretical evaluation

Fever is an independent predictor of worse outcome in stroke patients. We hypothesized that a peripheral infusion of saline in chilled or ice slurry form can be a practical adjuvant therapy to maintain euthermia. We developed a theoretical model simulating systemic body cooling in response to 0 °C saline and 50% ice slurry. Temperature elevations up to 39 °C were studied with respect to the time needed to reach a core temperature of 37 °C. Mathematical modeling identified a cooling rate of 0.48 °C/hr and 0.24 °C/hr using a 450 mL/hr infusion of 50% ice slurry and chilled saline. A reduction of the infusion rate to 150 mL/hr decreased euthermia time by a factor of 3; however, the total amount of coolant remained constant. Thus, based on mathematical modeling, peripheral infusions of saline in chilled or ice slurry form can be used as an adjunct therapy to achieve euthermia and control fever. Using intravenous coolants in an on-demand, temperature-guided and supervised treatment setting seems most reasonable to avoid potentially unsafe use of extended fluid volumes and infusion times.

Hyperglycemia as An Independent Predictor of Worse Outcome in Non-diabetic Patients Presenting with Acute Ischemic Stroke

To determine if differences in outcome exist between diabetic and non-diabetic patients who present to the Emergency Department (ED) with acute ischemic stoke (AIS) and elevated blood glucose. The study population consisted of 447 consecutive patients who presented to the ED with AIS within 24 h of symptom onset and had blood glucose measured on presentation. Hyperglycemia was defined as >130 mg/dl. Outcomes studied included infarct volume, stroke severity (NIH Stroke Scale), functional impairment (modified Rankin Score), and 90-day mortality. Patients with hyperglycemia were then stratified into those with and without a prior history of diabetes mellitus (DM) for the purposes of analysis. Patients with hyperglycemia exhibited significantly greater stroke severity (P = 0.002) and greater functional impairment (P = 0.004) than those with normoglycemia. Patients with hyperglycemia were 2.3 times more likely to be dead at 90 days compared to those with normal glucose (P < 0.001). Stroke severity (P < 0.001) and functional impairment (P < 0.001) were both significantly worse in patients with hyperglycemia and no prior history of DM, when compared to patients with hyperglycemia and previously diagnosed DM. Among the patients without a prior history of DM, patients with hyperglycemia were 3.4 times more likely to die within 90 days (P < 0.001) when compared with patients with normoglycemia. In contrast, the hazard ratio was 1.6 among the patients with DM (P = 0.66). Hyperglycemia on presentation is associated with significantly poorer outcomes following AIS. Patients with hyperglycemia and no prior history of DM have a particularly poor prognosis, worse than that for patients with known diabetes and hyperglycemia.

Total cholesterol levels and mortality risk in nonischemic systolic heart failure

Prior studies have demonstrated that low serum total cholesterol (TC) is associated with increased mortality in heart failure (HF); however, this association has not been consistently observed in HF of nonischemic etiology. We analyzed a cohort of 614 patients with nonischemic systolic HF (left ventricular ejection fraction [LVEF] <40%). Fasting lipid panels were drawn at time of referral. Patients were stratified into quartiles of TC (Q1 <133, Q2 134-168, Q3 169-209, and Q4 >210 mg/dL). The cohort was 68% male, mean age was 48 +/- 13 years, and LVEF was 23% +/- 7%. Patients with lower serum TC had worse hemodynamic profiles, lower LVEF, and higher New York Heart Association class. Low TC was associated with increased risk of 1-year death and urgent transplant (UT) (49%, 29%, 18%, 14% for Q1-Q4 respectively, P < .0001) as well as all-cause mortality (P < .0001). On multivariate analysis, adjusting for multiple HF prognostic factors, low TC proved to be an independent predictor of worse outcomes, with hazard ratios for death and UT of 3.4, 1.8, and 1.6 for Q1 to Q3, respectively, compared with Q4. Based on receiver operating characteristic curve analysis, the best cutoff for prediction of death and UT for TC was 161 mg/dL. Low TC is strongly associated with increased mortality in patients with nonischemic, systolic HF. Further research is necessary to determine the nature of this relationship, optimal lipid levels, and the therapeutic role, if any, of statins in patients with established HF.

The Role of Abdominoperineal Resection as Surgical Therapy for Anorectal Melanoma

1) Characterize changes in the surgical treatment of anorectal melanoma over time. 2) Determine if the extent of surgical resection is associated with outcome. 3) Identify prognostic factors correlating with survival. Although early data suggested improved survival in patients undergoing abdominoperineal resection (APR) for primary anorectal melanoma, such an aggressive approach may be unwarranted as distant relapse rates are high. We have seen a trend toward less aggressive surgical treatment of the local disease over the past 20 years. A retrospective review was performed of all patients with anorectal melanoma treated at our institution between 1984 and 2003. Extent of primary resection and pathologic factors were studied. Forty-six patients underwent a curative resection with a median follow-up of 29 months, and 5-year disease-specific survival (DSS) rate of 35%. While patient and tumor characteristics remained similar, there was a dramatic shift in surgical treatment toward less radical procedures. Prior to 1997, the majority of patients (15 of 21, 71%) underwent APR. After 1997, the majority of patients (21 of 25, 84%) underwent local excision (LE) (P < 0.0001). Local recurrence was noted in 11 of 46 (24%) patients: 4 of 19 (21%) who underwent APR and 7 of 27 (26%) who underwent LE (P = not significant). Five-year DSS was similar: 34% following APR and 35% following LE. Tumor perineural invasion (PNI) was the only factor identified as an independent predictor of worse outcome (P = 0.01). The extent of surgical treatment is not associated with outcome in primary anorectal melanoma. Therefore, LE of the primary tumor is recommended when technically feasible. The presence of PNI is an important prognostic factor and should be considered in future clinical trials.

Renal Function as a Predictor of Outcome in a Broad Spectrum of Patients With Heart Failure

Decreased renal function has been found to be an independent risk factor for cardiovascular outcomes in patients with chronic heart failure (CHF) with markedly reduced left ventricular ejection fraction (LVEF). The aim of this analysis was to evaluate the prognostic importance of renal function in a broader spectrum of patients with CHF. The Candesartan in Heart Failure:Assessment of Reduction in Mortality and Morbidity (CHARM) program consisted of three component trials that enrolled patients with symptomatic CHF, based on use of ACE inhibitors and reduced (< or =40%) or preserved LVEF (>40%). Entry baseline creatinine was required to be below 3.0 mg/dL (265 micromol/L). Routine baseline serum creatinine assessments were done in 2680 North American patients. An analysis of the estimated glomerular filtration rate (eGFR), using the Modification of Diet in Renal Disease equation and LVEF on risk of cardiovascular death or hospitalization for heart failure, as well as on all-cause mortality, was conducted on these 2680 patients. The proportion of patients with eGFR <60 mL/min per 1.73 m2 was 36.0%; 42.6% for CHARM-Alternative, 33.0% for CHARM-Added, and 34.7% for CHARM-Preserved. During the median follow-up of 34.4 months (total 6493 person-years), the primary outcome of cardiovascular death or hospital admission for worsening CHF occurred in 950 of 2680 subjects. Both reduced eGFR and lower LVEF were found to be significant independent predictors of worse outcome after adjustment for major confounding baseline clinical characteristics. The risk for cardiovascular death or hospitalization for worsening CHF as well as the risk for all-cause mortality increased significantly below an eGFR of 60 mL/min per 1.73 m2 (adjusted hazard ratio, 1.54 for 45 to 60 mL/min per 1.73 m2 and 1.86 for <45 mL/min per 1.73 m2 for the primary outcome, both P<0.001, and hazard ratio of 1.50, P=0.006, and 1.91, P=0.001, respectively, for all-cause mortality). The prognostic value of eGFR was not significantly different among the three component trials. There was no significant interaction between renal function, the effect of candesartan, and clinical outcome. Impaired renal function is independently associated with heightened risk for death, cardiovascular death, and hospitalization for heart failure in patients with CHF with both preserved as well as reduced LVEF. There was no evidence that the beneficial effect of candesartan was modified by baseline eGFR.

Elevated creatine kinase-MB with normal creatine kinase predicts worse outcomes in patients with acute coronary syndromes: Results from 4 large clinical trials

The degree to which elevated creatine kinase (CK)-MB in the presence of normal CK is predictive of outcome is not well understood despite having been studied for decades. This analysis examined whether normal CK with elevated CK-MB in patients with non-ST-segment elevation acute coronary syndrome (NSTE ACS) is an independent predictor of worse outcomes. A concomitant goal was to contribute insight to the debate over how patients with NSTE ACS should be managed. Data for 25,960 patients from the GUSTO IIb, PARAGON A and B, and PURSUIT trials were analyzed. Of these patients, 6402 were excluded from primary analysis because of missing (unmeasured) biomarkers. Patients with complete laboratory data (n = 19,558) were grouped by CK and CK-MB results. To confirm the primary analysis results, data from patients with missing biomarkers were used in an imputation model. Patients were categorized in 1 of 4 groups: normal CK + normal CK-MB; normal CK + elevated CK-MB; elevated CK + normal CK-MB; or elevated CK + elevated CK-MB. For the primary outcome, 180-day death, or myocardial infarction, Kaplan-Meier estimates were 14.9%, 20.8%, 14.5%, and 18.2%, respectively. Regardless of total CK, elevated CK-MB was associated with a 25% to 49% increased relative risk of worse outcomes. Findings from the analyses were verified by the multivariable model. CK-MB remains a reliable marker for myocardial necrosis and a strong predictor of worse prognosis. All patients with ACS should have CK-MB measurement to search for cardiac ischemia. Patients with elevated CK-MB should receive aggressive management commensurate with their increased risks.

Glomerular monocytes predict worse outcomes after acute renal allograft rejection independent of C4d status

Both peritubular capillary (PTC) C4d deposition and macrophage/monocyte (MO) infiltration in acute rejection (AR) have separately been shown to be associated with reduced graft survival and recently were demonstrated to be closely correlated in AR. Whether MO infiltration is an independent predictor of graft outcome is uncertain. All patients with biopsy-proven AR (over a 3-year period) were included (N= 96). All biopsies (N= 121) were graded according to the Banff 97 criteria and immunohistochemically stained for C4d and MO (CD68). The primary outcome was glomerular filtration rate (GFR) <30 mL/min 1-year posttransplant as estimated by the Modified Diet in Renal Disease (MDRD) Formula. Secondary outcomes at 2 and 4 years' posttransplant were also explored. A variety of clinical and biopsy variables were statistically analyzed to establish univariate predictors of graft outcome. Stepwise multivariate logistic regression modeling was applied to determine independent predictors of outcomes. There was a close correlation between PTC C4d and glomerular MO infiltration (P < 0.001). Univariate predictors of primary outcome (GFR <30 mL/min 1-year posttransplant) included mean glomerular MO count > or =1.0 MO/glomerulus (P= 0.014), female sex (P= 0.02), higher peak (P= 0.005), and pretransplant (P= 0.003) panel-reactive antibody levels, cadaveric donor (P= 0.006), transplant glomerulitis (P= 0.004), and longer cold ischemic time (CIT) (P= 0.002). Mean MO/glomerulus > or =1.0 [OR 10.3 (1.23, 87.1)], female sex [OR 5.27(1.31, 21.1)], and CIT [OR 1.14 (1.06, 1.25)] were identified as independent predictors of adverse graft outcome. Furthermore, mean MO/glomerulus > or =1.0 independently predicted poor renal function at 2 years [OR 3.89 (1.19, 12.70)] and 4 years [OR 4.03 (1.22, 13.28)] posttransplant. The results demonstrate that glomerular MO infiltration is an independent predictor of worse outcomes posttransplant following acute renal allograft rejection.