Traditional Clinical Factors Research Articles

Clinical Characteristics and Prognosis of 84 Elderly Patients with Acute Myeloid Leukemia

To explore the prognostic factors of elderly AML patients, as well as the application and prognostic value of comprehensive geriatric assessment（CGA） in elderly AML patients in China, so as to determine a suitable comprehensive assessment method that can predict survival and guide treatment of patients in Chinese people. Retrospective analysis was performed on the medical records of 84 AML patients aged over 60 years old, and diagnosed in our department from October 2007 to December 2017, and the clinical, pathological and comprehensive evaluation of related prognostic factors was analyzed. The median age of all patients was 70 (60-91) years old, ratio of male to female was 1.9∶1 (55∶29) , the median OS time was 9 (1-125) months, 1 year OS rate was 35.3%, and 5 year OS rate was 12.6%. The age grouping, remission of induction chemotherapy, whether refractory/relapse, WBC count grouping at initial diagnosis, levels of lactate dehydrogenase and creatinine were risk factors for OS. Remission of induction chemotherapy, whether refractory/relapse, WBC count grouping and co-infections at initial diagnosis, levels of lactate dehydrogenase, and ECOG score were the risk factors for DFS. In the assessment of comorbidities, the two score classifications of charlson comorbidity index(CCI) were the risk factor of OS, however,whose effects for DFS were not statistically different. The effects of 3 score classifications of hemaotopoietic cell transplantation comorbidity index (HCT-CI), 4 score classifications of comulative illness kating scale for geriatrics (CIRS-G) and 3 score classifications of CIRS-G on OS and DFS were not statistically different. The impact of the ACA index on OS and DFS was statistically significant in elderly patients. All indexes related with patients self factors and disease-related factors were no independent prognostic factors for OS and DFS, so the judgment of prognosis needs to be comprehensively evaluated. The prognosis and treatment selection of elderly AML patients should be combined with traditional clinical and pathological prognostic factors as well as comprehensive assessment of the elderly patients.

Development of a prognostic risk model for small cell lung cancer: Identification of high-, intermediate-, and low-risk cohorts based on clinical-genomic data.

8554 Background: Although many clinical prognostic factors for SCLC outcome have been described, there are no models that incorporate the combination of clinical and genomic details into a risk model defining high and low risk patients. Methods: From a total of 791 SCLC patients seen between 2013-2018, 91 were evaluated by exome sequencing. Using the univariate Cox regression model, 19 genes were prognostic for survival and included RET, ERBB4 MAP3K1, ABL1, CCND1, TSC1, PRKCI, FGFR3, JAK3, ZNF217, BRCA1, GPR124, LRP1B, GNAS, TAF1, FGF3, STAT3, CD79A and FLT. LASSO, elastic-net Cox and traditional Cox model with stepwise selection along with traditional clinical factors (age and stage) were further used to build the final model. The final risk groups were defined based upon the prognostic index from multivariable Cox model involving age, stage (extensive/limited) and 6 genes ( MAP3K1, ABL1, CCND1, PRKCI, BRCA1, GNAS). Results: The overall survival (OS) for the entire cohort was 11.2 (95% CI: 9 – 13.4) months and the median age was 65 (range: 39 - 90) years. Eighty percent (N = 74) of evaluated patients had extensive stage (ES) disease. The HR for death of age and stage (ES/LS) was 1.06 (CI: 1.03-1.08, p < 0.0001) and 4.33 (CI: 2.23-8.41, p < 0.0001) respectively. ABL1 demonstrated the highest HR of 10.14 (2.81-36.6, p = 0.0004) followed by PRKCI (HR: 5.05, CI: 1.43-17.8 , p < 0.012), CCND1 (HR: 4.52, CI: 1.23-16.57, p < 0.023), MAP3K1 (HR: 3.38, CI: 1.37- 8.33, p = 0.008) and GNAS (HR: 2.21, CI: 1.11-4.43, p < 0.025). Interestingly, BRACA1 mutation was protective as patients with BRACA1 mutation had significantly better overall survival (HR: 0.3, CI: 0.1- 0.85, p < 0.023). Our model categorized patients into three groups of low risk ( N= 31), intermediate risk ( N= 30) and high risk ( N= 30) with significantly different survival outcomes ( p < 0.0001). Those with low risk had the median OS of 27.4 (95% CI: 16.8-55.5) months, intermediate risk with median OS of 10.8 (95% CI: 7 – 14.7) months and high risk with median OS of 5.4 (95% CI: 3.9- 9) months. Conclusions: This clinical-genomic risk group stratification represents a useful model to estimate SCLC survival outcome and may have value in future clinical trials.

Patient-reported distress and symptoms predict post-esophagectomy outcomes.

e15567 Background: Esophagectomy is accompanied by significant morbidity, mortality and altered quality of life. Understanding the factors responsible for adverse post-operative outcomes is essential for risk stratification in the selection of patients for surgery. Patient-reported measures are important not only as treatment outcome metrics, but also in predicting tolerance to therapy. Postoperative length of stay is a convenient measurement of patient tolerance of surgery. Our study aim was to determine whether preoperative patient-reported measures could add additional predictive power to clinical variables in predicting postoperative length of stay. Methods: A tablet-based symptom screening tool measured Distress, Anxiety (GAD-2), and cancer-related symptoms preoperatively. A generalized linear model predicting postoperative length of stay was constructed using age, gender, insurance status, income, T stage, and sarcopenia (hand-grip strength < 25kg). Patient-reported variables were then evaluated for their ability to predict length of stay in addition to these clinical factors. Factors found not significant (p > 0.05) are indicated N.S. Results: Esophagectomy (n = 58): Median age 62 (IQR 54-70) and 46 men (79%). Adenocarcinoma in 52 (90%). Neoadjuvant chemoradiation administered in 37 (64%). Major complications occurred in 13 (22%). Median postoperative length of stay was 8 days (IQR 6-10). Distress, Pain, Nausea/Vomiting, Trouble Swallowing, and Insurance or Financial Concerns independently predicted postoperative longer length of stay on multivariable analysis, while accounting for preoperative clinical factors. Conclusions: Preoperative cancer patient symptom reporting adds additional information to traditional clinical factors in predicting length of stay post-esophagectomy. Patient-reported measures may identify patients who benefit from interventions for preoperative optimization.[Table: see text]

Abstract P5-18-09: Performance of Oncotype DX DCIS score across diverse ethnic populations

Abstract There is a paucity of data on Oncotype DX DCIS Score and ethnic variation. It has been postulated that there are different molecular features /drivers among different ethnic populations. The Oncotype DX DCIS Score is a genomic test designed to analyze the expression of a group of 12 genes which can quantify 10-year local recurrence risk after surgery. The purpose of this study is to evaluate diverse ethnic patients with DCIS relative to traditional clinical pathologic factors and Oncotype DX DCIS Score We analyzed consecutive cases of DCIS from 2011-2017 who underwent Oncotype DX DCIS Score testing at a single institution. Eighty-four female patients were divided into 5 groups based on self-reported ethnicity: White (36%), African American (AA) (48%), Asian (8%), Hispanic (4%) and Other (4%). Clinical and traditional pathologic factors were collected including age, nuclear grade (NG), ER/PR status and Oncotype DX DCIS Score. The distribution of NG and Oncotype DX DCIS Score was analyzed across ethnic groups. The mean age at diagnosis was 63. Overall 99 % of cases were hormone positive. Comparison of White and AA patients revealed a correlation between ethnic group and DCIS Score, with a p value of 0.0087 (Table 1). Similarly, we looked at all five ethnic groups and Oncotype DX DCIS Score and found a p value of 0.022. We evaluated ethnicity with White and AA patients versus NG and obtained a p value of 0.084 (Table 2). In addition, we assessed all five ethnic groups and NG. We obtained a p value of 0.068. No AA patients with DCIS had a high DCIS Score. No patients with low NG DCIS had a high DCIS Score. Analysis of the three factors (NG, ethnicity and DCIS Score) concurrently showed that they are not independent. In summary, our study provides valuable data on Oncotype DX DCIS Score and NG across a diverse patient population. These data highlight the importance of incorporating both traditional clinical pathologic factors and DCIS Score molecular testing for making treatment decision across different ethnic patient populations. Table 1.Comparison of DCIS Score and Ethnic GroupEthnic GroupLow DCIS ScoreIntermediate DCIS ScoreHigh DCIS ScoreAA3730White2704p=0.0087 Table 2.Comparison of Nuclear Grade and Ethnic GroupEthnic GroupNuclear Grade 1Nuclear Grade 2Nuclear Grade 3AA17194White1399p=0.084 Citation Format: Mittar P, Casella S, Bombonati A, Emiloju O, Jablon L, Schultz D, Leighton JC, Solin LJ. Performance of Oncotype DX DCIS score across diverse ethnic populations [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-18-09.

Using Neighborhood-Level Census Data to Predict Diabetes Progression in Patients with Laboratory-Defined Prediabetes.

Research on predictors of clinical outcomes usually focuses on the impact of individual patient factors, despite known relationships between neighborhood environment and health. To determine whether US census information on where a patient resides is associated with diabetes development among patients with prediabetes. Retrospective cohort study of all 157,752 patients aged 18 years or older from Kaiser Permanente Northern California with laboratory-defined prediabetes (fasting plasma glucose, 100 mg/dL-125 mg/dL, and/or glycated hemoglobin, 5.7%-6.4%). We assessed whether census data on education, income, and percentage of households receiving benefits through the US Department of Agriculture's Supplemental Nutrition Assistance Program (SNAP) was associated with diabetes development using logistic regression controlling for age, sex, race/ethnicity, blood glucose levels, and body mass index. Progression to diabetes within 36 months. Patients were more likely to progress to diabetes if they lived in an area where less than 16% of adults had obtained a bachelor's degree or higher (odds ratio [OR] =1.22, 95% confidence interval [CI] = 1.09-1.36), where median annual income was below $79,999 (OR = 1.16 95% CI = 1.03-1.31), or where SNAP benefits were received by 10% or more of households (OR = 1.24, 95% CI = 1.1-1.4). Area-level socioeconomic and food assistance data predict the development of diabetes, even after adjusting for traditional individual demographic and clinical factors. Clinical interventions should take these factors into account, and health care systems should consider addressing social needs and community resources as a path to improving health outcomes.

A Single-Institution Experience in the Preoperative Selection of DCIS Patients for IORT using the ASTRO Consensus Guidelines

PurposeIntraoperative radiation therapy (IORT) as a form of accelerated partial breast irradiation (APBI) is controversial given the limited evidence to support its efficacy. However, it remains an attractive option for low-risk patients with ductal carcinoma in situ (DCIS), who derive a small absolute benefit in local control with standard whole breast irradiation (WBI). We examine how the American Society for Therapeutic Radiation Oncology (ASTRO) APBI consensus guidelines (CG) may be applied to the preoperative selection of patients with DCIS for IORT and determine treatment outcomes by CG group. Methods and MaterialsWe identified patients with biopsy-proven pure DCIS enrolled in an institutional prospective registry IORT database using the Zeiss Intrabeam® device between September 2013 and February 2017. Based on available preoperative clinicopathologic information, patients were deemed suitable, cautionary, or unsuitable for IORT according to the ASTRO CG. Change in CG group based on final pathologic diagnosis was determined, and additional therapy was recommended for unsuitable patients. Outcome in terms of ipsilateral breast tumor recurrence was determined. ResultsA total of 61 DCIS lesions in 60 patients were treated with IORT. Preoperatively, 21 patients (35%) were suitable and 36 (59%) were cautionary. Four (6%) were unsuitable because of lesion size but declined WBI. Final pathologic diagnosis changed the CG grouping of 10 patients (16%) because of either occult high-grade disease in 2 (3%) or close/positive margins in 8 (13%). Ultimately 12 patients total were considered unsuitable, of whom 8 (66%) accepted additional WBI after IORT. At a median follow-up of 2.2 years, ipsilateral breast tumor recurrence was identified among 2 suitable, 1 cautionary, and no unsuitable patients. ConclusionFurther investigation is necessary to refine selection of patients with DCIS who may be optimally treated with IORT alone. High acceptance of additional therapy among unsuitable patients resulted in excellent outcomes. The use of biomarkers in addition to traditional clinical and pathologic factors may help to better select patients for IORT.

Atherogenic index of plasma (AIP): a novel predictive indicator for the coronary artery disease in postmenopausal women

BackgroundDyslipidemia is one of the most important factors for coronary artery disease (CAD). Atherogenic index of plasma (AIP) is a novel indicator involved in dyslipidemia. However, the relation between AIP and CAD in postmenopausal women remains unclear. We hypotheses that AIP is a strong predictive indicator of CAD in postmenopausal women.MethodsA propensity score matching case–control study including 348 postmenopausal CAD cases and 348 controls was conducted in the present study.ResultsCompared with controls, CAD patients had higher levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (APOB), but lower high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-1 (APOA-1). The values of nontraditional lipid profiles, including non-HDL-C, TC/HDL-C, LDL-C/HDL-C, non-HDL-C/HDL-C (atherogenic index, AI), TC∗TG∗LDL/HDL-C (lipoprotein combine index, LCI), log(TG/HDL-C) (atherogenic index of plasma, AIP) and APOB/APOA-1 were all significantly higher in the CAD patients. The results of Pearson correlation analyses showed AIP was positively and significantly correlated with TC (r = 0.092, P < 0.001), TG (r = 0.775, P = 0.015), APOB (r = 0.140, P < 0.001), non-HDL-C (r = 0.295, P < 0.001), TC/HDL-C (r = 0.626, P < 0.001), LDL-C/HDL-C (r = 0.469, P < 0.001), AI (r = 0.626, P < 0.001), LCI (r = 0.665, P < 0.001), APOB/APOA-1(r = 0.290, P < 0.001) and was negatively correlated with APOA-1 (r = − 0.278, P < 0.001) and HDL-C (r = − 0.665, P < 0.001). In the multivariate logistic regression analysis, AIP was an independent predictor of CAD. After adjusting for the traditional clinical prognostic factors including diabetes and hypertension, we found AIP could be an independent risk factor for CAD (odds ratio [OR], 3.290; 95% confidence interval [CI], 1.842–5.877, P < 0.001). After adjusting for multiple clinical factors include diabetes, hypertension, smoking, heart ratio, fasting blood glucose, we found AIP also could a powerful risk factor, OR = 3.619, 95%CI (2.003–6.538), P < 0.001.ConclusionThe present study indicated that AIP might be a strong marker for predicting the risk of CAD in postmenopausal women.

The prognostic role of HBV infection in chronic lymphocytic leukemia.

We attempt to assess the impact of hepatis-B virus (HBV) status on the prognosis of chronic lymphocytic leukemia (CLL) using a Chinese case cohort. Five hundred and one consecutive newly diagnosed subjects with CLL were enrolled in this case cohort. HBV infection was defined as hepatitis B surface antigen (HBsAg) positive or hepatitis-B core antibody (HBcAb) positive. Univariate and stepwise multivariate Cox regression analyses were used to screen the prognostic risk factors associated with the end point of time-to-treatment (TTT) or overall survival (OS). Bootstrap re-sampling method was used to evaluate the model's internal validity. The discriminative ability of the models was evaluated using time-dependent receiver-operator characteristic (ROC) curves and corresponding areas under the curve (AUC). One hundred and twenty-one subjects (24%) among 501 patients were HBV positive. HBV infection was an independent predictor for the prognosis of TTT (HR = 1.37; 95% CI 1.04-1.80) or OS (HR =2.85; 95% CI 1.80-4.52). The AUCs for HBV infection were 0.62 (95% CI 0.58-0.66) for TTT and 0.69 (95%CI 0.66-0.72) for OS, respectively. When we combined HBV infection with the traditional clinical and biological factors, significant improvements for model's discrimination were observed for TTT [AUC: 0.81 (95% CI: 0.77-0.85) vs. 0.78 (95% CI: 0.74-0.82), P < 0.001] and OS [AUC: 0.81 (95% CI 0.76-0.86) vs. 0.76 (95% CI 0.71-0.82), P < 0.001). Further bootstrap re-sampling method revealed good internal consistence for the final optimal models (Average AUC: 0.78 for TTT and 0.79 for OS based on 1000 bootstraps). Our results indicated that HBV infection should be served as an important risk predictor for prognosis of CLL (TTT and OS).

Risk stratification including FOXO1 fusion status (FOXO1) in patients with rhabdomyosarcoma (RMS) treated on six recent frontline trials: A report from the Children's Oncology Group (COG).

10528 Background: Clinical risk factors associated with outcome in children with either localized or metastatic RMS were identified by Meza et al. (2006) and Oberlin et al. (2008). We re-examined risk stratification by adding FOXO1 to traditional clinical prognostic factors in children with localized or metastatic RMS in a large cohort from COG frontline clinical trials. Methods: Data from six COG clinical trials (D9602, D9802, D9803, ARST0331, ARTS0431, ARST0531) accruing previously untreated patients with RMS from 1997 to 2013 yielded 1,853 eligible patients (two studies each for low, intermediate and high risk patients). Survival tree regression for event-free survival (EFS) and overall survival (OS) was conducted to determine prognostic impact of risk factors. Recursively, the factor most strongly associated with outcome was selected for branching and split using a goodness of fit measure. Factors included were age, FOXO1, group, histology, nodal status, number of metastatic sites, primary site, sex, tumor size, and presence of metastases in bone/bone marrow, soft tissue, effusions, lung, distant lymph nodes, and other sites. Results: 5-year overall EFS and OS was 0.67 (SE, 0.01) and 0.77 (SE, 0.01), respectively. Survival trees for EFS and OS found localized versus metastatic at the first split and included FOXO1 as a significant risk factor. Conclusions: FOXO1 improves risk stratification of patients with localized RMS, although histology and pattern of metastases are more predictive for patients with metastatic RMS. Our findings support incorporation of FOXO1 in risk stratified clinical trials. [Table: see text]

MMP11 and CD2 as novel prognostic factors in hormone receptor-negative, HER2-positive breast cancer

PurposeMore accurate prediction of patient outcome based on molecular subtype is required to identify patients who will benefit from specific treatments.MethodsWe selected novel 16 candidate prognostic genes, including 10 proliferation-related genes (p-genes) and 6 immune response-related genes (i-genes), from the gene list identified in our previous study. We then analyzed the association between their expression, measured by quantitative real-time reverse transcription-PCR in formalin-fixed, paraffin-embedded tissues, and clinical outcome in 819 breast cancer patients according to molecular subtype.ResultsThe prognostic significance of clinical and gene variables varied according to the molecular subtype. Univariate analysis showed that positive lymph node status was significantly correlated with the increased risk of distant metastasis in all subtypes except the hormone receptor-negative, HER2-positive (HR−/HER2+) subtype. Most p-genes were significantly associated with poor prognosis in patients with the HR+/HER2− subtype, whereas i-genes correlated with a favorable outcome in patients with HR−/HER2+ breast cancer. In HR−/HER2+ breast cancer, four genes (three i-genes BTN3A2, CD2, and TRBC1 and the p-gene MMP11) were significantly associated with distant metastasis-free survival (DMFS). A new prognostic model for HR−/HER2+ breast cancer based on the expression of MMP11 and CD2 was developed and the DMFS for patients in the high-risk group according to our model was significantly lower than that for those in the low-risk group. Multivariate analyses revealed that our risk score is an independent prognostic factor for DMFS. Moreover, C-index showed that our risk score has a superior prognostic performance to traditional clinicopathological factors.ConclusionsOur new prognostic model for HR−/HER2+ breast cancer provides more accurate information on the risk of distant metastasis than traditional clinical prognostic factors and may be used to identify patients with a good prognosis in this aggressive subtype of breast cancer.

Reactive Hyperemia Index in Patients on Maintenance Hemodialysis: Cross-sectional Data from a Cohort Study

Previous studies suggested that the reactive hyperemia index (RHI) is a promising cardiovascular risk predictor. We aimed to evaluate clinical determinants of RHI and its association with circulating endothelial injury and cardiac markers in hemodialysis patients. Among 368 patients recruited, RHI was evaluated by peripheral arterial tonometry (PAT) on a midweek nondialysis day. Clinical determinants of RHI were explored by multiple stepwise regression analysis and associations between RHI and circulating markers were evaluated by general linear models. The major cause of a failed PAT test was poor signal (82.1%). Intraclass correlation coefficient for reproducibility evaluation was 0.74. Multiple regression analysis showed traditional clinical factors only explained 7% of the variance of natural logarithm RHI (LnRHI) in the patients. In association analyses, LnRHI showed significant positive associations with Von Willebrand factor (vWF) (p = 0.04) and tissue factor (p = 0.047). It also associated positively with troponins (p ≤ 0.02 for both). In conclusion, performance of the PAT test was acceptable in dialysis patients and traditional clinical variables had very limited influence on RHI in these subjects. Among a panel of conventional endothelial injury markers, RHI showed very modest associations with only vWF and tissue factor. RHI associated positively with troponins in the patients.

Community Mental Health Care Providers' Understanding of Recovery Principles and Accounts of Directiveness with Consumers.

The present qualitative study examined community mental health providers' accounts of their therapeutic interactions with adults with serious mental illness in a recovery-oriented model of care. Ten long-time mental health care providers discussed their understanding of recovery principles, their use of directive practices, and factors that shape their work with consumers. Content analysis of mental health providers' accounts suggest that providers had no difficulty articulating basic principles of recovery-oriented care. Providers reported engaging in directive practices with consumers and described using traditional clinical factors such as level of functioning, degree of psychiatric symptoms, safety concerns, and legal status to assess consumers' ability for autonomous decision making. Providers generally did not express tension between their views of mental health recovery and their beliefs about utilizing directive approaches with consumers. Implications of present findings for research and practice are discussed.

Comparison of generic and lung cancer-specific quality of life instruments for predictive ability of survival in patients with advanced lung cancer.

BackgroundOur purpose is to examine the relationship of Health related quality of life measured by EORTC QLQc30, QLQ-LC13; FACT-L, LCSS, Eq5D) with survival in advanced lung cancer patients. A total of 299 Lung Cancer (LC) patients were, included in this national multicenter Project entitled of “the LC Quality of Life Project (AKAYAK). Baseline scores were analyzed by using Cox’s proportional hazard regression to identify factors that influenced survival. Univariate and multivariate models were run for each of the scales included in the study.ResultsMean and median survival were 12.5 and 8.0 months respectively. Clinical stage (as TNM), comorbidity; symptom scales of fatigue, insomnia, appetit loss and constipation were associated with survival after adjustment for age and sex. Global, physical and role functioning scales of QLQc30; physical and functional scales of LCS and TOI of the FACT-L was also associated with survival. Mobility and Usual activities dimensions of the Eq5D; Physical functioning and the constipation symptom scale of the QLQ-c30; and LCS and TOI scores of the FACT-L remained statistically significant after adjustment. LC13 and LCSS scales were not predictors of survival.ConclusionsHRQOL serves as an additional predictive factor for survival that supplements traditional clinical factors. Besides the strong predictive ability of ECOG on survival, FACT-L and the Eq5D are the most promising HRQOL instruments for this purpose.

A two-stage approach for combining gene expression and mutation with clinical data improves survival prediction in myelodysplastic syndromes and ovarian cancer.

Many traditional clinical prognostic factors have been known for cancer for years, but usually provide poor survival prediction. Genomic information is more easily available now which offers opportunities to build more accurate prognostic models. The challenge is how to integrate them to improve survival prediction. The common approach of jointly analyzing all type of covariates directly in one single model may not improve the prediction due to increased model complexity and cannot be easily applied to different datasets. We proposed a two-stage procedure to better combine different sources of information for survival prediction, and applied the two-stage procedure in two cancer datasets: myelodysplastic syndromes (MDS) and ovarian cancer. Our analysis suggests that the prediction performance of different data types are very different, and combining clinical, gene expression and mutation data using the two-stage procedure improves survival prediction in terms of improved concordance index and reduced prediction error. The two-stage procedure can be implemented in BhGLM package which is freely available at http://www.ssg.uab.edu/bhglm/. nyi@uab.edu.

Integrating Positive and Clinical Psychology: Viewing Human Functioning as Continua from Positive to Negative Can Benefit Clinical Assessment, Interventions and Understandings of Resilience

In this review we argue in favour of further integration between the disciplines of positive and clinical psychology. We argue that most of the constructs studied by both positive and clinical psychology exist on continua ranging from positive to negative (e.g., gratitude to ingratitude, anxiety to calmness) and so it is meaningless to speak of one or other field studying the “positive” or the “negative”. However, we highlight historical and cultural factors which have led positive and clinical psychologies to focus on different constructs; thus the difference between the fields is more due to the constructs of study rather than their being inherently “positive” or “negative”. We argue that there is much benefit to clinical psychology of considering positive psychology constructs because; (a) constructs studied by positive psychology researchers can independently predict wellbeing when accounting for traditional clinical factors, both cross-sectionally and prospectively, (2) the constructs studied by positive psychologists can interact with risk factors to predict outcomes, thereby conferring resilience, (3) interventions that aim to increase movement towards the positive pole of well-being can be used encourage movement away from the negative pole, either in isolation or alongside traditional clinical interventions, and (4) research from positive psychology can support clinical psychology as it seeks to adapt therapies developed in Western nations to other cultures.

Next generation sequencing profiling identifies miR-574-3p and miR-660-5p as potential novel prognostic markers for breast cancer.

BackgroundPrognostication of Breast Cancer (BC) relies largely on traditional clinical factors and biomarkers such as hormone or growth factor receptors. Due to their suboptimal specificities, it is challenging to accurately identify the subset of patients who are likely to undergo recurrence and there remains a major need for markers of higher utility to guide therapeutic decisions. MicroRNAs (miRNAs) are small non-coding RNAs that function as post-transcriptional regulators of gene expression and have shown promise as potential prognostic markers in several cancer types including BC.ResultsIn our study, we sequenced miRNAs from 104 BC samples and 11 apparently healthy normal (reduction mammoplasty) breast tissues. We used Case–control (CC) and Case-only (CO) statistical paradigm to identify prognostic markers. Cox-proportional hazards regression model was employed and risk score analysis was performed to identify miRNA signature independent of potential confounders. Representative miRNAs were validated using qRT-PCR. Gene targets for prognostic miRNAs were identified using in silico predictions and in-house BC transcriptome dataset. Gene ontology terms were identified using DAVID bioinformatics v6.7. A total of 1,423 miRNAs were captured. In the CC approach, 126 miRNAs were retained with predetermined criteria for good read counts, from which 80 miRNAs were differentially expressed. Of these, four and two miRNAs were significant for Overall Survival (OS) and Recurrence Free Survival (RFS), respectively. In the CO approach, from 147 miRNAs retained after filtering, 11 and 4 miRNAs were significant for OS and RFS, respectively. In both the approaches, the risk scores were significant after adjusting for potential confounders. The miRNAs associated with OS identified in our cohort were validated using an external dataset from The Cancer Genome Atlas (TCGA) project. Targets for the identified miRNAs were enriched for cell proliferation, invasion and migration.ConclusionsThe study identified twelve non-redundant miRNAs associated with OS and/or RFS. These signatures include those that were reported by others in BC or other cancers. Importantly we report for the first time two new candidate miRNAs (miR-574-3p and miR-660-5p) as promising prognostic markers. Independent validation of signatures (for OS) using an external dataset from TCGA further strengthened the study findings.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-1899-0) contains supplementary material, which is available to authorized users.

The value of noncoronary atherosclerosis for identifying coronary artery disease: results of the Leipzig LIFE Heart Study.

BackgroundDespite the widespread use of noninvasive testing prior to invasive coronary diagnostic the diagnostic yield of elective coronary angiography has been reported low in subjects with suspected obstructive CAD.ObjectiveTo determine the predictive value of noncoronary atherosclerosis (NCA) in subjects with suspected stable coronary artery disease (CAD) intended to invasive coronary angiography.MethodsUltrasound-based assessment of carotid artery plaque (CAP), carotid intima-media thickness (CIMT) and ankle-brachial index (ABI) was performed in 2216 subjects with suspected CAD prior to coronary angiography. Logistic regression and c-statistics were used to analyze the diagnostic value of NCA for the presence of obstructive CAD and the intention to revascularization.ResultsPercentage of positive results of elective coronary angiography was low but comparable to other studies (41 % obstructive CAD). We identified 1323 subjects (60 %) with NCA, most of them were characterized by CAP (93 %). CAP independently predicted obstructive CAD in addition to traditional risk factors and clinical factors while CIMT and ABI failed to improve the prediction. The presence of NCA and typical angina were the strongest predictors for obstructive CAD (OR 4.0 and 2.4, respectively). A large subgroup of patients (n = 703, 32 %) with atypical clinical presentation and lack of NCA revealed a low indication for revascularization <15 % indicating a large proportion of subjects with non-obstructive CAD in this subgroup.ConclusionThe evaluation of noncoronary atherosclerosis has the potential to impact clinical decision making and to direct subsequent diagnostic procedures in subjects with suspected coronary artery disease.Clinical trial registrationNCT00497887.Electronic supplementary materialThe online version of this article (doi:10.1007/s00392-015-0900-x) contains supplementary material, which is available to authorized users.

Ion channel gene expression predicts survival in glioma patients.

Ion channels are important regulators in cell proliferation, migration, and apoptosis. The malfunction and/or aberrant expression of ion channels may disrupt these important biological processes and influence cancer progression. In this study, we investigate the expression pattern of ion channel genes in glioma. We designate 18 ion channel genes that are differentially expressed in high-grade glioma as a prognostic molecular signature. This ion channel gene expression based signature predicts glioma outcome in three independent validation cohorts. Interestingly, 16 of these 18 genes were down-regulated in high-grade glioma. This signature is independent of traditional clinical, molecular, and histological factors. Resampling tests indicate that the prognostic power of the signature outperforms random gene sets selected from human genome in all the validation cohorts. More importantly, this signature performs better than the random gene signatures selected from glioma-associated genes in two out of three validation datasets. This study implicates ion channels in brain cancer, thus expanding on knowledge of their roles in other cancers. Individualized profiling of ion channel gene expression serves as a superior and independent prognostic tool for glioma patients.

Associations between proteasomal activator PA28γ and outcome of oral squamous cell carcinoma: Evidence from cohort studies and functional analyses

SummaryBackgroundPA28γ was suggested to play a role in malignant progression. This paper aimed to investigate the association between PA28γ and the prognosis of oral squamous cell carcinoma (OSCC) in cohort studies.MethodsThe PA28γ expression level was assessed by immunohistochemistry in a total of 368 OSCC patients from three independent cohorts. The Cox proportional hazards regression model was used to determine multivariate hazard ratios for Overall Survival (OS). Model discrimination was measured using C Statistic. Additionally, OS was analyzed in Head Neck Squamous Cell Carcinoma (HNSCC) patients from The Cancer Genome Atlas (TCGA) data set. Functional analyses were conducted both in-vitro and in-vivo.FindingsThe median follow-up times of patients in the three studies were 60, 52, and 51 months. High expression of PA28γ was identified in tumors from 179 of 368 patients (48.6%). Compared with low expression, high expression of PA28γ was strongly associated with worse OS, with relative risks of 5.14 (95% CI, 2.51–10.5; P < 0.001), 2.82 (95% CI, 1.73–4.61; P < 0.001), and 3.85 (95% CI, 1.59–9.37; P = 0.003). PA28γ expression was also associated with disease-free survival in all three cohorts (P < 0.005). These findings are consistent with TCGA HNSCC data (P < 0.006). The prediction of all-cause mortality was significantly improved when PA28γ was added to the traditional clinical factors (Model 3, C statistic value: 0.78 VS 0.73, P = 0.016). In functional analyses, we found that PA28γ silencing dramatically inhibited the growth, proliferation and mobility of OSCC cells in vitro and reduced tumor growth and angiogenesis in tumor-bearing mice.InterpretationPA28γ overexpression is associated with adverse prognosis in patients with OSCC. The aberrant expression of PA28γ may contribute to the pathogenesis and progression of OSCC.Research in contextOSCC is one of the most common HNSCC, which have a high lethally rate. However, few prognostic markers have been applied in the clinical practice. We found that PA28γ in OSCC tumor tissues were significantly high expression than those in normal tissues. As the results of the three cohorts from two independent research centers and from an additional validation cohort from a US population in the TCGA dataset, we demonstrate PA28γ is a good predictor of the risk of death in OSCC. Meanwhile, we demonstrate PA28γ have a potential role in OSCC tumorigenesis.

Abstract OT3-2-02: MINT I: Multi-Institutional Neo-adjuvant Therapy, MammaPrint Project I

Abstract Background: Women with locally advanced breast cancer (LABC) are often treated with neo-adjuvant chemotherapy to reduce the size of the tumor prior to surgery, to enable breast conserving surgery and to observe the clinical effect of therapy in real time. Studies have shown that the 25–27% of individuals who have a pathologic complete response (pCR) to neoadjuvant therapy have a survival advantage of 80% in 5 years, which is double the expected survival of the remaining patients without pCR. If patients who are likely to show a pCR could be identified prior to initiation of therapy, it would enable more informed treatment decisions – patients likely to respond would be served well by current neoadjuvant chemotherapy protocols, while those unlikely to respond may be better suited to innovative new strategies for drug discovery [von Minckwitz et al. JCO 2006]. Genomic assays, which are widely used to provide prognostic and predictive information in early breast cancer, have the potential to provide information on the likelihood of a patient with LABC responding to neo-adjuvant therapy [Glück et al. BRCRT2013]. Trial design: MINT I is a prospective study designed to test the ability of molecular profiling, as well as traditional pathologic and clinical prognostic factors, to predict response to neo-adjuvant chemotherapy in patients with LABC. MammaPrint risk profile, BluePrint molecular subtyping profile, TargetPrint estrogen receptor (ER), progesterone receptor (PR) and HER2 single gene readout, and TheraPrint Research Gene Panel will be analyzed on a fresh tumor specimen using the whole genome array. Patients will receive neo-adjuvant chemotherapy pre-specified in the protocol. Response will be measured centrally. pCR is defined as the absence of invasive carcinoma in both the breast and axilla at microscopic examination of the resection specimen, regardless of the presence of carcinoma in situ. Eligibility: The study will include women ≥18 years with histologically-proven invasive breast cancer T2 (≥3.5cm)-T4, N0M0 or T2-T4N1M0, adequate bone marrow reserves and normal renal and hepatic function who signed an IRB approved informed consent. Objectives: The objectives of the study are to: 1. Determine the predictive power of MammaPrint and BluePrint for sensitivity to neo-adjuvant chemotherapy as measured by pCR. 2. Compare TargetPrint ER, PR and HER2 with local and centralized IHC and/or CISH/FISH assessment. 3. Identify correlations between TheraPrint and response to neo-adjuvant chemotherapy. 4. Identify and/or validate predictive gene expression profiles of clinical response or resistance to neo-adjuvant chemotherapy. 5. Compare BluePrint with IHC-based subtype classification. Statistical methods: Standard statistical tests such as the Pearson Chi-square test will be used to characterize and evaluate the relationship between chemoresponsiveness and gene expression patterns. Accrual: A total of 226 eligible patients will be enrolled from multiple institutions. To date (June 06, 2014), 103 patients have been enrolled. Citation Format: Charles E Cox, Peter Blumencranz, Ruben Saez, Robert Wesolowski, William Dooley, Lisette Stork-Sloots, Femke de Snoo, Sarah Untch, Eli Avisar. MINT I: Multi-Institutional Neo-adjuvant Therapy, MammaPrint Project I [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr OT3-2-02.