Distinct Survival Curves Research Articles

MSR53 Bayesian Parametric Mixture Survival Models in Immuno-Oncology Applications: Leveraging Control Arm Observations to Model Heterogeneous Response in the Experimental Arm

Heterogeneous response to an intervention is a common feature of survival patterns in randomized clinical trials (RCTs) of immuno-oncology therapies. This effect is usually inadequately represented by standard parametric models. Instead, it is desirable to employ parametric mixture models (PMMs), which represent the cohort as a combination of two latent subpopulations with distinct survival curves. However, classical PMMs are often too complex to parameterize reliably given the limited observations in RCT data.

Renal Sarcoma: A Population-Based Study.

Renal sarcomas are exceedingly rare and lack a prognostic stage classification. We thus aimed to investigate the contemporary clinicopathologic characteristics and outcomes of renal sarcomas at a national level. We utilized the Surveillance, Epidemiology, and End Results database to extract data on patients with renal sarcoma diagnosed between 2004 and 2015. We estimated median, 1-, 3-, and 5-year overall survival (OS) probabilities via Kaplan-Meier curves and used multivariable regression to compare OS between different patient groups. We identified 365 patients; at diagnosis, 104 patients (28.5%) had stage I disease (T1N0M0), 133 patients (36.4%) patients had stage II disease (T2-4N0M0), and 117 patients (32.1%) patients had stage III disease (any T, N1, or M1). Median survival was 105 months (interquartile range [IQR], 29 - not reached) for stage I disease, 46 months (IQR 14-118 months) for stage II disease, 8 months (IQR 3-28 months) for stage III disease, and 32 months (IQR, 8-116 months) for the entire cohort. Patient age (hazard ratio [HR] for death [per year] 1.02, 95% confidence interval [95% CI] 1.00-1.04), stage (II vs. I: HR 1.71, 95% CI 1.00-2.92; III vs. I: HR 4.93, 95% CI 2.68-9.05), grade (grade 3 vs. grade 1: 3.07, 95% CI 1.18-8.00; grade 4 vs. grade 1: HR 3.66, 95% CI 1.41-9.49), and possessing medical insurance (HR 0.40, 95% CI 0.16-0.94) were independently and significantly associated with OS. Performance of nephrectomy also trended towards independently improving OS (HR 0.23, 95% CI 0.05-1.09). A novel staging classification for renal sarcomas into a 3-stage system based on Tumor Node Metastasis (TNM) criteria produces distinct survival curves, although further studies are needed to robustly assess its validity.

A longitudinal population-based study of predictors of mortality from bloodstream infections in Calgary, Alberta, Canada.

Aim: To study the predictors of mortality from nine major pathogens causing approximately70% of cases over a 7-year period. Materials & methods: A population-based surveillance cohort of all adult and pediatric patients in the Calgary Zone with an initial episode of bloodstream infections (BSI). Results: The 1-year mortality was 29.2% among 9524 patients (5164 males [54%]). Incidence rates for BSI increased annually to 119.7/100,000 persons by 2016. Distinct survival curves were found for each specific pathogen. Age, comorbidity burden and infecting organism were significantly associated with increased hazard of death. No relationship occurred between the time to positivity for blood cultures and overall mortality. Conclusion: BSI has a high mortality, but overall survival depends on underlying host health and the type of pathogen acquired.

Impact of Post-Hematopoietic Cell Transplant (HCT) Survival on Cost-Effectiveness of CPX-351 Versus 7+3 in the Treatment of Therapy-Related AML or AML-MRC in the United States

Background: A central goal of treatment for high-risk AML is enabling patients to receive HCT. CPX-351 is a dual-drug liposomal encapsulation of cytarabine and daunorubicin at a synergistic ratio. A large randomized, open-label, multicenter, phase 3 trial demonstrated superior outcomes, including significantly longer overall survival and a larger fraction of patients reaching HCT, for CPX-351 versus conventional cytarabine/daunorubicin (7+3 regimen) in patients aged 60 to 75 years with newly diagnosed therapy-related AML (tAML) or AML with myelodysplasia-related changes (AML-MRC; Lancet JE, et al. J Clin Oncol. 2018). In order to estimate the cost-effectiveness of treatments for AML, and for CPX-351 in particular, it is necessary to extrapolate survival of patients undergoing HCT to the long-term. The objective of this analysis was to assess the impact of different estimates of post-HCT mortality on cost-effectiveness of CPX-351.Methods: An existing economic model of CPX-351 versus 7+3 for the treatment of tAML or AML-MRC was used to project lifetime health and cost outcomes. The modeled population included 30% patients <60 years of age and 70% between 60 and 75 years of age. The model uses a survival-partition approach, with distinct survival curves for cohorts defined by treatment pathways (response and transplantation). Projected life expectancy for each cohort was estimated based on trial data (for those 60-75 years of age), US population life-tables, and published data. For patients younger than age 60, response rates were adjusted based on published literature. Standardized mortality ratio (SMR) values following HCT were selected individually for the younger and older cohorts. SMR values were calibrated in the model to match the literature finding that post-HCT mortality results in a loss of approximately 30% of life expectancy. This yielded an SMR of 2.25 for older patients and 4.0 for younger patients. Values ranged from 1.0 to 4.0 in sensitivity analyses based on recent appraisals by the United Kingdom's National Institute for Health and Care Excellence (NICE). Model outputs included survival, quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratio (ICER).Results: In the base case with different SMR values by age, the model yielded a predicted ICER value of $111,841/QALY in the overall cohort, which compares favorably to the typical $150,000/QALY threshold (Bae 2014) for good value care in the United States. Using the same estimates of SMR in all patients yielded ICER values of $125,280/QALY and $151,793/QALY for SMR values of 2.25 and 4.0, respectively. Assuming no excess mortality post-HCT relative to the general population, using an SMR of 1.0, resulted in modest improvements in cost-effectiveness (ICER = $102,298/QALY).Conclusions: CPX-351 is a cost-effective option for the treatment of patients with tAML or AML-MRC when accounting for potentially increased mortality following HCT. DisclosuresKansal:Jazz Pharmaceuticals: Consultancy. Reifsnider:Jazz Pharmaceuticals: Consultancy. Todorova:Jazz Pharmaceuticals: Employment, Equity Ownership. Coughlan:Jazz Pharmaceuticals: Consultancy. Villa:Jazz Pharmaceuticals: Employment, Equity Ownership, Other: Stock and stock options.

Albumin-Bilirubin and Platelet-Albumin-Bilirubin Grades Accurately Predict Overall Survival in High-Risk Patients Undergoing Conventional Transarterial Chemoembolization for Hepatocellular Carcinoma

PurposeTo evaluate albumin-bilirubin (ALBI) and platelet-albumin-bilirubin (PALBI) grades in predicting overall survival in high-risk patients undergoing conventional transarterial chemoembolization for hepatocellular carcinoma (HCC). Materials and MethodsThis single-center retrospective study included 180 high-risk patients (142 men, 59 y ± 9) between April 2007 and January 2015. Patients were considered high-risk based on laboratory abnormalities before the procedure (bilirubin > 2.0 mg/dL, albumin < 3.5 mg/dL, platelet count < 60,000/mL, creatinine > 1.2 mg/dL); presence of ascites, encephalopathy, portal vein thrombus, or transjugular intrahepatic portosystemic shunt; or Model for End-Stage Liver Disease score > 15. Serum albumin, bilirubin, and platelet values were used to determine ALBI and PALBI grades. Overall survival was stratified by ALBI and PALBI grades with substratification by Child-Pugh class (CPC) and Barcelona Liver Clinic Cancer (BCLC) stage using Kaplan-Meier analysis. C-index was used to determine discriminatory ability and survival prediction accuracy. ResultsMedian survival for 79 ALBI grade 2 patients and 101 ALBI grade 3 patients was 20.3 and 10.7 months, respectively (P < .0001). Median survival for 30 PALBI grade 2 and 144 PALBI grade 3 patients was 20.3 and 12.9 months, respectively (P = .0667). Substratification yielded distinct ALBI grade survival curves for CPC B (P = .0022, C-index 0.892), BCLC A (P = .0308, C-index 0.887), and BCLC C (P = .0287, C-index 0.839). PALBI grade demonstrated distinct survival curves for BCLC A (P = 0.0229, C-index 0.869). CPC yielded distinct survival curves for the entire cohort (P = .0019) but not when substratified by BCLC stage (all P > .05). ConclusionsALBI and PALBI grades are accurate survival metrics in high-risk patients undergoing conventional transarterial chemoembolization for HCC. Use of these scores allows for more refined survival stratification within CPC and BCLC stage.

Independent Analysis of Albumin-Bilirubin Grade in a 765-Patient Cohort Treated with Transarterial Locoregional Therapy for Hepatocellular Carcinoma

PurposeTo assess validity of albumin-bilirubin (ALBI) grade as a predictor of survival in patients undergoing transarterial embolization for hepatocellular carcinoma. Materials and MethodsBaseline albumin and bilirubin values of 765 consecutive patients treated with conventional transarterial chemoembolization or yttrium-90 (90Y) radioembolization at a single institution were used to determine liver function according to ALBI grade. Survival outcomes were stratified by ALBI grade using Kaplan-Meier and stratified by Child-Pugh (C-P) class and Barcelona Clinic Liver Cancer (BCLC) stage. Discriminatory ability was assessed by C-index. ResultsFor 428 patients receiving 90Y radioembolization, ALBI grade yielded distinct survival curves (P < .001). When stratified by C-P class and BCLC stage, ALBI grade revealed different survival outcomes for C-P B (P = .001), BCLC A (P < .001), BCLC B (P = .001), and BCLC C (P < .001). When substratified by BCLC stage, ALBI grade was a better discriminator of survival than C-P class (C-index 0.792, 0.763, respectively). For 337 patients receiving transarterial chemoembolization, ALBI grade yielded distinct survival curves (P < .001). When stratified by C-P class and BCLC stage, ALBI grade provided distinct survival curves for C-P B (P = .02), BCLC B (P = .001), and BCLC C (P = .02). When substratified by BCLC stage, ALBI grade was a better discriminator of survival than C-P class (C-index 0.739, 0.735, respectively). ConclusionsALBI grade outperforms C-P class at discriminating survival in patients receiving transarterial chemoembolization or 90Y radioembolization. ALBI grade is also valuable in patients with moderate liver dysfunction and BCLC B disease.

Tyrosine kinases in soft tissue tumors

The development of therapeutic agents that specifically target the molecular alterations critical for tumorigenesis has a tremendous impact on the management of cancer patients. The successful treatment of advanced gastrointestinal stromal tumors (GIST) with receptor tyrosine kinase (RTK) inhibitors has raised the hope that other malignancies could also benefit from a similar treatment. Tyrosine kinase receptors are promising targets for personalized medicine and new drugs are currently in phase 2 and phase 3 clinical trials. We analyzed a large cohort of soft tissue sarcomas for different tyrosine kinase receptors and correlated the results with clinicopathological parameters. A total of 275 soft tissue sarcomas from the Ludwig-Maximilians University (LMU) were revisited and catagorized according to the current World Health Organization (WHO) classification system. Different entities showed distinct survival curves in 10-year long-term survival. Furthermore, different subtypes of sarcomas showed distinct expression profiles at the protein level. The expression of vascular endothelial growth factor (VEGF) receptors is associated with tumor progression. Due to the fact that not all patients respond to RTK inhibitor therapy, protein signatures should be evaluated before targeting therapy to give a rationale for a viable personalized therapy.

Clinical Relevance of Concomitant Gene Mutations in CEBPA Double-Mutated Acute Myeloid Leukemia.

Abstract 2400 Background:CEBPA mutations occur in 5–14% of patients with acute myeloid leukemia (AML). A difference in clinical outcome between single- (sm) and double-mutated (dm) cases has been reported, whereupon dm cases were shown to be associated with longer overall (OS) and event-free survival (EFS). Aims:1. Determine the frequency and clinical impact of CEBPA sm and dm in a large AML cohort. 2. Evaluate the spectrum of additional molecular mutations in CEBPA dm AML and their prognostic influence. Patients and Methods:First, we investigated CEBPA mutations in a cohort of 997 AML cases (462 female, 535 male; median age: 66.8 years) by 454 deep-sequencing (454 Life Sciences, Branford, CT). The cohort included: t(15;17)(q22;q12) n=33; t(8;21)(q22;q22) n=39; inv(16)(p13q22) n=31; normal karyotype (NK) n=447; complex karyotype (CK) (≥4 abnormalities) n=116; other abnormalities n=331. Second, we investigated an additional cohort of 111 AML dm CEBPA cases for mutations in ASXL1, DNMT3A, FLT3-ITD, FLT3-TKD, GATA2, IDH1/2, KRAS, MLL-PTD, NPM1, NRAS, RUNX1, TET2, TP53, and WT1 using 454 sequencing, Sanger sequencing, conventional PCR and melting curve analyses. This cohort was composed of 60 female and 51 male cases; median age: 62.3 years; 76 cases showed NK, 19 aberrant karyotype (n=4 n.a.). Survival data was available in 90/111 (81.1%) cases. Results:1. In total, CEBPA mutations were detected in 75/997 (7.5%) of cases (t(15;17)(q22;q12) n=2/33; NK n=52/447; CK n=1/116; other abnormalities n=20/331). Of the 75 patients with CEPBA mutations 31 (41.3%) were sm, while 44 (58.7%) were dm. Patients with dm CEPBA showed better outcome compared to sm cases (OS at 3 yrs: 78.9% vs 38.5%, P=0.014; EFS after 3 yrs: 53.9% vs 36.6%, P=0.108). OS and EFS of CEBPA sm cases were comparable to CEPBA wt cases (OS at 3 yrs: 38.5% and 43.6%, P=0.689, EFS at 3 yrs: 36.6% and 29.4%, P=0.678). OS of CEBPA dm cases was comparable to patients with t(15;17)(q22;q12) (OS after 3 yrs: 78.9% vs 86.1%, P=0.597).2. In the cohort of 111 patients we detected 227 CEBPA mutations. In 106 (95.5%) cases two mutations, and in 5 (4.5%) cases three mutations were detected. The median mutation load was 42% (range: 2–98%). The majority of mutations were frame-shift (n=135) and in-frame (n=66). Further, missense (n=19) and nonsense (n=7) mutations were observed. Most cases showed one N- and one C-terminal mutation (92/111, 82.8%), 10 (9.0%) cases harbored two N-terminal mutations, and 4 (3.6%) cases showed two C-terminal mutations. In addition, two cases showed one N- and two C-terminal mutations, two cases two N- and one C-terminal mutations, and one case harbored three N-terminal mutations.In 92/111 (82.9%) cases we observed at least one additional mutation (mean: 1.6 mutations; range: 1–4): TET2 39/109 (35.8%), ASXL1 20/111 (18.0%), GATA2 20/111 (18.0%), WT1 14/111 (12.6%), DNMT3A 11/109 (10.1%), IDH1/2 9/111 (8.1%) (IDH1 n=2, IDH2 n=7), NRAS 9/111 (8.1%), RUNX1 7/111 (6.3%), FLT3-ITD 7/111 (6.3%), KRAS 4/109 (3.7%), NPM1 3/111 (2.7%), FLT3-TKD 2/110 (1.8%), MLL-PTD 1/111 (1.0%), and TP53 1/110 (1.0%). With respect to clinical outcome we observed no differences in OS for concomitant mutations in DNMT3A, FLT3-ITD, IDH1/2, NRAS, TET2 and WT1. Cases with additional GATA2 mutations showed longer survival than wt cases (OS at 3 yrs: 100% versus 73.4%, P=0.026, EFS at 3 yrs: 67.5% versus 48.5%, P=0.137). In contrast, cases harboring additional ASXL1 or RUNX1 mutations were associated with worse outcome (ASXL1: OS at 3 yrs: 32.8% versus 85.7%, P<0.001, EFS at 3 yrs: 0% versus 57.9%, P=0.002; RUNX1: OS at 3 yrs: 0% versus 81.8%, P=0.001, EFS at 3 yeaers: 0% versus 53.8%, P=0.003). Since mutations in ASXL1 and RUNX1 frequently occurred concomitantly, they were grouped together (n=21). When then separating cases into (1) GATA2 mut, (2) GATA2 wt, ASXL1wt, RUNX1wt and (3) ASXL1mut and/or RUNX1mut we observed 3 distinct survival curves (OS at 3 yrs: 100% vs 81.2% vs 32.8, P<0.001, EFS at 3 yrs: 67.5% and 55.3% and 0%, P=0.005). No statistical analysis was performed for FLT3-TKD, KRAS, MLL-PTD, NPM1, TP53 due to the low number of mutations. Conclusions:1. In CEBPA dm cases a high frequency of concomitant mutations (82.9%) was observed. 2. Most common mutated genes were TET2 (35.8%), ASXL1 (18.0%), GATA2 (18.0%), WT1 (12.6%), DNMT3A (10.1%), and RUNX1 (6.3%). 3. In CEBPA dm cases GATA2 mutations were associated with longer OS, whereas OS was poor in ASXL1 and/or RUNX1 mutated cases. Disclosures:Grossmann:MLL Munich Leukemia Laboratory: Employment. Schnittger:MLL Munich Leukemia Laboratory: Equity Ownership. Nadarajah:MLL Munich Leukemia Laboratory: Employment. Weissmann:MLL Munich Leukemia Laboratory: Employment. Fasan:MLL Munich Leukemia Laboratory: Employment. Eder:MLL Munich Leukemia Laboratory: Employment. Stopp:MLL Munich Leukemia Laboratory: Employment. Kern:MLL Munich Leukemia Laboratory: Equity Ownership. Haferlach:MLL Munich Leukemia Laboratory: Equity Ownership. Kohlmann:MLL Munich Leukemia Laboratory: Employment. Haferlach:MLL Munich Leukemia Laboratory: Equity Ownership.

Genetic modifiers of -thalassemia and clinical severity as assessed by age at first transfusion

The clinical and hematologic features of β-thalassemia are modulated by different factors, resulting in a wide range of clinical severity. The main factors are the type of disease-causing mutation and the ability to produce α-globin and γ-globin chains. In the present study we investigated the respective contributions of known modifiers to the prediction of the clinical severity of β-thalassemia as assessed by the patients' age at first transfusion. We studied the effect of seven loci in a cohort of 316 Sardinian patients with β(0)-thalassemia. In addition to characterizing the β-globin gene mutations, α-globin gene defects and HBG2:g.-158C>T polymorphism, we genotyped two different markers in the BCL11A gene and three in the HBS1L-MYB intergenic region using single nucleotide polymorphism microarrays, imputation and direct genotyping. We performed Cox proportional hazard analysis of the time to first transfusion. According to the resulting model, we were able to explain phenotypic severity to a large extent (Harrell's concordance index=0.72; Cox & Snell R(2)=0.394) and demonstrated that most of the model's discriminatory ability is attributable to the genetic variants affecting fetal hemoglobin production (HBG2:g.-158C>T, BCL11A and HBS1L-MYB loci: C-index=0.68, R(2)=0.272), while the remaining is due to α-globin gene defects and gender. Consequently, significantly distinct survival curves can be described in our population. This detailed analysis clarifies the impact of genetic modifiers on the clinical severity of the disease, measured by time to first transfusion, by determining their relative contributions in a homogeneous cohort of β(0)-thalassemia patients. It may also support clinical decisions regarding the beginning of transfusion therapy in patients with β-thalassemia.

Hyperfibrinolysis and Point-of-Care Thromboelastography: Rapid Detection of Hyperfibrinolysis without Immediate Antifibrinolysis Confers Worse Survival Results Than Prophylaxis, In Liver Transplantation

AbstractAbstract 1420 Background and Aims:Bleeding during orthotopic liver transplantation (OLT) can be due to pre-existing conditions associated with the primary disease, peri-operatory complications or systemic disease (such as sepsis or disseminated intravascular coagulation); the procedure itself is associated with pro-hemorrhagic states (reflecting the liver's importance in hemostasis), the most relevant of which is hyperfibrinolysis (HF) –starting in the anhepatic stage after the removal of the host liver, and worsening during reperfusion of the donor organ. Specific prophylaxis minimizes bleeding due to uncontrolled HF; aprotinin was used successfully for prophylaxis until its approval was discontinued. Patients with severe hemorrhages can be stabilized through blood product (BP) transfusion, which is associated with non-negligible morbidity and mortality, and may contribute to decreased survival. Therefore, when HF is identified as a cause of bleeding, it should be addressed and specifically treated with antifibrinolytics; point-of-care (POC) rotational thromboelastography (ROTEG) can quickly evaluate the cumulative function of platelets, coagulation and fibrinolysis, and help identify bleeding due to HF. We have previously found that in our center the use of BP in patients undergoing HF-prophylaxis with aprotinin was identical to those who spontaneously never developed HF, and significantly lower than in those with POC ROTEG-identified HF treated with antifibrinolytics after bleeding had started. We proposed that antifibrinolysis should be instituted as soon as ROTEG-evidence of HF was found, regardless of bleeding status, to decrease the amount of BP transfused. This study aims to determine whether there was a survival difference between the use of prophylaxis and POC ROTEG, as could be suggested by the differences in BP consumption. Methods:We reviewed 293 OLTs performed in our center from January 2004 to December 2009; we excluded 64 transplants which involved pediatric patients (defined as being under 18 years of age), 10 cases with incomplete charts, 30 re-transplants and 14 emergency OLTs for acute toxic hepatic failure. We thus included 175 patients in our survival analysis (Kaplan-Meier). Results:We found that patients undergoing prophylaxis for HF showed no difference in survival (p=0.810) compared to those who did not undergo prophylaxis and in whom ROTEG demonstrated an absence of spontaneous HF. We also found that those patients who were not subjected to prophylaxis - excluding those transplanted for familial amyloid polyneuropathy (FAP) - and in whom (due to logistic reasons) ROTEG was not available to guide treatment, had no difference in survival (p=0.928) compared to those who had ROTEG-confirmed HF (in whom antifibrinolytic treatment was usually not immediately started). In our series of patients we identified three distinct survival curves. Patients transplanted for FAP (a condition which does not affect liver structure or function, but in which OLT can replace a defective metabolic function), who did not undergo prophylaxis or ROTEG, had an overall survival (OS) of 95.1% at 78.0 months of follow-up; patients without HF (either confirmed by ROTEG or as a result of prophylaxis) had an OS of 87.0%; patients with ROTEG-confirmed HF and those without prophylaxis or ROTEG had an OS of 76.5% (p=0.028). Discussion and Conclusions:We conclude that prophylaxis with aprotinin was effective and abolished HF, conferring identical survival results to the subset of patients who spontaneously do not develop HF (as confirmed by ROTEG), while late treatment of confirmed HF with antifibrinolytics produces identical survival results to blind ROTEG-unguided empiricism. Considering patient OS, ROTEG-guided treatment of HF, when not consistently instituted as soon as HF is identified (regardless of bleeding status), confers worse survival results than those previously obtained when HF-prophylaxis was possible using aprotinin. These findings add support to the hypothesis that antifibrinolysis should be started immediately upon recognition of HF on POC ROTEG, to improve overall survival (and, as we previously found, to decrease the consumption of BP). We suggest that operating room protocols should be developed by the surgical and clinical and laboratorial hematology teams, to optimize the choice and dose of antifibrinolytic drugs, and the timing of ROTEG analysis during OLT. Disclosures:No relevant conflicts of interest to declare.

Comparison of two prognostic scores for patients with parotid carcinoma

Salivary glands present a wide diversity in histopathologic types and biologic behaviors, thus complicating the search for prognostic factors. We compared 2 prognostic scores that were previously published for patients with parotid carcinoma in a retrospective series of 175 patients treated in a single institution. Cox multivariate analysis indicated clinical skin invasion, facial nerve function, and perineural growth as the most significant recurrent disease-related prognostic factors. According to the Vander Poorten score, 148 patients were divided into 4 groups, with the 5-year disease-free survival of 76%, 81%, 69%, and 35%, respectively. In the Carrillo's score, the patients were divided into 3 groups: low-risk, intermediate-risk, and high-risk, with the 5-year disease-free survival of 84%, 73%, and 34%, respectively. Carrillo's score showed more distinct survival curves, and determination of groups with a more favorable prognosis was difficult for both scores. Therefore, both scores were not totally reproducible for our group of patients.

Potential demographic and baselines variables for risk stratification of high-risk post-myocardial infarction patients in the era of implantable cardioverter-defibrillator — A prognostic indicator

Background Risk stratification after myocardial infarction (MI) remains expensive and disappointing. We designed a prognostic indicator using demographic information to select patients at risk of dying after MI. Method and results We combined individual patient data from the placebo arms of EMIAT, CAMIAT, TRACE and DIAMOND-MI with LVEF ≤ 40% or ventricular arrhythmias (i.e. > 10 ventricular premature beats/hour or a run of ventricular tachycardia). Risk factors for mortality beginning at day 45 post-MI up to 2 years were examined using Cox regression analysis. Risk scores were derived from the equation of a Cox regression model containing only significant variables. The prognostic index was the sum of the individual contribution from the risk factors. 2707 patients were pooled (age: 66 (23–92) years, 78.8% M) with 480 deaths at 2-years (44% arrhythmic and 35.6% non-arrhythmic cardiac deaths). Variables predicting mortality were age, sex, previous MI or angina, hypertension, diabetes, systolic blood pressure, heart rate, NYHA functional class and non-Q wave infarct on electrocardiogram. Distinct survival curves were obtained for 3 risk groups based on the median and inter-quartile range for the prognostic index. In the high-risk group, up to 40% of patients died (all-cause mortality), 19.1% died of arrhythmic and 18.2% died of non-arrhythmic cardiac causes at 2-years. Conclusion In post-MI patients with LVEF ≤ 40% or frequent ventricular premature beats, the additional use of a simple prognostic indicator based on demographic information was able to provide clinically meaningful risk stratification on patients that were at high risk of dying and may be used to identify patients for prophylactic implantable cardioverter-defibrillator therapy.

Use of Palliative Performance Scale in End-of-Life Prognostication

Current literature suggests clinicians are not accurate in prognostication when estimating survival times of palliative care patients. There are reported studies in which the Palliative Performance Scale (PPS) is used as a prognostic tool to predict survival of these patients. Yet, their findings are different in terms of the presence of distinct PPS survival profiles and significant covariates. This study investigates the use of PPS as a prognostication tool for estimating survival times of patients with life-limiting illness in a palliative care unit. These findings are compared to those from earlier studies in terms of PPS survival profiles and covariates. This is a retrospective cohort study in which the admission PPS scores of 733 palliative care patients admitted between March 3, 2000 and August 9, 2002 were examined for survival patterns. Other predictors for survival included were age, gender, and diagnosis. Study findings revealed that admission PPS score was a strong predictor of survival in patients already identified as palliative, along with gender and age, but diagnosis was not significantly related to survival. We also found that scores of PPS 10% through PPS 50% led to distinct survival curves, and male patients had consistently lower survival rates than females regardless of PPS score. Our findings differ somewhat from earlier studies that suggested the presence of three distinct PPS survival profiles or bands, with diagnosis and noncancer as significant covariates. Such differences are likely attributed to the size and characteristics of the patient populations involved and further analysis with larger patient samples may help clarify PPS use in prognosis.

Identification of Prognostic Factors Associated with Early Mortality after Surgical Resection for Pancreatic Cancer—Under‐analysis of Cumulative Survival Curve

The cumulative survival curve after surgery for advanced pancreatic cancer is characterized by a steep downward slope in the early postoperative period. The aim of this investigation was to identify the characteristics associated with early mortality in patients undergoing pancreatic resection for pancreatic cancer. Thirty-seven patients with extended radical pancreatectomy combined with intraoperative radiation therapy were studied. The cumulative survival curve in this series was depicted using the Kaplan-Meier method. Assuming that there were two distinct survival curves, below and above the breakpoint, each part of the curve was modeled as an exponential distribution. Three parameters, the breakpoint, the high hazard rate below the breakpoint, and the low hazard rate above the breakpoint were estimated by the maximum likelihood method. Prognostic factors associated with early mortality after surgery were evaluated using univariate and multivariate Cox proportional hazards regression analyses. The breakpoint of the survival curve was estimated at 41 months. The short-survival group (SSG) was defined as deceased earlier than 41 months after surgery, and included 31 patients (83.8 %). The long-survival patient group (LSG) consisted of 6 patients who were alive more than 41 months after surgery. Eighteen SSG patients (58.1 %) died of hepatic metastases, whereas no LSG patients died of hepatic metastases. Abdominal pain and/or back pain during clinical course was identified by multivariate analysis as a prognostic factor for patients undergoing pancreatic resection. The high hazard rate in the early postoperative period was closely linked with death due to liver metastases. The preoperative presence of local pain was a prognostic factor associated with early mortality.

Tiller population dynamics and production on Spartina densiflora (Brong) on the floodplain of the Paraná River, Argentina

Abstract Tiller dynamics and net aerial primary productivity (NAPP) were studied in permanent sample plots of Spartina densiflora at Otamendi Natural Reserve (Buenos Aires Province, Argentina) from June 1996 to December 1997. Emergence, growth, senescence, survival, biomass dynamics, and tiller productivity were analyzed. These population attributes varied seasonally during the first study year, whereas variations were not detected in the subsequent year. Tiller density increased slightly during the first twelve months, attaining 2445 ± 869 tillers·m−2, then remaining constant until the end of the study period. Senescence rate was lower than emergence rate on most sampling occasions. Cohorts originated in different seasons showed distinct survival curves. The life span of tillers was at least 18 months. Green biomass reached maximum values (771 ± 410 g·m−2) during the first year but decreased during the last six months of observations. Annual NAPP was 1450 ± 566 g·m−2·y−1. Average productivity rate was hi...

Prognostic criteria in nonfunctioning pancreatic endocrine tumours.

To identify prognostic subgroups among non-functioning (nonsyndromic) pancreatic endocrine tumours, a series of 61 tumours were analysed systematically for macroscopic, histopathological and immunohistochemical variables potentially predictive of malignancy. High-grade nuclear atypia, elevated mitotic rate and multifocal necrosis allowed us to separate 5 poorly differentiated carcinomas from 56 well differentiated tumours. Among the latter, 29 well-differentiated carcinomas showing gross local invasion or metastases were identified. Vascular or perineural microinvasion, Ki67 proliferative index > 2%, mitotic rate > or = 2, size > or = 4 cm, capsular penetration, nuclear atypia, lack of progesterone receptors and presence of calcitonin were among the variables correlated with malignancy. The first two were the most sensitive and specific. Their presence or absence was used in the 27 tumours lacking evidence of malignancy at the time of surgery to separate 11 cases with increased risk of malignancy (in 2 of which metastases developed during follow-up) from 16 cases with limited risk. The resulting four prognostic groups of non-functioning pancreatic endocrine tumours (limited- and increased-risk tumours, well-differentiated carcinomas and poorly differentiated carcinomas) showed distinct survival curves, which were significantly affected by vascular microinvasion, Ki67 proliferative index and metastases.