Prognostic value of inflammation-based scores in patients with osteosarcoma

PubMed Central

Liu, Bangjian; Huang, Yujing; Sun, Yuanjue; Zhang, Jianjun; Yao, Yang; Shen, Zan; Xiang, Dongxi; He, Aina

2016-01-01

Systemic inflammation responses have been associated with cancer development and progression. C-reactive protein (CRP), Glasgow prognostic score (GPS), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), lymphocyte-monocyte ratio (LMR), and neutrophil-platelet score (NPS) have been shown to be independent risk factors in various types of malignant tumors. This retrospective analysis of 162 osteosarcoma cases was performed to estimate their predictive value of survival in osteosarcoma. All statistical analyses were performed by SPSS statistical software. Receiver operating characteristic (ROC) analysis was generated to set optimal thresholds; area under the curve (AUC) was used to show the discriminatory abilities of inflammation-based scores; Kaplan-Meier analysis was performed to plot the survival curve; cox regression models were employed to determine the independent prognostic factors. The optimal cut-off points of NLR, PLR, and LMR were 2.57, 123.5 and 4.73, respectively. GPS and NLR had a markedly larger AUC than CRP, PLR and LMR. High levels of CRP, GPS, NLR, PLR, and low level of LMR were significantly associated with adverse prognosis (P < 0.05). Multivariate Cox regression analyses revealed that GPS, NLR, and occurrence of metastasis were top risk factors associated with death of osteosarcoma patients. PMID:28008988

Electrolyte and Metabolic Disturbances in Ebola Patients during a Clinical Trial, Guinea, 2015

PubMed Central

Bah, Elhadj Ibrahima; Haba, Nyankoye; Delamou, Alexandre; Camara, Bienvenu Salim; Olivier, Kadio Jean-Jacques; De Clerck, Hilde; Nordenstedt, Helena; Semple, Malcolm G.; Van Herp, Michel; Buyze, Jozefien; De Crop, Maaike; Van Den Broucke, Steven; Lynen, Lutgarde; De Weggheleire, Anja

2016-01-01

By using data from a 2015 clinical trial on Ebola convalescent-phase plasma in Guinea, we assessed the prevalence of electrolyte and metabolic abnormalities at admission and their predictive value to stratify patients into risk groups. Patients underwent testing with a point-of-care device. We used logistic regression to construct a prognostic model and summarized the predictive value with the area under the receiver operating curve. Abnormalities were common among patients, particularly hypokalemia, hypocalcemia, hyponatremia, raised creatinine, high anion gap, and anemia. Besides age and PCR cycle threshold value, renal dysfunction, low calcium levels, and low hemoglobin levels were independently associated with increased risk for death. A prognostic model using all 5 factors was highly discriminatory (area under the receiver operating curve 0.95; 95% CI 0.90–0.99) and enabled the definition of risk criteria to guide targeted care. Most patients had a very low (<5%) or very high (>80%) risk for death. PMID:27869610

Electrolyte and Metabolic Disturbances in Ebola Patients during a Clinical Trial, Guinea, 2015.

PubMed

van Griensven, Johan; Bah, Elhadj Ibrahima; Haba, Nyankoye; Delamou, Alexandre; Camara, Bienvenu Salim; Olivier, Kadio Jean-Jacques; De Clerck, Hilde; Nordenstedt, Helena; Semple, Malcolm G; Van Herp, Michel; Buyze, Jozefien; De Crop, Maaike; Van Den Broucke, Steven; Lynen, Lutgarde; De Weggheleire, Anja

2016-12-01

By using data from a 2015 clinical trial on Ebola convalescent-phase plasma in Guinea, we assessed the prevalence of electrolyte and metabolic abnormalities at admission and their predictive value to stratify patients into risk groups. Patients underwent testing with a point-of-care device. We used logistic regression to construct a prognostic model and summarized the predictive value with the area under the receiver operating curve. Abnormalities were common among patients, particularly hypokalemia, hypocalcemia, hyponatremia, raised creatinine, high anion gap, and anemia. Besides age and PCR cycle threshold value, renal dysfunction, low calcium levels, and low hemoglobin levels were independently associated with increased risk for death. A prognostic model using all 5 factors was highly discriminatory (area under the receiver operating curve 0.95; 95% CI 0.90-0.99) and enabled the definition of risk criteria to guide targeted care. Most patients had a very low (<5%) or very high (>80%) risk for death.

Lymph node ratio as a prognostic factor in metastatic cutaneous head and neck squamous cell carcinoma.

PubMed

Vasan, Kartik; Low, Tsu-Hui Hubert; Gupta, Ruta; Ashford, Bruce; Asher, Rebecca; Gao, Kan; Ch'ng, Sydney; Palme, Carsten E; Clark, Jonathan R

2018-05-01

The prognostic impact of the size and number of nodal metastases in head and neck cutaneous squamous cell carcinoma (SCC) is well established. The purpose of this study was to validate the prognostic significance of the lymph node ratio in metastatic head and neck cutaneous SCC. A retrospective review of 326 patients with head and neck cutaneous SCC with parotid and/or cervical nodal metastases was performed. The primary endpoints were overall survival (OS) and disease-free survival (DFS). The minimal-P approach was used to investigate the optimal lymph node ratio threshold. Our data included 77 recurrences and 101 deaths. A lymph node ratio of 6% was a significant predictor of shorter DFS (hazard ratio [HR] 1.62; 95% confidence interval [CI] 1.11-2.38; P = .01) and OS (HR 1.63; 95% CI 1.03-2.58; P = 0.04) on multivariable analysis. The lymph node ratio is an independent prognosticator of survival outcomes in patients presenting with metastatic head and neck cutaneous SCC. A lymph node ratio >6% is a significant threshold to categorize patients into low and high risk. © 2018 Wiley Periodicals, Inc.

ExSurv: A Web Resource for Prognostic Analyses of Exons Across Human Cancers Using Clinical Transcriptomes

PubMed Central

Hashemikhabir, Seyedsasan; Budak, Gungor; Janga, Sarath Chandra

2016-01-01

Survival analysis in biomedical sciences is generally performed by correlating the levels of cellular components with patients’ clinical features as a common practice in prognostic biomarker discovery. While the common and primary focus of such analysis in cancer genomics so far has been to identify the potential prognostic genes, alternative splicing – a posttranscriptional regulatory mechanism that affects the functional form of a protein due to inclusion or exclusion of individual exons giving rise to alternative protein products, has increasingly gained attention due to the prevalence of splicing aberrations in cancer transcriptomes. Hence, uncovering the potential prognostic exons can not only help in rationally designing exon-specific therapeutics but also increase specificity toward more personalized treatment options. To address this gap and to provide a platform for rational identification of prognostic exons from cancer transcriptomes, we developed ExSurv (https://exsurv.soic.iupui.edu), a web-based platform for predicting the survival contribution of all annotated exons in the human genome using RNA sequencing-based expression profiles for cancer samples from four cancer types available from The Cancer Genome Atlas. ExSurv enables users to search for a gene of interest and shows survival probabilities for all the exons associated with a gene and found to be significant at the chosen threshold. ExSurv also includes raw expression values across the cancer cohort as well as the survival plots for prognostic exons. Our analysis of the resulting prognostic exons across four cancer types revealed that most of the survival-associated exons are unique to a cancer type with few processes such as cell adhesion, carboxylic, fatty acid metabolism, and regulation of T-cell signaling common across cancer types, possibly suggesting significant differences in the posttranscriptional regulatory pathways contributing to prognosis. PMID:27528797

Prognostics for Microgrid Components

NASA Technical Reports Server (NTRS)

Saxena, Abhinav

2012-01-01

Prognostics is the science of predicting future performance and potential failures based on targeted condition monitoring. Moving away from the traditional reliability centric view, prognostics aims at detecting and quantifying the time to impending failures. This advance warning provides the opportunity to take actions that can preserve uptime, reduce cost of damage, or extend the life of the component. The talk will focus on the concepts and basics of prognostics from the viewpoint of condition-based systems health management. Differences with other techniques used in systems health management and philosophies of prognostics used in other domains will be shown. Examples relevant to micro grid systems and subsystems will be used to illustrate various types of prediction scenarios and the resources it take to set up a desired prognostic system. Specifically, the implementation results for power storage and power semiconductor components will demonstrate specific solution approaches of prognostics. The role of constituent elements of prognostics, such as model, prediction algorithms, failure threshold, run-to-failure data, requirements and specifications, and post-prognostic reasoning will be explained. A discussion on performance evaluation and performance metrics will conclude the technical discussion followed by general comments on open research problems and challenges in prognostics.

Predictive value of neuron-specific enolase for prognosis in patients with moderate or severe traumatic brain injury: a systematic review and meta-analysis

PubMed Central

Mercier, Eric; Boutin, Amélie; Shemilt, Michèle; Lauzier, François; Zarychanski, Ryan; Fergusson, Dean A.; Moore, Lynne; McIntyre, Lauralyn A.; Archambault, Patrick; Légaré, France; Rousseau, François; Lamontagne, François; Nadeau, Linda; Turgeon, Alexis F.

2016-01-01

Background: Prognosis is difficult to establish early after moderate or severe traumatic brain injury despite representing an important concern for patients, families and medical teams. Biomarkers, such as neuron-specific enolase, have been proposed as potential early prognostic indicators. Our objective was to determine the association between neuron-specific enolase and clinical outcomes, and the prognostic value of neuron-specific enolase after a moderate or severe traumatic brain injury. Methods: We searched MEDLINE, Embase, The Cochrane Library and Biosis Previews, and reviewed reference lists of eligible articles to identify studies. We included cohort studies and randomized controlled trials that evaluated the prognostic value of neuron-specific enolase to predict mortality or Glasgow Outcome Scale score in patients with moderate or severe traumatic brain injury. Two reviewers independently collected data. The pooled mean differences were analyzed using random-effects models. We assessed risk of bias using a customized Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Subgroup and sensitivity analyses were performed based on a priori hypotheses. Results: We screened 5026 citations from which 30 studies (involving 1321 participants) met our eligibility criteria. We found a significant positive association between neuron-specific enolase serum levels and mortality (10 studies, n = 474; mean difference [MD] 18.46 µg/L, 95% confidence interval [CI] 10.81 to 26.11 µg/L; I2 = 83%) and a Glasgow Outcome Scale ≤ 3 (14 studies, n = 603; MD 17.25 µg/L, 95% CI 11.42 to 23.07 µg/L; I2 = 82%). We were unable to determine a clinical threshold value using the available patient data. Interpretation: In patients with moderate or severe traumatic brain injury, increased neuron-specific enolase serum levels are associated with unfavourable outcomes. The optimal neuron-specific enolase threshold value to predict unfavourable prognosis remains unknown and clinical decision-making is currently not recommended until additional studies are made available. PMID:27975043

Hemoglobin levels above anemia thresholds are maximally predictive for long-term survival in COPD with chronic respiratory failure.

PubMed

Kollert, Florian; Tippelt, Andrea; Müller, Carolin; Jörres, Rudolf A; Porzelius, Christine; Pfeifer, Michael; Budweiser, Stephan

2013-07-01

In patients with COPD, chronic anemia is known as an unfavorable prognostic factor. Whether the association between hemoglobin (Hb) levels and long-term survival is restricted to anemia or extends to higher Hb levels has not yet been systematically assessed. We determined Hb levels in 309 subjects with COPD and chronic respiratory failure prior to initiation of noninvasive ventilation, accounting for confounders that might affect Hb. Subjects were categorized as anemic (Hb < 12 g/dL in females, Hb < 13 g/dL in males), polycythemic (Hb ≥ 15 g/dL in females, Hb ≥ 17 g/dL in males), or normocythemic. In addition, percentiles of Hb values were analyzed with regard to mortality from any cause. Two-hundred seven subjects (67.0%) showed normal Hb levels, 46 (14.9%) had anemia, and 56 (18.1%) had polycythemia. Polycythemic subjects showed a higher survival rate than anemic (P = .01) and normocythemic subjects (P = .043). In a univariate Cox hazards model, Hb was associated with long-term survival (hazard ratio 0.855; 95% CI 0.783-0.934, P < .001). The 58th percentiles of Hb (14.3 g/dL in females, 15.1 g/dL in males) yielded the highest discriminative value for predicting survival (hazard ratio 0.463, 95% CI 0.324-0.660, P < .001). In the multivariate analysis this cutoff was an independent predictor for survival (hazard ratio 0.627, 95% CI 0.414-0.949, P = .03), in addition to age and body mass index. In subjects with COPD and chronic respiratory failure undergoing treatment with noninvasive ventilation and LTOT, high Hb levels are associated with better long-term survival. The optimal cutoff level for prediction was above the established threshold defining anemia. Thus, predicting survival only on the basis of anemia does not fully utilize the prognostic potential of Hb values in COPD.

Identifying the most appropriate age threshold for TNM stage grouping of well-differentiated thyroid cancer.

PubMed

Hendrickson-Rebizant, J; Sigvaldason, H; Nason, R W; Pathak, K A

2015-08-01

Age is integrated in most risk stratification systems for well-differentiated thyroid cancer (WDTC). The most appropriate age threshold for stage grouping of WDTC is debatable. The objective of this study was to evaluate the best age threshold for stage grouping by comparing multivariable models designed to evaluate the independent impact of various prognostic factors, including age based stage grouping, on the disease specific survival (DSS) of our population-based cohort. Data from population-based thyroid cancer cohort of 2125 consecutive WDTC, diagnosed during 1970-2010, with a median follow-up of 11.5 years, was used to calculate DSS using the Kaplan Meier method. Multivariable analysis with Cox proportional hazard model was used to assess independent impact of different prognostic factors on DSS. The Akaike information criterion (AIC), a measure of statistical model fit, was used to identify the most appropriate age threshold model. Delta AIC, Akaike weight, and evidence ratios were calculated to compare the relative strength of different models. The mean age of the patients was 47.3 years. DSS of the cohort was 95.6% and 92.8% at 10 and 20 years respectively. A threshold of 55 years, with the lowest AIC, was identified as the best model. Akaike weight indicated an 85% chance that this age threshold is the best among the compared models, and is 16.8 times more likely to be the best model as compared to a threshold of 45 years. The age threshold of 55 years was found to be the best for TNM stage grouping. Copyright © 2015 Elsevier Ltd. All rights reserved.

Cost-Utility of a Prognostic Test Guiding Adjuvant Chemotherapy Decisions in Early-Stage Non-Small Cell Lung Cancer.

PubMed

Stenehjem, David D; Bellows, Brandon K; Yager, Kraig M; Jones, Joshua; Kaldate, Rajesh; Siebert, Uwe; Brixner, Diana I

2016-02-01

A prognostic test was developed to guide adjuvant chemotherapy (ACT) decisions in early-stage non-small cell lung cancer (NSCLC) adenocarcinomas. The objective of this study was to compare the cost-utility of the prognostic test to the current standard of care (SoC) in patients with early-stage NSCLC. Lifetime costs (2014 U.S. dollars) and effectiveness (quality-adjusted life-years [QALYs]) of ACT treatment decisions were examined using a Markov microsimulation model from a U.S. third-party payer perspective. Cancer stage distribution and probability of receiving ACT with the SoC were based on data from an academic cancer center. The probability of receiving ACT with the prognostic test was estimated from a physician survey. Risk classification was based on the 5-year predicted NSCLC-related mortality. Treatment benefit with ACT was based on the prognostic score. Discounting at a 3% annual rate was applied to costs and QALYs. Deterministic one-way and probabilistic sensitivity analyses examined parameter uncertainty. Lifetime costs and effectiveness were $137,403 and 5.45 QALYs with the prognostic test and $127,359 and 5.17 QALYs with the SoC. The resulting incremental cost-effectiveness ratio for the prognostic test versus the SoC was $35,867/QALY gained. One-way sensitivity analyses indicated the model was most sensitive to the utility of patients without recurrence after ACT and the ACT treatment benefit. Probabilistic sensitivity analysis indicated the prognostic test was cost-effective in 65.5% of simulations at a willingness to pay of $50,000/QALY. The study suggests using a prognostic test to guide ACT decisions in early-stage NSCLC is potentially cost-effective compared with using the SoC based on globally accepted willingness-to-pay thresholds. Providing prognostic information to decision makers may help some patients with high-risk early stage non-small cell lung cancer receive appropriate adjuvant chemotherapy while avoiding the associated toxicities and costs in patients with low-risk disease. This study used an economic model to assess the effectiveness and costs associated with using a prognostic test to guide adjuvant chemotherapy decisions compared with the current standard of care in patients with non-small cell lung cancer. When compared with current standard care, the prognostic test was potentially cost effective at commonly accepted thresholds in the U.S. This study can be used to help inform decision makers who are considering using prognostic tests. ©AlphaMed Press.

Normal standards for computer-ECG programs for prognostically and diagnostically important ECG variables derived from a large ethnically diverse female cohort: the Women's Health Initiative (WHI).

PubMed

Rautaharju, Pentti M; Zhang, Zhu-ming; Gregg, Richard E; Haisty, Wesley K; Z Vitolins, Mara; Curtis, Anne B; Warren, James; Horaĉek, Milan B; Zhou, Sophia H; Soliman, Elsayed Z

2013-01-01

Substantial new information has emerged recently about the prognostic value for a variety of new ECG variables. The objective of the present study was to establish reference standards for these novel risk predictors in a large, ethnically diverse cohort of healthy women from the Women's Health Initiative (WHI) study. The study population consisted of 36,299 healthy women. Racial differences in rate-adjusted QT end (QT(ea)) and QT peak (QT(pa)) intervals as linear functions of RR were small, leading to the conclusion that 450 and 390 ms are applicable as thresholds for prolonged and shortened QT(ea) and similarly, 365 and 295 ms for prolonged and shortened QT(pa), respectively. As a threshold for increased dispersion of global repolarization (T(peak)T(end) interval), 110 ms was established for white and Hispanic women and 120 ms for African-American and Asian women. ST elevation and depression values for the monitoring leads of each person with limb electrodes at Mason-Likar positions and chest leads at level of V1 and V2 were first computed from standard leads using lead transformation coefficients derived from 892 body surface maps, and subsequently normal standards were determined for the monitoring leads, including vessel-specific bipolar left anterior descending, left circumflex artery and right coronary artery leads. The results support the choice 150 μV as a tentative threshold for abnormal ST-onset elevation for all monitoring leads. Body mass index (BMI) had a profound effect on Cornell voltage and Sokolow-Lyon voltage in all racial groups and their utility for left ventricular hypertrophy classification remains open. Common thresholds for all racial groups are applicable for QT(ea), and QT(pa) intervals and ST elevation. Race-specific normal standards are required for many other ECG parameters. Copyright © 2013 Elsevier Inc. All rights reserved.

Predictive and prognostic value of 18F-DOPA PET/CT in patients affected by recurrent medullary carcinoma of the thyroid.

PubMed

Caobelli, Federico; Chiaravalloti, Agostino; Evangelista, Laura; Saladini, Giorgio; Schillaci, Orazio; Vadrucci, Manuela; Scalorbi, Federica; Donner, Davide; Alongi, Pierpaolo

2018-01-01

Medullary thyroid carcinoma (MTC) is a malignancy accounting for about 5-8% of thyroid cancers. Serum calcitonin and carcinoembryonic antigen (CEA) levels are widely used to monitor disease progression. However, prognostic factors able to predict outcomes are highly desirable. We, therefore, aimed to assess the prognostic role of 18 F-DOPA PET/CT in patients with recurrent MTC. 60 patients (mean age 64 ± 13 years, range 44-82) with recurrent MTC were eligible from a multicenter database. All patients underwent a restaging 18 F-DOPA PET/CT, performed at least 6 months after surgery. CEA/calcitonin levels, local recurrences, nodal involvement and metastases at PET/CT were recorded. SUVmax, SUVmean (also normalized to mediastinal uptake) and metabolic tumor volume were automatically calculated for each lesion, by placing a volume of interest around the lesion with 40% of peak activity as threshold for the automatic contouring. The patients were clinically and radiologically followed up for 21 ± 11 months. Rate of progression-free survival (PFS), disease-specific survival (DSS) and incremental prognostic value of 18 F-DOPA PET/CT over conventional imaging modalities were assessed by Kaplan-Meier curves and Log-Rank test. Cox regression univariate and multivariate analyses were performed for assessing predictors of prognosis. 18 F-DOPA PET/CT showed abnormal findings in 27 patients (45%) and resulted unremarkable in 33 (55%). PFS was significantly longer in patients with an unremarkable PET/CT scan (p = 0.018). Similarly, an unremarkable PET/CT study was associated with a significantly longer DSS (p = 0.04). 18 F-DOPA PET/CT added prognostic value over other imaging modalities both for PFS and for DSS (p < 0.001 and p = 0.012, respectively). Neither semiquantitative PET parameters nor clinical or laboratory data were predictive of a worse PFS and DSS in patients with recurrent MTC. 18 F-DOPA PET/CT scan has an important prognostic value in predicting disease progression and mortality rate.

Consideration of a new definition of clinically relevant myocardial infarction after coronary revascularization: an expert consensus document from the Society for Cardiovascular Angiography and Interventions (SCAI).

PubMed

Moussa, Issam D; Klein, Lloyd W; Shah, Binita; Mehran, Roxana; Mack, Michael J; Brilakis, Emmanouil S; Reilly, John P; Zoghbi, Gilbert; Holper, Elizabeth; Stone, Gregg W

2014-01-01

Numerous definitions have been proposed for the diagnosis of myocardial infarction (MI) after coronary revascularization. The universal definition for MI designates post procedural biomarker thresholds for defining percutaneous coronary intervention (PCI)-related MI (type 4a) and coronary artery bypass grafting (CABG)-related MI (type 5) which are of uncertain prognostic importance. In addition, for both MI types cTn is recommended as the biomarker of choice, the prognostic significance of which is less well validated than CK-MB. Widespread adoption of a MI definition not clearly linked to subsequent adverse events such as mortality or heart failure may have serious consequences for the appropriate assessment of devices and therapies, may affect clinical care pathways, and may result in misinterpretation of physician competence. Rather than employing an MI definition sensitive for small degrees of myonecrosis (the occurrence of which, based on contemporary large-scale studies, are unlikely to have important clinical consequences), it is instead recommended that a threshold level of biomarker elevation which has been strongly linked to subsequent adverse events in clinical studies be used to define a "clinically relevant MI." The present document introduces a new definition for "clinically relevant MI" after coronary revascularization (PCI or CABG) which is applicable for use in clinical trials, patient care, and quality outcomes assessment. Copyright © 2013 Wiley Periodicals, Inc.

The prognostic value of serum C-reactive protein, ferritin, and albumin prior to allogeneic transplantation for acute myeloid leukemia and myelodysplastic syndromes

PubMed Central

Artz, Andrew S.; Logan, Brent; Zhu, Xiaochun; Akpek, Gorgun; Bufarull, Rodrigo Martino; Gupta, Vikas; Lazarus, Hillard M.; Litzow, Mark; Loren, Alison; Majhail, Navneet S.; Maziarz, Richard T.; McCarthy, Philip; Popat, Uday; Saber, Wael; Spellman, Stephen; Ringden, Olle; Wickrema, Amittha; Pasquini, Marcelo C.; Cooke, Kenneth R.

2016-01-01

We sought to confirm the prognostic importance of simple clinically available biomarkers of C-reactive protein, serum albumin, and ferritin prior to allogeneic hematopoietic cell transplantation. The study population consisted of 784 adults with acute myeloid leukemia in remission or myelodysplastic syndromes undergoing unrelated donor transplant reported to the Center for International Blood and Marrow Transplant Research. C-reactive protein and ferritin were centrally quantified by ELISA from cryopreserved plasma whereas each center provided pre-transplant albumin. In multivariate analysis, transplant-related mortality was associated with the pre-specified thresholds of C-reactive protein more than 10 mg/L (P=0.008) and albumin less than 3.5 g/dL (P=0.01) but not ferritin more than 2500 ng/mL. Only low albumin independently influenced overall mortality. Optimal thresholds affecting transplant-related mortality were defined as: C-reactive protein more than 3.67 mg/L, log(ferritin), and albumin less than 3.4 g/dL. A 3-level biomarker risk group based on these values separated risks of transplant-related mortality: low risk (reference), intermediate (HR=1.66, P=0.015), and high risk (HR=2.7, P<0.001). One-year survival was 74%, 67% and 56% for low-, intermediate- and high-risk groups. Routinely available pre-transplant biomarkers independently risk-stratify for transplant-related mortality and survival. PMID:27662010

Continuous Amplitude-Integrated Electroencephalographic Monitoring Is a Useful Prognostic Tool for Hypothermia-Treated Cardiac Arrest Patients.

PubMed

Oh, Sang Hoon; Park, Kyu Nam; Shon, Young-Min; Kim, Young-Min; Kim, Han Joon; Youn, Chun Song; Kim, Soo Hyun; Choi, Seung Pill; Kim, Seok Chan

2015-09-22

Modern treatments have improved the survival rate following cardiac arrest, but prognostication remains a challenge. We examined the prognostic value of continuous electroencephalography according to time by performing amplitude-integrated electroencephalography on patients with cardiac arrest receiving therapeutic hypothermia. We prospectively studied 130 comatose patients treated with hypothermia from September 2010 to April 2013. We evaluated the time to normal trace (TTNT) as a neurological outcome predictor and determined the prognostic value of burst suppression and status epilepticus, with a particular focus on their time of occurrence. Fifty-five patients exhibited a cerebral performance category score of 1 to 2. The area under the curve for TTNT was 0.97 (95% confidence interval, 0.92-0.99), and the sensitivity and specificity of TTNT<24 hours after resuscitation as a threshold for predicting good neurological outcome were 94.6% (95% confidence interval, 84.9%-98.9%) and 90.7% (95% confidence interval, 81.7%-96.2%), respectively. The threshold displaying 100% specificity for predicting poor neurological outcome was TTNT>36 hours. Burst suppression and status epilepticus predicted poor neurological outcome (positive predictive value of 98.3% and 96.4%, respectively). The combination of these factors predicted a negative outcome at a median of 6.2 hours after resuscitation (sensitivity and specificity of 92.0% and 96.4%, respectively). A TTNT<24 hours was associated with good neurological outcome. The lack of normal trace development within 36 hours, status epilepticus, and burst suppression were predictors of poor outcome. The combination of these negative predictors may improve their prognostic performance at an earlier stage. © 2015 The Authors.

Prognostic value of metabolic metrics extracted from baseline PET images in NSCLC

PubMed Central

Carvalho, Sara; Leijenaar, Ralph T.H.; Velazquez, Emmanuel Rios; Oberije, Cary; Parmar, Chintan; van Elmpt, Wouter; Reymen, Bart; Troost, Esther G.C.; Oellers, Michel; Dekker, Andre; Gillies, Robert; Aerts, Hugo J.W.L.; Lambin, Philippe

2015-01-01

Background Maximum, mean and peak SUV of primary tumor at baseline FDG-PET scans, have often been found predictive for overall survival in non-small cell lung cancer (NSCLC) patients. In this study we further investigated the prognostic power of advanced metabolic metrics derived from Intensity-Volume Histograms (IVH) extracted from PET imaging. Methods A cohort of 220 NSCLC patients (mean age, 66.6 years; 149 men, 71 women), stages I-IIIB, treated with radiotherapy with curative intent were included (NCT00522639). Each patient underwent standardized pre-treatment CT-PET imaging. Primary GTV was delineated by an experienced radiation oncologist on CT-PET images. Common PET descriptors such as maximum, mean and peak SUV, and metabolic tumor volume (MTV) were quantified. Advanced descriptors of metabolic activity were quantified by IVH. These comprised 5 groups of features: Absolute and Relative Volume above Relative Intensity threshold (AVRI and RVRI), Absolute and Relative Volume above Absolute Intensity threshold (AVAI and RVAI), and Absolute Intensity above Relative Volume threshold (AIRV). MTV was derived from the IVH curves for volumes with SUV above 2.5, 3 and 4, and of 40% and 50% maximum SUV. Univariable analysis using Cox Proportional Hazard Regression was performed for overall survival assessment. Results Relative volume above higher SUV (80 %) was an independent predictor of OS (p = 0.05). None of the possible surrogates for MTV based on volumes above SUV of 3, 40% and 50% of maximum SUV showed significant associations with OS (p (AVAI3) = 0.10, p (AVAI4) = 0.22, p (AVRI40%) = 0.15, p (AVRI50%) = 0.17). Maximum and peak SUV (r = 0.99) revealed no prognostic value for OS (p (maximum SUV) = 0.20, p (peak SUV) = 0.22). Conclusions New methods using more advanced imaging features extracted from PET were analyzed. Best prognostic value for OS of NSCLC patients was found for relative portions of the tumor above higher uptakes (80% SUV). PMID:24047338

A Distributed Approach to System-Level Prognostics

NASA Technical Reports Server (NTRS)

Daigle, Matthew J.; Bregon, Anibal; Roychoudhury, Indranil

2012-01-01

Prognostics, which deals with predicting remaining useful life of components, subsystems, and systems, is a key technology for systems health management that leads to improved safety and reliability with reduced costs. The prognostics problem is often approached from a component-centric view. However, in most cases, it is not specifically component lifetimes that are important, but, rather, the lifetimes of the systems in which these components reside. The system-level prognostics problem can be quite difficult due to the increased scale and scope of the prognostics problem and the relative Jack of scalability and efficiency of typical prognostics approaches. In order to address these is ues, we develop a distributed solution to the system-level prognostics problem, based on the concept of structural model decomposition. The system model is decomposed into independent submodels. Independent local prognostics subproblems are then formed based on these local submodels, resul ting in a scalable, efficient, and flexible distributed approach to the system-level prognostics problem. We provide a formulation of the system-level prognostics problem and demonstrate the approach on a four-wheeled rover simulation testbed. The results show that the system-level prognostics problem can be accurately and efficiently solved in a distributed fashion.

How Radiation Oncologists Evaluate and Incorporate Life Expectancy Estimates Into the Treatment of Palliative Cancer Patients: A Survey-Based Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tseng, Yolanda D., E-mail: ydtseng@partners.org; Krishnan, Monica S.; Sullivan, Adam J.

2013-11-01

Purpose: We surveyed how radiation oncologists think about and incorporate a palliative cancer patient’s life expectancy (LE) into their treatment recommendations. Methods and Materials: A 41-item survey was e-mailed to 113 radiation oncology attending physicians and residents at radiation oncology centers within the Boston area. Physicians estimated how frequently they assessed the LE of their palliative cancer patients and rated the importance of 18 factors in formulating LE estimates. For 3 common palliative case scenarios, physicians estimated LE and reported whether they had an LE threshold below which they would modify their treatment recommendation. LE estimates were considered accurate whenmore » within the 95% confidence interval of median survival estimates from an established prognostic model. Results: Among 92 respondents (81%), the majority were male (62%), from an academic practice (75%), and an attending physician (70%). Physicians reported assessing LE in 91% of their evaluations and most frequently rated performance status (92%), overall metastatic burden (90%), presence of central nervous system metastases (75%), and primary cancer site (73%) as “very important” in assessing LE. Across the 3 cases, most (88%-97%) had LE thresholds that would alter treatment recommendations. Overall, physicians’ LE estimates were 22% accurate with 67% over the range predicted by the prognostic model. Conclusions: Physicians often incorporate LE estimates into palliative cancer care and identify important prognostic factors. Most have LE thresholds that guide their treatment recommendations. However, physicians overestimated patient survival times in most cases. Future studies focused on improving LE assessment are needed.« less

Decision curve analysis: a novel method for evaluating prediction models.

PubMed

Vickers, Andrew J; Elkin, Elena B

2006-01-01

Diagnostic and prognostic models are typically evaluated with measures of accuracy that do not address clinical consequences. Decision-analytic techniques allow assessment of clinical outcomes but often require collection of additional information and may be cumbersome to apply to models that yield a continuous result. The authors sought a method for evaluating and comparing prediction models that incorporates clinical consequences,requires only the data set on which the models are tested,and can be applied to models that have either continuous or dichotomous results. The authors describe decision curve analysis, a simple, novel method of evaluating predictive models. They start by assuming that the threshold probability of a disease or event at which a patient would opt for treatment is informative of how the patient weighs the relative harms of a false-positive and a false-negative prediction. This theoretical relationship is then used to derive the net benefit of the model across different threshold probabilities. Plotting net benefit against threshold probability yields the "decision curve." The authors apply the method to models for the prediction of seminal vesicle invasion in prostate cancer patients. Decision curve analysis identified the range of threshold probabilities in which a model was of value, the magnitude of benefit, and which of several models was optimal. Decision curve analysis is a suitable method for evaluating alternative diagnostic and prognostic strategies that has advantages over other commonly used measures and techniques.

The prognostic value of serum C-reactive protein, ferritin, and albumin prior to allogeneic transplantation for acute myeloid leukemia and myelodysplastic syndromes.

PubMed

Artz, Andrew S; Logan, Brent; Zhu, Xiaochun; Akpek, Gorgun; Bufarull, Rodrigo Martino; Gupta, Vikas; Lazarus, Hillard M; Litzow, Mark; Loren, Alison; Majhail, Navneet S; Maziarz, Richard T; McCarthy, Philip; Popat, Uday; Saber, Wael; Spellman, Stephen; Ringden, Olle; Wickrema, Amittha; Pasquini, Marcelo C; Cooke, Kenneth R

2016-11-01

We sought to confirm the prognostic importance of simple clinically available biomarkers of C-reactive protein, serum albumin, and ferritin prior to allogeneic hematopoietic cell transplantation. The study population consisted of 784 adults with acute myeloid leukemia in remission or myelodysplastic syndromes undergoing unrelated donor transplant reported to the Center for International Blood and Marrow Transplant Research. C-reactive protein and ferritin were centrally quantified by ELISA from cryopreserved plasma whereas each center provided pre-transplant albumin. In multivariate analysis, transplant-related mortality was associated with the pre-specified thresholds of C-reactive protein more than 10 mg/L (P=0.008) and albumin less than 3.5 g/dL (P=0.01) but not ferritin more than 2500 ng/mL. Only low albumin independently influenced overall mortality. Optimal thresholds affecting transplant-related mortality were defined as: C-reactive protein more than 3.67 mg/L, log(ferritin), and albumin less than 3.4 g/dL. A 3-level biomarker risk group based on these values separated risks of transplant-related mortality: low risk (reference), intermediate (HR=1.66, P=0.015), and high risk (HR=2.7, P<0.001). One-year survival was 74%, 67% and 56% for low-, intermediate- and high-risk groups. Routinely available pre-transplant biomarkers independently risk-stratify for transplant-related mortality and survival. Copyright© Ferrata Storti Foundation.

Consideration of a new definition of clinically relevant myocardial infarction after coronary revascularization: an expert consensus document from the Society for Cardiovascular Angiography and Interventions (SCAI).

PubMed

Moussa, Issam D; Klein, Lloyd W; Shah, Binita; Mehran, Roxana; Mack, Michael J; Brilakis, Emmanouil S; Reilly, John P; Zoghbi, Gilbert; Holper, Elizabeth; Stone, Gregg W

2013-10-22

Numerous definitions have been proposed for the diagnosis of myocardial infarction (MI) after coronary revascularization. The universal definition for MI designates post procedural biomarker thresholds for defining percutaneous coronary intervention (PCI)-related MI (type 4a) and coronary artery bypass grafting (CABG)-related MI (type 5), which are of uncertain prognostic importance. In addition, for both the MI types, cTn is recommended as the biomarker of choice, the prognostic significance of which is less well validated than CK-MB. Widespread adoption of a MI definition not clearly linked to subsequent adverse events such as mortality or heart failure may have serious consequences for the appropriate assessment of devices and therapies, may affect clinical care pathways, and may result in misinterpretation of physician competence. Rather than using an MI definition sensitive for small degrees of myonecrosis (the occurrence of which, based on contemporary large-scale studies, are unlikely to have important clinical consequences), it is instead recommended that a threshold level of biomarker elevation which has been strongly linked to subsequent adverse events in clinical studies be used to define a "clinically relevant MI." The present document introduces a new definition for "clinically relevant MI" after coronary revascularization (PCI or CABG), which is applicable for use in clinical trials, patient care, and quality outcomes assessment. Copyright © 2013. Published by Elsevier Inc.

State of the art and taxonomy of prognostics approaches, trends of prognostics applications and open issues towards maturity at different technology readiness levels

NASA Astrophysics Data System (ADS)

Javed, Kamran; Gouriveau, Rafael; Zerhouni, Noureddine

2017-09-01

Integrating prognostics to a real application requires a certain maturity level and for this reason there is a lack of success stories about development of a complete Prognostics and Health Management system. In fact, the maturity of prognostics is closely linked to data and domain specific entities like modeling. Basically, prognostics task aims at predicting the degradation of engineering assets. However, practically it is not possible to precisely predict the impending failure, which requires a thorough understanding to encounter different sources of uncertainty that affect prognostics. Therefore, different aspects crucial to the prognostics framework, i.e., from monitoring data to remaining useful life of equipment need to be addressed. To this aim, the paper contributes to state of the art and taxonomy of prognostics approaches and their application perspectives. In addition, factors for prognostics approach selection are identified, and new case studies from component-system level are discussed. Moreover, open challenges toward maturity of the prognostics under uncertainty are highlighted and scheme for an efficient prognostics approach is presented. Finally, the existing challenges for verification and validation of prognostics at different technology readiness levels are discussed with respect to open challenges.

Ovarian stimulation length, number of follicles higher than 17 mm and estradiol on the day of human chorionic gonadotropin administration are risk factors for multiple pregnancy in intrauterine insemination

PubMed Central

MELO, MARCO A.B.; SIMÓN, CARLOS; REMOHÍ, JOSÉ; PELLICER, ANTONIO; MESEGUER, MARCOS

2007-01-01

Aim:  The aim of the present study was to identify the risk factors, their prognostic value on multiple pregnancies (MP) prediction and their thresholds in women undergoing controlled ovarian hyperstimulation (COH) with follicle stimulating hormone (FSH) and intrauterine insemination (IUI). Methods:  A case‐control study was carried out by identifying in our database all the pregnancies reached by donor and conjugal IUI (DIUI and CIUI, respectively), and compared cycle features, patients’ characteristics and sperm analysis results between women achieving single pregnancy (SP) versus MP. The number of gestational sacs, follicular sizes and estradiol levels on the human chorionic gonadotropin (hCG) administration day, COH length and semen parameters were obtained from each cycle and compared. Student's t‐tests for mean comparisons, receiver–operator curve (ROC) analysis to determine the predictive value of each parameter on MP achievement and multiple regression analysis to determine single parameter influence were carried out. Results:  Women with MP in IUI stimulated cycles reached the adequate size of the dominant follicle (17 mm) significantly earlier than those achieving SP. Also, the mean follicles number, and estradiol levels on the hCG day were higher in the CIUI and DIUI MP group. Nevertheless, only ROC curve analysis revealed good prognostic value for estradiol and follicles higher than 17 mm. Multiple regression analysis confirmed these results. No feature of the basic sperm analysis, either in the ejaculate or in the prepared sample, was different or predictive of MP. When using donor sperm, different thresholds of follicle number, stimulation length and estradiol in the prediction of MP were noted, in comparison with CIUI. Conclusions:  MP in stimulated IUI cycles are closely associated to stimulation length, number of developed follicles higher than 17 mm on the day of hCG administration and estradiol levels. Also, estradiol has a good predictive value over MP in IUI stimulated cycles. The establishment of clinical thresholds will certainly help in the management of these couples to avoid undesired multiple pregnancies by canceling cycles or converting them into in vitro fertilization procedures. (Reprod Med Biol 2007; 6: 19–26) PMID:29699262

CA19-9 serum levels predict micrometastases in patients with gastric cancer

PubMed Central

Potrc, Stojan; Mis, Katarina; Plankl, Mojca; Mars, Tomaz

2016-01-01

Abstract Background We explored the prognostic value of the up-regulated carbohydrate antigen (CA19-9) in node-negative patients with gastric cancer as a surrogate marker for micrometastases. Patients and methods Micrometastases were determined using reverse transcription quantitative polymerase chain reaction (RT-qPCR) for a subgroup of 30 node-negative patients. This group was used to determine the cut-off for preoperative CA19-9 serum levels as a surrogate marker for micrometastases. Then 187 node-negative T1 to T4 patients were selected to validate the predictive value of this CA19-9 threshold. Results Patients with micrometastases had significantly higher preoperative CA19-9 serum levels compared to patients without micrometastases (p = 0.046). CA19-9 serum levels were significantly correlated with tumour site, tumour diameter, and perineural invasion. Although not reaching significance, subgroup analysis showed better five-year survival rates for patients with CA19-9 serum levels below the threshold, compared to patients with CA19-9 serum levels above the cut-off. The cumulative survival for T2 to T4 node-negative patients was significantly better with CA19-9 serum levels below the cut-off (p = 0.04). Conclusions Preoperative CA19-9 serum levels can be used to predict higher risk for haematogenous spread and micrometastases in node-negative patients. However, CA19-9 serum levels lack the necessary sensitivity and specificity to reliably predict micrometastases. PMID:27247553

Unavailability of thymidine kinase does not preclude the use of German comprehensive prognostic index: results of an external validation analysis in early chronic lymphocytic leukemia and comparison with MD Anderson Cancer Center model.

PubMed

Molica, Stefano; Giannarelli, Diana; Mirabelli, Rosanna; Levato, Luciano; Russo, Antonio; Linardi, Maria; Gentile, Massimo; Morabito, Fortunato

2016-01-01

A comprehensive prognostic index that includes clinical (i.e., age, sex, ECOG performance status), serum (i.e., ß2-microglobulin, thymidine kinase [TK]), and molecular (i.e., IGVH mutational status, del 17p, del 11q) markers developed by the German CLL Study Group (GCLLSG) was externally validated in a prospective, community-based cohort consisting of 338 patients with early chronic lymphocytic leukemia (CLL) using as endpoint the time to first treatment (TTFT). Because serum TK was not available, a slightly modified version of the model based on seven instead of eight prognostic variables was used. By German index, 62.9% of patients were scored as having low-risk CLL (score 0-2), whereas 37.1% had intermediate-risk CLL (score 3-5). This stratification translated into a significant difference in the TTFT [HR = 4.21; 95% C.I. (2.71-6.53); P < 0.0001]. Also the 2007 MD Anderson Cancer Center (MDACC) score, barely based on traditional clinical parameters, showed comparable reliability [HR = 2.73; 95% C.I. (1.79-4.17); P < 0.0001]. A comparative performance assessment between the two models revealed that prediction of the TTFT was more accurate with German score. The c-statistic of the MDACC model was 0.65 (range, 0.53-0.78) a level below that of the German index [0.71 (range, 0.60-0.82)] and below the accepted 0.7 threshold necessary to have value at the individual patient level. Results of this external comparative validation analysis strongly support the German score as the benchmark for comparison of any novel prognostic scheme aimed at evaluating the TTFT in patients with early CLL even when a modified version which does not include TK is utilized. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Serum C-Reactive Protein as a Prognostic Biomarker in Amyotrophic Lateral Sclerosis

PubMed Central

Lizio, Andrea; Maestri, Eleonora; Sansone, Valeria Ada; Mora, Gabriele; Miller, Robert G.; Appel, Stanley H.; Chiò, Adriano

2017-01-01

Importance Various factors have been proposed as possible candidates associated with the prognosis of amyotrophic lateral sclerosis (ALS); however, there is still no consensus on which biomarkers are reliable prognostic factors. C-reactive protein (CRP) is a biomarker of the inflammatory response that shows significant prognostic value for several diseases. Objective To examine the prognostic significance of CRP in ALS. Design, Setting, and Participants Patients’ serum CRP levels were evaluated from January 1, 2009, to June 30, 2015, in a large cohort of patients with ALS observed by an Italian tertiary multidisciplinary center. Results were replicated in an independent cohort obtained from a population-based registry of patients with ALS. A post hoc analysis was performed of the phase 2 trial of NP001 to determine whether stratification by levels of CRP improves differentiation of responders and nonresponders to the drug. Main Outcomes and Measures Serum CRP levels from the first examination were recorded to assess their effect on disease progression and survival. Results A total of 394 patients with ALS (168 women and 226 men; mean [SD] age at diagnosis, 60.18 [13.60] years) were observed in a tertiary multidisciplinary center, and the analysis was replicated in an independent cohort of 116 patients with ALS (50 women and 66 men; mean [SD] age at diagnosis, 67.00 [10.74] years) identified through a regional population-based registry. Serum CRP levels in the 394 patients with ALS correlated with severity of functional impairment, as measured by total score on the ALS Functional Rating Scale–Revised, at first evaluation (r = –0.14818; P = .004), and with patient survival (hazard ratio, 1.129; 95% CI, 1.033-1.234; P = .007). Similar results were found in the independent cohort (hazard ratio, 1.044; 95% CI, 1.016-1.056; P ≤ .001). Moreover, a post hoc analysis of the phase 2 trial of NP001 using the same CRP threshold showed that patients with elevated baseline CRP levels receiving the higher dose of NP001 had significantly less functional impairment after the treatment period compared with patients with normal baseline CRP, regardless of whether patients with normal CRP levels received NP001 or placebo (3.00 [3.62] vs –7.31 [6.23]; P = .04). Conclusions and Relevance These findings suggest that patients with ALS and elevated serum CRP levels progress more rapidly than do those with lower CRP levels and that this elevation may reflect a neuroinflammatory state potentially responsive to the immune regulators such as NP001. PMID:28384752

Distilling the Verification Process for Prognostics Algorithms

NASA Technical Reports Server (NTRS)

Roychoudhury, Indranil; Saxena, Abhinav; Celaya, Jose R.; Goebel, Kai

2013-01-01

The goal of prognostics and health management (PHM) systems is to ensure system safety, and reduce downtime and maintenance costs. It is important that a PHM system is verified and validated before it can be successfully deployed. Prognostics algorithms are integral parts of PHM systems. This paper investigates a systematic process of verification of such prognostics algorithms. To this end, first, this paper distinguishes between technology maturation and product development. Then, the paper describes the verification process for a prognostics algorithm as it moves up to higher maturity levels. This process is shown to be an iterative process where verification activities are interleaved with validation activities at each maturation level. In this work, we adopt the concept of technology readiness levels (TRLs) to represent the different maturity levels of a prognostics algorithm. It is shown that at each TRL, the verification of a prognostics algorithm depends on verifying the different components of the algorithm according to the requirements laid out by the PHM system that adopts this prognostics algorithm. Finally, using simplified examples, the systematic process for verifying a prognostics algorithm is demonstrated as the prognostics algorithm moves up TRLs.

Serum osteoprotegerin is increased and predicts survival in idiopathic pulmonary arterial hypertension

PubMed Central

Condliffe, Robin; Pickworth, Josephine A.; Hopkinson, Kay; Walker, Sara J.; Hameed, Abdul G.; Suntharaligam, Jay; Soon, Elaine; Treacy, Carmen; Pepke-Zaba, Joanna; Francis, Sheila E.; Crossman, David C.; Newman, Christopher M. H.; Elliot, Charles A.; Morton, Allison C.; Morrell, Nicholas W.; Kiely, David G.; Lawrie, Allan

2012-01-01

We previously reported that osteoprotegerin (OPG) is regulated by pathways associated with pulmonary arterial hypertension (PAH), and is present at elevated levels within pulmonary vascular lesions and sera from patients with idiopathic PAH (IPAH). Since OPG is a naturally secreted protein, we investigated the relationship between serum OPG and disease severity and outcome in patients with IPAH and animal models. OPG mRNA expression was measured in pulmonary artery smooth muscle cells (PASMC) from pulmonary arteries of patients with and without IPAH. Serum concentrations of OPG were measured in a retrospective and prospective group of patients. OPG levels were compared with phenotypic data and other putative PAH biomarkers. Prognostic significance was assessed and levels compared with healthy controls. Correlation of OPG and pulmonary vascular remodeling was also performed in rodent models of PAH. OPG mRNA was significantly increased 2-fold in PASMC isolated from explanted PAH lungs compared with control. Serum OPG concentrations were markedly elevated in IPAH compared with controls. In Cohort 1 OPG levels significantly correlated with mean right atrial pressure and cardiac index, while in Cohort 2 significant correlations existed between age-adjusted OPG levels and gas transfer. In both cohorts an OPG concentration above a ROC-derived threshold of 4728 pg/ml predicted poorer survival. In two rodent models, OPG correlated with the degree of pulmonary vascular remodeling. OPG levels are significantly elevated in patients with idiopathic PAH and are of prognostic significance. The role of OPG as a potential biomarker and therapeutic target merits further investigation. PMID:22558516

Match and mismatch - comparing plant phenological metrics from ground-observations and from a prognostic model

NASA Astrophysics Data System (ADS)

Rutishauser, This; Stöckli, Reto; Jeanneret, François; Peñuelas, Josep

2010-05-01

Changes in the seasonality of life cycles of plants as recorded in phenological observations have been widely analysed at the species level with data available for many decades back in time. At the same time, seasonality changes in satellite-based observations and prognostic phenology models comprise information at the pixel-size or landscape scale. Change analysis of satellite-based records is restricted due to relatively short satellite records that further include gaps while model-based analyses are biased due to current model deficiencies., At 30 selected sites across Europe, we analysed three different sources of plant seasonality during the 1971-2000 period. Data consisted of (1) species-specific development stages of flowering and leave-out with different species observed at each site. (2) We used a synthetic phenological metric that integrates the common interannual phenological signal across all species at one site. (3) We estimated daily Leaf Area Index with a prognostic phenology model. The prior uncertainties of the model's empirical parameter space are constrained by assimilating the Fraction of Photosynthetically Active Radiation absorbed by vegetation (FPAR) and Leaf Area Index (LAI) from the MODerate Resolution Imaging Spectroradiometer (MODIS). We extracted the day of year when the 25%, 50% and 75% thresholds were passed each spring. The question arises how the three phenological signals compare and correlate across climate zones in Europe. Is there a match between single species observations, species-based ground-observed metrics and the landscape-scale prognostic model? Are there single key-species across Europe that best represent a landscape scale measure from the prognostic model? Can one source substitute another and serve as proxy-data? What can we learn from potential mismatches? Focusing on changes in spring this contribution presents first results of an ongoing comparison study from a number of European test sites that will be extended to the pan-European phenological database Cost725 and PEP725.

Deceptive meaning of oxygen uptake measured at the anaerobic threshold in patients with systolic heart failure and atrial fibrillation.

PubMed

Magrì, Damiano; Agostoni, Piergiuseppe; Corrà, Ugo; Passino, Claudio; Scrutinio, Domenico; Perrone-Filardi, Pasquale; Correale, Michele; Cattadori, Gaia; Metra, Marco; Girola, Davide; Piepoli, Massimo F; Iorio, AnnaMaria; Emdin, Michele; Raimondo, Rosa; Re, Federica; Cicoira, Mariantonietta; Belardinelli, Romualdo; Guazzi, Marco; Limongelli, Giuseppe; Clemenza, Francesco; Parati, Gianfranco; Frigerio, Maria; Casenghi, Matteo; Scardovi, Angela B; Ferraironi, Alessandro; Di Lenarda, Andrea; Bussotti, Maurizio; Apostolo, Anna; Paolillo, Stefania; La Gioia, Rocco; Gargiulo, Paola; Palermo, Pietro; Minà, Chiara; Farina, Stefania; Battaia, Elisa; Maruotti, Antonello; Pacileo, Giuseppe; Contini, Mauro; Oliva, Fabrizio; Ricci, Roberto; Sinagra, Gianfranco

2015-08-01

Oxygen uptake at the anaerobic threshold (VO2AT), a submaximal exercise-derived variable, independent of patients' motivation, is a marker of outcome in heart failure (HF). However, previous evidence of VO2AT values paradoxically higher in HF patients with permanent atrial fibrillation (AF) than in those with sinus rhythm (SR) raised uncertainties. We tested the prognostic role of VO2AT in a large cohort of systolic HF patients, focusing on possible differences between SR and AF. Altogether 2976 HF patients (2578 with SR and 398 with AF) were prospectively followed. Besides a clinical examination, each patient underwent a maximal cardiopulmonary exercise test (CPET). The follow-up was analysed for up to 1500 days. Cardiovascular death or urgent cardiac transplantation occurred in 303 patients (250 (9.6%) patients with SR and 53 (13.3%) patients with AF, p = 0.023). In the entire population, multivariate analysis including peak oxygen uptake (VO2) showed a prognostic capacity (C-index) similar to that obtained including VO2AT (0.76 vs 0.72). Also, left ventricular ejection fraction, ventilation vs carbon dioxide production slope, β-blocker and digoxin therapy proved to be significant prognostic indexes. The receiver-operating characteristic (ROC) curves analysis showed that the best predictive VO2AT cut-off for the SR group was 11.7 ml/kg/min, while it was 12.8 ml/kg/min for the AF group. VO2AT, a submaximal CPET-derived parameter, is reliable for long-term cardiovascular mortality prognostication in stable systolic HF. However, different VO2AT cut-off values between SR and AF HF patients should be adopted. © The European Society of Cardiology 2014.

Prognostic and survival analysis of 837 Chinese colorectal cancer patients.

PubMed

Yuan, Ying; Li, Mo-Dan; Hu, Han-Guang; Dong, Cai-Xia; Chen, Jia-Qi; Li, Xiao-Fen; Li, Jing-Jing; Shen, Hong

2013-05-07

To develop a prognostic model to predict survival of patients with colorectal cancer (CRC). Survival data of 837 CRC patients undergoing surgery between 1996 and 2006 were collected and analyzed by univariate analysis and Cox proportional hazard regression model to reveal the prognostic factors for CRC. All data were recorded using a standard data form and analyzed using SPSS version 18.0 (SPSS, Chicago, IL, United States). Survival curves were calculated by the Kaplan-Meier method. The log rank test was used to assess differences in survival. Univariate hazard ratios and significant and independent predictors of disease-specific survival and were identified by Cox proportional hazard analysis. The stepwise procedure was set to a threshold of 0.05. Statistical significance was defined as P < 0.05. The survival rate was 74% at 3 years and 68% at 5 years. The results of univariate analysis suggested age, preoperative obstruction, serum carcinoembryonic antigen level at diagnosis, status of resection, tumor size, histological grade, pathological type, lymphovascular invasion, invasion of adjacent organs, and tumor node metastasis (TNM) staging were positive prognostic factors (P < 0.05). Lymph node ratio (LNR) was also a strong prognostic factor in stage III CRC (P < 0.0001). We divided 341 stage III patients into three groups according to LNR values (LNR1, LNR ≤ 0.33, n = 211; LNR2, LNR 0.34-0.66, n = 76; and LNR3, LNR ≥ 0.67, n = 54). Univariate analysis showed a significant statistical difference in 3-year survival among these groups: LNR1, 73%; LNR2, 55%; and LNR3, 42% (P < 0.0001). The multivariate analysis results showed that histological grade, depth of bowel wall invasion, and number of metastatic lymph nodes were the most important prognostic factors for CRC if we did not consider the interaction of the TNM staging system (P < 0.05). When the TNM staging was taken into account, histological grade lost its statistical significance, while the specific TNM staging system showed a statistically significant difference (P < 0.0001). The overall survival of CRC patients has improved between 1996 and 2006. LNR is a powerful factor for estimating the survival of stage III CRC patients.

Particle filter based hybrid prognostics for health monitoring of uncertain systems in bond graph framework

NASA Astrophysics Data System (ADS)

Jha, Mayank Shekhar; Dauphin-Tanguy, G.; Ould-Bouamama, B.

2016-06-01

The paper's main objective is to address the problem of health monitoring of system parameters in Bond Graph (BG) modeling framework, by exploiting its structural and causal properties. The system in feedback control loop is considered uncertain globally. Parametric uncertainty is modeled in interval form. The system parameter is undergoing degradation (prognostic candidate) and its degradation model is assumed to be known a priori. The detection of degradation commencement is done in a passive manner which involves interval valued robust adaptive thresholds over the nominal part of the uncertain BG-derived interval valued analytical redundancy relations (I-ARRs). The latter forms an efficient diagnostic module. The prognostics problem is cast as joint state-parameter estimation problem, a hybrid prognostic approach, wherein the fault model is constructed by considering the statistical degradation model of the system parameter (prognostic candidate). The observation equation is constructed from nominal part of the I-ARR. Using particle filter (PF) algorithms; the estimation of state of health (state of prognostic candidate) and associated hidden time-varying degradation progression parameters is achieved in probabilistic terms. A simplified variance adaptation scheme is proposed. Associated uncertainties which arise out of noisy measurements, parametric degradation process, environmental conditions etc. are effectively managed by PF. This allows the production of effective predictions of the remaining useful life of the prognostic candidate with suitable confidence bounds. The effectiveness of the novel methodology is demonstrated through simulations and experiments on a mechatronic system.

Comparison of Standardized Cytomegalovirus (CMV) Viral Load Thresholds in Whole Blood and Plasma of Solid Organ and Hematopoietic Stem Cell Transplant Recipients with CMV Infection and Disease.

PubMed

Dioverti, M Veronica; Lahr, Brian D; Germer, Jeffrey J; Yao, Joseph D; Gartner, Michelle L; Razonable, Raymund R

2017-01-01

Quantification of cytomegalovirus (CMV) deoxyribonucleic acid (DNA) has important diagnostic, prognostic, and therapeutic implications in the management of transplant recipients. We aimed to assess a viral load in plasma and whole blood that distinguishes CMV disease from asymptomatic infection in a cohort of solid organ and hematopoietic stem cell transplantation. We prospectively measured and compared CMV viral load in paired plasma and whole blood samples collected from transplant recipients with CMV infection and disease. Cytomegalovirus viral loads were determined by a commercially available US Food and Drug Administration-approved quantitative assay (COBAS AmpliPrep/COBAS TaqMan CMV Test [CAP/CTM CMV]) calibrated to the first World Health Organization International Standard for CMV DNA quantification. Moderate agreement of CMV viral load was observed between plasma and whole blood, with 31% of samples having discordant findings, particularly among samples with low DNA levels. Among the subset of samples where both paired samples had quantifiable levels, we observed a systematic bias that reflected higher viral load in whole blood compared with plasma. Based on receiver operating curve analysis, an initial plasma CMV viral load threshold of 1700 IU/mL in solid organ transplant recipients (sensitivity 80%, specificity 74%) and 1350 IU/mL in allogeneic hematopoietic stem cell transplant recipients (sensitivity 87%, specificity 87%) distinguished CMV disease and asymptomatic infection. This study identifies standardized viral load thresholds that distinguish CMV disease from asymptomatic infection using CAP/CTM CMV assay. We propose these thresholds as potential triggers to be evaluated in prospective studies of preemptive therapy. Plasma was better than whole blood for measuring viral load using the CAP/CTM CMV assay.

Diagnosis of psychosocial risk factors in prevention of low back pain in athletes (MiSpEx).

PubMed

Wippert, Pia-Maria; Puschmann, Anne-Katrin; Arampatzis, Adamantios; Schiltenwolf, Marcus; Mayer, Frank

2017-01-01

Low back pain (LBP) is a common pain syndrome in athletes, responsible for 28% of missed training days/year. Psychosocial factors contribute to chronic pain development. This study aims to investigate the transferability of psychosocial screening tools developed in the general population to athletes and to define athlete-specific thresholds. Data from a prospective multicentre study on LBP were collected at baseline and 1-year follow-up (n=52 athletes, n=289 recreational athletes and n=246 non-athletes). Pain was assessed using the Chronic Pain Grade questionnaire. The psychosocial Risk Stratification Index (RSI) was used to obtain prognostic information regarding the risk of chronic LBP (CLBP). Individual psychosocial risk profile was gained with the Risk Prevention Index - Social (RPI-S). Differences between groups were calculated using general linear models and planned contrasts. Discrimination thresholds for athletes were defined with receiver operating characteristics (ROC) curves. Athletes and recreational athletes showed significantly lower psychosocial risk profiles and prognostic risk for CLBP than non-athletes. ROC curves suggested discrimination thresholds for athletes were different compared with non-athletes. Both screenings demonstrated very good sensitivity (RSI=100%; RPI-S: 75%-100%) and specificity (RSI: 76%-93%; RPI-S: 71%-93%). RSI revealed two risk classes for pain intensity (area under the curve (AUC) 0.92(95% CI 0.85 to 1.0)) and pain disability (AUC 0.88(95% CI 0.71 to 1.0)). Both screening tools can be used for athletes. Athlete-specific thresholds will improve physicians' decision making and allow stratified treatment and prevention.

Serum C-reactive protein (CRP) as a simple and independent prognostic factor in extranodal natural killer/T-cell lymphoma, nasal type.

PubMed

Li, Ya-Jun; Li, Zhi-Ming; Xia, Yi; Huang, Jia-Jia; Huang, Hui-Qiang; Xia, Zhong-Jun; Lin, Tong-Yu; Li, Su; Cai, Xiu-Yu; Wu-Xiao, Zhi-Jun; Jiang, Wen-Qi

2013-01-01

C-reactive protein (CRP) is a biomarker of the inflammatory response, and it shows significant prognostic value for several types of solid tumors. The prognostic significance of CRP for lymphoma has not been fully examined. We evaluated the prognostic role of baseline serum CRP levels in patients with extranodal natural killer (NK)/T-cell lymphoma (ENKTL). We retrospectively analyzed 185 patients with newly diagnosed ENKTL. The prognostic value of the serum CRP level was evaluated for the low-CRP group (CRP≤10 mg/L) versus the high-CRP group (CRP>10 mg/L). The prognostic value of the International Prognostic Index (IPI) and the Korean Prognostic Index (KPI) were evaluated and compared with the newly developed prognostic model. Patients in the high-CRP group tended to display increased adverse clinical characteristics, lower rates of complete remission (P<0.001), inferior progression-free survival (PFS, P = 0.001), and inferior overall survival (OS, P<0.001). Multivariate analysis demonstrated that elevated serum CRP levels, age >60 years, hypoalbuminemia, and elevated lactate dehydrogenase levels were independent adverse predictors of OS. Based on these four independent predictors, we constructed a new prognostic model that identified 4 groups with varying OS: group 1, no adverse factors; group 2, 1 factor; group 3, 2 factors; and group 4, 3 or 4 factors (P<0.001). The novel prognostic model was found to be superior to both the IPI in discriminating patients with different outcomes in the IPI low-risk group and the KPI in distinguishing between the low- and intermediate-low-risk groups, the intermediate-low- and high-intermediate-risk groups, and the high-intermediate- and high-risk groups. Our results suggest that pretreatment serum CRP levels represent an independent predictor of clinical outcome for patients with ENKTL. The prognostic value of the new prognostic model is superior to both IPI and KPI.

Serum C-Reactive Protein (CRP) as a Simple and Independent Prognostic Factor in Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type

PubMed Central

Xia, Yi; Huang, Jia-Jia; Huang, Hui-Qiang; Xia, Zhong-Jun; Lin, Tong-Yu; Li, Su; Cai, Xiu-Yu; Wu-Xiao, Zhi-Jun; Jiang, Wen-Qi

2013-01-01

Background C-reactive protein (CRP) is a biomarker of the inflammatory response, and it shows significant prognostic value for several types of solid tumors. The prognostic significance of CRP for lymphoma has not been fully examined. We evaluated the prognostic role of baseline serum CRP levels in patients with extranodal natural killer (NK)/T-cell lymphoma (ENKTL). Methods We retrospectively analyzed 185 patients with newly diagnosed ENKTL. The prognostic value of the serum CRP level was evaluated for the low-CRP group (CRP≤10 mg/L) versus the high-CRP group (CRP>10 mg/L). The prognostic value of the International Prognostic Index (IPI) and the Korean Prognostic Index (KPI) were evaluated and compared with the newly developed prognostic model. Results Patients in the high-CRP group tended to display increased adverse clinical characteristics, lower rates of complete remission (P<0.001), inferior progression-free survival (PFS, P = 0.001), and inferior overall survival (OS, P<0.001). Multivariate analysis demonstrated that elevated serum CRP levels, age >60 years, hypoalbuminemia, and elevated lactate dehydrogenase levels were independent adverse predictors of OS. Based on these four independent predictors, we constructed a new prognostic model that identified 4 groups with varying OS: group 1, no adverse factors; group 2, 1 factor; group 3, 2 factors; and group 4, 3 or 4 factors (P<0.001). The novel prognostic model was found to be superior to both the IPI in discriminating patients with different outcomes in the IPI low-risk group and the KPI in distinguishing between the low- and intermediate-low-risk groups, the intermediate-low- and high-intermediate-risk groups, and the high-intermediate- and high-risk groups. Conclusions Our results suggest that pretreatment serum CRP levels represent an independent predictor of clinical outcome for patients with ENKTL. The prognostic value of the new prognostic model is superior to both IPI and KPI. PMID:23724031

Clinical potentials of methylator phenotype in stage 4 high-risk neuroblastoma: an open challenge.

PubMed

Banelli, Barbara; Merlo, Domenico Franco; Allemanni, Giorgio; Forlani, Alessandra; Romani, Massimo

2013-01-01

Approximately 20% of stage 4 high-risk neuroblastoma patients are alive and disease-free 5 years after disease onset while the remaining experience rapid and fatal progression. Numerous findings underline the prognostic role of methylation of defined target genes in neuroblastoma without taking into account the clinical and biological heterogeneity of this disease. In this report we have investigated the methylation of the PCDHB cluster, the most informative member of the "Methylator Phenotype" in neuroblastoma, hypothesizing that if this epigenetic mark can predict overall and progression free survival in high-risk stage 4 neuroblastoma, it could be utilized to improve the risk stratification of the patients, alone or in conjunction with the previously identified methylation of the SFN gene (14.3.3sigma) that can accurately predict outcome in these patients. We have utilized univariate and multivariate models to compare the prognostic power of PCDHB methylation in terms of overall and progression free survival, quantitatively determined by pyrosequencing, with that of other markers utilized for the patients' stratification utilizing methylation thresholds calculated on neuroblastoma at stage 1-4 and only on stage 4, high-risk patients. Our results indicate that PCDHB accurately distinguishes between high- and intermediate/low risk stage 4 neuroblastoma in agreement with the established risk stratification criteria. However PCDHB cannot predict outcome in the subgroup of stage 4 patients at high-risk whereas methylation levels of SFN are suggestive of a "methylation gradient" associated with tumor aggressiveness as suggested by the finding of a higher threshold that defines a subset of patients with an extremely severe disease (OS <24 months). Because of the heterogeneity of neuroblastoma we believe that clinically relevant methylation markers should be selected and tested on homogeneous groups of patients rather than on patients at all stages.

Visual and semiquantitative 11C-methionine PET: an independent prognostic factor for survival of newly diagnosed and treatment-naïve gliomas.

PubMed

Poetsch, Nina; Woehrer, Adelheid; Gesperger, Johanna; Furtner, Julia; Haug, Alexander R; Wilhelm, Dorothee; Widhalm, Georg; Karanikas, Georgios; Weber, Michael; Rausch, Ivo; Mitterhauser, Markus; Wadsak, Wolfgang; Hacker, Marcus; Preusser, Matthias; Traub-Weidinger, Tatjana

2018-02-19

Few data exist regarding the prognostic value of L-[S-methyl-11C]methionine (MET) PET for treatment-naïve gliomas. A total of 160 glioma patients (89 men, 71 women; mean age: 45, range 18-84 y) underwent a MET PET prior to any therapy. The PET scans were evaluated visually and semiquantitatively by tumor-to-background (T/N) ratio thresholds chosen by analysis of receiver operating characteristics. Additionally, isocitrate dehydrogenase 1-R132H (IDH1-R132H) immunohistochemistry was performed. Survival analysis was done using Kaplan-Meier estimates and the Cox proportional hazards model. Significantly shorter mean survival times (7.2 vs 8.6 y; P = 0.024) were seen in patients with amino acid avid gliomas (n = 137) compared with visually negative tumors (n = 33) in MET PET. T/N ratio thresholds of 2.1 and 3.5 were significantly associated with survival (10.3 vs 7 vs 4.3 y; P < 0.001). Mean survival differed significantly using the median T/N ratio of 2.4 as cutoff, independent of histopathology (P < 0.01; mean survival: 10.2 ± 0.8 y vs 5.5 ± 0.6 y). In the subgroup of 142 glioma patients characterized by IDH1-R132H status, METT/N ratio demonstrated a significant prognostic impact in IDH1-R132H wildtype astrocytomas and glioblastoma (P = 0.001). Additionally, multivariate testing revealed semiquantitative MET PET as an independent prognostic parameter for treatment-naïve glioma patients without (P = 0.031) and with IDH1-R132H characterization of gliomas (P = 0.024; odds ratio 1.57). This retrospective analysis demonstrates the value of MET PET as a prognostic parameter on survival in treatment-naïve glioma patients. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

A Distributed Prognostic Health Management Architecture

NASA Technical Reports Server (NTRS)

Bhaskar, Saha; Saha, Sankalita; Goebel, Kai

2009-01-01

This paper introduces a generic distributed prognostic health management (PHM) architecture with specific application to the electrical power systems domain. Current state-of-the-art PHM systems are mostly centralized in nature, where all the processing is reliant on a single processor. This can lead to loss of functionality in case of a crash of the central processor or monitor. Furthermore, with increases in the volume of sensor data as well as the complexity of algorithms, traditional centralized systems become unsuitable for successful deployment, and efficient distributed architectures are required. A distributed architecture though, is not effective unless there is an algorithmic framework to take advantage of its unique abilities. The health management paradigm envisaged here incorporates a heterogeneous set of system components monitored by a varied suite of sensors and a particle filtering (PF) framework that has the power and the flexibility to adapt to the different diagnostic and prognostic needs. Both the diagnostic and prognostic tasks are formulated as a particle filtering problem in order to explicitly represent and manage uncertainties; however, typically the complexity of the prognostic routine is higher than the computational power of one computational element ( CE). Individual CEs run diagnostic routines until the system variable being monitored crosses beyond a nominal threshold, upon which it coordinates with other networked CEs to run the prognostic routine in a distributed fashion. Implementation results from a network of distributed embedded devices monitoring a prototypical aircraft electrical power system are presented, where the CEs are Sun Microsystems Small Programmable Object Technology (SPOT) devices.

Independent Prognostic Factors for Acute Organophosphorus Pesticide Poisoning.

PubMed

Tang, Weidong; Ruan, Feng; Chen, Qi; Chen, Suping; Shao, Xuebo; Gao, Jianbo; Zhang, Mao

2016-07-01

Acute organophosphorus pesticide poisoning (AOPP) is becoming a significant problem and a potential cause of human mortality because of the abuse of organophosphate compounds. This study aims to determine the independent prognostic factors of AOPP by using multivariate logistic regression analysis. The clinical data for 71 subjects with AOPP admitted to our hospital were retrospectively analyzed. This information included the Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, 6-h post-admission blood lactate levels, post-admission 6-h lactate clearance rates, admission blood cholinesterase levels, 6-h post-admission blood cholinesterase levels, cholinesterase activity, blood pH, and other factors. Univariate analysis and multivariate logistic regression analyses were conducted to identify all prognostic factors and independent prognostic factors, respectively. A receiver operating characteristic curve was plotted to analyze the testing power of independent prognostic factors. Twelve of 71 subjects died. Admission blood lactate levels, 6-h post-admission blood lactate levels, post-admission 6-h lactate clearance rates, blood pH, and APACHE II scores were identified as prognostic factors for AOPP according to the univariate analysis, whereas only 6-h post-admission blood lactate levels, post-admission 6-h lactate clearance rates, and blood pH were independent prognostic factors identified by multivariate logistic regression analysis. The receiver operating characteristic analysis suggested that post-admission 6-h lactate clearance rates were of moderate diagnostic value. High 6-h post-admission blood lactate levels, low blood pH, and low post-admission 6-h lactate clearance rates were independent prognostic factors identified by multivariate logistic regression analysis. Copyright © 2016 by Daedalus Enterprises.

Baseline plasma chromogranin A levels in patients with well-differentiated neuroendocrine tumors of the pancreas: A potential predictor of postoperative recurrence.

PubMed

Nanno, Yoshihide; Toyama, Hirochika; Matsumoto, Ippei; Otani, Kyoko; Asari, Sadaki; Goto, Tadahiro; Ajiki, Tetsuo; Zen, Yoh; Fukumoto, Takumi; Ku, Yonson

The present study aimed to elucidate prognostic values of baseline plasma chromogranin A (CgA) concentrations in patients with resectable, well-differentiated pancreatic neuroendocrine tumors (PNETs). Preoperative CgA levels in 21 patients with PNET were correlated with clinicopathological factors and patients' survival. Plasma CgA levels ranged 2.9-30.8 pmol/mL (median 6.0), and were significantly elevated in patients with post-operative recurrence (P = 0.004). Using the receiver operating characteristic curve, the optimal cutoff value to predict tumor recurrence was determined as 17.0 pmol/mL. This threshold identified patients with recurrence with 60% sensitivity, 100% specificity, and 90% overall accuracy. Patients with higher CgA levels showed worse recurrence-free survival than those with low CgA levels, both in total (P < 0.001) and in G2 patients (P = 0.020). Combined plasma CgA concentrations and WHO grading may assist in better stratification of PNET patients in terms of the risk of recurrence. Copyright © 2016. Published by Elsevier B.V.

A combined pulmonary function and emphysema score prognostic index for staging in Chronic Obstructive Pulmonary Disease.

PubMed

Boutou, Afroditi K; Nair, Arjun; Douraghi-Zadeh, Dariush; Sandhu, Ranbir; Hansell, David M; Wells, Athol U; Polkey, Michael I; Hopkinson, Nicholas S

2014-01-01

Chronic Obstructive Pulmonary Disease (COPD) is characterized by high morbidity and mortality. Lung computed tomography parameters, individually or as part of a composite index, may provide more prognostic information than pulmonary function tests alone. To investigate the prognostic value of emphysema score and pulmonary artery measurements compared with lung function parameters in COPD and construct a prognostic index using a contingent staging approach. Predictors of mortality were assessed in COPD outpatients whose lung computed tomography, spirometry, lung volumes and gas transfer data were collected prospectively in a clinical database. Univariate and multivariate Cox proportional hazard analysis models with bootstrap techniques were used. 169 patients were included (59.8% male, 61.1 years old; Forced Expiratory Volume in 1 second % predicted: 40.5±19.2). 20.1% died; mean survival was 115.4 months. Age (HR = 1.098, 95% Cl = 1.04-1.252) and emphysema score (HR = 1.034, 95% CI = 1.007-1.07) were the only independent predictors of mortality. Pulmonary artery dimensions were not associated with survival. An emphysema score of 55% was chosen as the optimal threshold and 30% and 65% as suboptimals. Where emphysema score was between 30% and 65% (intermediate risk) the optimal lung volume threshold, a functional residual capacity of 210% predicted, was applied. This contingent staging approach separated patients with an intermediate risk based on emphysema score alone into high risk (Functional Residual Capacity ≥210% predicted) or low risk (Functional Residual Capacity <210% predicted). This approach was more discriminatory for survival (HR = 3.123; 95% CI = 1.094-10.412) than either individual component alone. Although to an extent limited by the small sample size, this preliminary study indicates that the composite Emphysema score-Functional Residual Capacity index might provide a better separation of high and low risk patients with COPD, than other individual predictors alone.

Extensions to regret-based decision curve analysis: an application to hospice referral for terminal patients.

PubMed

Tsalatsanis, Athanasios; Barnes, Laura E; Hozo, Iztok; Djulbegovic, Benjamin

2011-12-23

Despite the well documented advantages of hospice care, most terminally ill patients do not reap the maximum benefit from hospice services, with the majority of them receiving hospice care either prematurely or delayed. Decision systems to improve the hospice referral process are sorely needed. We present a novel theoretical framework that is based on well-established methodologies of prognostication and decision analysis to assist with the hospice referral process for terminally ill patients. We linked the SUPPORT statistical model, widely regarded as one of the most accurate models for prognostication of terminally ill patients, with the recently developed regret based decision curve analysis (regret DCA). We extend the regret DCA methodology to consider harms associated with the prognostication test as well as harms and effects of the management strategies. In order to enable patients and physicians in making these complex decisions in real-time, we developed an easily accessible web-based decision support system available at the point of care. The web-based decision support system facilitates the hospice referral process in three steps. First, the patient or surrogate is interviewed to elicit his/her personal preferences regarding the continuation of life-sustaining treatment vs. palliative care. Then, regret DCA is employed to identify the best strategy for the particular patient in terms of threshold probability at which he/she is indifferent between continuation of treatment and of hospice referral. Finally, if necessary, the probabilities of survival and death for the particular patient are computed based on the SUPPORT prognostication model and contrasted with the patient's threshold probability. The web-based design of the CDSS enables patients, physicians, and family members to participate in the decision process from anywhere internet access is available. We present a theoretical framework to facilitate the hospice referral process. Further rigorous clinical evaluation including testing in a prospective randomized controlled trial is required and planned.

Extensions to Regret-based Decision Curve Analysis: An application to hospice referral for terminal patients

PubMed Central

2011-01-01

Background Despite the well documented advantages of hospice care, most terminally ill patients do not reap the maximum benefit from hospice services, with the majority of them receiving hospice care either prematurely or delayed. Decision systems to improve the hospice referral process are sorely needed. Methods We present a novel theoretical framework that is based on well-established methodologies of prognostication and decision analysis to assist with the hospice referral process for terminally ill patients. We linked the SUPPORT statistical model, widely regarded as one of the most accurate models for prognostication of terminally ill patients, with the recently developed regret based decision curve analysis (regret DCA). We extend the regret DCA methodology to consider harms associated with the prognostication test as well as harms and effects of the management strategies. In order to enable patients and physicians in making these complex decisions in real-time, we developed an easily accessible web-based decision support system available at the point of care. Results The web-based decision support system facilitates the hospice referral process in three steps. First, the patient or surrogate is interviewed to elicit his/her personal preferences regarding the continuation of life-sustaining treatment vs. palliative care. Then, regret DCA is employed to identify the best strategy for the particular patient in terms of threshold probability at which he/she is indifferent between continuation of treatment and of hospice referral. Finally, if necessary, the probabilities of survival and death for the particular patient are computed based on the SUPPORT prognostication model and contrasted with the patient's threshold probability. The web-based design of the CDSS enables patients, physicians, and family members to participate in the decision process from anywhere internet access is available. Conclusions We present a theoretical framework to facilitate the hospice referral process. Further rigorous clinical evaluation including testing in a prospective randomized controlled trial is required and planned. PMID:22196308

Exercise oscillatory breathing and increased ventilation to carbon dioxide production slope in heart failure: an unfavorable combination with high prognostic value.

PubMed

Guazzi, Marco; Arena, Ross; Ascione, Aniello; Piepoli, Massimo; Guazzi, Maurizio D

2007-05-01

Increased slope of exercise ventilation to carbon dioxide production (VE/VCO2) is an established prognosticator in patients with heart failure. Recently, the occurrence of exercise oscillatory breathing (EOB) has emerged as an additional strong indicator of survival. The aim of this study is to define the respective prognostic significance of these variables and whether excess risk may be identified when either respiratory disorder is present. In 288 stable chronic HF patients (average left ventricular ejection fraction, 33 +/- 13%) who underwent cardiopulmonary exercise testing, the prognostic relevance of VE/VCO2 slope, EOB, and peak VO2 was evaluated by multivariate Cox regression. During a mean interval of 28 +/- 13 months, 62 patients died of cardiac reasons. Thirty-five percent presented with EOB. Among patients exhibiting EOB, 54% had an elevated VE/VCO2 slope. The optimal threshold value for the VE/VCO2 slope identified by receiver operating characteristic analysis was < 36.2 or > or = 36.2 (sensitivity, 77%; specificity, 64%; P < .001). Univariate predictors of death included low left ventricular ejection fraction, low peak VO2, high VE/VCO2 slope, and EOB presence. Multivariate analysis selected EOB as the strongest predictor (chi2, 46.5; P < .001). The VE/VCO2 slope (threshold, < 36.2 or > or = 36.2) was the only other exercise test variable retained in the regression (residual chi2, 5.9; P = .02). The hazard ratio for subjects with EOB and a VE/VCO2 slope > or = 36.2 was 11.4 (95% confidence interval, 4.9-26.5; P < .001). These findings identify EOB as a strong survival predictor even more powerful than VE/VCO2 slope. Exercise oscillatory breathing presence does not necessarily imply an elevated VE/VCO2 slope, but combination of either both yields to a burden of risk remarkably high.

A critical prognostic analysis of neutrophil-lymphocyte ratio for patients undergoing nephroureterectomy due to upper urinary tract urothelial carcinoma.

PubMed

Altan, Mesut; Haberal, Hakan Bahadır; Akdoğan, Bülent; Özen, Haluk

2017-10-01

To determine preoperative serum complete blood count parameters that affects survival of patients who underwent surgery for upper urinary tract urothelial cancer (UUT-UC). Since 1990, 150 patients underwent nephroureterectomy with bladder cuff excision for UUT-UC at Hacettepe University. Patients with a history of muscle-invasive bladder cancer, adjuvant chemotherapy or metastasis at the time of diagnosis were excluded. One hundred and thirteen patients without infective symptoms and with a full set of serum data were evaluated retrospectively. Effects of the neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR), platelet-lymphocyte ratio (PLR), and leukocyte count on disease-free survival (DFS) and progression-free survival (PFS) were investigated. Threshold values for each parameter to predict PFS were calculated. The mean age and median follow-up were 63.7 ± 11.1 years and 34 (3-186) months, respectively. Male to female ratio was 86/27. The 5-years PFS (bladder recurrence was excluded) and DFS were 59.6 and 38.4%, respectively. In multivariate analysis, NLR was independent prognostic factor for PFS and DFS (p = 0.006 and p = 0.021, respectively) while LMR was prognostic only for PFS (p = 0.037). For UUT-UC, NLR is a prognostic factor for PFS and DFS, while LMR is a prognostic indicator for PFS in present series.

Survivin expression in canine spontaneous cutaneous and subcutaneous tumors and its prognostic importance.

PubMed

Kavya, N; Rao, S; Sathyanarayana, M L; Narayanaswamy, H D; Byregowda, S M; Ranganath, L; Kamaran, A; Purushotham, K M; Kishore, T K

2017-10-01

The present study was carried out to know the expression level of survivin, an inhibitor of apoptosis protein with an objective to determine its prognostic importance in cutaneous and subcutaneous tissue tumors of dogs. Forty cases of canine cutaneous and subcutaneous tissue tumors on histopathological examination revealed various round cell, epithelial, and mesenchymal cell tumors. Survivin gene expression was detected in all tumors tested by TaqMan real-time polymerase chain reaction assay by comparative cycle threshold method. The mean survivin gene expression value of benign tumors was 0.94±0.63 folds and that of malignant tumors was 18.87±5.30 folds. Postsurgical follow up of 30 malignant tumor cases revealed death in 8, recurrence in 7, and neoplastic free alive status in 15 dogs with mean survivin fold difference values of 48.49±12.39, 14.63±6.37, and 5.034±2.27, respectively. The mean survivin gene expression value was significantly higher in malignant (30 cases, 18.87±5.30) compared to benign tumors (10 cases, 0.94±0.63), and it varied between various postsurgical follow-up groups (p<0.05). Survival analysis, using survivin gene expression median cutoff value of 3.74 in 30 malignant tumors, was performed to predict probable survival period in malignant cutaneous and subcutaneous tumors of dogs. Results of the present study indicated that the expression of survivin in canine cutaneous and subcutaneous tumors has prognostic value, and survivin expression greater than median cutoff value of 3.74 has a poor prognosis.

Prognostic Role of Carcinoembryonic Antigen Level after Preoperative Chemoradiotherapy in Patients with Rectal Cancer.

PubMed

Huh, Jung Wook; Yun, Seong Hyeon; Kim, Seok Hyung; Park, Yoon Ah; Cho, Yong Beom; Kim, Hee Cheol; Lee, Woo Yong; Park, Hee Chul; Choi, Doo Ho; Park, Joon Oh; Park, Young Suk; Chun, Ho-Kyung

2018-05-29

The prognostic role of post-chemoradiotherapy (CRT) carcinoembryonic antigen (CEA) level is not clear. We evaluated the prognostic significance of post-CRT CEA level in patients with rectal cancer after preoperative CRT. We reviewed 659 consecutive patients who underwent preoperative CRT and total mesorectal excision for non-metastatic rectal cancer. Patients were categorized into two groups according to post-CRT serum CEA level: low CEA (< 5 ng/mL) and high CEA (≥ 5 ng/mL). Median post-CRT CEA level was 1.7 ng/mL (range, 0.1-207.0). A high post-CRT level was significantly associated with ypStage, ypT category, tumor regression grade, and pre-CRT CEA level. The 5-year overall survival rate of the 659 patients was 87.8% with a median follow-up period of 57.0 months (range, 1.4-176.4). When the post-CRT CEA groups were divided into groups according to pre-CRT CEA level, the 5-year overall survival rates were significantly different (P < 0.001 and P = 0.001, respectively). Post-CRT CEA level was an independent prognostic factor for overall survival. Multivariate analysis revealed that operation method, differentiation, perineural invasion, postoperative chemotherapy, tumor regression grade, and post-CRT CEA level were independent prognostic factors for overall survival. The level of serum CEA after preoperative CRT was an independent prognostic factor for overall survival in patients with rectal cancer.

Added prognostic value of ischaemic threshold in radionuclide myocardial perfusion imaging: a common-sense integration of exercise tolerance and ischaemia severity.

PubMed

Marini, Cecilia; Acampa, Wanda; Bauckneht, Matteo; Daniele, Stefania; Capitanio, Selene; Cantoni, Valeria; Fiz, Francesco; Zampella, Emilia; Dib, Bassam; Assante, Roberta; Bruzzi, Paolo; Sambuceti, Gianmario; Cuocolo, Alberto

2015-04-01

Reversible ischaemia at radionuclide myocardial perfusion imaging (MPI) accurately predicts risk of cardiac death and nonfatal myocardial infarction (major adverse cardiac events, MACE). This prognostic penetrance might be empowered by accounting for exercise tolerance as an indirect index of ischaemia severity. The present study aimed to verify this hypothesis integrating imaging assessment of ischaemia severity with exercise maximal rate pressure product (RPP) in a large cohort of patients with suspected or known coronary artery disease (CAD). We analysed 1,502 consecutive patients (1,014 men aged 59 ± 10 years) submitted to exercise stress/rest MPI. To account for exercise tolerance, the summed difference score (SDS) was divided by RPP at tracer injection providing a clinical prognostic index (CPI). Reversible ischaemia was documented in 357 patients (24 %) and was classified by SDS as mild (SDS 2-4) in 180, moderate (SDS 5-7) in 118 and severe (SDS >7) in 59. CPI values of ischaemic patients were clustered into tertiles with lowest and highest values indicating low and high risk, respectively. CPI modified SDS risk prediction in 119/357 (33 %) patients. During a 60-month follow-up, MACE occurred in 68 patients. Kaplan-Meier analysis revealed that CPI significantly improved predictive power for MACE incidence with respect to SDS alone. Multivariate Cox analysis confirmed the additive independent value of CPI-derived information. Integration of ischaemic threshold and ischaemia extension and severity can improve accuracy of exercise MPI in predicting long-term outcome in a large cohort of patients with suspected or known CAD.

Uncertainty Representation and Interpretation in Model-based Prognostics Algorithms based on Kalman Filter Estimation

DTIC Science & Technology

2012-09-01

interpreting the state vector as the health indicator and a threshold is used on this variable in order to compute EOL (end-of-life) and RUL. Here, we...End-of-life ( EOL ) would match the true spread and would not change from one experiment to another. This is, however, in practice impossible to achieve

Plants and pixels: Comparing phenologies from the ground and from space (Invited)

NASA Astrophysics Data System (ADS)

Rutishauser, T.; Stoekli, R.; Jeanneret, F.; Peñuelas, J.

2010-12-01

Changes in the seasonality of life cycles of plants as recorded in phenological observations have been widely analysed at the species level with data available for many decades back in time. At the same time, seasonality changes in satellite-based observations and prognostic phenology models comprise information at the pixel-size or landscape scale. Change analysis of satellite-based records is restricted due to relatively short satellite records that further include gaps while model-based analyses are biased due to current model deficiencies. At 30 selected sites across Europe, we analysed three different sources of plant seasonality during the 1971-2000 period. Data consisted of (1) species-specific development stages of flowering and leave-out with different species observed at each site. (2) We used a synthetic phenological metric that integrates the common interannual phenological signal across all species at one site. (3) We estimated daily Leaf Area Index with a prognostic phenology model. The prior uncertainties of the model’s empirical parameter space are constrained by assimilating the Fraction of Photosynthetically Active Radiation absorbed by vegetation (FPAR) and Leaf Area Index (LAI) from the MODerate Resolution Imaging Spectroradiometer (MODIS). We extracted the day of year when the 25%, 50% and 75% thresholds were passed each spring. The question arises how the three phenological signals compare and correlate across climate zones in Europe. Is there a match between single species observations, species-based ground-observed metrics and the landscape-scale prognostic model? Are there single key-species across Europe that best represent a landscape scale measure from the prognostic model? Can one source substitute another and serve as proxy-data? What can we learn from potential mismatches? Focusing on changes in spring this contribution presents first results of an ongoing comparison study from a number of European test sites that will be extended to the pan-European phenological database Cost725 and PEP725.

Analysis of RET promoter CpG island methylation using methylation-specific PCR (MSP), pyrosequencing, and methylation-sensitive high-resolution melting (MS-HRM): impact on stage II colon cancer patient outcome.

PubMed

Draht, Muriel X G; Smits, Kim M; Jooste, Valérie; Tournier, Benjamin; Vervoort, Martijn; Ramaekers, Chantal; Chapusot, Caroline; Weijenberg, Matty P; van Engeland, Manon; Melotte, Veerle

2016-01-01

Already since the 1990s, promoter CpG island methylation markers have been considered promising diagnostic, prognostic, and predictive cancer biomarkers. However, so far, only a limited number of DNA methylation markers have been introduced into clinical practice. One reason why the vast majority of methylation markers do not translate into clinical applications is lack of independent validation of methylation markers, often caused by differences in methylation analysis techniques. We recently described RET promoter CpG island methylation as a potential prognostic marker in stage II colorectal cancer (CRC) patients of two independent series. In the current study, we analyzed the RET promoter CpG island methylation of 241 stage II colon cancer patients by direct methylation-specific PCR (MSP), nested-MSP, pyrosequencing, and methylation-sensitive high-resolution melting (MS-HRM). All primers were designed as close as possible to the same genomic region. In order to investigate the effect of different DNA methylation assays on patient outcome, we assessed the clinical sensitivity and specificity as well as the association of RET methylation with overall survival for three and five years of follow-up. Using direct-MSP and nested-MSP, 12.0 % (25/209) and 29.6 % (71/240) of the patients showed RET promoter CpG island methylation. Methylation frequencies detected by pyrosequencing were related to the threshold for positivity that defined RET methylation. Methylation frequencies obtained by pyrosequencing (threshold for positivity at 20 %) and MS-HRM were 13.3 % (32/240) and 13.8 % (33/239), respectively. The pyrosequencing threshold for positivity of 20 % showed the best correlation with MS-HRM and direct-MSP results. Nested-MSP detected RET promoter CpG island methylation in deceased patients with a higher sensitivity (33.1 %) compared to direct-MSP (10.7 %), pyrosequencing (14.4 %), and MS-HRM (15.4 %). While RET methylation frequencies detected by nested-MSP, pyrosequencing, and MS-HRM varied, the prognostic effect seemed similar (HR 1.74, 95 % CI 0.97-3.15; HR 1.85, 95 % CI 0.93-3.86; HR 1.83, 95 % CI 0.92-3.65, respectively). Our results show that upon optimizing and aligning four RET methylation assays with regard to primer location and sensitivity, differences in methylation frequencies and clinical sensitivities are observed; however, the effect on the marker's prognostic outcome is minimal.

[Expression of BAG3 Gene in Acute Myeloid Leukemia and Its Prognostic Value].

PubMed

Zhu, Hua-Yuan; Fu, Yuan; Wu, Wei; Xu, Jia-Dai; Chen, Ting-Mei; Qiao, Chun; Li, Jian-Yong; Liu, Peng

2015-08-01

To investigate the expression of BAG3 gene in acue myeloid leukemia (AML) and its prognostic value. Real-time quantitative RT-PCR was used to detect the expression of BAG3 mRNA in 88 previously untreated AML patients. The corelation of BAG3 expression level with clinical characteristics and known prognostic markers of AML was analyzed. In 88 patients with AML, the expression of BAG3 mRNA in NPMI mutated AML patients was obviously lower than that in NPMI unmutated patients (P = 0.018). The expression level of BAG3 mRNA did not related to clinical parameters, such as age, sex, FAB subtype, WBC count, extra-modullary presentation, and to prognostic factors including cytogenetics, FLT3-ITD, c-kit and CEBPα mutation status (P > 0.05). The expression level of BAG3 had no obvious effect on complete remission (CR) of patients in first treatment. The expression level of BAG3 in non-M3 patients was higher than that in relapsed patients (P = 0.036). The expression level of BAG3 had no effect on overall survival (OS) of patients. The expression level of BAG3 does not correlated with known-prognostic markers of AML, only the expression level of BAG3 in NPM1 mutated patients is lower than that in NPM1 unmutated patients. The expression level of BAG3 has no effect on OS of AML patients, the BAG3 can not be difined as a prognostic marker in AML.

Oxygen-modifying treatment with ARCON reduces the prognostic significance of hemoglobin in squamous cell carcinoma of the head and neck

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hoogsteen, Ilse J.; Pop, Lucas A.M.; Marres, Henri A.M.

2006-01-01

Purpose: To evaluate the prognostic significance of hemoglobin (Hb) levels measured before and during treatment with accelerated radiotherapy with carbogen and nicotinamide (ARCON). Methods and Materials: Two hundred fifteen patients with locally advanced tumors of the head and neck were included in a phase II trial of ARCON. This treatment regimen combines accelerated radiotherapy for reduction of repopulation with carbogen breathing and nicotinamide to reduce hypoxia. In these patients, Hb levels were measured before, during, and after radiotherapy. Results: Preirradiation and postirradiation Hb levels were available for 206 and 195 patients respectively. Hb levels below normal were most frequently seenmore » among patients with T4 (p < 0.001) and N2 (p < 0.01) disease. Patients with a larynx tumor had significantly higher Hb levels (p < 0.01) than other tumor sites. During radiotherapy, 69 patients experienced a decrease in Hb level. In a multivariate analysis there was no prognostic impact of Hb level on locoregional control, disease-free survival, and overall survival. Primary tumor site was independently prognostic for locoregional control (p = 0.018), and gender was the only prognostic factor for disease-free and overall survival (p < 0.05). High locoregional control rates were obtained for tumors of the larynx (77%) and oropharynx (72%). Conclusion: Hemoglobin level was not found to be of prognostic significance for outcome in patients with squamous cell carcinoma of the head and neck after oxygen-modifying treatment with ARCON.« less

The effects of segmentation algorithms on the measurement of 18F-FDG PET texture parameters in non-small cell lung cancer.

PubMed

Bashir, Usman; Azad, Gurdip; Siddique, Muhammad Musib; Dhillon, Saana; Patel, Nikheel; Bassett, Paul; Landau, David; Goh, Vicky; Cook, Gary

2017-12-01

Measures of tumour heterogeneity derived from 18-fluoro-2-deoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT) scans are increasingly reported as potential biomarkers of non-small cell lung cancer (NSCLC) for classification and prognostication. Several segmentation algorithms have been used to delineate tumours, but their effects on the reproducibility and predictive and prognostic capability of derived parameters have not been evaluated. The purpose of our study was to retrospectively compare various segmentation algorithms in terms of inter-observer reproducibility and prognostic capability of texture parameters derived from non-small cell lung cancer (NSCLC) 18 F-FDG PET/CT images. Fifty three NSCLC patients (mean age 65.8 years; 31 males) underwent pre-chemoradiotherapy 18 F-FDG PET/CT scans. Three readers segmented tumours using freehand (FH), 40% of maximum intensity threshold (40P), and fuzzy locally adaptive Bayesian (FLAB) algorithms. Intraclass correlation coefficient (ICC) was used to measure the inter-observer variability of the texture features derived by the three segmentation algorithms. Univariate cox regression was used on 12 commonly reported texture features to predict overall survival (OS) for each segmentation algorithm. Model quality was compared across segmentation algorithms using Akaike information criterion (AIC). 40P was the most reproducible algorithm (median ICC 0.9; interquartile range [IQR] 0.85-0.92) compared with FLAB (median ICC 0.83; IQR 0.77-0.86) and FH (median ICC 0.77; IQR 0.7-0.85). On univariate cox regression analysis, 40P found 2 out of 12 variables, i.e. first-order entropy and grey-level co-occurence matrix (GLCM) entropy, to be significantly associated with OS; FH and FLAB found 1, i.e., first-order entropy. For each tested variable, survival models for all three segmentation algorithms were of similar quality, exhibiting comparable AIC values with overlapping 95% CIs. Compared with both FLAB and FH, segmentation with 40P yields superior inter-observer reproducibility of texture features. Survival models generated by all three segmentation algorithms are of at least equivalent utility. Our findings suggest that a segmentation algorithm using a 40% of maximum threshold is acceptable for texture analysis of 18 F-FDG PET in NSCLC.

Measurable residual disease detection by high-throughput sequencing improves risk stratification for pediatric B-ALL

PubMed Central

Wood, Brent; Wu, David; Crossley, Beryl; Dai, Yunfeng; Williamson, David; Gawad, Charles; Borowitz, Michael J.; Devidas, Meenakshi; Maloney, Kelly W.; Larsen, Eric; Winick, Naomi; Raetz, Elizabeth; Carroll, William L.; Hunger, Stephen P.; Loh, Mignon L.; Robins, Harlan

2018-01-01

Early response to induction chemotherapy is an important prognostic factor in B-lymphoblastic leukemia (B-ALL). Here, we compare high-throughput sequencing (HTS) of IGH and TRG genes vs flow cytometry (FC) for measurable residual disease (MRD) detection at the end of induction chemotherapy in pediatric patients with newly diagnosed B-ALL. Six hundred nineteen paired pretreatment and end-of-induction bone marrow samples from Children’s Oncology Group studies AALL0331 (clinicaltrials.gov #NCT00103285) (standard risk [SR]; with MRD by FC at any level) and AALL0232 (clinicaltrials.gov #NCT00075725) (high risk; with day 29 MRD <0.1% by FC) were evaluated by HTS and FC for event-free (EFS) and overall survival (OS). HTS and FC showed similar 5-year EFS and OS for MRD-positive and -negative patients using an MRD threshold of 0.01%. However, there was a high discordant rate with HTS identifying 55 (38.7%) more patients MRD positive at this threshold. These discrepant patients have worse outcomes than FC MRD-negative patients. In addition, the increased analytic sensitivity of HTS permitted identification of 19.9% of SR patients without MRD at any detectable level who had excellent 5-year EFS (98.1%) and OS (100%). The higher analytic sensitivity and lower false-negative rate of HTS improves upon FC for MRD detection in pediatric B-ALL by identifying a novel subset of patients at end of induction who are essentially cured using current chemotherapy and identifying MRD at 0.01% in up to one-third of patients who are missed at the same threshold by FC. PMID:29284596

Home blood pressure monitoring. Current knowledge and directions for future research.

PubMed

Reims, H; Fossum, E; Kjeldsen, S E; Julius, S

2001-01-01

Home blood pressure (BP) monitoring has become popular in clinical practice and several automated devices for home BP measurement are now recommendable. Home BP is generally lower than clinic BP, and similar to daytime ambulatory BP. Home BP measurement eliminates the white coat effect and provides a high number of readings, and it is considered more accurate and reproducible than clinic BP. It can improve the sensitivity and statistical power of clinical drug trials and may have a higher prognostic value than clinic BP. Home monitoring may improve compliance and BP control, and reduce costs of hypertension management. Diagnostic thresholds and treatment target values for home BP remain to be established by longitudinal studies. Until then, home BP monitoring is to be considered a supplement. However, high home BP may support or confirm the diagnosis made in the doctor's office, and low home BP may warrant ambulatory BP monitoring. During long-term follow-up, home BP monitoring provides an opportunity for close attention to BP levels and variations. The first international guidelines have established a consensus document with recommendations, including a proposal of preliminary diagnostic thresholds, but further research is needed to define the precise role of home BP monitoring in clinical practice.

Vehicle Integrated Prognostic Reasoner (VIPR) Metric Report

NASA Technical Reports Server (NTRS)

Cornhill, Dennis; Bharadwaj, Raj; Mylaraswamy, Dinkar

2013-01-01

This document outlines a set of metrics for evaluating the diagnostic and prognostic schemes developed for the Vehicle Integrated Prognostic Reasoner (VIPR), a system-level reasoner that encompasses the multiple levels of large, complex systems such as those for aircraft and spacecraft. VIPR health managers are organized hierarchically and operate together to derive diagnostic and prognostic inferences from symptoms and conditions reported by a set of diagnostic and prognostic monitors. For layered reasoners such as VIPR, the overall performance cannot be evaluated by metrics solely directed toward timely detection and accuracy of estimation of the faults in individual components. Among other factors, overall vehicle reasoner performance is governed by the effectiveness of the communication schemes between monitors and reasoners in the architecture, and the ability to propagate and fuse relevant information to make accurate, consistent, and timely predictions at different levels of the reasoner hierarchy. We outline an extended set of diagnostic and prognostics metrics that can be broadly categorized as evaluation measures for diagnostic coverage, prognostic coverage, accuracy of inferences, latency in making inferences, computational cost, and sensitivity to different fault and degradation conditions. We report metrics from Monte Carlo experiments using two variations of an aircraft reference model that supported both flat and hierarchical reasoning.

Survivin expression in canine spontaneous cutaneous and subcutaneous tumors and its prognostic importance

PubMed Central

Kavya, N.; Rao, S.; Sathyanarayana, M. L.; Narayanaswamy, H. D.; Byregowda, S. M.; Ranganath, L.; Kamaran, A.; Purushotham, K. M.; Kishore, T. K.

2017-01-01

Aim: The present study was carried out to know the expression level of survivin, an inhibitor of apoptosis protein with an objective to determine its prognostic importance in cutaneous and subcutaneous tissue tumors of dogs. Materials and Methods: Forty cases of canine cutaneous and subcutaneous tissue tumors on histopathological examination revealed various round cell, epithelial, and mesenchymal cell tumors. Survivin gene expression was detected in all tumors tested by TaqMan real-time polymerase chain reaction assay by comparative cycle threshold method. Results: The mean survivin gene expression value of benign tumors was 0.94±0.63 folds and that of malignant tumors was 18.87±5.30 folds. Postsurgical follow up of 30 malignant tumor cases revealed death in 8, recurrence in 7, and neoplastic free alive status in 15 dogs with mean survivin fold difference values of 48.49±12.39, 14.63±6.37, and 5.034±2.27, respectively. The mean survivin gene expression value was significantly higher in malignant (30 cases, 18.87±5.30) compared to benign tumors (10 cases, 0.94±0.63), and it varied between various postsurgical follow-up groups (p<0.05). Survival analysis, using survivin gene expression median cutoff value of 3.74 in 30 malignant tumors, was performed to predict probable survival period in malignant cutaneous and subcutaneous tumors of dogs. Conclusions: Results of the present study indicated that the expression of survivin in canine cutaneous and subcutaneous tumors has prognostic value, and survivin expression greater than median cutoff value of 3.74 has a poor prognosis. PMID:29184378

Prognostics Applied to Electric Propulsion UAV

NASA Technical Reports Server (NTRS)

Goebel, Kai; Saha, Bhaskar

2013-01-01

Health management plays an important role in operations of UAV. If there is equipment malfunction on critical components, safe operation of the UAV might possibly be compromised. A technology with particular promise in this arena is equipment prognostics. This technology provides a state assessment of the health of components of interest and, if a degraded state has been found, it estimates how long it will take before the equipment will reach a failure threshold, conditional on assumptions about future operating conditions and future environmental conditions. This chapter explores the technical underpinnings of how to perform prognostics and shows an implementation on the propulsion of an electric UAV. A particle filter is shown as the method of choice in performing state assessment and predicting future degradation. The method is then applied to the batteries that provide power to the propeller motors. An accurate run-time battery life prediction algorithm is of critical importance to ensure the safe operation of the vehicle if one wants to maximize in-air time. Current reliability based techniques turn out to be insufficient to manage the use of such batteries where loads vary frequently in uncertain environments.

Serum total hCGβ level is an independent prognostic factor in transitional cell carcinoma of the urothelial tract.

PubMed

Douglas, J; Sharp, A; Chau, C; Head, J; Drake, T; Wheater, M; Geldart, T; Mead, G; Crabb, S J

2014-04-02

Serum total human chorionic gonadotrophin β subunit (hCGβ) level might have prognostic value in urothelial transitional cell carcinoma (TCC) but has not been investigated for independence from other prognostic variables. We utilised a clinical database of patients receiving chemotherapy between 2005 and 2011 for urothelial TCC and an independent cohort of radical cystectomy patients for validation purposes. Prognostic variables were tested by univariate Kaplan-Meier analyses and log-rank tests. Statistically significant variables were then assessed by multivariate Cox regression. Total hCGβ level was dichotomised at < vs ≥2 IU l(-1). A total of 235 chemotherapy patients were eligible. For neoadjuvant chemotherapy, established prognostic factors including low ECOG performance status, normal haemoglobin, lower T stage and suitability for cisplatin-based chemotherapy were associated with favourable survival in univariate analyses. In addition, low hCGβ level was favourable when assessed either before (median survival not reached vs 1.86 years, P=0.001) or on completion of chemotherapy (4.27 vs 0.42 years, P=0.000002). This was confirmed in multivariate analyses and in patients receiving first- and second-line palliative chemotherapy, and in a radical cystectomy validation set. Serum total hCGβ level is an independent prognostic factor in patients receiving chemotherapy for urothelial TCC in both curative and palliative settings.

The influence of speed abilities and technical skills in early adolescence on adult success in soccer: A long-term prospective analysis using ANOVA and SEM approaches

PubMed Central

2017-01-01

Several talent development programs in youth soccer have implemented motor diagnostics measuring performance factors. However, the predictive value of such tests for adult success is a controversial topic in talent research. This prospective cohort study evaluated the long-term predictive value of 1) motor tests and 2) players’ speed abilities (SA) and technical skills (TS) in early adolescence. The sample consisted of 14,178 U12 players from the German talent development program. Five tests (sprint, agility, dribbling, ball control, shooting) were conducted and players’ height, weight as well as relative age were assessed at nationwide diagnostics between 2004 and 2006. In the 2014/15 season, the players were then categorized as professional (n = 89), semi-professional (n = 913), or non-professional players (n = 13,176), indicating their adult performance level (APL). The motor tests’ prognostic relevance was determined using ANOVAs. Players’ future success was predicted by a logistic regression threshold model. This structural equation model comprised a measurement model with the motor tests and two correlated latent factors, SA and TS, with simultaneous consideration for the manifest covariates height, weight and relative age. Each motor predictor and anthropometric characteristic discriminated significantly between the APL (p < .001; η2 ≤ .02). The threshold model significantly predicted the APL (R2 = 24.8%), and in early adolescence the factor TS (p < .001) seems to have a stronger effect on adult performance than SA (p < .05). Both approaches (ANOVA, SEM) verified the diagnostics’ predictive validity over a long-term period (≈ 9 years). However, because of the limited effect sizes, the motor tests’ prognostic relevance remains ambiguous. A challenge for future research lies in the integration of different (e.g., person-oriented or multilevel) multivariate approaches that expand beyond the “traditional” topic of single tests’ predictive validity and toward more theoretically founded issues. PMID:28806410

Prognostic value of indeterminable anaerobic threshold in heart failure.

PubMed

Agostoni, Piergiuseppe; Corrà, Ugo; Cattadori, Gaia; Veglia, Fabrizio; Battaia, Elisa; La Gioia, Rocco; Scardovi, Angela B; Emdin, Michele; Metra, Marco; Sinagra, Gianfranco; Limongelli, Giuseppe; Raimondo, Rosa; Re, Federica; Guazzi, Marco; Belardinelli, Romualdo; Parati, Gianfranco; Magrì, Damiano; Fiorentini, Cesare; Cicoira, Mariantonietta; Salvioni, Elisabetta; Giovannardi, Marta; Mezzani, Alessandro; Scrutinio, Domenico; Di Lenarda, Andrea; Mantegazza, Valentina; Ricci, Roberto; Apostolo, Anna; Iorio, Annamaria; Paolillo, Stefania; Palermo, Pietro; Contini, Mauro; Vassanelli, Corrado; Passino, Claudio; Piepoli, Massimo F

2013-09-01

In patients with heart failure (HF), during maximal cardiopulmonary exercise test, anaerobic threshold (AT) is not always identified. We evaluated whether this finding has a prognostic meaning. We recruited and prospectively followed up, in 14 dedicated HF units, 3058 patients with systolic (left ventricular ejection fraction <40%) HF in stable clinical conditions, New York Heart Association class I to III, who underwent clinical, laboratory, echocardiographic, and cardiopulmonary exercise test investigations at study enrollment. We excluded 921 patients who did not perform a maximal exercise, based on lack of achievement of anaerobic metabolism (peak respiratory quotient ≤1.05). Primary study end point was a composite of cardiovascular death and urgent cardiac transplant, and secondary end point was all-cause death. Median follow-up was 3.01 (1.39-4.98) years. AT was identified in 1935 out of 2137 patients (90.54%). At multivariable logistic analysis, failure in detecting AT resulted significantly in reduced peak oxygen uptake and higher metabolic exercise and cardiac and kidney index score value, a powerful prognostic composite HF index (P<0.001). At multivariable analysis, the following variables were significantly associated with primary study end point: peak oxygen uptake (% pred; P<0.001; hazard ratio [HR]=0.977; confidence interval [CI]=0.97-0.98), ventilatory efficiency slope (P=0.01; HR=1.02; CI=1.01-1.03), hemoglobin (P<0.05; HR=0.931; CI=0.87-1.00), left ventricular ejection fraction (P<0.001; HR=0.948; CI=0.94-0.96), renal function (modification of diet in renal disease; P<0.001; HR=0.990; CI=0.98-0.99), sodium (P<0.05; HR=0.967; CI=0.94-0.99), and AT nonidentification (P<0.05; HR=1.41; CI=1.06-1.89). Nonidentification of AT remained associated to prognosis also when compared with metabolic exercise and cardiac and kidney index score (P<0.01; HR=1.459; CI=1.09-1.10). Similar results were obtained for the secondary study end point. The inability to identify AT most often occurs in patients with severe HF, and it has an independent prognostic role in HF.

Prognostic value of 6-minute walk corridor test in patients with mild to moderate heart failure: comparison with other methods of functional evaluation.

PubMed

Rostagno, Carlo; Olivo, Giuseppe; Comeglio, Marco; Boddi, Vieri; Banchelli, Michela; Galanti, Giorgio; Gensini, Gian Franco

2003-06-01

The study was designed to evaluate the prognostic value of the 6-min walk test (6MWT) in patients with mild to moderate congestive heart failure (CHF). Two hundred and fourteen patients (119 men and 95 women, mean age 64 years) were followed for a mean period of 34 months to assess event-free survival (death, heart transplantation). Sixty-six patients (34%) died (63 cardiovascular causes, 2 cancer and 1 stroke) and five patients underwent heart transplantation. For patients who walked <300 m during the 6MWT, survival was 62% compared with 82% in patients who walked 300-450 m or>450 m. With univariate analysis, NYHA class was the strongest predictor of death. LVEF (P<0.0001), aetiology of heart failure (P<0.001), LV filling pattern (P=0.002) and 6MWT distance (P<0.01) were all significantly related to survival. No significant relationship was found between survival, peak oxygen consumption or anaerobic threshold. Multivariate analysis using the Cox-stepwise regression model showed that LV fractional shortening (P<0.009) and 6MWT distance (P<0.0005) were the strongest prognostic markers. A 6MWT distance of <300 m is a simple and useful prognostic marker of subsequent cardiac death in unselected patients with mild to moderate CHF.

Intravoxel Incoherent Motion and Quantitative Non-Gaussian Diffusion MR Imaging: Evaluation of the Diagnostic and Prognostic Value of Several Markers of Malignant and Benign Breast Lesions.

PubMed

Iima, Mami; Kataoka, Masako; Kanao, Shotaro; Onishi, Natsuko; Kawai, Makiko; Ohashi, Akane; Sakaguchi, Rena; Toi, Masakazu; Togashi, Kaori

2018-05-01

Purpose To investigate the performance of integrated approaches that combined intravoxel incoherent motion (IVIM) and non-Gaussian diffusion parameters compared with the Breast Imaging and Reporting Data System (BI-RADS) to establish multiparameter thresholds scores or probabilities by using Bayesian analysis to distinguish malignant from benign breast lesions and their correlation with molecular prognostic factors. Materials and Methods Between May 2013 and March 2015, 411 patients were prospectively enrolled and 199 patients (allocated to training [n = 99] and validation [n = 100] sets) were included in this study. IVIM parameters (flowing blood volume fraction [fIVIM] and pseudodiffusion coefficient [D*]) and non-Gaussian diffusion parameters (theoretical apparent diffusion coefficient [ADC] at b value of 0 sec/mm 2 [ADC 0 ] and kurtosis [K]) by using IVIM and kurtosis models were estimated from diffusion-weighted image series (16 b values up to 2500 sec/mm 2 ), as well as a synthetic ADC (sADC) calculated by using b values of 200 and 1500 (sADC 200-1500 ) and a standard ADC calculated by using b values of 0 and 800 sec/mm 2 (ADC 0-800 ). The performance of two diagnostic approaches (combined parameter thresholds and Bayesian analysis) combining IVIM and diffusion parameters was evaluated and compared with BI-RADS performance. The Mann-Whitney U test and a nonparametric multiple comparison test were used to compare their performance to determine benignity or malignancy and as molecular prognostic biomarkers and subtypes of breast cancer. Results Significant differences were found between malignant and benign breast lesions for IVIM and non-Gaussian diffusion parameters (ADC 0 , K, fIVIM, fIVIM · D*, sADC 200-1500, and ADC 0-800 ; P < .05). Sensitivity and specificity for the validation set by radiologists A and B were as follows: sensitivity, 94.7% and 89.5%, and specificity, 75.0% and 79.2% for sADC 200-1500 , respectively; sensitivity, 94.7% and 96.1%, and specificity, 75.0% and 66.7%, for the combined thresholds approach, respectively; sensitivity, 92.1% and 92.1%, and specificity, 83.3% and 66.7%, for Bayesian analysis, respectively; and sensitivity and specificity, 100% and 79.2%, for BI-RADS, respectively. The significant difference in values of sADC 200-1500 in progesterone receptor status (P = .002) was noted. sADC 200-1500 was significantly different between histologic subtypes (P = .006). Conclusion Approaches that combined various IVIM and non-Gaussian diffusion MR imaging parameters may provide BI-RADS-equivalent scores almost comparable to BI-RADS categories without the use of contrast agents. Non-Gaussian diffusion parameters also differed by biologic prognostic factors. © RSNA, 2017 Online supplemental material is available for this article.

aPKCλ/ι is a beneficial prognostic marker for pancreatic neoplasms.

PubMed

Kato, Shingo; Akimoto, Kazunori; Nagashima, Yoji; Ishiguro, Hitoshi; Kubota, Kensuke; Kobayashi, Noritoshi; Hosono, Kunihiro; Watanabe, Seitaro; Sekino, Yusuke; Sato, Takamitsu; Sasaki, Kazunori; Nakaigawa, Noboru; Kubota, Yoshinobu; Inayama, Yoshiaki; Endo, Itaru; Ohno, Shigeo; Maeda, Shin; Nakajima, Atsushi

2013-01-01

Pancreatic cancer is a lethal disease. Overall survival is typically 6 months from diagnosis. Determination of prognostic factors in pancreatic cancer that would allow identification of patients who could potentially benefit from aggressive treatment is important. However, until date, there are no established reliable prognostic factors for pancreatic cancer patients. Herein, we propose a beneficial biomarker which is significantly correlated with the prognosis in pancreatic cancer patients. Atypical protein kinase C λ/ι (aPKCλ/ι) is overexpressed and has been implicated in the progression of several cancers. We tested the expression levels of aPKCλ/ι in two types of pancreatic neoplasm, pancreatic ductal adenocarcinoma (PDAC) and intraductal papillary mucinous neoplasms (IPMNs), by immunohistochemistry. Examination of the aPKCλ/ι expression levels in surgically resected specimens of PDCA (n = 115) demonstrated that the expression levels of aPKCλ/ιin PDAC had prognostic implications, independent of the Tumor-Node-Metastasis classification and World Health Organization tumor grade. In the case of IPMNs (n = 46) also, the expression levels of aPKCλ/ιin IPMN were found to be of prognostic importance, independent of the World Health Organization histological grade or morphological type. Interestingly, high expression levels of aPKCλ/ι were significantly correlated with a worse histological grade (p = 0.010) and advanced stage of the tumor (p = 0.0050) in IPMN patients. These findings suggest that high expression levels of aPKCλ/ι could be involved in the malignant transformation of IPMNs. Based on these observations, we propose the expression level of aPKCλ/ι as a prognostic marker common to different types of pancreatic neoplasms. Copyright © 2013 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Intrahepatic cholangiocarcinoma prognostic determination using pre-operative serum C-reactive protein levels.

PubMed

Lin, Zi-Ying; Liang, Zhen-Xing; Zhuang, Pei-Lin; Chen, Jie-Wei; Cao, Yun; Yan, Li-Xu; Yun, Jing-Ping; Xie, Dan; Cai, Mu-Yan

2016-10-12

Serum C-reactive protein (CRP), an acute inflammatory response biomarker, has been recognized as an indicator of malignant disease progression. However, the prognostic significance of CRP levels collected before tumor removal in intrahepatic cholangiocarcinoma requires further investigation. We sampled the CRP levels in 140 patients with intrahepatic cholangiocarcinoma who underwent hepatectomies with regional lymphadenectomies between 2006 and 2013. A retrospective analysis of the clinicopathological data was performed. We focused on the impact of serum CRP on the patients' cancer-specific survival and recurrence-free survival rates. High levels of preoperative serum CRP were significantly associated with well-established clinicopathologic features, including gender, advanced tumor stage, and elevated carcinoembryonic antigen and carbohydrate antigen 19-9 levels (P < 0.05). Univariate analysis demonstrated a significant association between high levels of serum CRP and adverse cancer-specific survival (P = 0.001) and recurrence-free survival (P < 0.001). In patients with stage I/II intrahepatic cholangiocarcinoma, the serum CRP level was a prognostic indicator for cancer-specific survival. In patients with stage I/II or stage III/IV, the serum CRP level was a prognostic indicator for recurrence-free survival (P < 0.05). Additionally, multivariate analysis identified serum CRP level in intrahepatic cholangiocarcinoma as an independent prognostic factor (P < 0.05). We confirmed a significant association of elevated pre-operative CRP levels with poor clinical outcomes for the tested patients with intrahepatic cholangiocarcinoma. Our results indicate that the serum CRP level may represent a useful factor for patient stratification in intrahepatic cholangiocarcinoma management.

Independent Prognostic Value of Serum Markers in Diffuse Large B-Cell Lymphoma in the Era of the NCCN-IPI.

PubMed

Melchardt, Thomas; Troppan, Katharina; Weiss, Lukas; Hufnagl, Clemens; Neureiter, Daniel; Tränkenschuh, Wolfgang; Schlick, Konstantin; Huemer, Florian; Deutsch, Alexander; Neumeister, Peter; Greil, Richard; Pichler, Martin; Egle, Alexander

2015-12-01

Several serum parameters have been evaluated for adding prognostic value to clinical scoring systems in diffuse large B-cell lymphoma (DLBCL), but none of the reports used multivariate testing of more than one parameter at a time. The goal of this study was to validate widely available serum parameters for their independent prognostic impact in the era of the National Comprehensive Cancer Network-International Prognostic Index (NCCN-IPI) score to determine which were the most useful. This retrospective bicenter analysis includes 515 unselected patients with DLBCL who were treated with rituximab and anthracycline-based chemoimmunotherapy between 2004 and January 2014. Anemia, high C-reactive protein, and high bilirubin levels had an independent prognostic value for survival in multivariate analyses in addition to the NCCN-IPI, whereas neutrophil-to-lymphocyte ratio, high gamma-glutamyl transferase levels, and platelets-to-lymphocyte ratio did not. In our cohort, we describe the most promising markers to improve the NCCN-IPI. Anemia and high C-reactive protein levels retain their power in multivariate testing even in the era of the NCCN-IPI. The negative role of high bilirubin levels may be associated as a marker of liver function. Further studies are warranted to incorporate these markers into prognostic models and define their role opposite novel molecular markers. Copyright © 2015 by the National Comprehensive Cancer Network.

Distributed Prognostics and Health Management with a Wireless Network Architecture

NASA Technical Reports Server (NTRS)

Goebel, Kai; Saha, Sankalita; Sha, Bhaskar

2013-01-01

A heterogeneous set of system components monitored by a varied suite of sensors and a particle-filtering (PF) framework, with the power and the flexibility to adapt to the different diagnostic and prognostic needs, has been developed. Both the diagnostic and prognostic tasks are formulated as a particle-filtering problem in order to explicitly represent and manage uncertainties in state estimation and remaining life estimation. Current state-of-the-art prognostic health management (PHM) systems are mostly centralized in nature, where all the processing is reliant on a single processor. This can lead to a loss in functionality in case of a crash of the central processor or monitor. Furthermore, with increases in the volume of sensor data as well as the complexity of algorithms, traditional centralized systems become for a number of reasons somewhat ungainly for successful deployment, and efficient distributed architectures can be more beneficial. The distributed health management architecture is comprised of a network of smart sensor devices. These devices monitor the health of various subsystems or modules. They perform diagnostics operations and trigger prognostics operations based on user-defined thresholds and rules. The sensor devices, called computing elements (CEs), consist of a sensor, or set of sensors, and a communication device (i.e., a wireless transceiver beside an embedded processing element). The CE runs in either a diagnostic or prognostic operating mode. The diagnostic mode is the default mode where a CE monitors a given subsystem or component through a low-weight diagnostic algorithm. If a CE detects a critical condition during monitoring, it raises a flag. Depending on availability of resources, a networked local cluster of CEs is formed that then carries out prognostics and fault mitigation by efficient distribution of the tasks. It should be noted that the CEs are expected not to suspend their previous tasks in the prognostic mode. When the prognostics task is over, and after appropriate actions have been taken, all CEs return to their original default configuration. Wireless technology-based implementation would ensure more flexibility in terms of sensor placement. It would also allow more sensors to be deployed because the overhead related to weights of wired systems is not present. Distributed architectures are furthermore generally robust with regard to recovery from node failures.

Transcranial Magnetic Stimulation (TMS) as a Tool for Early Diagnosis and Prognostication in Cortico-Basal Ganglia Degeneration (CBD) Syndromes: Review of Literature and Case Report.

PubMed

Issac, Thomas Gregor; Chandra, Sadanandavalli Retnaswami; Nagaraju, B C

2016-01-01

Cortico basal degeneration (CBD) of the brain is a rare progressive neurodegenerative disease which encompasses unique neuropsychiatric manifestations. Early diagnosis is essential for initiating proper treatment and favorable outcome. Transcranial Magnetic Stimulation (TMS), a well-known technique for assessment of cortical excitatory and inhibitory properties. It was suggested that in a degenerative disease like CBD which involves the cortex as well as the subcortical structures, comparing both hemispheres, a differential pattern in TMS can be obtained which would help in early identification, prognostication and early therapeutic intervention. We describe a case of CBD with corroborative clinical and imaging picture wherein single pulse TMS was used over both the hemispheres measuring the following parameters of interest which included: Motor Threshold (MT), Central Motor Conduction Time (CMCT) and Silent Period (SP). Differential patterns of MT, CMCT and SP was obtained by stimulating over both the hemispheres with the affected hemisphere showing significantly reduced MT and prolonged CMCT implying early impairment of cortical and subcortical structures thereby revealing the potential application of TMS being utilized in a novel way for early detection and prognostication in CBD syndromes.

Prognostic value of changes in galectin-3 levels over time in patients with heart failure: data from CORONA and COACH.

PubMed

van der Velde, A Rogier; Gullestad, Lars; Ueland, Thor; Aukrust, Pål; Guo, Yu; Adourian, Aram; Muntendam, Pieter; van Veldhuisen, Dirk J; de Boer, Rudolf A

2013-03-01

In several cross-sectional analyses, circulating baseline levels of galectin-3, a protein involved in myocardial fibrosis and remodeling, have been associated with increased risk for morbidity and mortality in patients with heart failure (HF). The importance and clinical use of repeated measurements of galectin-3 have not yet been reported. Plasma galectin-3 was measured at baseline and at 3 months in patients enrolled in the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA) trial (n=1329), and at baseline and at 6 months in patients enrolled in the Coordinating Study Evaluating Outcomes of Advising and Counseling Failure (COACH) trial (n=324). Patient results were analyzed by categorical and percentage changes in galectin-3 level. A threshold value of 17.8 ng/mL or 15% change from baseline was used to categorize patients. Increasing galectin-3 levels over time, from a low to high galectin-3 category, were associated with significantly more HF hospitalization and mortality compared with stable or decreasing galectin-3 levels (hazard ratio in CORONA, 1.60; 95% confidence interval, 1.13-2.25; P=0.007; hazard ratio in COACH, 2.38; 95% confidence interval, 1.02-5.55; P=0.046). In addition, patients whose galectin-3 increased by >15% between measurements had a 50% higher relative hazard of adverse event than those whose galectin-3 stayed within ±15% of the baseline value, independent of age, sex, diabetes mellitus, left ventricular ejection fraction, renal function, medication (β-blocker, angiotensin converting enzyme inhibitor, and angiotensin receptor blocker), and N-terminal probrain natriuretic peptide (hazard ratio in CORONA, 1.50; 95% confidence interval, 1.17-1.92; P=0.001). The impact of changing galectin-3 levels on other secondary end points was comparable. In 2 large cohorts of patients with chronic and acute decompensated HF, repeated measurements of galectin-3 level provided important and significant prognostic value in identifying patients with HF at elevated risk for subsequent HF morbidity and mortality.

The expression level of BAALC-associated microRNA miR-3151 is an independent prognostic factor in younger patients with cytogenetic intermediate-risk acute myeloid leukemia

PubMed Central

Díaz-Beyá, M; Brunet, S; Nomdedéu, J; Cordeiro, A; Tormo, M; Escoda, L; Ribera, J M; Arnan, M; Heras, I; Gallardo, D; Bargay, J; Queipo de Llano, M P; Salamero, O; Martí, J M; Sampol, A; Pedro, C; Hoyos, M; Pratcorona, M; Castellano, J J; Nomdedeu, M; Risueño, R M; Sierra, J; Monzó, M; Navarro, A; Esteve, J

2015-01-01

Acute myeloid leukemia (AML) is a heterogeneous disease whose prognosis is mainly related to the biological risk conferred by cytogenetics and molecular profiling. In elderly patients (⩾60 years) with normal karyotype AML miR-3151 have been identified as a prognostic factor. However, miR-3151 prognostic value has not been examined in younger AML patients. In the present work, we have studied miR-3151 alone and in combination with BAALC, its host gene, in a cohort of 181 younger intermediate-risk AML (IR-AML) patients. Patients with higher expression of miR-3151 had shorter overall survival (P=0.0025), shorter leukemia-free survival (P=0.026) and higher cumulative incidence of relapse (P=0.082). Moreover, in the multivariate analysis miR-3151 emerged as independent prognostic marker in both the overall series and within the unfavorable molecular prognostic category. Interestingly, the combined determination of both miR-3151 and BAALC improved this prognostic stratification, with patients with low levels of both parameters showing a better outcome compared with those patients harboring increased levels of one or both markers (P=0.003). In addition, we studied the microRNA expression profile associated with miR-3151 identifying a six-microRNA signature. In conclusion, the analysis of miR-3151 and BAALC expression may well contribute to an improved prognostic stratification of younger patients with IR-AML. PMID:26430723

Prognostic significance of perioperative nutritional parameters in patients with gastric cancer.

PubMed

Oh, Sung Eun; Choi, Min-Gew; Seo, Jeong-Meen; An, Ji Yeong; Lee, Jun Ho; Sohn, Tae Sung; Bae, Jae Moon; Kim, Sung

2018-02-20

It has been suggested that nutritional status is related to the survival outcomes of cancer patients. The purpose of the current research is to evaluate the importance of the prognosis of various nutritional parameters during the perioperative period in patients with gastric cancer. This study enrolled patients with gastric cancer who underwent D2 gastrectomy at the Department of Surgery, Samsung Medical Center, in 2008. The prognostic significance of nutritional parameters was analyzed, along with other clinical and pathological variables, preoperatively and postoperatively at 3, 6, and 12 months. The total number of patients was 1415. The mean values of nutritional parameters, weight, body mass index (BMI), hemoglobin, total cholesterol, and total lymphocyte count (TLC) decreased significantly over time after surgery. On the contrary, albumin and prognostic nutritional index (PNI) score increased significantly during the postoperative follow-up period. Preoperatively, low BMI (<18.5 kg/m 2 ) and low TLC level (<1000 per mm 3 ) were revealed as independent prognostic factors in multivariate analysis. Low preoperative TLC level and decline in PNI (ΔPNI < -2.2) at postoperative 3 months; low preoperative TLC level and decline in TLC (ΔTLC < -279.9 per mm 3 ) at postoperative 6 months; and low preoperative BMI, albumin, and TLC levels at postoperative 12 months were independent nutritional prognostic indicators. Various perioperative nutritional parameters were confirmed as independent prognostic factors in patients with gastric cancer. Our results imply prognostic benefit from careful nutritional support for patients with poor nutritional parameters. Copyright © 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Health-related quality-of-life parameters as independent prognostic factors in advanced or metastatic bladder cancer.

PubMed

Roychowdhury, D F; Hayden, A; Liepa, A M

2003-02-15

This retrospective analysis examined prognostic significance of health-related quality-of-life (HRQoL) parameters combined with baseline clinical factors on outcomes (overall survival, time to progressive disease, and time to treatment failure) in bladder cancer. Outcome and HRQoL (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30) data were collected prospectively in a phase III study assessing gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in locally advanced or metastatic bladder cancer. Prespecified baseline clinical factors (performance status, tumor-node-metastasis staging, visceral metastases [VM], alkaline phosphatase [AP] level, number of metastatic sites, prior radiotherapy, disease measurability, sex, time from diagnosis, and sites of disease) and selected HRQoL parameters (global QoL; all functional scales; symptoms: pain, fatigue, insomnia, dyspnea, anorexia) were evaluated using Cox's proportional hazards model. Factors with individual prognostic value (P <.05) on outcomes in univariate models were assessed for joint prognostic value in a multivariate model. A final model was developed using a backward selection strategy. Patients with baseline HRQoL were included (364 of 405, 90%). The final model predicted longer survival with low/normal AP levels, no VM, high physical functioning, low role functioning, and no anorexia. Positive prognostic factors for time to progressive disease were good performance status, low/normal AP levels, no VM, and minimal fatigue; for time to treatment failure, they were low/normal AP levels, minimal fatigue, and no anorexia. Global QoL was a significant predictor of outcome in univariate analyses but was not retained in the multivariate model. HRQoL parameters are independent prognostic factors for outcome in advanced bladder cancer; their prognostic importance needs further evaluation.

Tumour functional sphericity from PET images: prognostic value in NSCLC and impact of delineation method.

PubMed

Hatt, Mathieu; Laurent, Baptiste; Fayad, Hadi; Jaouen, Vincent; Visvikis, Dimitris; Le Rest, Catherine Cheze

2018-04-01

Sphericity has been proposed as a parameter for characterizing PET tumour volumes, with complementary prognostic value with respect to SUV and volume in both head and neck cancer and lung cancer. The objective of the present study was to investigate its dependency on tumour delineation and the resulting impact on its prognostic value. Five segmentation methods were considered: two thresholds (40% and 50% of SUV max ), ant colony optimization, fuzzy locally adaptive Bayesian (FLAB), and gradient-aided region-based active contour. The accuracy of each method in extracting sphericity was evaluated using a dataset of 176 simulated, phantom and clinical PET images of tumours with associated ground truth. The prognostic value of sphericity and its complementary value with respect to volume for each segmentation method was evaluated in a cohort of 87 patients with stage II/III lung cancer. Volume and associated sphericity values were dependent on the segmentation method. The correlation between segmentation accuracy and sphericity error was moderate (|ρ| from 0.24 to 0.57). The accuracy in measuring sphericity was not dependent on volume (|ρ| < 0.4). In the patients with lung cancer, sphericity had prognostic value, although lower than that of volume, except for that derived using FLAB for which when combined with volume showed a small improvement over volume alone (hazard ratio 2.67, compared with 2.5). Substantial differences in patient prognosis stratification were observed depending on the segmentation method used. Tumour functional sphericity was found to be dependent on the segmentation method, although the accuracy in retrieving the true sphericity was not dependent on tumour volume. In addition, even accurate segmentation can lead to an inaccurate sphericity value, and vice versa. Sphericity had similar or lower prognostic value than volume alone in the patients with lung cancer, except when determined using the FLAB method for which there was a small improvement in stratification when the parameters were combined.

A Prospective Randomized Trial of Prognostic Genicular Nerve Blocks to Determine the Predictive Value for the Outcome of Cooled Radiofrequency Ablation for Chronic Knee Pain Due to Osteoarthritis.

PubMed

McCormick, Zachary L; Reddy, Rajiv; Korn, Marc; Dayanim, David; Syed, Raafay H; Bhave, Meghan; Zhukalin, Mikhail; Choxi, Sarah; Ebrahimi, Ali; Kendall, Mark C; McCarthy, Robert J; Khan, Dost; Nagpal, Geeta; Bouffard, Karina; Walega, David R

2017-12-28

Genicular nerve radiofrequency ablation is an effective treatment for patients with chronic pain due to knee osteoarthritis; however, little is known about factors that predict procedure success. The current study evaluated the utility of genicular nerve blocks to predict the outcome of genicular nerve cooled radiofrequency ablation (cRFA) in patients with osteoarthritis. This randomized comparative trial included patients with chronic knee pain due to osteoarthritis. Participants were randomized to receive a genicular nerve block or no block prior to cRFA. Patients receiving a prognostic block that demonstrated ≥50% pain relief for six hours received cRFA. The primary outcome was the proportion of participants with ≥50% reduction in knee pain at six months. Twenty-nine participants (36 knees) had cRFA following a prognostic block, and 25 patients (35 knees) had cRFA without a block. Seventeen participants (58.6%) in the prognostic block group and 16 (64.0%) in the no block group had ≥50% pain relief at six months (P = 0.34). A 15-point decrease in the Western Ontario and McMaster Universities Osteoarthritis Index at six months was present in 17 of 29 (55.2%) in the prognostic block group and 15 of 25 (60%) in the no block group (P = 0.36). This study demonstrated clinically meaningful improvements in pain and physical function up to six months following cRFA. A prognostic genicular nerve block using a local anesthetic volume of 1 mL at each injection site and a threshold of ≥ 50% pain relief for subsequent cRFA eligibility did not improve the rate of treatment success. © 2017 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Prognostic value of (18)F-FDG PET/CT volumetric parameters in recurrent epithelial ovarian cancer.

PubMed

Mayoral, M; Fernandez-Martinez, A; Vidal, L; Fuster, D; Aya, F; Pavia, J; Pons, F; Lomeña, F; Paredes, P

2016-01-01

Metabolic tumour volume (MTV) and total lesion glycolysis (TLG) from (18)F-FDG PET/CT are emerging prognostic biomarkers in various solid neoplasms. These volumetric parameters and the SUVmax have shown to be useful criteria for disease prognostication in preoperative and post-treatment epithelial ovarian cancer (EOC) patients. The purpose of this study was to evaluate the utility of (18)F-FDG PET/CT measurements to predict survival in patients with recurrent EOC. Twenty-six patients with EOC who underwent a total of 31 (18)F-FDG PET/CT studies for suspected recurrence were retrospectively included. SUVmax and volumetric parameters whole-body MTV (wbMTV) and whole-body TLG (wbTLG) with a threshold of 40% and 50% of the SUVmax were obtained. Correlation between PET parameters and progression-free survival (PFS) and the survival analysis of prognostic factors were calculated. Serous cancer was the most common histological subtype (76.9%). The median PFS was 12.5 months (range 10.7-20.6 months). Volumetric parameters showed moderate inverse correlation with PFS but there was no significant correlation in the case of SUVmax. The correlation was stronger for first recurrences. By Kaplan-Meier analysis and log-rank test, wbMTV 40%, wbMTV 50% and wbTLG 50% correlated with PFS. However, SUVmax and wbTLG 40% were not statistically significant predictors for PFS. Volumetric parameters wbMTV and wbTLG 50% measured by (18)F-FDG PET/CT appear to be useful prognostic predictors of outcome and may provide valuable information to individualize treatment strategies in patients with recurrent EOC. Copyright © 2015 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

Brachial-to-ankle pulse wave velocity as an independent prognostic factor for ovulatory response to clomiphene citrate in women with polycystic ovary syndrome.

PubMed

Takahashi, Toshifumi; Igarashi, Hideki; Hara, Shuichiro; Amita, Mitsuyoshi; Matsuo, Koki; Hasegawa, Ayumi; Kurachi, Hirohisa

2014-01-01

Polycystic ovary syndrome (PCOS) has a risk for cardiovascular disease. Increased arterial stiffness has been observed in women with PCOS. The purpose of the present study was to investigate whether the brachial-to-ankle pulse wave velocity (baPWV) is a prognostic factor for ovulatory response to clomiphene citrate (CC) in women with PCOS. This study was a retrospective cohort study of 62 women with PCOS conducted from January 2009 to December 2012 at the university hospital, Yamagata, Japan. We analyzed 62 infertile PCOS patients who received CC. Ovulation was induced by 100 mg CC for 5 days. CC non-responder was defined as failure to ovulate for at least 2 consecutive CC-treatment cycles. The endocrine, metabolic, and cardiovascular parameters between CC responder (38 patients) and non-responder (24 patients) groups were analyzed. In univariate analysis, waist-to-hip ratio, level of free testosterone, percentages of patients with dyslipidemia, impaired glucose tolerance, and diabetes mellitus, blood glucose and insulin levels at 60 min and 120 min, the area under the curve of glucose and insulin after 75-g oral glucose intolerance test, and baPWV were significantly higher in CC non-responders compared with responders. In multivariate logistic regression analysis, both waist-to-hip ratio (odds ratio, 1.77; 95% confidence interval, 2.2-14.1; P=0.04) and baPWV (odds ratio, 1.71; 95% confidence interval, 1.1-2.8; P=0.03) were independent predictors of ovulation induction by CC in PCOS patients. The predictive values of waist-to-hip ratio and baPWV for the CC resistance in PCOS patients were determined by the receiver operating characteristic curves. The area under the curves for waist-to-hip ratio and baPWV were 0.76 and 0.77, respectively. Setting the threshold at 0.83 for waist-to-hip ratio offered the best compromise between specificity (0.65) and sensitivity (0.84), while the setting the threshold at 1,182 cm/s for baPWV offered the best compromise between specificity (0.80) and sensitivity (0.71). Both metabolic and cardiovascular parameters were predictive for CC resistance in PCOS patients. The measurement of baPWV may be a useful tool to predict ovulation in PCOS patients who receive CC.

Prognostic significance of hyperfibrinogenemia in patients with esophageal squamous cell carcinoma.

PubMed

Suzuki, Takashi; Shimada, Hideaki; Nanami, Tatsuki; Oshima, Yoko; Yajima, Satoshi; Washizawa, Naohiro; Kaneko, Hironori

2017-06-01

Preoperative hyperfibrinogenemia is associated with inflammatory mediators and a poor prognosis in several types of cancer. However, there is no published information on the monitoring of patients with preoperative hyperfibrinogenemia after surgery. The aim of the study reported here was to assess the clinicopathological and prognostic significance of plasma fibrinogen levels in patients with esophageal squamous cell carcinoma before and after surgical treatment. Plasma fibrinogen levels were analyzed before surgical treatment (endoscopic submucosal dissection and surgery) in 82 patients with esophageal squamous cell carcinoma. The clinicopathological significance of plasma fibrinogen levels and the relationship of plasma fibrinogen levels with several biomarkers were evaluated. The cutoff value for hyperfibrinogenemia was 321 mg/dl. Univariate and multivariate analysis using the Cox proportional hazards model were performed to evaluate the prognostic significance of plasma fibrinogen levels. The changing patterns of plasma fibrinogen were monitored after surgical treatment to evaluate prognostic impact. Hyperfibrinogenemia was significantly associated with advanced pathological stage of cancer and high C-reactive protein levels. Plasma fibrinogen levels significantly decreased after surgical treatment in recurrence-free patients but did not decrease in patients with recurrence. The multivariate analysis indicated that preoperative hyperfibrinogenemia was an independent prognostic factor for poor survival (hazard ratio 1.005, 95% confidence interval 1.000-1.010; P = 0.039). Preoperative hyperfibrinogenemia was associated with inflammatory mediators, tumor progression, and poor survival in patients with esophageal squamous cell carcinoma. The absence of a decrease in plasma fibrinogen levels after surgical treatment may indicate the possibility of tumor recurrence.

Pre-Treatment Anemia Is a Poor Prognostic Factor in Soft Tissue Sarcoma Patients

PubMed Central

Szkandera, Joanna; Gerger, Armin; Liegl-Atzwanger, Bernadette; Stotz, Michael; Samonigg, Hellmut; Ploner, Ferdinand; Stojakovic, Tatjana; Leithner, Andreas; Pichler, Martin

2014-01-01

Background Anemia refers to low hemoglobin (Hb) levels, represents a common symptom and complication in cancer patients and was reported to negatively influence survival in patients with various malignancies. In the present study, we aimed to explore the prognostic impact of pre-operative Hb levels on clinical outcome in a large cohort of soft tissue sarcoma (STS) patients after curative surgery. Methods Retrospective data from 367 STS patients, which were operated between 1998 and 2013, were included in the study. Cut-off levels for anemia were defined as Hb<13 g/dl in males and Hb<12 g/dl in females according to the current WHO guidelines. The impact of pre-operative Hb levels on cancer-specific survival (CSS) and overall survival (OS) was assessed using Kaplan-Meier curves. Additionally, Hb levels were compared for the prognostic influence on CSS and OS applying univariate and multivariate Cox proportional models. Results Hb level was associated with established prognostic factors, including age, tumor grade, size and depth (p<0.05). Kaplan-Meier curves showed that low Hb levels were significantly associated with decreased CSS and OS in STS patients (p<0.001 for both endpoints, log-rank test). In multivariate analysis, we found an independent association between low Hb levels and poor CSS and OS (HR = 0.46, Cl 95% = 0.25–0.85, p = 0.012; HR = 0.34, Cl 95% = 0.23–0.51, p<0.001). Conclusion The present data underline a negative prognostic impact of low pre-operative Hb levels on clinical outcome in STS patients. Thus, Hb levels may provide an additional and cost-effective tool to discriminate between STS patients that are at high risk of mortality. PMID:25207808

Requirements Flowdown for Prognostics and Health Management

NASA Technical Reports Server (NTRS)

Goebel, Kai; Saxena, Abhinav; Roychoudhury, Indranil; Celaya, Jose R.; Saha, Bhaskar; Saha, Sankalita

2012-01-01

Prognostics and Health Management (PHM) principles have considerable promise to change the game of lifecycle cost of engineering systems at high safety levels by providing a reliable estimate of future system states. This estimate is a key for planning and decision making in an operational setting. While technology solutions have made considerable advances, the tie-in into the systems engineering process is lagging behind, which delays fielding of PHM-enabled systems. The derivation of specifications from high level requirements for algorithm performance to ensure quality predictions is not well developed. From an engineering perspective some key parameters driving the requirements for prognostics performance include: (1) maximum allowable Probability of Failure (PoF) of the prognostic system to bound the risk of losing an asset, (2) tolerable limits on proactive maintenance to minimize missed opportunity of asset usage, (3) lead time to specify the amount of advanced warning needed for actionable decisions, and (4) required confidence to specify when prognosis is sufficiently good to be used. This paper takes a systems engineering view towards the requirements specification process and presents a method for the flowdown process. A case study based on an electric Unmanned Aerial Vehicle (e-UAV) scenario demonstrates how top level requirements for performance, cost, and safety flow down to the health management level and specify quantitative requirements for prognostic algorithm performance.

Robustness of equations that define molecular subtypes of glioblastoma tumors based on five transcripts measured by RT-PCR.

PubMed

Castells, Xavier; Acebes, Juan José; Majós, Carles; Boluda, Susana; Julià-Sapé, Margarida; Candiota, Ana Paula; Ariño, Joaquín; Barceló, Anna; Arús, Carles

2015-01-01

Glioblastoma (Gb) is one of the most deadly tumors. Its molecular subtypes are yet to be fully characterized while the attendant efforts for personalized medicine need to be intensified in relation to glioblastoma diagnosis, treatment, and prognosis. Several molecular signatures based on gene expression microarrays were reported, but the use of microarrays for routine clinical practice is challenged by attendant economic costs. Several authors have proposed discriminant equations based on RT-PCR. Still, the discriminant threshold is often incompletely described, which makes proper validation difficult. In a previous work, we have reported two Gb subtypes based on the expression levels of four genes: CHI3L1, LDHA, LGALS1, and IGFBP3. One Gb subtype presented with low expression of the four genes mentioned, and of MGMT in a large portion of the patients (with anticipated high methylation of its promoter), and mutated IDH1. Here, we evaluate the robustness of the equations fitted with these genes using RT-PCR values in a set of 64 cases and importantly, define an unequivocal discriminant threshold with a view to prognostic implications. We developed two approaches to generate the discriminant equations: 1) using the expression level of the four genes mentioned above, and 2) using those genes displaying the highest correlation with survival among the aforementioned four ones, plus MGMT, as an attempt to further reduce the number of genes. The ease of equations' applicability, reduction in cost for raw data, and robustness in terms of resampling-based classification accuracy warrant further evaluation of these equations to discern Gb tumor biopsy heterogeneity at molecular level, diagnose potential malignancy, and prognosis of individual patients with glioblastomas.

Prognostic Significance of Pre-treatment Serum C-Reactive Protein Level in Patients with Adenocarcinoma of the Uterine Cervix.

PubMed

Bodner-Adler, Barbara; Kimberger, Oliver; Schneidinger, Cora; Kölbl, Heinz; Bodner, Klaus

2016-09-01

To evaluate pre-treatment serum C-reactive protein (CRP) level as a prognostic parameter in patients with adenocarcinoma of the uterine cervix. Pre-treatment CRP levels were analyzed to determine potential associations with clinicopathological parameters and to assess prognostic value in 46 patients with sole adenocarcinoma of the uterine cervix. The mean (±SD) pre-treatment serum CRP level was 5.82 (7.21) mg/l. Serum CRP concentration significantly correlated positively with age at diagnosis (p=0.001), lymphovascular space invasion (p=0.0026), recurrent disease (p=0.0001) and International Federation of Gynecology and Obstetrics (FIGO) stage (p=0.0002). In multivariate Cox regression models with age, FIGO stage, histological grade and lymph node status, elevated CRP and cancer antigen 125 levels were associated with shortened survival (p<0.05). Overall 5-year survival rate of patients with pre-treatment serum CRP level <5.0 mg/l was 100% compared to 46.9% for patients with pre-treatment CRP level ≥5.0 mg/l. Serum CRP level can be seen as an additional independent prognostic parameter in patients with the rare histological subtype adenocarcinoma of the uterine cervix. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

[The alpha-fetoprotein in prognosis of survival of and functional rehabilitation of patients with ischemic stroke].

PubMed

Arkhipkin, A A; Liang, O V; Kochetov, A G

2014-10-01

The study was carried out to determine the prognostic value of alpha-fetoprotein in development of lethal outcome and degree of functional rehabilitation of patients with ischemic stroke. The sampling included 216 patients in acute period of ischemic stroke. At the first day of development of disease they were measured the level of human alpha-fetoprotein. At the second day of disease patients were evaluated the degree of functional rehabilitation and the rate of lethal outcomes was calculated. Previously, the reference interval for alpha-fetoprotein was calculated according the guidelines of the International federation of clinical chemistry and national standard. The reference interval amounted to 0.59-3.78 mE/l. The study results demonstrated that low level of alpha-fetoprotein is related to higher risk of lethal outcome (SE=1.7, p=0.012). The increasing of level of alpha-fetoprotein over mentioned threshold value statistically significant increases probability of survival of patients. The further increasing more than 2.28 mE/l is related to subsequent good functional rehabilitation according the modifies Rankine scale (SE=1.4, p=0.001) and Barthel index (SE=1.49, p<0.001).

Prognostic Value of Lymphocyte G Protein-Coupled Receptor Kinase-2 Protein Levels in Patients With Heart Failure

PubMed Central

Rengo, Giuseppe; Pagano, Gennaro; Filardi, Pasquale Perrone; Femminella, Grazia Daniela; Parisi, Valentina; Cannavo, Alessandro; Liccardo, Daniela; Komici, Klara; Gambino, Giuseppina; D’Amico, Maria Loreta; de Lucia, Claudio; Paolillo, Stefania; Trimarco, Bruno; Vitale, Dino Franco; Ferrara, Nicola; Koch, Walter J; Leosco, Dario

2016-01-01

Rationale Sympathetic nervous system (SNS) hyperactivity is associated with poor prognosis in patients with HF, yet routine assessment of SNS activation is not recommended for clinical practice. Myocardial G protein-coupled receptor kinase 2 (GRK2) is up-regulated in heart failure (HF) patients, causing dysfunctional β-adrenergic receptor signaling. Importantly, myocardial GRK2 levels correlate with levels found in peripheral lymphocytes of HF patients. Objective The independent prognostic value of blood GRK2 measurements in HF patients has never been investigated, thus, the purpose of the present study was to evaluate whether lymphocyte GRK2 levels predict clinical outcome in HF patients. Methods and Results We prospectively studied 257 HF patients with mean left ventricular ejection fraction (LVEF) of 31.4±8.5%. At the time of enrollment, plasma norepinephrine, serum NT-proBNP and lymphocyte GRK2 levels, as well as clinical and instrumental variables were measured. The prognostic value of GRK2 to predict cardiovascular (CV) death and all-cause mortality was assessed using the Cox proportional hazard model including demographic, clinical, instrumental and laboratory data. Over a mean follow-up period of 37.5±20.2 months (range: 3–60 months) there were 102 CV deaths. Age, LVEF, NYHA class, Chronic Obstructive Pulmonary Disease, Chronic Kidney Disease, N-terminal-pro Brain Natriuretic Peptide, and lymphocyte GRK2 protein levels were independent predictors of CV mortality in HF patients. GRK2 levels showed an additional prognostic and clinical value over demographic and clinical variables. The independent prognostic value of lymphocyte GRK2 levels was also confirmed for all-cause mortality. Conclusion Lymphocyte GRK2 protein levels can independently predict prognosis in patients with HF. PMID:26884616

Prognostic Value of Pretherapeutic Tumor-to-Blood Standardized Uptake Ratio in Patients with Esophageal Carcinoma.

PubMed

Bütof, Rebecca; Hofheinz, Frank; Zöphel, Klaus; Stadelmann, Tobias; Schmollack, Julia; Jentsch, Christina; Löck, Steffen; Kotzerke, Jörg; Baumann, Michael; van den Hoff, Jörg

2015-08-01

Despite ongoing efforts to develop new treatment options, the prognosis for patients with inoperable esophageal carcinoma is still poor and the reliability of individual therapy outcome prediction based on clinical parameters is not convincing. The aim of this work was to investigate whether PET can provide independent prognostic information in such a patient group and whether the tumor-to-blood standardized uptake ratio (SUR) can improve the prognostic value of tracer uptake values. (18)F-FDG PET/CT was performed in 130 consecutive patients (mean age ± SD, 63 ± 11 y; 113 men, 17 women) with newly diagnosed esophageal cancer before definitive radiochemotherapy. In the PET images, the metabolically active tumor volume (MTV) of the primary tumor was delineated with an adaptive threshold method. The blood standardized uptake value (SUV) was determined by manually delineating the aorta in the low-dose CT. SUR values were computed as the ratio of tumor SUV and blood SUV. Uptake values were scan-time-corrected to 60 min after injection. Univariate Cox regression and Kaplan-Meier analysis with respect to overall survival (OS), distant metastases-free survival (DM), and locoregional tumor control (LRC) was performed. Additionally, a multivariate Cox regression including clinically relevant parameters was performed. In multivariate Cox regression with respect to OS, including T stage, N stage, and smoking state, MTV- and SUR-based parameters were significant prognostic factors for OS with similar effect size. Multivariate analysis with respect to DM revealed smoking state, MTV, and all SUR-based parameters as significant prognostic factors. The highest hazard ratios (HRs) were found for scan-time-corrected maximum SUR (HR = 3.9) and mean SUR (HR = 4.4). None of the PET parameters was associated with LRC. Univariate Cox regression with respect to LRC revealed a significant effect only for N stage greater than 0 (P = 0.048). PET provides independent prognostic information for OS and DM but not for LRC in patients with locally advanced esophageal carcinoma treated with definitive radiochemotherapy in addition to clinical parameters. Among the investigated uptake-based parameters, only SUR was an independent prognostic factor for OS and DM. These results suggest that the prognostic value of tracer uptake can be improved when characterized by SUR instead of SUV. Further investigations are required to confirm these preliminary results. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Effect of Beta-Blocker Therapy, Maximal Heart Rate, and Exercise Capacity During Stress Testing on Long-Term Survival (from The Henry Ford Exercise Testing Project).

PubMed

Hung, Rupert K; Al-Mallah, Mouaz H; Whelton, Seamus P; Michos, Erin D; Blumenthal, Roger S; Ehrman, Jonathan K; Brawner, Clinton A; Keteyian, Steven J; Blaha, Michael J

2016-12-01

Whether lower heart rate thresholds (defined as the percentage of age-predicted maximal heart rate achieved, or ppMHR) should be used to determine chronotropic incompetence in patients on beta-blocker therapy (BBT) remains unclear. In this retrospective cohort study, we analyzed 64,549 adults without congestive heart failure or atrial fibrillation (54 ± 13 years old, 46% women, 29% black) who underwent clinician-referred exercise stress testing at a single health care system in Detroit, Michigan from 1991 to 2009, with median follow-up of 10.6 years for all-cause mortality (interquartile range 7.7 to 14.7 years). Using Cox regression models, we assessed the effect of BBT, ppMHR, and estimated exercise capacity on mortality, with adjustment for demographic data, medical history, pertinent medications, and propensity to be on BBT. There were 9,259 deaths during follow-up. BBT was associated with an 8% lower adjusted achieved ppMHR (91% in no BBT vs 83% in BBT). ppMHR was inversely associated with all-cause mortality but with significant attenuation by BBT (per 10% ppMHR HR: no BBT: 0.80 [0.78 to 0.82] vs BBT: 0.89 [0.87 to 0.92]). Patients on BBT who achieved 65% ppMHR had a similar adjusted mortality rate as those not on BBT who achieved 85% ppMHR (p >0.05). Estimated exercise capacity further attenuated the prognostic value of ppMHR (per-10%-ppMHR HR: no BBT: 0.88 [0.86 to 0.90] vs BBT: 0.95 [0.93 to 0.98]). In conclusion, the prognostic value of ppMHR was significantly attenuated by BBT. For patients on BBT, a lower threshold of 65% ppMHR may be considered for determining worsened prognosis. Estimated exercise capacity further diminished the prognostic value of ppMHR particularly in patients on BBT. Copyright © 2016 Elsevier Inc. All rights reserved.

Prognostic value of circulating VEGFR2+ bone marrow-derived progenitor cells in patients with advanced cancer.

PubMed

Massard, Christophe; Borget, Isabelle; Le Deley, Marie Cécile; Taylor, Melissa; Gomez-Roca, Carlos; Soria, Jean Charles; Farace, Françoise

2012-06-01

We hypothesised that host-related markers, possibly reflecting tumour aggressiveness, such as circulating endothelial cells (CEC) and circulating VEGFR2(+) bone marrow-derived (BMD) progenitor cells, could have prognostic value in patients with advanced cancer enrolled in early anticancer drug development trials. Baseline CECs (CD45(-)CD31(+)CD146(+)7AAD(-) cells) and circulating VEGFR2(+)-BMD progenitor cells (defined as CD45(dim)CD34(+)VEGFR2(+)7AAD(-) cells) were measured by flow-cytometry in 71 and 58 patients included in phase 1 trials testing novel anti-vascular or anti-angiogenic agents. Correlations between levels of CECs, circulating VEGFR2(+)-BMD progenitor cells, clinical and biological prognostic factors (i.e. the Royal Marsden Hospital (RMH) score), and overall survival (OS) were studied. The median value of CECs was 12 CEC/ml (range 0-154/ml). The median level of VEGFR2(+)-BMD progenitor cells was 1.3% (range 0-32.5%) of circulating BMD-CD34(+) progenitors. While OS was not correlated with CEC levels, it was significantly worse in patients with high VEGFR2(+)-BMD progenitor levels (>1%) (median OS 9.0 versus 17.0 months), and with a RMH prognostic score >0 (median OS 9.0 versus 24.2 months). The prognostic value of VEGFR2(+)-BMD progenitor levels remained significant (hazard ratio (HR) = 2.3, 95% confidence interval (CI), 1.1-4.6, p = 0.02) after multivariate analysis. A composite VEGFR2(+)-BMD progenitor level/RHM score ≥ 2 was significantly associated with an increased risk of death compared to scores of 0 or 1 (median OS 9.0 versus 18.4 months, HR = 2.6 (95%CI, 1.2-5.8, p = 0.02)). High circulating VEGFR2(+)-BMD progenitor levels are associated with poor prognostics and when combined to classical clinical and biological parameters could provide a new tool for patient selection in early anticancer drug trials. Copyright © 2012 Elsevier Ltd. All rights reserved.

An inflammation-based cumulative prognostic score system in patients with diffuse large B cell lymphoma in rituximab era.

PubMed

Sun, Feifei; Zhu, Jia; Lu, Suying; Zhen, Zijun; Wang, Juan; Huang, Junting; Ding, Zonghui; Zeng, Musheng; Sun, Xiaofei

2018-01-02

Systemic inflammatory parameters are associated with poor outcomes in malignant patients. Several inflammation-based cumulative prognostic score systems were established for various solid tumors. However, there is few inflammation based cumulative prognostic score system for patients with diffuse large B cell lymphoma (DLBCL). We retrospectively reviewed 564 adult DLBCL patients who had received rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) therapy between Nov 1 2006 and Dec 30 2013 and assessed the prognostic significance of six systemic inflammatory parameters evaluated in previous studies by univariate and multivariate analysis:C-reactive protein(CRP), albumin levels, the lymphocyte-monocyte ratio (LMR), the neutrophil-lymphocyte ratio(NLR), the platelet-lymphocyte ratio(PLR)and fibrinogen levels. Multivariate analysis identified CRP, albumin levels and the LMR are three independent prognostic parameters for overall survival (OS). Based on these three factors, we constructed a novel inflammation-based cumulative prognostic score (ICPS) system. Four risk groups were formed: group ICPS = 0, ICPS = 1, ICPS = 2 and ICPS = 3. Advanced multivariate analysis indicated that the ICPS model is a prognostic score system independent of International Prognostic Index (IPI) for both progression-free survival (PFS) (p < 0.001) and OS (p < 0.001). The 3-year OS for patients with ICPS =0, ICPS =1, ICPS =2 and ICPS =3 were 95.6, 88.2, 76.0 and 62.2%, respectively (p < 0.001). The 3-year PFS for patients with ICPS = 0-1, ICPS = 2 and ICPS = 3 were 84.8, 71.6 and 54.5%, respectively (p < 0.001). The prognostic value of the ICPS model indicated that the degree of systemic inflammatory status was associated with clinical outcomes of patients with DLBCL in rituximab era. The ICPS model was shown to classify risk groups more accurately than any single inflammatory prognostic parameters. These findings may be useful for identifying candidates for further inflammation-related mechanism research or novel anti-inflammation target therapies.

LPL is the strongest prognostic factor in a comparative analysis of RNA-based markers in early chronic lymphocytic leukemia.

PubMed

Kaderi, Mohd Arifin; Kanduri, Meena; Buhl, Anne Mette; Sevov, Marie; Cahill, Nicola; Gunnarsson, Rebeqa; Jansson, Mattias; Smedby, Karin Ekström; Hjalgrim, Henrik; Jurlander, Jesper; Juliusson, Gunnar; Mansouri, Larry; Rosenquist, Richard

2011-08-01

The expression levels of LPL, ZAP70, TCL1A, CLLU1 and MCL1 have recently been proposed as prognostic factors in chronic lymphocytic leukemia. However, few studies have systematically compared these different RNA-based markers. Using real-time quantitative PCR, we measured the mRNA expression levels of these genes in unsorted samples from 252 newly diagnosed chronic lymphocytic leukemia patients and correlated our data with established prognostic markers (for example Binet stage, CD38, IGHV gene mutational status and genomic aberrations) and clinical outcome. High expression levels of all RNA-based markers, except MCL1, predicted shorter overall survival and time to treatment, with LPL being the most significant. In multivariate analysis including the RNA-based markers, LPL expression was the only independent prognostic marker for overall survival and time to treatment. When studying LPL expression and the established markers, LPL expression retained its independent prognostic strength for overall survival. All of the RNA-based markers, albeit with varying ability, added prognostic information to established markers, with LPL expression giving the most significant results. Notably, high LPL expression predicted a worse outcome in good-prognosis subgroups, such as patients with mutated IGHV genes, Binet stage A, CD38 negativity or favorable cytogenetics. In particular, the combination of LPL expression and CD38 could further stratify Binet stage A patients. LPL expression is the strongest RNA-based prognostic marker in chronic lymphocytic leukemia that could potentially be applied to predict outcome in the clinical setting, particularly in the large group of patients with favorable prognosis.

Baseline prostate-specific antigen levels following treatment with abiraterone acetate as a prognostic factor in castration-resistant prostate cancer

PubMed Central

Hiroshige, Tasuku; Eguchi, Yoshiro; Yoshizumi, Osamu; Chikui, Katsuaki; Kumagai, Hisaji; Kawaguchi, Yoshihiro; Onishi, Rei; Hayashi, Tokumasa; Watanabe, Kouta; Mitani, Tomotaro; Saito, Koujiro; Igawa, Tsukasa

2018-01-01

The aim of the present study was to investigate the prognostic factors associated with progression-free survival (PFS) and overall survival (OS) times in patients with castration-resistant prostate cancer (CRPC) who received treatment with abiraterone acetate (AA) in routine clinical settings. A total of 93 patients treated with AA between September 2014 and February 2017 were selected and their medical records were analyzed retrospectively. The median PFS time of docetaxel (DTX)-naïve patients was 171 days, and that of post-DTX patients was 56 days. The OS time of DTX-naïve patients did not reach the median. The median OS time of post-DTX patients was 761 days. Multivariate analyses identified baseline prostate-specific antigen (PSA) level prior to treatment with AA and the PSA response rate as independent prognostic factors for PFS time, and baseline PSA prior to treatment with AA as the only independent prognostic factor for OS time. The results of the present study indicate that the baseline PSA level prior to treatment with AA is a notable prognostic factor in patients with CRPC. PMID:29725416

Baseline prostate-specific antigen levels following treatment with abiraterone acetate as a prognostic factor in castration-resistant prostate cancer.

PubMed

Hiroshige, Tasuku; Eguchi, Yoshiro; Yoshizumi, Osamu; Chikui, Katsuaki; Kumagai, Hisaji; Kawaguchi, Yoshihiro; Onishi, Rei; Hayashi, Tokumasa; Watanabe, Kouta; Mitani, Tomotaro; Saito, Koujiro; Igawa, Tsukasa

2018-05-01

The aim of the present study was to investigate the prognostic factors associated with progression-free survival (PFS) and overall survival (OS) times in patients with castration-resistant prostate cancer (CRPC) who received treatment with abiraterone acetate (AA) in routine clinical settings. A total of 93 patients treated with AA between September 2014 and February 2017 were selected and their medical records were analyzed retrospectively. The median PFS time of docetaxel (DTX)-naïve patients was 171 days, and that of post-DTX patients was 56 days. The OS time of DTX-naïve patients did not reach the median. The median OS time of post-DTX patients was 761 days. Multivariate analyses identified baseline prostate-specific antigen (PSA) level prior to treatment with AA and the PSA response rate as independent prognostic factors for PFS time, and baseline PSA prior to treatment with AA as the only independent prognostic factor for OS time. The results of the present study indicate that the baseline PSA level prior to treatment with AA is a notable prognostic factor in patients with CRPC.

beta(2)microglobulin mRNA expression levels are prognostic for lymph node metastasis in colorectal cancer patients.

PubMed

Shrout, J; Yousefzadeh, M; Dodd, A; Kirven, K; Blum, C; Graham, A; Benjamin, K; Hoda, R; Krishna, M; Romano, M; Wallace, M; Garrett-Mayer, E; Mitas, M

2008-06-17

Colorectal cancer (CRC) is the fourth most common non-cutaneous malignancy in the United States and the second most frequent cause of cancer-related death. One of the most important determinants of CRC survival is lymph node metastasis. To determine whether molecular markers might be prognostic for lymph node metastases, we measured by quantitative real-time RT-PCR the expression levels of 15 cancer-associated genes in formalin-fixed paraffin-embedded primary tissues derived from stage I-IV CRC patients with (n=20) and without (n=18) nodal metastases. Using the mean of the 15 genes as an internal reference control, we observed that low expression of beta(2)microglobulin (B2M) was a strong prognostic indicator of lymph node metastases (area under the curve (AUC)=0.85; 95% confidence interval (CI)=0.69-0.94). We also observed that the expression ratio of B2M/Spint2 had the highest prognostic accuracy (AUC=0.87; 95% CI=0.71-0.96) of all potential two-gene combinations. Expression values of Spint2 correlated with the mean of the entire gene set at an R(2) value of 0.97, providing evidence that Spint2 serves not as an independent prognostic gene, but rather as a reliable reference control gene. These studies are the first to demonstrate a prognostic role of B2M at the mRNA level and suggest that low B2M expression levels might be useful for identifying patients with lymph node metastasis and/or poor survival.

Elevated levels of serum nidogen-2 in esophageal squamous cell carcinoma.

PubMed

Chai, Annie Wai Yeeng; Cheung, Arthur Kwok Leung; Dai, Wei; Ko, Josephine Mun Yee; Lee, Nikki Pui Yue; Chan, Kin Tak; Law, Simon Ying-Kit; Lung, Maria Li

2018-02-14

Nidogen-2 (NID2), a secretory basement membrane protein, has been implicated as a potential biomarker in ovarian cancer and hepatocellular carcinoma. In this study, we aimed to investigate the utility of detecting serum NID2 levels for identification of esophageal squamous cell carcinoma (ESCC) patients and prediction of poor survival outcome. Using an in-house NID2 enzyme-linked immunosorbent assay (ELISA), serum samples from 101 ESCC patients and 50 healthy controls were screened for their NID2 levels. The serum NID2 levels in ESCC patients (median 24.4 μg/L) are significantly higher (p= 4.3e-09) than that of the healthy controls (median 15.85 μg/L). The receiver operating characteristic (ROC) curve demonstrated an area under the curve of 0.756. At the threshold of 17.95 μg/L, the sensitivity and specificity achieved are 0.76 and 0.63, respectively. Kaplan-Meier survival analysis revealed that patients with high serum NID2 levels (⩾ 32.6 μg/L) have significantly higher risk of death (HR = 1.984, 95% CI: 1.175-3.349; log-rank p-value = 0.012) compared to those with low serum NID2 levels (< 20.0 μg/L). In conclusion, we show that detecting the elevation of serum NID2 levels has potential diagnostic and prognostic value for ESCC patients.

Prognostic significance of serum lactate dehydrogenase levels in Ewing's sarcoma: A meta-analysis.

PubMed

Li, Suoyuan; Yang, Qing; Wang, Hongsheng; Wang, Zhuoying; Zuo, Dongqing; Cai, Zhengdong; Hua, Yingqi

2016-12-01

A number of studies have investigated the role of serum lactate dehydrogenase (LDH) levels in patients with Ewing's sarcoma, although these have yielded inconsistent and inconclusive results. Therefore, the present study aimed to systematically review the published studies and conduct a meta-analysis to assess its prognostic value more precisely. Cohort studies assessing the prognostic role of LDH levels in patients with Ewing's sarcoma were included. A pooled hazard ratio (HR) with 95% confidence intervals (CIs) of overall survival (OS) or 5-year disease-free survival (DFS) was used to assess the prognostic role of the levels of serum LDH. Nine studies published between 1980 and 2014, with a total of 1,412 patients with Ewing's sarcoma, were included. Six studies, with a total of 644 patients, used OS as the primary endpoint and four studies, with 795 patients, used 5-year DFS. Overall, the pooled HR evaluating high LDH levels was 2.90 (95% CI: 2.09-4.04) for OS and 2.40 (95% CI: 1.93-2.98) for 5-year DFS. This meta-analysis demonstrates that high levels of serum LDH are associated with lower OS and 5-year DFS rates in patients with Ewing's sarcoma. Therefore, serum LDH levels are an effective biomarker of Ewing's sarcoma prognosis.

SU-E-J-242: Volume-Dependence of Quantitative Imaging Features From CT and CE-CT Images of NSCLC

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fave, X; Fried, D; UT Health Science Center Graduate School of Biomedical Sciences, Houston, TX

Purpose: To determine whether tumor volume plays a significant role in the values obtained for texture features when they are extracted from computed tomography (CT) images of non-small cell lung cancer (NSCLC). We also sought to identify whether features can be reliably measured at all volumes or if a minimum volume threshold should be recommended. Methods: Eleven features were measured on 40 CT and 32 contrast-enhanced CT (CECT) patient images for this study. Features were selected for their prognostic/diagnostic value in previous publications. Direct correlations between these textures and volume were evaluated using the Spearman correlation coefficient. Any texture thatmore » the Wilcoxon rank-sum test was used to compare the variation above and below a volume cutoff. Four different volume thresholds (5, 10, 15, and 20 cm{sup 3}) were tested. Results: Four textures were found to be significantly correlated with volume in both the CT and CE-CT images. These were busyness, coarseness, gray-level nonuniformity, and run-length nonuniformity with correlation coefficients of 0.92, −0.96, 0.94, and 0.98 for the CT images and 0.95, −0.97, 0.98, and 0.98 for the CE-CT images. After volume normalization, the correlation coefficients decreased substantially. For the data obtained from the CT images, the results of the Wilcoxon rank-sum test were significant when volume thresholds of 5–15 cm3 were used. No volume threshold was shown to be significant for the CE-CT data. Conclusion: Equations for four features that have been used in several published studies were found to be volume-dependent. Future studies should consider implementing normalization factors or removing these features entirely to prevent this potential source of redundancy or bias. This work was supported in part by National Cancer Institute grant R03CA178495-01. Xenia Fave is a recipient of the American Association of Physicists in Medicine Graduate Fellowship.« less

The preoperative plasma fibrinogen level is an independent prognostic factor for overall survival of breast cancer patients who underwent surgical treatment.

PubMed

Wen, Jiahuai; Yang, Yanning; Ye, Feng; Huang, Xiaojia; Li, Shuaijie; Wang, Qiong; Xie, Xiaoming

2015-12-01

Previous studies have suggested that plasma fibrinogen contributes to tumor cell proliferation, progression and metastasis. The current study was performed to evaluate the prognostic relevance of preoperative plasma fibrinogen in breast cancer patients. Data of 2073 consecutive breast cancer patients, who underwent surgery between January 2002 and December 2008 at the Sun Yat-sen University Cancer Center, were retrospectively evaluated. Plasma fibrinogen levels were routinely measured before surgeries. Participants were grouped by the cutoff value estimated by the receiver operating characteristic (ROC) curve analysis. Overall survival (OS) was assessed using Kaplan-Meier analysis, and multivariate Cox proportional hazards regression model was performed to evaluate the independent prognostic value of plasma fibrinogen level. The optimal cutoff value of preoperative plasma fibrinogen was determined to be 2.83 g/L. The Kaplan-Meier analysis showed that patients with high fibrinogen levels had shorter OS than patients with low fibrinogen levels (p < 0.001). Multivariate analysis suggested preoperative plasma fibrinogen as an independent prognostic factor for OS in breast cancer patients (HR = 1.475, 95% confidence interval (CI): 1.177-1.848, p = 0.001). Subgroup analyses revealed that plasma fibrinogen level was an unfavorable prognostic parameter in stage II-III, Luminal subtypes and triple-negative breast cancer patients. Elevated preoperative plasma fibrinogen was independently associated with poor prognosis in breast cancer patients and may serve as a valuable parameter for risk assessment in breast cancer patients. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Identification of men with low-risk biopsy-confirmed prostate cancer as candidates for active surveillance.

PubMed

Lin, Daniel W; Crawford, E David; Keane, Thomas; Evans, Brent; Reid, Julia; Rajamani, Saradha; Brown, Krystal; Gutin, Alexander; Tward, Jonathan; Scardino, Peter; Brawer, Michael; Stone, Steven; Cuzick, Jack

2018-06-01

A combined clinical cell-cycle risk (CCR) score that incorporates prognostic molecular and clinical information has been recently developed and validated to improve prostate cancer mortality (PCM) risk stratification over clinical features alone. As clinical features are currently used to select men for active surveillance (AS), we developed and validated a CCR score threshold to improve the identification of men with low-risk disease who are appropriate for AS. The score threshold was selected based on the 90th percentile of CCR scores among men who might typically be considered for AS based on NCCN low/favorable-intermediate risk criteria (CCR = 0.8). The threshold was validated using 10-year PCM in an unselected, conservatively managed cohort and in the subset of the same cohort after excluding men with high-risk features. The clinical effect was evaluated in a contemporary clinical cohort. In the unselected validation cohort, men with CCR scores below the threshold had a predicted mean 10-year PCM of 2.7%, and the threshold significantly dichotomized low- and high-risk disease (P = 1.2 × 10 -5 ). After excluding high-risk men from the validation cohort, men with CCR scores below the threshold had a predicted mean 10-year PCM of 2.3%, and the threshold significantly dichotomized low- and high-risk disease (P = 0.020). There were no prostate cancer-specific deaths in men with CCR scores below the threshold in either analysis. The proportion of men in the clinical testing cohort identified as candidates for AS was substantially higher using the threshold (68.8%) compared to clinicopathologic features alone (42.6%), while mean 10-year predicted PCM risks remained essentially identical (1.9% vs. 2.0%, respectively). The CCR score threshold appropriately dichotomized patients into low- and high-risk groups for 10-year PCM, and may enable more appropriate selection of patients for AS. Copyright © 2018 Elsevier Inc. All rights reserved.

The Relationship Between Human Papillomavirus Status and Other Molecular Prognostic Markers in Head and Neck Squamous Cell Carcinomas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kong, Christina S.; Narasimhan, Balasubramanian; Cao Hongbin

2009-06-01

Purpose: To evaluate the relationship between human papillomavirus (HPV) status and known prognostic makers for head and neck cancers including tumor hypoxia, epidermal growth factor receptor (EGFR) expression and intratumoral T-cell levels and to determine the prognostic impact of these markers by HPV status. Methods and Materials: HPV status in 82 evaluable head and neck squamous cell carcinomas patients was determined by pyrosequencing and related to p16{sup INK4a} staining and treatment outcomes. It was correlated with tumor hypoxia (tumor pO{sub 2} and carbonic anhydrase [CAIX] staining), EGFR status, and intratumoral lymphocyte expression (CD3 staining). Results: Forty-four percent of evaluable tumorsmore » had strong HPV signal by pyrosequencing. There was a significant relationship between strong HPV signal and p16{sup INK4a} staining as well as oropharynx location. The strong HPV signal group fared significantly better than others, both in time to progression (TTP, p = 0.008) and overall survival (OS, p = 0.004) for all patients and for the oropharyngeal subset. Positive p16{sup INK4a} staining was associated with better TTP (p = 0.014) and OS (p = 0.00002). There was no relationship between HPV status and tumor pO{sub 2} or CAIX staining. However, HPV status correlated inversely with EGFR reactivity (p = 0.0006) and directly with CD3(+) T-lymphocyte level (p = 0.03). Whereas CAIX and EGFR overexpression were negative prognostic factors regardless of HPV status, CD3(+) T-cell levels was prognostic only in HPV(-) tumors. Conclusion: HPV status was a prognostic factor for progression and survival. It correlated inversely with EGFR expression and directly with T-cell infiltration. The prognostic effect of CAIX and EGFR expression was not influenced by HPV status, whereas intratumoral T-cell levels was significant only for HPV(-) tumors.« less

The prognostic role of hemoglobin levels in patients undergoing concurrent chemo-radiation for anal cancer.

PubMed

Franco, Pierfrancesco; Montagnani, Francesco; Arcadipane, Francesca; Casadei, Chiara; Andrikou, Kalliopi; Martini, Stefania; Iorio, Giuseppe Carlo; Scartozzi, Mario; Mistrangelo, Massimiliano; Fornaro, Lorenzo; Cassoni, Paola; Cascinu, Stefano; Ricardi, Umberto; Casadei Gardini, Andrea

2018-05-02

Concurrent chemo-radiation (CT-RT) is a standard therapy for squamous cell carcinoma of anal canal. Different clinical and biological factors may potentially affect outcome. We investigated the prognostic role of baseline hemoglobin (Hb) in a cohort of anal cancer patients submitted to CT-RT with 5-fluorouracil and mitomycin C. Up to 161 patients with clinical stage T1-T4/N0-N3/M0 were treated. Response was assessed at 6 weeks and thereafter at 3, 6 and 12 months. Two different approaches were used:a)simultaneous integrated boost following RTOG 05-29 indications;b)first sequence of 45Gy/25 fractions to the pelvis followed by 9-14.4 Gy/5-8 fractions to the macroscopic disease. Primary endpoints were progression-free survival (PFS) and overall survival (OS). On multivariate analysis, pre-treatment Hb level had a significant correlation to OS (HR:0.53;95% CI:0.33-0.87; p = 0.001), but not to PFS (HR:0.78;95% CI:0.53-1.15; p = 0.12) Patients with pre-treatment Hb ≥ 12 g/dl had 5-year PFS and OS of 82.2%, compared to 29.3% and 32.8% for those below the threshold. The likelihood to achieve a complete remission increased by 5.6% for every single-unit (g/dl) increase in baseline Hb level over 11 g/dl. On multivariate analysis, response to treatment had a significant correlation to PFS (incomplete vs complete response - HR:5.43;95% CI:2.75-10.7; p < 0.0001) and OS (HR: 6.96;95% CI:2.96-16.5; p < 0.0001). We showed that baseline Hb level is a strong indicator for poor response to RT-CT in anal cancer patients. A close clinical monitoring for incomplete response to treatment should be advised in patients with low pre-treatment Hb. The hypothesis that the preservation of adequate Hb level during treatment may lead to a better outcome needs prospective evaluation.

Increased body mass index is associated with improved overall survival in extranodal natural killer/T-cell lymphoma, nasal type.

PubMed

Li, Ya-Jun; Yi, Ping-Yong; Li, Ji-Wei; Liu, Xian-Ling; Liu, Xi-Yu; Zhou, Fang; OuYang, Zhou; Sun, Zhong-Yi; Huang, Li-Jun; He, Jun-Qiao; Yao, Yuan; Fan, Zhou; Tang, Tian; Jiang, Wen-Qi

2017-01-17

The role of body mass index (BMI) in lymphoma survival outcomes is controversial. The prognostic significance of BMI in extranodal natural killer (NK)/T-cell lymphoma (ENKTL) is unclear. We evaluated the prognostic role of BMI in patients with ENKTL. We retrospectively analyzed 742 patients with newly diagnosed ENKTL. The prognostic value of BMI was compared between patients with low BMIs (< 20.0 kg/m2) and patients with high BMIs (≥ 20.0 kg/m2). The prognostic value of the International Prognostic Index (IPI) and the Korean Prognostic Index (KPI) was also evaluated and compared with that of the BMI classification. Patients with low BMIs tended to exhibit higher Eastern Cooperative Oncology Group performance status (ECOG PS) scores (≥ 2) (P = 0.001), more frequent B symptoms (P < 0.001), lower albumin levels (P < 0.001), higher KPI scores (P = 0.03), and lower rates of complete remission (P < 0.001) than patients with high BMIs, as well as inferior progression-free survival (PFS, P = 0.003), and inferior overall survival (OS, P = 0.001). Multivariate analysis demonstrated that age > 60 years, mass > 5 cm, stage III/IV, elevated LDH levels, albumin levels < 35 g/L and low BMIs were independent adverse predictors of OS. The BMI classification was found to be superior to the IPI with respect to predicting patient outcomes among low-risk patients and the KPI with respect to distinguishing between intermediate-low- and high-intermediate-risk patients. Higher BMI at the time of diagnosis is associated with improved overall survival in ENKTL. Using the BMI classification may improve the IPI and KPI prognostic models.

Increased body mass index is associated with improved overall survival in extranodal natural killer/T-cell lymphoma, nasal type

PubMed Central

Li, Ya-Jun; Yi, Ping-Yong; Li, Ji-Wei; Liu, Xian-Ling; Liu, Xi-Yu; Zhou, Fang; OuYang, Zhou; Sun, Zhong-Yi; Huang, Li-Jun; He, Jun-Qiao; Yao, Yuan; Fan, Zhou; Tang, Tian; Jiang, Wen-Qi

2017-01-01

Objectives: The role of body mass index (BMI) in lymphoma survival outcomes is controversial. The prognostic significance of BMI in extranodal natural killer (NK)/T-cell lymphoma (ENKTL) is unclear. We evaluated the prognostic role of BMI in patients with ENKTL. Methods: We retrospectively analyzed 742 patients with newly diagnosed ENKTL. The prognostic value of BMI was compared between patients with low BMIs (< 20.0 kg/m2) and patients with high BMIs (≥ 20.0 kg/m2). The prognostic value of the International Prognostic Index (IPI) and the Korean Prognostic Index (KPI) was also evaluated and compared with that of the BMI classification. Results: Patients with low BMIs tended to exhibit higher Eastern Cooperative Oncology Group performance status (ECOG PS) scores (≥ 2) (P = 0.001), more frequent B symptoms (P < 0.001), lower albumin levels (P < 0.001), higher KPI scores (P = 0.03), and lower rates of complete remission (P < 0.001) than patients with high BMIs, as well as inferior progression-free survival (PFS, P = 0.003), and inferior overall survival (OS, P = 0.001). Multivariate analysis demonstrated that age > 60 years, mass > 5 cm, stage III/IV, elevated LDH levels, albumin levels < 35 g/L and low BMIs were independent adverse predictors of OS. The BMI classification was found to be superior to the IPI with respect to predicting patient outcomes among low-risk patients and the KPI with respect to distinguishing between intermediate-low- and high-intermediate-risk patients. Conclusions: Higher BMI at the time of diagnosis is associated with improved overall survival in ENKTL. Using the BMI classification may improve the IPI and KPI prognostic models. PMID:28002803

Assessment of Diagnostic and Prognostic Role of Copeptin in the Clinical Setting of Sepsis.

PubMed

Battista, Stefania; Audisio, Umberto; Galluzzo, Claudia; Maggiorotto, Matteo; Masoero, Monica; Forno, Daniela; Pizzolato, Elisa; Ulla, Marco; Lucchiari, Manuela; Vitale, Annarita; Moiraghi, Corrado; Lupia, Enrico; Settanni, Fabio; Mengozzi, Giulio

2016-01-01

The diagnostic and prognostic usefulness of copeptin were evaluated in septic patients, as compared to procalcitonin assessment. In this single centre and observational study 105 patients were enrolled: 24 with sepsis, 25 with severe sepsis, 15 with septic shock, and 41 controls, divided in two subgroups (15 patients with gastrointestinal bleeding and 26 with suspected SIRS secondary to trauma, acute coronary syndrome, and pulmonary embolism). Biomarkers were determined at the first medical evaluation and thereafter 24, 48, and 72 hours after admission. Definitive diagnosis and in-hospital survival rates at 30 days were obtained through analysis of medical records. At entry, copeptin proved to be able to distinguish cases from controls and also sepsis group from septic shock group, while procalcitonin could distinguish also severe sepsis from septic shock group. Areas under the ROC curve for copeptin and procalcitonin were 0.845 and 0.861, respectively. Noteworthy, patients with copeptin concentrations higher than the threshold value (23.2 pmol/L), calculated from the ROC curve, at admission presented higher 30-day mortality. No significant differences were found in copeptin temporal profile among different subgroups. Copeptin showed promising diagnostic and prognostic role in the management of sepsis, together with its possible role in monitoring the response to treatment.

Assessment of Diagnostic and Prognostic Role of Copeptin in the Clinical Setting of Sepsis

PubMed Central

Battista, Stefania; Audisio, Umberto; Galluzzo, Claudia; Maggiorotto, Matteo; Masoero, Monica; Forno, Daniela; Pizzolato, Elisa; Ulla, Marco; Lucchiari, Manuela; Vitale, Annarita; Moiraghi, Corrado; Lupia, Enrico; Settanni, Fabio; Mengozzi, Giulio

2016-01-01

The diagnostic and prognostic usefulness of copeptin were evaluated in septic patients, as compared to procalcitonin assessment. In this single centre and observational study 105 patients were enrolled: 24 with sepsis, 25 with severe sepsis, 15 with septic shock, and 41 controls, divided in two subgroups (15 patients with gastrointestinal bleeding and 26 with suspected SIRS secondary to trauma, acute coronary syndrome, and pulmonary embolism). Biomarkers were determined at the first medical evaluation and thereafter 24, 48, and 72 hours after admission. Definitive diagnosis and in-hospital survival rates at 30 days were obtained through analysis of medical records. At entry, copeptin proved to be able to distinguish cases from controls and also sepsis group from septic shock group, while procalcitonin could distinguish also severe sepsis from septic shock group. Areas under the ROC curve for copeptin and procalcitonin were 0.845 and 0.861, respectively. Noteworthy, patients with copeptin concentrations higher than the threshold value (23.2 pmol/L), calculated from the ROC curve, at admission presented higher 30-day mortality. No significant differences were found in copeptin temporal profile among different subgroups. Copeptin showed promising diagnostic and prognostic role in the management of sepsis, together with its possible role in monitoring the response to treatment. PMID:27366743

A prognostic model based on readily available clinical data enriched a pre-emptive pharmacogenetic testing program.

PubMed

Schildcrout, Jonathan S; Shi, Yaping; Danciu, Ioana; Bowton, Erica; Field, Julie R; Pulley, Jill M; Basford, Melissa A; Gregg, William; Cowan, James D; Harrell, Frank E; Roden, Dan M; Peterson, Josh F; Denny, Joshua C

2016-04-01

We describe the development, implementation, and evaluation of a model to pre-emptively select patients for genotyping based on medication exposure risk. Using deidentified electronic health records, we derived a prognostic model for the prescription of statins, warfarin, or clopidogrel. The model was implemented into a clinical decision support (CDS) tool to recommend pre-emptive genotyping for patients exceeding a prescription risk threshold. We evaluated the rule on an independent validation cohort and on an implementation cohort, representing the population in which the CDS tool was deployed. The model exhibited moderate discrimination with area under the receiver operator characteristic curves ranging from 0.68 to 0.75 at 1 and 2 years after index dates. Risk estimates tended to underestimate true risk. The cumulative incidences of medication prescriptions at 1 and 2 years were 0.35 and 0.48, respectively, among 1,673 patients flagged by the model. The cumulative incidences in the same number of randomly sampled subjects were 0.12 and 0.19, and in patients over 50 years with the highest body mass indices, they were 0.22 and 0.34. We demonstrate that prognostic algorithms can guide pre-emptive pharmacogenetic testing toward those likely to benefit from it. Copyright © 2016 Elsevier Inc. All rights reserved.

Platelet-lymphocyte ratio is an independent prognostic factor in patients with ALK-positive non-small-cell lung cancer.

PubMed

Han, Ying; Wang, Jing; Hong, Liping; Sun, Leina; Zhuang, Hongqing; Sun, Bingsheng; Wang, Hua; Zhang, Xinwei; Ren, Xiubao

2017-01-01

As the prognostic value of the neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) is unclear in patients with ALK-positive non-small-cell lung cancer (NSCLC), this study assessed the importance of these factors was in this patient subset. In 173 patients with primary ALK-positive NSCLC at pathological stages I-IV, neutrophil, platelet, lymphocyte, D-dimer and eosinophil levels were recorded before starting treatment. The patients' median NLR and PLR values were 2.10 and 127.69, respectively. Univariate analyses showed that NLR and PLR values, the D-dimer level and the eosinophil count were all associated with survival. Although multivariate analysis showed PLR to be an independent prognostic factor for overall survival (p = 0.018), NLR was not. PLR is an independent prognostic factor in ALK-positive NSCLC.

Dynamic thresholds and a summary ROC curve: Assessing prognostic accuracy of longitudinal markers.

PubMed

Saha-Chaudhuri, P; Heagerty, P J

2018-04-19

Cancer patients, chronic kidney disease patients, and subjects infected with HIV are routinely monitored over time using biomarkers that represent key health status indicators. Furthermore, biomarkers are frequently used to guide initiation of new treatments or to inform changes in intervention strategies. Since key medical decisions can be made on the basis of a longitudinal biomarker, it is important to evaluate the potential accuracy associated with longitudinal monitoring. To characterize the overall accuracy of a time-dependent marker, we introduce a summary ROC curve that displays the overall sensitivity associated with a time-dependent threshold that controls time-varying specificity. The proposed statistical methods are similar to concepts considered in disease screening, yet our methods are novel in choosing a potentially time-dependent threshold to define a positive test, and our methods allow time-specific control of the false-positive rate. The proposed summary ROC curve is a natural averaging of time-dependent incident/dynamic ROC curves and therefore provides a single summary of net error rates that can be achieved in the longitudinal setting. Copyright © 2018 John Wiley & Sons, Ltd.

Margin to tumor thickness ratio - A predictor of local recurrence and survival in oral squamous cell carcinoma.

PubMed

Heiduschka, Gregor; Virk, Sohaib A; Palme, Carsten E; Ch'ng, Sydney; Elliot, Michael; Gupta, Ruta; Clark, Jonathan

2016-04-01

To assess whether small oral squamous cell carcinomas (OSCC) require the same margin clearance as large tumors. We evaluated the association between the ratio of the closest margin to tumor size (MSR) and tumor thickness (MTR) with local control and survival. The clinicopathologic and follow up data were obtained for 501 OSCC patients who had surgical resection with curative intent at our institution. MTR and MSR were computed and their associations with local control and survival were assessed using multivariable Cox-regression model. Survival curves were generated using the Kaplan-Meier method. MTR was a better predictor of disease control than MSR. MTR was a predictor of local failure (p=0.033) and disease specific death (p=0.038) after adjusting for perineural invasion, lymphovascular involvement, nodal status, and radiotherapy. A threshold MTR value of 0.3 was identified, above which the risk of local recurrence was low. The ratio of margin to tumor thickness was an independent predictor for local recurrence and disease specific death in this cohort. A MTR>0.3 can serve as a useful tool for adjuvant therapy planning as it combines tumor thickness and margin clearance, two well established prognostic factors. The minimum safe margin can be calculated by multiplying the tumor thickness by 0.3. Further prospective studies in other institutions are warranted to confirm the prognostic utility of MTR and assess the generalizability of our threshold values. Copyright © 2016 Elsevier Ltd. All rights reserved.

Clinical Significance of Soluble Intercellular Adhesion Molecule-1 and Interleukin-6 in Patients with Extrahepatic Cholangiocarcinoma.

PubMed

Shimura, Tatsuo; Shibata, Masahiko; Gonda, Kenji; Kofunato, Yasuhide; Okada, Ryo; Ishigame, Teruhide; Kimura, Takashi; Kenjo, Akira; Marubashi, Shigeru; Kono, Koji; Takenoshita, Seiichi

2017-09-19

Purpose/Aim: Although several prognostic factors for extrahepatic cholangiocarcinoma (EHC) have been reported, preoperative prognostic factors have yet to be established. We investigated the serum concentration of angiogenic, inflammatory, and nutritional parameters. Twenty-five patients with EHC were enrolled before starting treatment. Preoperative prognostic factors were identified using multivariate analyses. The serum soluble intercellular adhesion molecule-1 (sICAM-1) levels were significantly higher in the patients with EHC (436.0 ± 43.2 ng/ml) than in the healthy volunteers (228.6 ± 22.0 ng/ml) (p <.001). In addition, the serum IL-6 levels were significantly higher in the patients (18.0 ± 5.6 pg/ml) than in the healthy volunteers (5.7 ± 0.8 pg/ml) (p <.05). The serum IL-6 and sICAM-1 showed a strong correlation (r = 0.559) in the patients with EHC (p <.01). The serum IL-6 (area under the curve = 0.764, p =.030, cut-off level = 11.6) and sICAM-1 (area under the curve = 0.818, p =.007, cutoff level = 322.6) were revealed to be useful as prognostic factors by the receiver operating characteristic curves. The high IL-6 group and the high sICAM-1 group showed poorer DSS than those of the respective low groups. In the multivariate analysis, IL-6 (hazard ratio: 1.050, 95% confidence interval: 1.002-1.100, p =.043) and sICAM-1 (hazard ratio: 1.009, 95% confidence interval: 1.002-1.015, p =.009) were independent prognostic factors for DSS. IL-6 and sICAM-1 were independent preoperative prognostic factors in EHC patients, causing continuous inflammation and malnutrition in collaboration with other pro-angiogenic factors.

CARA Risk Assessment Thresholds

NASA Technical Reports Server (NTRS)

Hejduk, M. D.

2016-01-01

Warning remediation threshold (Red threshold): Pc level at which warnings are issued, and active remediation considered and usually executed. Analysis threshold (Green to Yellow threshold): Pc level at which analysis of event is indicated, including seeking additional information if warranted. Post-remediation threshold: Pc level to which remediation maneuvers are sized in order to achieve event remediation and obviate any need for immediate follow-up maneuvers. Maneuver screening threshold: Pc compliance level for routine maneuver screenings (more demanding than regular Red threshold due to additional maneuver uncertainty).

Prognostic value of baseline seric Syndecan-1 in initially unresectable metastatic colorectal cancer patients: a simple biological score.

PubMed

Jary, Marine; Lecomte, Thierry; Bouché, Olivier; Kim, Stefano; Dobi, Erion; Queiroz, Lise; Ghiringhelli, Francois; Etienne, Hélène; Léger, Julie; Godet, Yann; Balland, Jérémy; Lakkis, Zaher; Adotevi, Olivier; Bonnetain, Franck; Borg, Christophe; Vernerey, Dewi

2016-11-15

In first-line metastatic colorectal cancer (mCRC), baseline prognostic factors allowing death risk and treatment strategy stratification are lacking. Syndecan-1 (CD138) soluble form was never described as a prognostic biomarker in mCRC. We investigated its additional prognostic value for overall survival (OS). mCRC patients with unresectable disease at diagnosis were treated with bevacizumab-based chemotherapy in two independent prospective clinical trials (development set: n = 126, validation set: n = 51, study NCT00489697 and study NCT00544011, respectively). Serums were collected at baseline for CD138 measurement. OS determinants were assessed and, based on the final multivariate model, a prognostic score was proposed. Two independent OS prognostic factors were identified: Lactate Dehydrogenase (LDH) high level (p = 0.0066) and log-CD138 high level (p = 0.0190). The determination of CD138 binary information (cutoff: 75 ng/mL) allowed the assessment of a biological prognostic score with CD138 and LDH values, identifying three risk groups for death (median OS= 38.9, 30.1 and 19.8 months for the low, intermediate and high risk groups, respectively; p < 0.0001). This score had a good discrimination ability (C-index = 0.63). These results were externally confirmed in the validation set. Our study provides robust evidence in favor of the additional baseline soluble CD138 prognostic value for OS, in mCRC patients. A simple biological scoring system is proposed including LDH and CD138 binary status values. © 2016 UICC.

I. RENAL THRESHOLDS FOR HEMOGLOBIN IN DOGS

PubMed Central

Lichty, John A.; Havill, William H.; Whipple, George H.

1932-01-01

We use the term "renal threshold for hemoglobin" to indicate the smallest amount of hemoglobin which given intravenously will effect the appearance of recognizable hemoglobin in the urine. The initial renal threshold level for dog hemoglobin is established by the methods employed at an average value of 155 mg. hemoglobin per kilo body weight with maximal values of 210 and minimal of 124. Repeated daily injections of hemoglobin will depress this initial renal threshold level on the average 46 per cent with maximal values of 110 and minimal values of 60 mg. hemoglobin per kilo body weight. This minimal or depression threshold is relatively constant if the injections are continued. Rest periods without injections cause a return of the renal threshold for hemoglobin toward the initial threshold levels—recovery threshold level. Injections of hemoglobin below the initial threshold level but above the minimal or depression threshold will eventually reduce the renal threshold for hemoglobin to its depression threshold level. We believe the depression threshold or minimal renal threshold level due to repeated hemoglobin injections is a little above the glomerular threshold which we assume is the base line threshold for hemoglobin. Our reasons for this belief in the glomerular threshold are given above and in the other papers of this series. PMID:19870016

Prognostic risk stratification derived from individual patient level data for men with advanced penile squamous cell carcinoma receiving first-line systemic therapy.

PubMed

Pond, Gregory R; Di Lorenzo, Giuseppe; Necchi, Andrea; Eigl, Bernhard J; Kolinsky, Michael P; Chacko, Raju T; Dorff, Tanya B; Harshman, Lauren C; Milowsky, Matthew I; Lee, Richard J; Galsky, Matthew D; Federico, Piera; Bolger, Graeme; DeShazo, Mollie; Mehta, Amitkumar; Goyal, Jatinder; Sonpavde, Guru

2014-05-01

Prognostic factors in men with penile squamous cell carcinoma (PSCC) receiving systemic therapy are unknown. A prognostic classification system in this disease may facilitate interpretation of outcomes and guide rational drug development. We performed a retrospective analysis to identify prognostic factors in men with PSCC receiving first-line systemic therapy for advanced disease. Individual patient level data were obtained from 13 institutions to study prognostic factors in the context of first-line systemic therapy for advanced PSCC. Cox proportional hazards regression analysis was conducted to examine the prognostic effect of these candidate factors on progression-free survival (PFS) and overall survival (OS): age, stage, hemoglobin, neutrophil count, lymphocyte count, albumin, site of metastasis (visceral or nonvisceral), smoking, circumcision, regimen, ECOG performance status (PS), lymphovascular invasion, precancerous lesion, and surgery following chemotherapy. The effect of different treatments was then evaluated adjusting for factors in the prognostic model. The study included 140 eligible men. Mean age across all men was 57.0 years. Among them, 8.6%, 21.4%, and 70.0% of patients had stage 2, 3, and 4 diseases, respectively; 40.7% had ECOG PS ≥ 1, 47.4% had visceral metastases, and 73.6% received cisplatin-based chemotherapy. The multivariate model of poor prognostic factors included visceral metastases (P<0.001) and ECOG PS ≥ 1 (P<0.001) for both PFS and OS. A risk stratification model constructed with 0, 1, and both poor prognostic factors was internally validated and demonstrated moderate discriminatory ability (c-statistic of 0.657 and 0.677 for OS and PFS, respectively). The median OS for the entire population was 9 months. Median OS was not reached, 8, and 7 months for those with 0, 1, and both risk factors, respectively. Cisplatin-based regimens were associated with better OS (P = 0.017) but not PFS (P = 0.37) compared with noncisplatin-based regimens after adjusting for the 2 prognostic factors. In men with advanced PSCC receiving first-line systemic therapy, visceral metastases and ECOG PS ≥ 1 were poor prognostic factors. A prognostic model including these factors exhibited moderate discriminatory ability for outcomes and warrants external validation. Patients receiving cisplatin-based regimens exhibited better outcomes compared with noncisplatin-based regimens after adjusting for prognostic factors. © 2013 Published by Elsevier Inc.

A Distributed Approach to System-Level Prognostics

DTIC Science & Technology

2012-09-01

the end of (useful) life ( EOL ) and/or the remaining useful life (RUL) of components, subsystems, or systems. The prognostics problem itself can be...system state estimate, computes EOL and/or RUL. In this paper, we focus on a model-based prognostics approach (Orchard & Vachtse- vanos, 2009; Daigle...been focused on individual components, and determining their EOL and RUL, e.g., (Orchard & Vachtsevanos, 2009; Saha & Goebel, 2009; Daigle & Goebel

Premature progesterone rise on day of hCG negatively correlated with live birth rate in IVF cycles: An analysis of 1022 cycles.

PubMed

Lepage, Julien; Keromnes, Gwenola; Epelboin, Sylvie; Luton, Dominique; Yazbeck, Chadi

2018-05-18

To investigate the relationship between serum P levels on the day of hCG administration and pregnancy outcomes in patients undergoing IVF. Retrospective study. Teaching hospital. A total of 1022 IVF-ICSI cycles, frozen embryo transfer excluded. Patients-all types of responder - underwent IVF with agonist or antagonist protocols. Clinical outcomes of IVF were analyzed according to plasma P levels. Ongoing pregnancy rates. We proposed a serum P level of 1.57ng/ml on day of hCG as a threshold for all types of responders and all protocols combined. Ongoing implantation rates were not affected by elevated progesterone. Live birth rate was inversely associated with serum P levels on day of hCG and more miscarriages were associated with P>1.57ng/ml. We have not found the progesterone>1.57ng/ml on the day of hCG as a prognostic factor for pregnancy. Elevated P level on the day of hCG administration negatively influence live birth rate and is correlated to an increase of miscarriage. The detrimental effect of P elevation on pregnancy seems not to be related substantially to endometrium receptivity. Thus, despite a comparable clinical pregnancy rate and an initial implantation rate, we demonstrate more spontaneous abortion and it would seem that the effect of progesterone is later. Copyright © 2018. Published by Elsevier Masson SAS.

Prognostics of slurry pumps based on a moving-average wear degradation index and a general sequential Monte Carlo method

NASA Astrophysics Data System (ADS)

Wang, Dong; Tse, Peter W.

2015-05-01

Slurry pumps are commonly used in oil-sand mining for pumping mixtures of abrasive liquids and solids. These operations cause constant wear of slurry pump impellers, which results in the breakdown of the slurry pumps. This paper develops a prognostic method for estimating remaining useful life of slurry pump impellers. First, a moving-average wear degradation index is proposed to assess the performance degradation of the slurry pump impeller. Secondly, the state space model of the proposed health index is constructed. A general sequential Monte Carlo method is employed to derive the parameters of the state space model. The remaining useful life of the slurry pump impeller is estimated by extrapolating the established state space model to a specified alert threshold. Data collected from an industrial oil sand pump were used to validate the developed method. The results show that the accuracy of the developed method improves as more data become available.

Abnormalities of Lipoprotein Levels in Liver Cirrhosis: Clinical Relevance.

PubMed

Privitera, Graziella; Spadaro, Luisa; Marchisello, Simona; Fede, Giuseppe; Purrello, Francesco

2018-01-01

Progressive lipoprotein impairment occurs in liver cirrhosis and is associated with increased morbidity and mortality. The present review aims to summarize the current evidence regarding the prognostic value of lipoprotein abnormalities in liver cirrhosis and to address the need of a better prognostic stratification of patients, including lipoprotein profile assessment. Low levels of lipoproteins are usual in cirrhosis. Much evidence supports the prognostic role of hypolipidemia in cirrhotic patients. In particular, hypocholesterolemia represents an independent predictor of survival in cirrhosis. In cirrhotic patients, lipoprotein impairment is associated with several complications: infections, malnutrition, adrenal function, and spur cell anemia. Alterations of liver function are associated with modifications of circulating lipids. Decreased levels of lipoproteins significantly impact the survival of cirrhotic patients and play an important role in the pathogenesis of some cirrhosis-related complications.

Audiophonological results after cochlear implantation in 40 congenitally deaf patients: preliminary results.

PubMed

Loundon, N; Busquet, D; Roger, G; Moatti, L; Garabedian, E N

2000-11-30

The aim of this study is to evaluate the prognostic factors of audiophonological results in cochlear implant in congenitally deaf patients. Between 1991 and 1996. 40 congenitally deaf children underwent cochlear implantation in our department, at an average age of 7 years (median: 5 years). The results of speech therapy were evaluated with a mean follow-up of 2 years and were classified according to four criteria: perception of sound, speech perception, speech production and the level of oral language. For each criterion, a score was established ranging from zero to four. These scores were weighted according to age such that the results before and after implantation only reflected the changes related to the implantation. The prognostic factors for good results were: a good level of oral communication before implantation, residual hearing, progressive deafness and implantation at a young age. On the other hand, poor prognostic factors were: the presence of behavioral disorders and poor communication skills prior to implantation. Overall, the major prognostic factor for a good outcome appeared to be the preoperative level of oral language, even if this was rudimentary.

Proceedings of the Annual Conference of the Prognostics and Health Management Society (PHM 2014) Held in Fort Worth, TX on September 29 - October 2, 2014. Invited Session on Corrosion Monitoring, Sensing, Detection and Prediction

DTIC Science & Technology

2014-12-23

Campbell 225 Using Johnson Distribution for Automatic Threshold Setting in Wind Turbine Condition Monitoring System Kun S. Marhadi and Georgios Alexandros...Victoria M. Catterson, Craig Love, and Andrew Robb 725 Detection of Wind Turbine Power Performance Abnormalities Using Eigenvalue Analysis Georgios...instance, in wind turbine gearbox analysis (Zappalà et al., 2012). Various other techniques for frequency domain analysis have been explored for

Validation of a Molecular and Pathological Model for Five-Year Mortality Risk in Patients with Early Stage Lung Adenocarcinoma

PubMed Central

Bueno, Raphael; Hughes, Elisha; Wagner, Susanne; Gutin, Alexander S.; Lanchbury, Jerry S.; Zheng, Yifan; Archer, Michael A.; Gustafson, Corinne; Jones, Joshua T.; Rushton, Kristen; Saam, Jennifer; Kim, Edward; Barberis, Massimo; Wistuba, Ignacio; Wenstrup, Richard J.; Wallace, William A.; Harrison, David J.

2015-01-01

Introduction: The aim of this study was to validate a molecular expression signature [cell cycle progression (CCP) score] that identifies patients with a higher risk of cancer-related death after surgical resection of early stage (I-II) lung adenocarcinoma in a large patient cohort and evaluate the effectiveness of combining CCP score and pathological stage for predicting lung cancer mortality. Methods: Formalin-fixed paraffin-embedded surgical tumor samples from 650 patients diagnosed with stage I and II adenocarcinoma who underwent definitive surgical treatment without adjuvant chemotherapy were analyzed for 31 proliferation genes by quantitative real-time polymerase chain reaction. The prognostic discrimination of the expression score was assessed by Cox proportional hazards analysis using 5-year lung cancer-specific death as primary outcome. Results: The CCP score was a significant predictor of lung cancer-specific mortality above clinical covariates [hazard ratio (HR) = 1.46 per interquartile range (95% confidence interval = 1.12–1.90; p = 0.0050)]. The prognostic score, a combination of CCP score and pathological stage, was a more significant indicator of lung cancer mortality risk than pathological stage in the full cohort (HR = 2.01; p = 2.8 × 10−11) and in stage I patients (HR = 1.67; p = 0.00027). Using the 85th percentile of the prognostic score as a threshold, there was a significant difference in lung cancer survival between low-risk and high-risk patient groups (p = 3.8 × 10−7). Conclusions: This study validates the CCP score and the prognostic score as independent predictors of lung cancer death in patients with early stage lung adenocarcinoma treated with surgery alone. Patients with resected stage I lung adenocarcinoma and a high prognostic score may be candidates for adjuvant therapy to reduce cancer-related mortality. PMID:25396679

Prophylactic Level VII Nodal Dissection as a Prognostic Factor in Papillary Thyroid Carcinoma: a Pilot Study of 27 Patients.

PubMed

Fayek, Ihab Samy

2015-01-01

Prognostic value of prophylactic level VII nodal dissection in papillary thyroid carcinoma has been highlighted. A total of 27 patients with papillary thyroid carcinoma with N0 neck underwent total thyroidectomy with level VI and VII nodal dissection through same collar neck incision. Multicentricity, bilaterality, extrathyroidal extension, level VI and VII lymph nodes were studied as separate and independent prognostic factors for DFS at 24 months. 21 females and 6 males with a mean age of 34.6 years old, tumor size was 5-24 mm. (mean 12.4 mm.), multicentricity in 11 patients 2-4 foci (mean 2.7), bilaterality in 8 patients and extrathyroidal extension in 8 patients. Dissected level VI LNs 2-8 (mean 5 LNs) and level VII LNs 1-4 (mean 1.9). Metastatic level VI LNs 0-3 (mean 1) and level VII LNs 0-2 (mean 0.5). Follow-up from 6-51 months (mean 25.6) with 7 patients showed recurrence (3 local and 4 distant). Cumulative DFS at 24 months was 87.8% and was significantly affected in relation to bilaterality (p-value<0.001), extrathyroidal extension (p-value<0.001), level VI positive ((p-value<0.001) and level VII positive ((p-value<0.001) LNs. No recurrences were detected during the follow-up period in the absence of level VI and level VII nodal involvement. Level VII prophylactic nodal dissection is an important and integral prognostic factor in papillary thyroid carcinoma. A larger multicenter study is crucial to reach a satisfactory conclusion about the necessity and safety of this approach.

Identifying prognostic signature in ovarian cancer using DirGenerank

PubMed Central

Wang, Jian-Yong; Chen, Ling-Ling; Zhou, Xiong-Hui

2017-01-01

Identifying the prognostic genes in cancer is essential not only for the treatment of cancer patients, but also for drug discovery. However, it's still a big challenge to select the prognostic genes that can distinguish the risk of cancer patients across various data sets because of tumor heterogeneity. In this situation, the selected genes whose expression levels are statistically related to prognostic risks may be passengers. In this paper, based on gene expression data and prognostic data of ovarian cancer patients, we used conditional mutual information to construct gene dependency network in which the nodes (genes) with more out-degrees have more chances to be the modulators of cancer prognosis. After that, we proposed DirGenerank (Generank in direct netowrk) algorithm, which concerns both the gene dependency network and genes’ correlations to prognostic risks, to identify the gene signature that can predict the prognostic risks of ovarian cancer patients. Using ovarian cancer data set from TCGA (The Cancer Genome Atlas) as training data set, 40 genes with the highest importance were selected as prognostic signature. Survival analysis of these patients divided by the prognostic signature in testing data set and four independent data sets showed the signature can distinguish the prognostic risks of cancer patients significantly. Enrichment analysis of the signature with curated cancer genes and the drugs selected by CMAP showed the genes in the signature may be drug targets for therapy. In summary, we have proposed a useful pipeline to identify prognostic genes of cancer patients. PMID:28615526

Expression of the cytoskeleton regulatory protein Mena in human gastric carcinoma and its prognostic significance

PubMed Central

Xu, Lihua; Tan, Huo; Liu, Ruiming; Huang, Qungai; Zhang, Nana; Li, Xi; Wang, Jiani

2017-01-01

The cytoskeleton regulatory protein Mena is reportedly overexpressed in breast cancer; however, data regarding its expression level and clinical significance in gastric carcinoma (GC) is limited. The aim of the present study was to investigate Mena expression levels and prognostic significance in GC. Mena mRNA expression level was determined by reverse transcription-quantitative polymerase chain reaction in 10 paired GC and adjacent normal tissues. The Mena protein expression level was analyzed in paraffin-embedded GC samples and adjacent normal tissues by immunohistochemistry. Statistical analyses were also performed to evaluate the clinicopathological significance of Mena. The results revealed that the mRNA expression level of Mena was significantly higher in G Ct issues compared with in adjacent normal tissues from10 paired samples. In the paraffin-embedded tissue samples, the protein expression level of Mena was higher in G Ct issues compared with in adjacent normal tissues. Compared with adjacent normal tissues, Mena overexpression was observed in 52.83% (56/106) of patients. The overexpression of Mena was significantly associated with the T stage (P=0.033), tumor-node-metastasis (TNM) stage (P<0.001) and decreased overall survival (P<0.001). Based on a multivariate analysis, Mena expression level was an independent prognostic factor for overall survival time. In conclusion, Mena wasoverexpressed in G C tissues and significantly associated with the T stage, TNM stage and overall survival time. Mena may therefore be suitable as a prognostic indicator for patients with GC. PMID:29113241

Expression of the cytoskeleton regulatory protein Mena in human gastric carcinoma and its prognostic significance.

PubMed

Xu, Lihua; Tan, Huo; Liu, Ruiming; Huang, Qungai; Zhang, Nana; Li, Xi; Wang, Jiani

2017-11-01

The cytoskeleton regulatory protein Mena is reportedly overexpressed in breast cancer; however, data regarding its expression level and clinical significance in gastric carcinoma (GC) is limited. The aim of the present study was to investigate Mena expression levels and prognostic significance in GC. Mena mRNA expression level was determined by reverse transcription-quantitative polymerase chain reaction in 10 paired GC and adjacent normal tissues. The Mena protein expression level was analyzed in paraffin-embedded GC samples and adjacent normal tissues by immunohistochemistry. Statistical analyses were also performed to evaluate the clinicopathological significance of Mena. The results revealed that the mRNA expression level of Mena was significantly higher in G Ct issues compared with in adjacent normal tissues from10 paired samples. In the paraffin-embedded tissue samples, the protein expression level of Mena was higher in G Ct issues compared with in adjacent normal tissues. Compared with adjacent normal tissues, Mena overexpression was observed in 52.83% (56/106) of patients. The overexpression of Mena was significantly associated with the T stage (P=0.033), tumor-node-metastasis (TNM) stage (P<0.001) and decreased overall survival (P<0.001). Based on a multivariate analysis, Mena expression level was an independent prognostic factor for overall survival time. In conclusion, Mena wasoverexpressed in G C tissues and significantly associated with the T stage, TNM stage and overall survival time. Mena may therefore be suitable as a prognostic indicator for patients with GC.

Prognostic value of serum phosphate level in adult patients resuscitated from cardiac arrest.

PubMed

Jung, Yong Hun; Lee, Byung Kook; Jeung, Kyung Woon; Youn, Chun Song; Lee, Dong Hun; Lee, Sung Min; Heo, Tag; Min, Yong Il

2018-07-01

Several studies have reported increased levels of phosphate after cardiac arrest. Given the relationship between phosphate level and the severity of ischaemic injury reported in previous studies, higher phosphate levels may be associated with worse outcomes. We investigated the prognostic value of phosphate level after the restoration of spontaneous circulation (ROSC) in adult cardiac arrest patients. This study was a retrospective observational study including adult cardiac arrest survivors treated at the Chonnam National University Hospital between January 2014 and June 2017. From medical records, data regarding clinical characteristics, outcome at hospital discharge, and laboratory parameters including phosphate levels after ROSC were collected. The primary outcome was poor outcome at hospital discharge, defined as Cerebral Performance Categories 3-5. Of the 674 included patients, 465 had poor outcome at hospital discharge. Serum phosphate level was significantly higher in patients with poor outcome than in those with good outcome (p < 0.001). Phosphate level was correlated with time to ROSC (r = 0.350, p < 0.001). Receiver operating characteristic curve analysis revealed an area under the curve of 0.805 (95% confidence interval [CI], 0.777-0.838) for phosphate level. In multivariate analysis, a higher phosphate level was independently associated with poor outcome at hospital discharge (odds ratio, 1.432; 95% CI, 1.245-1.626; p < 0.001). A higher phosphate level after ROSC was independently associated with poor outcome at hospital discharge in adult cardiac arrest patients. However, given its modest prognostic performance, phosphate level should be used in combination with other prognostic indicators. Copyright © 2018 Elsevier B.V. All rights reserved.

Serum miR-300 as a diagnostic and prognostic biomarker in osteosarcoma.

PubMed

Liu, Jian-Dong; Xin, Qun; Tao, Chun-Sheng; Sun, Pei-Feng; Xu, Peng; Wu, Bing; Qu, Liang; Li, Shu-Zhong

2016-11-01

In order to determine whether microRNA (miR)-300 is a diagnostic and prognostic biomarker in osteosarcoma, the miR-300 levels in serum of 114 osteosarcoma patients and 114 healthy controls were compared, followed by serum analysis of the differences between the pre-operative and post-operative sera of these osteosarcoma patients. It was observed that the concentration levels of miR-300 in the serum of osteosarcoma patients was significantly higher than those in the serum of healthy controls (P<0.01). Furthermore, the concentration levels of miR-300 in the post-operative serum were significantly reduced when compared with the pre-operative serum levels (P<0.001). High miR-300 levels in serum correlated significantly with clinical stage, distant metastasis and poor survival of osteosarcoma patients. Notably, serum miR-300 was an independent prognostic marker for osteosarcoma. In conclusion, our results suggested that serum miR-300 may be a potential and useful noninvasive biomarker for the early detection of osteosarcoma.

Serum miR-300 as a diagnostic and prognostic biomarker in osteosarcoma

PubMed Central

Liu, Jian-Dong; Xin, Qun; Tao, Chun-Sheng; Sun, Pei-Feng; Xu, Peng; Wu, Bing; Qu, Liang; Li, Shu-Zhong

2016-01-01

In order to determine whether microRNA (miR)-300 is a diagnostic and prognostic biomarker in osteosarcoma, the miR-300 levels in serum of 114 osteosarcoma patients and 114 healthy controls were compared, followed by serum analysis of the differences between the pre-operative and post-operative sera of these osteosarcoma patients. It was observed that the concentration levels of miR-300 in the serum of osteosarcoma patients was significantly higher than those in the serum of healthy controls (P<0.01). Furthermore, the concentration levels of miR-300 in the post-operative serum were significantly reduced when compared with the pre-operative serum levels (P<0.001). High miR-300 levels in serum correlated significantly with clinical stage, distant metastasis and poor survival of osteosarcoma patients. Notably, serum miR-300 was an independent prognostic marker for osteosarcoma. In conclusion, our results suggested that serum miR-300 may be a potential and useful noninvasive biomarker for the early detection of osteosarcoma. PMID:27895748

Prognostic relevance of motor talent predictors in early adolescence: A group- and individual-based evaluation considering different levels of achievement in youth football.

PubMed

Höner, Oliver; Votteler, Andreas

2016-12-01

In the debate about the usefulness of motor diagnostics in the talent identification process, the prognostic validity for tests conducted in early adolescence is of critical interest. Using a group- and individual-based statistical approach, this prospective cohort study evaluated a nationwide assessment of speed abilities and technical skills regarding its relevance for future achievement levels. The sample consisted of 22,843 U12-players belonging to the top 4% in German football. The U12-results in five tests served as predictors for players' selection levels in U16-U19 (youth national team, regional association, youth academy, not selected). Group-mean differences proved the prognostic relevance for all predictors. Low individual selection probabilities demonstrated limited predictive values, while excellent test results proved their particular prognostic relevance. Players scoring percentile ranks (PRs) ≥ 99 had a 12 times higher chance to become youth national team players than players scoring PR < 99. Simulating increasing score cut-off values not only enhanced specificity (correctly identified non-talents) but also led to lower sensitivity (loss of talents). Extending the current research, these different approaches revealed the ambiguity of the diagnostics' prognostic relevance, representing both the usefulness and several pitfalls of nationwide diagnostics. Therefore, the present diagnostics can support but not substitute for coaches' subjective decisions for talent identification, and multidisciplinary designs are required.

Problems of Pedagogical Creativity Development

ERIC Educational Resources Information Center

Ibragimkyzy, Shynar; Slambekova, Tolkyn S.; Saylaubay, Yerlan E.; Albytova, Nazymgul

2016-01-01

This article provides analysis of research papers by different scholars, dedicated to topical issues of pedagogical creativity development in the educational process. The authors determined that pedagogical creativity could be considered at five levels: information-reproducing, adaptive-prognostic, innovative, research and creative-prognostic. In…

Brachial-to-ankle pulse wave velocity as an independent prognostic factor for ovulatory response to clomiphene citrate in women with polycystic ovary syndrome

PubMed Central

2014-01-01

Background Polycystic ovary syndrome (PCOS) has a risk for cardiovascular disease. Increased arterial stiffness has been observed in women with PCOS. The purpose of the present study was to investigate whether the brachial-to-ankle pulse wave velocity (baPWV) is a prognostic factor for ovulatory response to clomiphene citrate (CC) in women with PCOS. Methods This study was a retrospective cohort study of 62 women with PCOS conducted from January 2009 to December 2012 at the university hospital, Yamagata, Japan. We analyzed 62 infertile PCOS patients who received CC. Ovulation was induced by 100 mg CC for 5 days. CC non-responder was defined as failure to ovulate for at least 2 consecutive CC-treatment cycles. The endocrine, metabolic, and cardiovascular parameters between CC responder (38 patients) and non-responder (24 patients) groups were analyzed. Results In univariate analysis, waist-to-hip ratio, level of free testosterone, percentages of patients with dyslipidemia, impaired glucose tolerance, and diabetes mellitus, blood glucose and insulin levels at 60 min and 120 min, the area under the curve of glucose and insulin after 75-g oral glucose intolerance test, and baPWV were significantly higher in CC non-responders compared with responders. In multivariate logistic regression analysis, both waist-to-hip ratio (odds ratio, 1.77; 95% confidence interval, 2.2–14.1; P = 0.04) and baPWV (odds ratio, 1.71; 95% confidence interval, 1.1–2.8; P = 0.03) were independent predictors of ovulation induction by CC in PCOS patients. The predictive values of waist-to-hip ratio and baPWV for the CC resistance in PCOS patients were determined by the receiver operating characteristic curves. The area under the curves for waist-to-hip ratio and baPWV were 0.76 and 0.77, respectively. Setting the threshold at 0.83 for waist-to-hip ratio offered the best compromise between specificity (0.65) and sensitivity (0.84), while the setting the threshold at 1,182 cm/s for baPWV offered the best compromise between specificity (0.80) and sensitivity (0.71). Conclusions Both metabolic and cardiovascular parameters were predictive for CC resistance in PCOS patients. The measurement of baPWV may be a useful tool to predict ovulation in PCOS patients who receive CC. PMID:25024746

Functional Capacity, Health Status and Inflammatory Biomarker Profile in a Cohort of Patients with COPD

PubMed Central

Kohli, Puja; Pinto-Plata, Victor; Divo, Miguel; Malhotra, Atul; Harris, Scott; Lazaar, Aili; Flynn, Aiden; Tal-Singer, Ruth; Panettieri, Reynold A.; Celli, Bartolome

2015-01-01

Purpose Prior research has shown a significant relationship between six minute walking distances (6MWD) and health related quality of life (HRQL) in patients with chronic obstructive pulmonary disease (COPD). However, few have examined this relationship above and below the 350 meters (m) threshold that prognosticates survival. We further investigated whether serum biomarkers could provide insight into the causes of quality of life differences above and below this threshold. Methods Measures of lung function, 6MWD, HRQL (SGRQ and SF-36) were compared in patients with COPD. Differences in HRQL domains and serum biomarkers were compared in patients whose 6MWD were > or < 350m. Results In patients walking <350m, scores in the physical domains of the SF-36 and SGRQ were significantly different than their counterparts with greater 6MWD. However, there was no association between any biomarkers and the physical domains of the SF-36 and the SGRQ. In patients walking <350m, only the Il-8 levels were associated with lower scores in SF-36 domains of emotional role, pain, vitality and mental health (average r=−0.702, p=0.01). In contrast, in patients walking >350m, surfactant protein D (SP-D) levels were associated with higher SF-36 scores in general pain, vitality and social functioning (average r = 0.42, p=0.04). Conclusions In COPD, there is an association between 6MWD and the physical domains of the SF-36 and SGRQ in those patients walking < 350m. The physical differences between patients walking less or more than 350m are not related to systemic inflammation. The association between IL-8 with nonphysical domains in patients with 6MWD < 350m suggests that inflammation may play a larger role in the perceptive domain than previously recognized. PMID:26309192

Clinical Prediction Models for Patients With Nontraumatic Knee Pain in Primary Care: A Systematic Review and Internal Validation Study.

PubMed

Panken, Guus; Verhagen, Arianne P; Terwee, Caroline B; Heymans, Martijn W

2017-08-01

Study Design Systematic review and validation study. Background Many prognostic models of knee pain outcomes have been developed for use in primary care. Variability among published studies with regard to patient population, outcome measures, and relevant prognostic factors hampers the generalizability and implementation of these models. Objectives To summarize existing prognostic models in patients with knee pain in a primary care setting and to develop and internally validate new summary prognostic models. Methods After a sensitive search strategy, 2 reviewers independently selected prognostic models for patients with nontraumatic knee pain and assessed the methodological quality of the included studies. All predictors of the included studies were evaluated, summarized, and classified. The predictors assessed in multiple studies of sufficient quality are presented in this review. Using data from the Musculoskeletal System Study (BAS) cohort of patients with a new episode of knee pain, recruited consecutively by Dutch general medical practitioners (n = 372), we used predictors with a strong level of evidence to develop new prognostic models for each outcome measure and internally validated these models. Results Sixteen studies were eligible for inclusion. We considered 11 studies to be of sufficient quality. None of these studies validated their models. Five predictors with strong evidence were related to function and 6 to recovery, and were used to compose 2 prognostic models for patients with knee pain at 1 year. Running these new models in another data set showed explained variances (R 2 ) of 0.36 (function) and 0.33 (recovery). The area under the curve of the recovery model was 0.79. After internal validation, the adjusted R 2 values of the models were 0.30 (function) and 0.20 (recovery), and the area under the curve was 0.73. Conclusion We developed 2 valid prognostic models for function and recovery for patients with nontraumatic knee pain, based on predictors with strong evidence. A longer duration of complaints predicted poorer function but did not adequately predict chance of recovery. Level of Evidence Prognosis, levels 1a and 1b. J Orthop Sports Phys Ther 2017;47(8):518-529. Epub 16 Jun 2017. doi:10.2519/jospt.2017.7142.

Prognostic Significance of Human Apurinic/Apyrimidinic Endonuclease (APE/Ref-1) Expression in Rectal Cancer Treated With Preoperative Radiochemotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Jun-Sang, E-mail: k423j@cnu.ac.kr; Cancer Research Institute, Chungnam National University, Daejeon; Kim, Jin-Man

Purpose: Human apurinic endonuclease/redox factor 1 (APE/Ref-1) mediates repair of radiation-induced DNA lesions and regulates transcription via redox-based activation. We investigated the predictive and prognostic significance of APE/Ref-1 expression in pretreatment biopsy specimens in locally advanced rectal cancer (LARC) (cT3-T4 or N+). Methods and Materials: APE/Ref-1 expression was analyzed by immunohistochemistry in pretreatment biopsy specimens obtained from 83 patients with LARC. Patients received preoperative radiotherapy of 50.4 Gy in 28 fractions, combined with oral capecitabine and leucovorin chemotherapy, followed by curative surgery. The prognostic significance of various clinicopathologic characteristics, including APE/Ref-1 protein expression, was evaluated. Results: APE/Ref-1 was expressed inmore » 97% of patient samples. Exclusive APE/Ref-1 nuclear staining was observed in 49 of 83 samples (59%), and mixed nuclear and cytoplasmic staining was observed in 31 samples (37%). APE/Ref-1 nuclear expression levels were low in 49 patients (59%) and high in 34 patients (41%). The level of APE/Ref-1 nuclear expression was not a prognostic factor for overall and disease-free survival. Cytoplasmic expression of APE/Ref-1 was a borderline-significant predictive factor for pathologic tumor response (p = 0.08) and a significant prognostic factor for disease-free survival, as shown by univariate analysis (p = 0.037). Multivariate analysis confirmed that cytoplasmic localization of APE/Ref-1 is a significant predictor of disease-free survival (hazard ratio, 0.45; p = 0.046). Conclusions: APE/Ref-1 was expressed in a majority of pretreatment biopsy specimens from patients with LARC. The level of APE/Ref-1 nuclear expression was not a significant predictive and prognostic factor; however, cytoplasmic localization of the protein was negatively associated with disease-free survival. These results indicate that cytoplasmic expression of APE/Ref-1 represents an adverse prognostic factor for LARC patients who receive preoperative radiochemotherapy.« less

Diagnosis and Prognosis of Weapon Systems

NASA Technical Reports Server (NTRS)

Nolan, Mary; Catania, Rebecca; deMare, Gregory

2005-01-01

The Prognostics Framework is a set of software tools with an open architecture that affords a capability to integrate various prognostic software mechanisms and to provide information for operational and battlefield decision-making and logistical planning pertaining to weapon systems. The Prognostics NASA Tech Briefs, February 2005 17 Framework is also a system-level health -management software system that (1) receives data from performance- monitoring and built-in-test sensors and from other prognostic software and (2) processes the received data to derive a diagnosis and a prognosis for a weapon system. This software relates the diagnostic and prognostic information to the overall health of the system, to the ability of the system to perform specific missions, and to needed maintenance actions and maintenance resources. In the development of the Prognostics Framework, effort was focused primarily on extending previously developed model-based diagnostic-reasoning software to add prognostic reasoning capabilities, including capabilities to perform statistical analyses and to utilize information pertaining to deterioration of parts, failure modes, time sensitivity of measured values, mission criticality, historical data, and trends in measurement data. As thus extended, the software offers an overall health-monitoring capability.

Anisotropy of Solid Breast Lesions in 2D Shear Wave Elastography is an Indicator of Malignancy.

PubMed

Skerl, Katrin; Vinnicombe, Sarah; Thomson, Kim; McLean, Denis; Giannotti, Elisabetta; Evans, Andrew

2016-01-01

To investigate if anisotropy at two-dimensional shear wave elastography (SWE) suggests malignancy and whether it correlates with prognostic and predictive factors in breast cancer. Study group A of 244 solid breast lesions was imaged with SWE between April 2013 and May 2014. Each lesion was imaged in radial and in antiradial planes, and the maximum elasticity, mean elasticity, and standard deviation were recorded and correlated with benign/malignant status, and if malignant, correlated with conventional predictive and prognostic factors. The results were compared to a study group B of 968 solid breast lesions, which were imaged in sagittal and in axial planes between 2010 and 2013. Neither benign nor malignant lesion anisotropy is plane dependent. However, malignant lesions are more anisotropic than benign lesions (P ≤ 0.001). Anisotropy correlates with increasing elasticity parameters, breast imaging-reporting and data system categories, core biopsy result, and tumor grade. Large cancers are significantly more anisotropic than small cancers (P ≤ 0.001). The optimal anisotropy cutoff threshold for benign/malignant differentiation of 150 kPa(2) achieves the best sensitivity (74%) with a reasonable specificity (63%). Anisotropy may be useful during benign/malignant differentiation of solid breast masses using SWE. Anisotropy also correlates with some prognostic factors in breast cancer. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

Gene expression profiling in multiple myeloma--reporting of entities, risk, and targets in clinical routine.

PubMed

Meissner, Tobias; Seckinger, Anja; Rème, Thierry; Hielscher, Thomas; Möhler, Thomas; Neben, Kai; Goldschmidt, Hartmut; Klein, Bernard; Hose, Dirk

2011-12-01

Multiple myeloma is an incurable malignant plasma cell disease characterized by survival ranging from several months to more than 15 years. Assessment of risk and underlying molecular heterogeneity can be excellently done by gene expression profiling (GEP), but its way into clinical routine is hampered by the lack of an appropriate reporting tool and the integration with other prognostic factors into a single "meta" risk stratification. The GEP-report (GEP-R) was built as an open-source software developed in R for gene expression reporting in clinical practice using Affymetrix microarrays. GEP-R processes new samples by applying a documentation-by-value strategy to the raw data to be able to assign thresholds and grouping algorithms defined on a reference cohort of 262 patients with multiple myeloma. Furthermore, we integrated expression-based and conventional prognostic factors within one risk stratification (HM-metascore). The GEP-R comprises (i) quality control, (ii) sample identity control, (iii) biologic classification, (iv) risk stratification, and (v) assessment of target genes. The resulting HM-metascore is defined as the sum over the weighted factors gene expression-based risk-assessment (UAMS-, IFM-score), proliferation, International Staging System (ISS) stage, t(4;14), and expression of prognostic target genes (AURKA, IGF1R) for which clinical grade inhibitors exist. The HM-score delineates three significantly different groups of 13.1%, 72.1%, and 14.7% of patients with a 6-year survival rate of 89.3%, 60.6%, and 18.6%, respectively. GEP reporting allows prospective assessment of risk and target gene expression and integration of current prognostic factors in clinical routine, being customizable about novel parameters or other cancer entities. ©2011 AACR.

Metabolic Tumor Volume as a Prognostic Imaging-Based Biomarker for Head-and-Neck Cancer: Pilot Results From Radiation Therapy Oncology Group Protocol 0522

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schwartz, David L., E-mail: david.schwartz@utsw.edu; Harris, Jonathan; Yao, Min

2015-03-15

Purpose: To evaluate candidate fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) imaging biomarkers for head-and-neck chemoradiotherapy outcomes in the cooperative group trial setting. Methods and Materials: Radiation Therapy Oncology Group (RTOG) protocol 0522 patients consenting to a secondary FDG-PET/CT substudy were serially imaged at baseline and 8 weeks after radiation. Maximum standardized uptake value (SUVmax), SUV peak (mean SUV within a 1-cm sphere centered on SUVmax), and metabolic tumor volume (MTV) using 40% of SUVmax as threshold were obtained from primary tumor and involved nodes. Results: Of 940 patients entered onto RTOG 0522, 74 were analyzable for this substudy. Neither high baselinemore » SUVmax nor SUVpeak from primary or nodal disease were associated with poor treatment outcomes. However, primary tumor MTV above the cohort median was associated with worse local-regional control (hazard ratio 4.01, 95% confidence interval 1.28-12.52, P=.02) and progression-free survival (hazard ratio 2.34, 95% confidence interval 1.02-5.37, P=.05). Although MTV and T stage seemed to correlate (mean MTV 6.4, 13.2, and 26.8 for T2, T3, and T4 tumors, respectively), MTV remained a strong independent prognostic factor for progression-free survival in bivariate analysis that included T stage. Primary MTV remained prognostic in p16-associated oropharyngeal cancer cases, although sample size was limited. Conclusion: High baseline primary tumor MTV was associated with worse treatment outcomes in this limited patient subset of RTOG 0522. Additional confirmatory work will be required to validate primary tumor MTV as a prognostic imaging biomarker for patient stratification in future trials.« less

Levelized cost-benefit analysis of proposed diagnostics for the Ammunition Transfer Arm of the US Army`s Future Armored Resupply Vehicle

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wilkinson, V.K.; Young, J.M.

1995-07-01

The US Army`s Project Manager, Advanced Field Artillery System/Future Armored Resupply Vehicle (PM-AFAS/FARV) is sponsoring the development of technologies that can be applied to the resupply vehicle for the Advanced Field Artillery System. The Engineering Technology Division of the Oak Ridge National Laboratory has proposed adding diagnostics/prognostics systems to four components of the Ammunition Transfer Arm of this vehicle, and a cost-benefit analysis was performed on the diagnostics/prognostics to show the potential savings that may be gained by incorporating these systems onto the vehicle. Possible savings could be in the form of reduced downtime, less unexpected or unnecessary maintenance, fewermore » regular maintenance checks. and/or tower collateral damage or loss. The diagnostics/prognostics systems are used to (1) help determine component problems, (2) determine the condition of the components, and (3) estimate the remaining life of the monitored components. The four components on the arm that are targeted for diagnostics/prognostics are (1) the electromechanical brakes, (2) the linear actuators, (3) the wheel/roller bearings, and (4) the conveyor drive system. These would be monitored using electrical signature analysis, vibration analysis, or a combination of both. Annual failure rates for the four components were obtained along with specifications for vehicle costs, crews, number of missions, etc. Accident scenarios based on component failures were postulated, and event trees for these scenarios were constructed to estimate the annual loss of the resupply vehicle, crew, arm. or mission aborts. A levelized cost-benefit analysis was then performed to examine the costs of such failures, both with and without some level of failure reduction due to the diagnostics/prognostics systems. Any savings resulting from using diagnostics/prognostics were calculated.« less

The predictive value of plasma biomarkers in discharged heart failure patients: role of plasma NT-proBNP.

PubMed

Leto, Laura; Testa, Marzia; Feola, Mauro

2016-04-01

Natriuretic peptides (NPs) have demonstrated their value to support clinical diagnosis of heart failure (HF); furthermore they are also studied for their prognostic role using them to guide appropriate management strategies. The present review gathers available evidence on prognostic role of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients hospitalized for acute decompensated heart failure (ADHF). We searched Medline for English-language studies with the sequent key-words: "acute heart failure/acute decompensated heart failure", "NT-proBNP/N-terminal pro-B type natriuretic peptide" and "prognosis/mortality/readmission". Almost 30 studies were included. NT-proBNP plasma levels at admission are strongly associated with all-cause short-term mortality (2-3 months), mid-term (6-11 months) or long- term mortality (more than one year) of follow-up. Regarding the prognostic power on cardiac death fewer data are available with uncertain results. NT-proBNP at discharge demonstrated its prognostic role for all-cause mortality at mid and long-term follow-up. The relation between NT-proBNP at discharge and cardiovascular mortality or composite end-point is under investigation. A decrease in NT-proBNP values during hospitalization provided prognostic prospects mainly for cardiovascular mortality and HF readmission. A 30% variation in NT-proBNP levels during in-hospital stay seemed to be an optimal cut-off for prognostic role. SNT-proBNP plasma levels proved to have a strong correlation with all-cause mortality, cardiovascular mortality, morbidity and composite outcomes in patients discharged after an ADHF. A better definition of the correct time of serial measurements and the cut-off values might be the challenge for the future investigations.

Association between textural and morphological tumor indices on baseline PET-CT and early metabolic response on interim PET-CT in bulky malignant lymphomas.

PubMed

Ben Bouallègue, Fayçal; Tabaa, Yassine Al; Kafrouni, Marilyne; Cartron, Guillaume; Vauchot, Fabien; Mariano-Goulart, Denis

2017-09-01

We investigated whether metabolic, textural, and morphological tumoral indices evaluated on baseline PET-CT were predictive of early metabolic response on interim PET-CT in a cohort of patients with bulky Hodgkin and non-Hodgkin malignant lymphomas. This retrospective study included 57 patients referred for initial PET-CT examination. In-house dedicated software was used to delineate tumor contours using a fixed 30% threshold of SUV max and then to compute tumoral metabolic parameters (SUV max, mean, peak, standard deviation, skewness and kurtosis, metabolic tumoral volume (MTV), total lesion glycolysis, and area under the curve of the cumulative histogram), textural parameters (Moran's and Geary's indices, energy, entropy, contrast, correlation derived from the gray-level co-occurrence matrix, area under the curve of the power spectral density, auto-correlation distance, and granularity), and shape parameters (surface, asphericity, convexity, surfacic extension, and 2D and 3D fractal dimensions). Early metabolic response was assessed on interim PET-CT using the Deauville 5-point scale and patients were ranked according to the Lugano classification as complete or not complete metabolic responders. The impact of the segmentation method (alternate threshold at 41%) and image resolution (Gaussian postsmoothing of 3, 5, and 7 mm) was investigated. The association of the proposed parameters with early response was assessed in univariate and multivariate analyses. Their added predictive value was explored using supervised classification by support vector machines (SVM). We evaluated in leave-one-out cross-validation three SVMs admitting as input features (a) MTV, (b) MTV + histological type, and (c) MTV + histology + relevant texture/shape indices. Features associated with complete metabolic response were low MTV (P = 0.01), low TLG (P = 0.003), high power spectral density AUC (P = 0.007), high surfacic extension (P = 0.006), low 2D fractal dimension (P = 0.007), and low 3D fractal dimension (P = 0.003). The prognostic value of these metrics was optimal with the 30% segmentation threshold and overall was progressively altered with decreasing image resolution. In cross-validation, the SVM accounting for texture and shape achieved the highest predictive value with ROC AUC of 0.82 and 80% accuracy (compared with 0.68 and 61% for MTV, and 0.65 and 68% for MTV + histology). The combination of usual prognostic factors with appropriately chosen textural and shape parameters evaluated on baseline PET-CT improves the prediction of early metabolic response in bulky lymphoma. © 2017 American Association of Physicists in Medicine.

Defining the Lower Limit of a "Critical Bone Defect" in Open Diaphyseal Tibial Fractures.

PubMed

Haines, Nikkole M; Lack, William D; Seymour, Rachel B; Bosse, Michael J

2016-05-01

To determine healing outcomes of open diaphyseal tibial shaft fractures treated with reamed intramedullary nailing (IMN) with a bone gap of 10-50 mm on ≥50% of the cortical circumference and to better define a "critical bone defect" based on healing outcome. Retrospective cohort study. Forty patients, age 18-65, with open diaphyseal tibial fractures with a bone gap of 10-50 mm on ≥50% of the circumference as measured on standard anteroposterior and lateral postoperative radiographs treated with IMN. IMN of an open diaphyseal tibial fracture with a bone gap. Level-1 trauma center. Healing outcomes, union or nonunion. Forty patients were analyzed. Twenty-one (52.5%) went on to nonunion and nineteen (47.5%) achieved union. Radiographic apparent bone gap (RABG) and infection were the only 2 covariates predicting nonunion outcome (P = 0.046 for infection). The RABG was determined by measuring the bone gap on each cortex and averaging over 4 cortices. Fractures achieving union had a RABG of 12 ± 1 mm versus 20 ± 2 mm in those going on to nonunion (P < 0.01). This remained significant when patients with infection were removed. Receiver operator characteristic analysis demonstrated that RABG was predictive of outcome (area under the curve of 0.79). A RABG of 25 mm was the statistically optimal threshold for prediction of healing outcome. Patients with open diaphyseal tibial fractures treated with IMN and a <25 mm RABG have a reasonable probability of achieving union without additional intervention, whereas those with larger gaps have a higher probability of nonunion. Research investigating interventions for RABGs should use a predictive threshold for defining a critical bone defect that is associated with greater than 50% risk of nonunion without supplementary treatment. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Effect of nutritional status on mortality in patients undergoing coronary artery bypass grafting.

PubMed

Keskin, Muhammed; İpek, Göktük; Aldağ, Mustafa; Altay, Servet; Hayıroğlu, Mert İlker; Börklü, Edibe Betül; İnan, Duygu; Kozan, Ömer

2018-04-01

The prognostic effects of poor nutritional status and cardiac cachexia on coronary artery disease (CAD) are not clearly understood. A well-accepted nutritional status parameter, the prognostic nutritional index (PNI), which was first demonstrated to be valuable in patients with cancer and those undergoing gastrointestinal surgery, was introduced to patients requiring coronary artery bypass grafting (CABG). The aim of the present study was to evaluate the prognostic value of PNI in patients with CAD undergoing CABG. We evaluated the in-hospital and long-term (3-y) prognostic effect of PNI on 644 patients with CAD undergoing CABG. Baseline characteristics and outcomes were compared among the patients by PNI and categorized accordingly: Q1, Q2, Q3, and Q4. Patients with lower PNI had significantly higher in-hospital and long-term mortality. Patients with lower PNI levels (Q1) had higher in-hospital mortality and had 12 times higher mortality rates than those with higher PNI levels (Q4). The higher PNI group had the lower rates and was used as the reference. Long-term mortality was higher in patients with lower PNI (Q1)-4.9 times higher than in the higher PNI group (Q4). In-hospital and long-term mortality rates were similar in the non-lower PNI groups (Q2-4). The present study demonstrated that PNI, calculated based on serum albumin level and lymphocyte count, is an independent prognostic factor for mortality in patients undergoing CABG. Copyright © 2017 Elsevier Inc. All rights reserved.

Prognostic Impact of Visceral Fat Amount and Branched-Chain Amino Acids (BCAA) in Hepatocellular Carcinoma.

PubMed

Higashi, Takaaki; Hayashi, Hiromitsu; Kaida, Takayoshi; Arima, Kota; Takeyama, Hideaki; Taki, Katsunobu; Izumi, Daisuke; Tokunaga, Ryuma; Kosumi, Keisuke; Nakagawa, Shigeki; Okabe, Hirohisa; Imai, Katsunobu; Nitta, Hidetoshi; Hashimoto, Daisuke; Chikamoto, Akira; Beppu, Toru; Baba, Hideo

2015-12-01

Dysregulation of lipid and amino acid metabolism in patients with liver diseases results in obesity-related carcinogenesis and decreased levels of branched-chain amino acids (BCAA), respectively. This study assessed the clinical and prognostic impact of visceral fat amount (VFA) and its association with amino acid metabolism in patients with hepatocellular carcinoma (HCC). In this study, 215 patients who underwent hepatic resection for HCC were divided into two groups based on VFA criteria for metabolic abnormalities in Japan. Computed tomography was used to measure VFA at the third lumbar vertebra in the inferior direction. Of the 215 patients, 132 had high and 83 had low VFA. High VFA was significantly associated with older age and higher body mass index (BMI), subcutaneous fat amount, and BCAA, but not with liver function, nutrient status, or tumoral factors. VFA was positively correlated with BMI (P < 0.0001; r = 0.63) and BCAA levels (P < 0.0001; r = 0.29). Overall survival was significantly greater in the high than in the low VFA group (P = 0.002). Multivariate analyses showed that high VFA [hazard ratio (HR) 7.06; P = 0.024] and neutrophil/lymphocyte ratio (HR 3.47; P = 0.049) were significantly prognostic of overall survival, whereas subcutaneous fat amount, BMI, BCAA, serum albumin, and prognostic nutritional index were not. High VFA was associated with a high BCAA level, with high VFA prognostic of improved overall survival in Japanese patients with HCC.

Circulating metastasis associated in colon cancer 1 transcripts in gastric cancer patient plasma as diagnostic and prognostic biomarker

PubMed Central

Burock, Susen; Herrmann, Pia; Wendler, Ina; Niederstrasser, Markus; Wernecke, Klaus-Dieter; Stein, Ulrike

2015-01-01

AIM: To evaluate the diagnostic and prognostic value of circulating Metastasis Associated in Colon Cancer 1 (MACC1) transcripts in plasma of gastric cancer patients. METHODS: We provide for the first time a blood-based assay for transcript quantification of the metastasis inducer MACC1 in a prospective study of gastric cancer patient plasma. MACC1 is a strong prognostic biomarker for tumor progression and metastasis in a variety of solid cancers. We conducted a study to define the diagnostic and prognostic power of MACC1 transcripts using 76 plasma samples from gastric cancer patients, either newly diagnosed with gastric cancer, newly diagnosed with metachronous metastasis of gastric cancer, as well as follow-up patients. Findings were controlled by using plasma samples from 54 tumor-free volunteers. Plasma was separated, RNA was isolated, and levels of MACC1 as well as S100A4 transcripts were determined by quantitative RT-PCR. RESULTS: Based on the levels of circulating MACC1 transcripts in plasma we significantly discriminated tumor-free volunteers and gastric cancer patients (P < 0.001). Levels of circulating MACC1 transcripts were increased in gastric cancer patients of each disease stage, compared to tumor-free volunteers: patients with tumors without metastasis (P = 0.005), with synchronous metastasis (P = 0.002), with metachronous metastasis (P = 0.005), and patients during follow-up (P = 0.021). Sensitivity was 0.68 (95%CI: 0.45-0.85) and specificity was 0.89 (95%CI: 0.77-0.95), respectively. Importantly, gastric cancer patients with high circulating MACC1 transcript levels in plasma demonstrated significantly shorter survival when compared with patients demonstrating low MACC1 levels (P = 0.0015). Furthermore, gastric cancer patients with high circulating transcript levels of MACC1 as well as of S100A4 in plasma demonstrated significantly shorter survival when compared with patients demonstrating low levels of both biomarkers or with only one biomarker elevated (P = 0.001). CONCLUSION: Levels of circulating MACC1 transcripts in plasma of gastric cancer patients are of diagnostic value and are prognostic for patient survival in a prospective study. PMID:25574109

Relationship between plasma levels of cardiac natriuretic peptides and soluble Fas: plasma soluble Fas as a prognostic predictor in patients with congestive heart failure.

PubMed

Tsutamoto, T; Wada, A; Maeda, K; Mabuchi, N; Hayashi, M; Tsutsui, T; Ohnishi, M; Fujii, M; Matsumoto, T; Yamamoto, T; Takayama, T; Kinoshita, M

2001-12-01

Cardiac natriuretic peptides may induce apoptosis in myocytes; however, the relationship between plasma levels of cardiac natriuretic peptides and those of soluble Fas (sFas) and tumor necrosis factor (TNF)-alpha remains unknown in patients with congestive heart failure (CHF). We measured plasma levels of sFas and TNF-alpha and those of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), norepinephrine, and endothelin 1 in 96 patients with CHF (ejection fraction < 45%). The patients were monitored for 3 years. Plasma levels of sFas and TNF-alpha increased with the severity of CHF. There was no significant correlation between sFas plasma levels and those of ANP and BNP. Cox proportional hazard analysis showed that high levels of sFas (P = .009) and BNP (P < .0001) and a low ejection fraction (P = .019) were independent significant prognostic predictors. There is no significant correlation between cardiac natriuretic peptide and sFas levels in plasma. Plasma sFas is a useful prognostic marker independent of neurohumoral factors, suggesting that immune activation and/or apoptosis play a significant role in the pathogenesis of CHF.

Prognostic role of ABO blood type in patients with extranodal natural killer/T cell lymphoma, nasal type: a triple-center study.

PubMed

Li, Ya-Jun; Yi, Ping-Yong; Li, Ji-Wei; Liu, Xian-Ling; Tang, Tian; Zhang, Pei-Ying; Jiang, Wen-Qi

2017-07-31

The prognostic significance of ABO blood type for lymphoma is largely unknown. We evaluated the prognostic role of ABO blood type in patients with extranodal natural killer (NK)/T-cell lymphoma (ENKTL). We retrospectively analyzed clinical data of 697 patients with newly diagnosed ENKTL from three cancer centers. The prognostic value of ABO blood type was evaluated using Kaplan-Meier curves and Cox proportional hazard models. The prognostic values of the International Prognostic Index (IPI) and the Korean Prognostic Index (KPI) were also evaluated. Compared with patients with blood type O, those with blood type non-O tended to display elevated baseline serum C-reactive protein levels (P = 0.038), lower rate of complete remission (P = 0.005), shorter progression-free survival (PFS, P < 0.001), and shorter overall survival (OS, P = 0.001). Patients with blood type O/AB had longer PFS (P < 0.001) and OS (P = 0.001) compared with those with blood type A/B. Multivariate analysis demonstrated that age >60 years (P < 0.001), mass ≥5 cm (P = 0.001), stage III/IV (P < 0.001), elevated serum lactate dehydrogenase (LDH) levels (P = 0.001), and blood type non-O were independent adverse predictors of OS (P = 0.001). ABO blood type was found to be superior to both the IPI in discriminating patients with different outcomes in the IPI low-risk group and the KPI in distinguishing between the intermediate-to-low- and high-to-intermediate-risk groups. ABO blood type was an independent predictor of clinical outcome for patients with ENKTL.

Communicating prognostic uncertainty in potential end-of-life contexts: experiences of family members.

PubMed

Krawczyk, Marian; Gallagher, Romayne

2016-07-12

This article reports on the concept of "communicating prognostic uncertainty" which emerged from a mixed methods survey asking family members to rank their satisfaction in seven domains of hospital end-of-life care. Open-ended questions were embedded within a previously validated survey asking family members about satisfaction with end-of-life care. The purpose was to understand, in the participants' own words, the connection between their numerical rankings of satisfaction and the experience of care. Our study found that nearly half of all family members wanted more information about possible outcomes of care, including knowledge that the patient was "sick enough to die". Prognostic uncertainty was often poorly communicated, if at all. Inappropriate techniques included information being cloaked in confusing euphemisms, providing unwanted false hope, and incongruence between message and the aggressive level of care being provided. In extreme cases, these techniques left a legacy of uncertainty and suspicion. Family members expressed an awareness of both the challenges and benefits of communicating prognostic uncertainty. Most importantly, respondents who acknowledged that they would have resisted (or did) knowing that the patient was sick enough to die also expressed a retrospective understanding that they would have liked, and benefitted, from more prognostic information that death was a possible or probable outcome of the patient's admission. Family members who reported discussion of prognostic uncertainty also reported high levels of effective communication and satisfaction with care. They also reported long-term benefits of knowing the patient was sick enough to die. While a patient who is sick enough to die may survive to discharge, foretelling with family members in potential end of life contexts facilitates the development of a shared and desired prognostic awareness that the patient is nearing end of life.

External validation of a Cox prognostic model: principles and methods

PubMed Central

2013-01-01

Background A prognostic model should not enter clinical practice unless it has been demonstrated that it performs a useful role. External validation denotes evaluation of model performance in a sample independent of that used to develop the model. Unlike for logistic regression models, external validation of Cox models is sparsely treated in the literature. Successful validation of a model means achieving satisfactory discrimination and calibration (prediction accuracy) in the validation sample. Validating Cox models is not straightforward because event probabilities are estimated relative to an unspecified baseline function. Methods We describe statistical approaches to external validation of a published Cox model according to the level of published information, specifically (1) the prognostic index only, (2) the prognostic index together with Kaplan-Meier curves for risk groups, and (3) the first two plus the baseline survival curve (the estimated survival function at the mean prognostic index across the sample). The most challenging task, requiring level 3 information, is assessing calibration, for which we suggest a method of approximating the baseline survival function. Results We apply the methods to two comparable datasets in primary breast cancer, treating one as derivation and the other as validation sample. Results are presented for discrimination and calibration. We demonstrate plots of survival probabilities that can assist model evaluation. Conclusions Our validation methods are applicable to a wide range of prognostic studies and provide researchers with a toolkit for external validation of a published Cox model. PMID:23496923

The BAX/BAK-like protein BOK is a prognostic marker in colorectal cancer.

PubMed

Carberry, Steven; D'Orsi, Beatrice; Monsefi, Naser; Salvucci, Manuela; Bacon, Orna; Fay, Joanna; Rehm, Markus; McNamara, Deborah; Kay, Elaine W; Prehn, Jochen H M

2018-01-26

The intrinsic or mitochondrial apoptosis pathway is controlled by the interaction of antiapoptotic and pro-apoptotic members of the BCL-2 protein family. Activation of this death pathway plays a crucial role in cancer progression and chemotherapy responses. The BCL-2-related ovarian killer (BOK) possesses three BCL-2 homology domains and has been proposed to act in a similar pro-apoptotic pathway as the pro-apoptotic proteins BAX and BAK. In this study, we showed that stage II and III colorectal cancer patients possessed decreased levels of BOK protein in their tumours compared to matched normal tissue. BOK protein levels in tumours were also prognostic of clinical outcome but increased BOK protein levels surprisingly associated with earlier disease recurrence and reduced overall survival. We found no significant association of BOK protein tumour levels with ER stress markers GRP78 or GRP94 or with cleaved caspase-3. In contrast, BOK protein levels correlated with Calreticulin. These data indicate BOK as a prognostic marker in colorectal cancer and suggest that different activities of BOK may contribute to cancer progression and prognosis.

Prognostic significance of preoperative metabolic tumour volume and total lesion glycolysis measured by (18)F-FDG PET/CT in squamous cell carcinoma of the oral cavity.

PubMed

Ryu, In Sun; Kim, Jae Seung; Roh, Jong-Lyel; Cho, Kyung-Ja; Choi, Seung-Ho; Nam, Soon Yuhl; Kim, Sang Yoon

2014-03-01

Metabolic tumour volume (MTV) and total lesion glycolysis (TLG) from (18)F-FDG PET/CT are emerging prognostic biomarkers in human solid cancers; yet few studies have investigated their clinical and prognostic significance in oral cavity squamous cell carcinoma (OSCC). The present retrospective study evaluated the utility of pretreatment MTV and TLG measured by (18)F-FDG PET/CT to predict survival and occult metastasis (OM) in OSCC. Of 162 patients with OSCC evaluated preoperatively by (18)F-FDG PET/CT, 105 who underwent definitive surgery with or without adjuvant therapy were eligible. Maximum standardized uptake value (SUVmax), MTV and TLG were measured. For calculation of MTV, 3-D regions of interest were drawn and a SUV threshold of 2.5 was used for defining regions. Univariate and multivariate analyses identified clinicopathological and imaging variables associated with OM, disease-free survival (DFS) and overall survival (OS). The median (range) SUVmax, MTV and TLG were 7.3 (0.7-41.9), 4.5 ml (0.7-115.1 ml) and 18.3 g (2.4-224.1 g), respectively. Of 53 patients with clinically negative lymph nodes, OM was detected in 19 (36%). By univariate and multivariate analyses, MTV (P = 0.018) and TLG (P = 0.011) were both independent predictive factors for OM, although they were not independent of each other. The 4-year DFS and OS rates were 53.0% and 62.0%, respectively. Univariate and multivariate analyses revealed that MTV (P = 0.001) and TLG (P = 0.006), with different cut-off levels, were both independent predictive factors for DFS, although they were not independent of each other, and MTV (P = 0.001), TLG (P = 0.002) and the involved resection margin (P = 0.007) were independent predictive factors for OS. Pretreatment MTV and TLG may be useful in stratifying the likelihood of survival and predicting OM in OSCC.

Plasma Level of Interleukin-35 as an Independent Prognostic Indicator in Hepatocellular Carcinoma.

PubMed

Qiu, Xiangting; Wang, Xinhua; Song, Yucui; Chen, Lingling

2016-12-01

Hepatocellular carcinoma is a major type of liver cancer with poor prognosis. The aim of the study was to determine the prognostic significance of plasma interleukin-35 level in hepatocellular carcinoma. A total of 153 hepatocellular carcinoma patients and 153 healthy controls were enrolled. Blood samples were obtained at admission. Plasma interleukin-35 level was analyzed by enzyme-linked immunosorbent assay. Distribution of T cell subset and expression of Fas/FasL protein were detected by flow cytometry. The patients were followed up for 2 years. Poor prognosis was defined as death of hepatocellular carcinoma. The plasma levels of interleukin-35 were significantly higher in the patients than the controls (25.1 ± 13.1, 9.3 ± 6.3 pg/mL, P < 0.001). After adjusted for multiple confounding factors, the multivariate logistic regression analyses reported that high level of interleukin-35 (≥25.0 pg/mL) was associated with the poor prognosis in the patients (OR 6.63, 95 % CI 3.27-13.47). Compared with the patients with low level of interleukin-35 (<25.0 pg/mL), the patients with high level of interleukin-35 showed higher frequencies of CD4+CD25+FoxP3+ and CD3+Foxp3+ regulatory T cells (P < 0.001 and P < 0.001) and also showed higher apoptosis levels of CD8+ T cells (P < 0.001). Circulating interleukin-35 concentration might be an independent prognostic indicator in hepatocellular carcinoma. Such prognostic significance could be partly involved in the activation of regulatory T cell and the apoptosis of CD8+ T cell.

Individualized cost-effective conventional ovulation induction treatment in normogonadotrophic anovulatory infertility (WHO group 2).

PubMed

Eijkemans, Marinus J C; Polinder, Suzanne; Mulders, Annemarie G M G J; Laven, Joop S E; Habbema, J Dik F; Fauser, Bart C J M

2005-10-01

Conventional treatment in normogonadotrophic anovulatory infertility (WHO 2) consists of clomiphene citrate (CC), followed by exogenous gonadotrophins (FSH) and IVF. Response to these treatments may be predicted on the basis of individual patient characteristics. We aimed to devise a patient-tailored, cost-effective treatment algorithm involving the above-mentioned treatment modalities, based on individual patient characteristics. Sixteen prognostic groups are defined, according to the presence or absence of: age >30 years, amenorrhea, elevated androgen levels and obesity. The chances of response with each of the three treatments were calculated using prediction models. Treatment costs were based on the data of 240 patients visiting a specialist academic fertility unit. Outcome was an ongoing pregnancy within 12 months after initiation of treatment. The costs per pregnancy of three different strategies were compared, with a threshold for cost-effectiveness of 10 000. The strategy CC + FSH + IVF compared with FSH + IVF generated more pregnancies against lower costs. Compared with CC + IVF, it also produced more pregnancies, but at higher costs. For <30 years of age with normal androgen levels, costs per pregnancy were less than 10 000. For women >30 years old, costs per pregnancy were 25 000 and over 200 000, when presenting with normal or elevated androgen levels, respectively. The conventional treatment protocol is efficient for women aged <30 years with normal androgen levels. For women >30 years old with elevated androgen levels, FSH may be skipped.

[Clinical and prognostic significance of preoperative serum CA153, CEA and TPS levels in patients with primary breast cancer].

PubMed

Chen, Yan; Zheng, Yu-hong; Lin, Ying-ying; Hu, Min-hua; Chen, Yan-song

2011-11-01

To investigate the clinical and prognostic values of preoperative serum CA153, CEA and TPS levels in patients with primary breast cancer. A total of 386 hospitalized patients with stage I ∼ IV breast cancer from Nov 1998 to Feb 2009 were followed up, and their clinicopathological data were analyzed retrospectively to determine the factors affecting their prognosis. First, preoperative serum CA153 expression level was significantly associated with the age of onset and tumor size (P < 0.05), the expression of serum CEA was correlated with tumor size (P < 0.05), and the expression of serum tissue polypeptide specific antigen (TPS) was correlated with tumor size and lymph node metastases (P < 0.05). Second, the overall survival was significantly shorter among patients with elevated serum CA153, CEA or TPS, respectively (P < 0.05 for overall). Finally, multivariate Cox regression analysis indicated that estrogen receptor status (ER) and elevated preoperative values of CA 153 are independent prognostic factors for overall survival (P < 0.05), and CA 153 is a risk factor but estrogen receptor status is a protective factor for overall survival. Higher preoperative expression of serum CA153, CEA or TPS is closely correlated with clinicopathological characteristics and overall survival. The prognosis is poorer in primary breast cancer patients with higher CA15-3 expression level, and pre-treatment CA153 expression level can be used as an independent prognostic parameter in patients with primarily breast cancer.

SU-D-9A-02: Relative Effects of Threshold Choice and Spatial Resolution Modeling On SUV and Volume Quantification in F18-FDG PET Imaging of Anal Cancer Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhao, F; Shandong Cancer Hospital and Insititute, Jinan, Shandong; Bowsher, J

2014-06-01

Purpose: PET imaging with F18-FDG is utilized for treatment planning, treatment assessment, and prognosis. A region of interest (ROI) encompassing the tumor may be determined on the PET image, often by a threshold T on the PET standard uptake values (SUVs). Several studies have shown prognostic value for relevant ROI properties including maximum SUV value (SUVmax), metabolic tumor volume (MTV), and total glycolytic activity (TGA). The choice of threshold T may affect mean SUV value (SUVmean), MTV, and TGA. Recently spatial resolution modeling (SRM) has been introduced on many PET systems. SRM may also affect these ROI properties. The purposemore » of this work is to investigate the relative influence of SRM and threshold choice T on SUVmean, MTV, TGA, and SUVmax. Methods: For 9 anal cancer patients, 18F-FDG PET scans were performed prior to treatment. PET images were reconstructed by 2 iterations of Ordered Subsets Expectation Maximization (OSEM), with and without SRM. ROI contours were generated by 5 different SUV threshold values T: 2.5, 3.0, 30%, 40%, and 50% of SUVmax. Paired-samples t tests were used to compare SUVmean, MTV, and TGA (a) for SRM on versus off and (b) between each pair of threshold values T. SUVmax was also compared for SRM on versus off. Results: For almost all (57/60) comparisons of 2 different threshold values, SUVmean, MTV, and TGA showed statistically significant variation. For comparison of SRM on versus off, there were no statistically significant changes in SUVmax and TGA, but there were statistically significant changes in MTV for T=2.5 and T=3.0 and in SUVmean for all T. Conclusion: The near-universal statistical significance of threshold choice T suggests that, regarding harmonization across sites, threshold choice may be a greater concern than choice of SRM. However, broader study is warranted, e.g. other iterations of OSEM should be considered.« less

The long non-coding RNA HOTAIR is transcriptionally activated by HOXA9 and is an independent prognostic marker in patients with malignant glioma

PubMed Central

Xavier-Magalhães, Ana; Gonçalves, Céline S.; Fogli, Anne; Lourenço, Tatiana; Pojo, Marta; Pereira, Bruno; Rocha, Miguel; Lopes, Maria Celeste; Crespo, Inês; Rebelo, Olinda; Tão, Herminio; Lima, João; Moreira, Ricardo; Pinto, Afonso A.; Jones, Chris; Reis, Rui M.; Costello, Joseph F.; Arnaud, Philippe; Sousa, Nuno; Costa, Bruno M.

2018-01-01

The lncRNA HOTAIR has been implicated in several human cancers. Here, we evaluated the molecular alterations and upstream regulatory mechanisms of HOTAIR in glioma, the most common primary brain tumors, and its clinical relevance. HOTAIR gene expression, methylation, copy-number and prognostic value were investigated in human gliomas integrating data from online datasets and our cohorts. High levels of HOTAIR were associated with higher grades of glioma, particularly IDH wild-type cases. Mechanistically, HOTAIR was overexpressed in a gene dosage-independent manner, while DNA methylation levels of particular CpGs in HOTAIR locus were associated with HOTAIR expression levels in GBM clinical specimens and cell lines. Concordantly, the demethylating agent 5-Aza-2′-deoxycytidine affected HOTAIR transcriptional levels in a cell line-dependent manner. Importantly, HOTAIR was frequently co-expressed with HOXA9 in high-grade gliomas from TCGA, Oncomine, and our Portuguese and French datasets. Integrated in silico analyses, chromatin immunoprecipitation, and qPCR data showed that HOXA9 binds directly to the promoter of HOTAIR. Clinically, GBM patients with high HOTAIR expression had a significantly reduced overall survival, independently of other prognostic variables. In summary, this work reveals HOXA9 as a novel direct regulator of HOTAIR, and establishes HOTAIR as an independent prognostic marker, providing new therapeutic opportunities to treat this highly aggressive cancer. PMID:29644006

The Diagnostic and Prognostic Value of Hematological and Chemical Abnormalities in Soft Tissue Sarcoma: A Comparative Study in Patients with Benign and Malignant Soft Tissue Tumors.

PubMed

Ariizumi, Takashi; Kawashima, Hiroyuki; Ogose, Akira; Sasaki, Taro; Hotta, Tetsuo; Hatano, Hiroshi; Morita, Tetsuro; Endo, Naoto

2018-01-01

The value of routine blood tests in malignant soft tissue tumors remains uncertain. To determine if these tests can be used for screening, the routine pretreatment blood test findings were retrospectively investigated in 359 patients with benign and malignant soft tissue tumors. Additionally, the prognostic potential of pretreatment blood abnormalities was evaluated in patients with soft tissue sarcomas. We compared clinical factors and blood tests findings between patients with benign and malignant soft tissue tumors using univariate and multivariate analysis. Subsequently, patients with malignant tumors were divided into two groups based on blood test reference values, and the prognostic significance of each parameter was evaluated. In the univariate analysis, age, tumor size, and tumor depth were significant clinical diagnostic factors. Significant increases in the granulocyte count, C-reactive protein (CRP) level, erythrocyte sedimentation rate (ESR), and γ-glutamyl transpeptidase (γ-GTP) levels were found in patients with malignant soft tissue tumors. Multiple logistic regression showed that tumor size and ESR were independent factors that predicted malignant soft tissue tumors. The Kaplan-Meier survival analysis revealed that granulocyte counts, γ-GTP levels, and CRP levels correlated significantly with overall survival. Thus, pretreatment routine blood tests are useful diagnostic and prognostic markers for diagnosing soft tissue sarcoma. © 2018 by the Association of Clinical Scientists, Inc.

PDGFRA amplification is common in pediatric and adult high-grade astrocytomas and identifies a poor prognostic group in IDH1 mutant glioblastoma

PubMed Central

Phillips, Joanna J.; Aranda, Derick; Ellison, David W.; Judkins, Alexander R.; Croul, Sidney E.; Brat, Daniel J.; Ligon, Keith L.; Horbinski, Craig; Venneti, Sriram; Zadeh, Gelareh; Santi, Mariarita; Zhou, Shengmei; Appin, Christina L.; Sioletic, Stefano; Sullivan, Lisa M.; Martinez-Lage, Maria; Robinson, Aaron E.; Yong, William H.; Cloughesy, Timothy; Lai, Albert; Phillips, Heidi S.; Marshall, Roxanne; Mueller, Sabine; Haas-Kogan, Daphne A.; Molinaro, Annette M.; Perry, Arie

2013-01-01

High-grade astrocytomas (HGAs), corresponding to WHO grades III (AA) and IV (GBM), are biologically aggressive and their molecular classification is increasingly relevant to clinical management. PDGFRA amplification is common in HGAs, although its prognostic significance remains unclear. Using fluorescence in situ hybridization (FISH), the most sensitive technique for detecting PDGFRA copy number gains, we determined PDGFRA amplification status in 123 pediatric and 263 adult HGAs. A range of PDGFRA FISH patterns were identified and cases were scored as non-amplified (normal and polysomy) or amplified (low-level and high-level). PDGFRA amplification was frequent in pediatric (29.3%) and adult (20.9%) tumors. Amplification was not prognostic in pediatric HGAs. In adult tumors diagnosed initially as GBM, the presence of combined PDGFRA amplification and IDH1R132H mutation was a significant independent prognostic factor (p=0.01). In HGAs, PDGFRA amplification is common and can manifest as high-level and focal or low-level amplifications. Our data indicate that the latter is more prevalent than previously reported with copy number averaging techniques. To our knowledge, this is the largest survey of PDGFRA status in adult and pediatric HGAs and suggests PDGFRA amplification increases with grade and is associated with a less favorable prognosis in IDH1 mutant de novo GBMs. PMID:23438035

Prognostic and Clinical Significance of miRNA-205 in Endometrioid Endometrial Cancer.

PubMed

Wilczynski, Milosz; Danielska, Justyna; Dzieniecka, Monika; Szymanska, Bozena; Wojciechowski, Michal; Malinowski, Andrzej

2016-01-01

Endometrial cancer is one of the most common malignancies of the reproductive female tract, with endometrioid endometrial cancer being the most frequent type. Despite the relatively favourable prognosis in cases of endometrial cancer, there is a necessity to evaluate clinical and prognostic utility of new molecular markers. MiRNAs are small, non-coding RNA molecules that take part in RNA silencing and post-transcriptional regulation of gene expression. Altered expression of miRNAs may be associated with cancer initiation, progression and metastatic capabilities. MiRNA-205 seems to be one of the key regulators of gene expression in endometrial cancer. In this study, we investigated clinical and prognostic role of miRNA-205 in endometrioid endometrial cancer. After total RNA extraction from 100 archival formalin-fixed paraffin-embedded tissues, real-time quantitative RT-PCR was used to define miRNA-205 expression levels. The aim of the study was to evaluate miRNA-205 expression levels in regard to patients' clinical and histopathological features, such as: survival rate, recurrence rate, staging, myometrial invasion, grading and lymph nodes involvement. Higher levels of miRNA-205 expression were observed in tumours with less than half of myometrial invasion and non-advanced cancers. Kaplan-Maier analysis revealed that higher levels of miRNA-205 were associated with better overall survival (p = 0,034). These results indicate potential clinical utility of miRNA-205 as a prognostic marker.

High serum uric acid levels are a protective factor against unfavourable neurological functional outcome in patients with ischaemic stroke.

PubMed

Wang, Yu-Fang; Li, Jiao-Xing; Sun, Xun-Sha; Lai, Rong; Sheng, Wen-Li

2018-05-01

Objective We aimed to evaluate the association between serum uric acid levels at the onset and prognostic outcome in patients with acute ischaemic stroke. Methods We retrospectively analysed the outcomes of 1166 patients with ischaemic stroke who were hospitalized in our centre during August 2008 to November 2012. Correlations of serum uric acid levels and prognostic outcomes were analysed. Results Men had higher serum uric acid levels and better neurological functional outcomes compared with women. There was a strong negative correlation between serum uric acid levels and unfavourable neurological functional outcomes. Generalized estimated equation analysis showed that a higher serum uric acid level (>237 µmol/L) was a protective factor for neurological functional outcome in male, but not female, patients. Among five trial of ORG 10172 in acute stroke treatment classification subtypes, only patients with the large-artery atherosclerosis subtype had a significant protective effect of serum uric acid levels on neurological outcome. Conclusions Our study shows that high serum uric acid levels are a significant protective factor in men and in the large-artery atherosclerosis subtype in patients with ischaemic stroke. This is helpful for determining the prognostic value of serum uric acid levels for neurological outcome of acute ischaemic stroke.

Triiodothyronine and brain natriuretic peptide: similar long-term prognostic values for chronic heart failure.

PubMed

Kozdag, Guliz; Ertas, Gokhan; Kilic, Teoman; Acar, Eser; Sahin, Tayfun; Ural, Dilek

2010-01-01

Although low levels of free triiodothyronine and high levels of brain natriuretic peptide have been shown as independent predictors of death in chronic heart failure patients, few studies have compared their prognostic values. The aim of this prospective study was to measure free triiodothyronine and brain natriuretic peptide levels and to compare their prognostic values among such patients.A total of 334 patients (mean age, 62 ± 13 yr; 218 men) with ischemic and nonischemic dilated cardiomyopathy were included in the study. The primary endpoint was a major cardiac event.During the follow-up period, 92 patients (28%) experienced a major cardiac event. Mean free triiodothyronine levels were lower and median brain natriuretic peptide levels were higher in patients with major cardiac events than in those without. A significant negative correlation was found between free triiodothyronine and brain natriuretic peptide levels. Receiver operating characteristic curve analysis showed that the predictive cutoff values were < 2.12 pg/mL for free triiodothyronine and > 686 pg/mL for brain natriuretic peptide. Cumulative survival was significantly lower among patients with free triiodothyronine < 2.12 pg/mL and among patients with brain natriuretic peptide > 686 pg/mL. In multivariate analysis, the significant independent predictors of major cardiac events were age, free triiodothyronine, and brain natriuretic peptide.In the present study, free triiodothyronine and brain natriuretic peptide had similar prognostic values for predicting long-term prognosis in chronic heart failure patients. These results also suggested that combining these biomarkers may provide an important risk indicator for patients with heart failure.

Can Preoperative Patient-reported Outcome Measures Be Used to Predict Meaningful Improvement in Function After TKA?

PubMed

Berliner, Jonathan L; Brodke, Dane J; Chan, Vanessa; SooHoo, Nelson F; Bozic, Kevin J

2017-01-01

Despite the overall effectiveness of total knee arthroplasty (TKA), a subset of patients do not experience expected improvements in pain, physical function, and quality of life as documented by patient-reported outcome measures (PROMs), which assess a patient's physical and emotional health and pain. It is therefore important to develop preoperative tools capable of identifying patients unlikely to improve by a clinically important margin after surgery. The purpose of this study was to determine if an association exists between preoperative PROM scores and patients' likelihood of experiencing a clinically meaningful change in function 1 year after TKA. A retrospective study design was used to evaluate preoperative and 1-year postoperative Knee injury and Osteoarthritis Outcome Score (KOOS) and SF-12 version 2 (SF12v2) scores from 562 patients who underwent primary unilateral TKA. This cohort represented 75% of the 750 patients who underwent surgery during that time period; a total of 188 others (25%) either did not complete PROM scores at the designated times or were lost to follow-up. Minimum clinically important differences (MCIDs) were calculated for each PROM using a distribution-based method and were used to define meaningful clinical improvement. MCID values for KOOS and SF12v2 physical component summary (PCS) scores were calculated to be 10 and 5, respectively. A receiver operating characteristic analysis was used to determine threshold values for preoperative KOOS and SF12v2 PCS scores and their respective predictive abilities. Threshold values defined the point after which the likelihood of clinically meaningful improvement began to diminish. Multivariate regression was used to control for the effect of preoperative mental and emotional health, patient attributes quantified by SF12v2 mental component summary (MCS) scores, on patients' likelihood of experiencing meaningful improvement in function after surgery. Threshold values for preoperative KOOS and SF12v2 PCS scores were a maximum of 58 (area under the curve [AUC], 0.76; p < 0.001) and 34 (AUC, 0.65; p < 0.001), respectively. Patients scoring above these thresholds, indicating better preoperative function, were less likely to experience a clinically meaningful improvement in function after TKA. When accounting for mental and emotional health with a multivariate analysis, the predictive ability of both KOOS and SF12v2 PCS threshold values improved (AUCs increased to 0.80 and 0.71, respectively). Better preoperative mental and emotional health, as reflected by a higher MCS score, resulted in higher threshold values for KOOS and SF12v2 PCS. We identified preoperative PROM threshold values that are associated with clinically meaningful improvements in functional outcome after TKA. Patients with preoperative KOOS or SF12v2 PCS scores above the defined threshold values have a diminishing probability of experiencing clinically meaningful improvement after TKA. Patients with worse baseline mental and emotional health (as defined by SF12v2 MCS score) have a lower probability of experiencing clinically important levels of functional improvement after surgery. The results of this study are directly applicable to patient-centered informed decision-making tools and may be used to facilitate discussions with patients regarding the expected benefit after TKA. Level III, prognostic study.

Prostate-specific antigen 1.5-4.0 ng/mL: a diagnostic challenge and danger zone.

PubMed

Crawford, E David; Moul, Judd W; Rove, Kyle O; Pettaway, Curtis A; Lamerato, Lois E; Hughes, Alexa

2011-12-01

What's known on the subject? and What does the study add? Large population screening trials like the ERSPC, PCPT and PLCO have noted that men with seemingly low PSA (even as low as 0.5 ng/dL) still can have prostate cancer. Despite these findings, PSA is still predominantly used as a current indicator for possible presence of prostate cancer rather than also serving as a prognostic marker. This study examines a larger number of men in a diverse US population to determine the prognostic value of a man's baseline or first PSA. • To assess the value of a PSA threshold of 1.5 ng/mL as a predictor of increased prostate cancer risk over a four-year period based on a man's first PSA test, including racial differences. • To review the risk of progression of benign prostatic hyperplasia (BPH) based on a similar PSA threshold. • A retrospective review involving 21,502 men from a large Midwestern health system was performed. • Men at least 40 years old with baseline PSA values between 0 and 4.0 ng/mL and at least four years of follow-up after initial PSA test were included. • Optimal PSA threshold and predictive value of PSA for development of prostate cancer were calculated. • Prostate cancer rates were 15-fold higher in patients with PSA ≥1.5 ng/mL vs patients with PSA <1.5 ng/mL (7.85% vs 0.51%). • African American patients with baseline PSA <1.5 ng/mL faced prostate cancer rates similar to the whole study population (0.54% vs 0.51%, respectively), while African American patients with PSA 1.5-4.0 ng/mL faced a 19-fold increase in prostate cancer. • Both Caucasian and African American men with baseline PSA values between 1.5 and 4.0 ng/mL are at increased risk for future prostate cancer compared with those who have an initial PSA value below the 1.5 ng/mL threshold. • Based on a growing body of literature and this analysis, it is recommended that a first PSA test threshold of 1.5 ng/mL and above, or somewhere between 1.5 and 4.0 ng/mL, represent the Early-Warning PSA Zone (EWP Zone). • This should serve to inform patients and clinicians alike to future clinical activities with respect to prostate cancer and BPH. © 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.

Influence of aging on thermal and vibratory thresholds of quantitative sensory testing.

PubMed

Lin, Yea-Huey; Hsieh, Song-Chou; Chao, Chi-Chao; Chang, Yang-Chyuan; Hsieh, Sung-Tsang

2005-09-01

Quantitative sensory testing has become a common approach to evaluate thermal and vibratory thresholds in various types of neuropathies. To understand the effect of aging on sensory perception, we measured warm, cold, and vibratory thresholds by performing quantitative sensory testing on a population of 484 normal subjects (175 males and 309 females), aged 48.61 +/- 14.10 (range 20-86) years. Sensory thresholds of the hand and foot were measured with two algorithms: the method of limits (Limits) and the method of level (Level). Thresholds measured by Limits are reaction-time-dependent, while those measured by Level are independent of reaction time. In addition, we explored (1) the correlations of thresholds between these two algorithms, (2) the effect of age on differences in thresholds between algorithms, and (3) differences in sensory thresholds between the two test sites. Age was consistently and significantly correlated with sensory thresholds of all tested modalities measured by both algorithms on multivariate regression analysis compared with other factors, including gender, body height, body weight, and body mass index. When thresholds were plotted against age, slopes differed between sensory thresholds of the hand and those of the foot: for the foot, slopes were steeper compared with those for the hand for each sensory modality. Sensory thresholds of both test sites measured by Level were highly correlated with those measured by Limits, and thresholds measured by Limits were higher than those measured by Level. Differences in sensory thresholds between the two algorithms were also correlated with age: thresholds of the foot were higher than those of the hand for each sensory modality. This difference in thresholds (measured with both Level and Limits) between the hand and foot was also correlated with age. These findings suggest that age is the most significant factor in determining sensory thresholds compared with the other factors of gender and anthropometric parameters, and this provides a foundation for investigating the neurobiologic significance of aging on the processing of sensory stimuli.

Damage Propagation Modeling for Aircraft Engine Prognostics

NASA Technical Reports Server (NTRS)

Saxena, Abhinav; Goebel, Kai; Simon, Don; Eklund, Neil

2008-01-01

This paper describes how damage propagation can be modeled within the modules of aircraft gas turbine engines. To that end, response surfaces of all sensors are generated via a thermo-dynamical simulation model for the engine as a function of variations of flow and efficiency of the modules of interest. An exponential rate of change for flow and efficiency loss was imposed for each data set, starting at a randomly chosen initial deterioration set point. The rate of change of the flow and efficiency denotes an otherwise unspecified fault with increasingly worsening effect. The rates of change of the faults were constrained to an upper threshold but were otherwise chosen randomly. Damage propagation was allowed to continue until a failure criterion was reached. A health index was defined as the minimum of several superimposed operational margins at any given time instant and the failure criterion is reached when health index reaches zero. Output of the model was the time series (cycles) of sensed measurements typically available from aircraft gas turbine engines. The data generated were used as challenge data for the Prognostics and Health Management (PHM) data competition at PHM 08.

Local-Level Prognostics Health Management Systems Framework for Passive AdvSMR Components. Interim Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ramuhalli, Pradeep; Roy, Surajit; Hirt, Evelyn H.

2014-09-12

This report describes research results to date in support of the integration and demonstration of diagnostics technologies for prototypical AdvSMR passive components (to establish condition indices for monitoring) with model-based prognostics methods. The focus of the PHM methodology and algorithm development in this study is at the localized scale. Multiple localized measurements of material condition (using advanced nondestructive measurement methods), along with available measurements of the stressor environment, enhance the performance of localized diagnostics and prognostics of passive AdvSMR components and systems.

High-mobility group B1 proteins in canine lymphoma: prognostic value of initial and sequential serum levels in treatment outcome following combination chemotherapy.

PubMed

Meyer, A; Eberle, N; Bullerdiek, J; Nolte, I; Simon, D

2010-06-01

Elevated high-mobility group box 1 (HMGB1) levels have been demonstrated in different human neoplasias. Information on serum HMGB1 before and during chemotherapy is lacking, as is data pertaining to its prognostic significance. The aim of this study was to characterize serum HMGB1 level in dogs with lymphoma and to assess its influence on the outcome following chemotherapy. Serum HMGB1 concentrations were measured in 16 dogs with lymphoma before treatment (W1) and on weeks 2 (W2), 6 (W6) and 12 (W12) of treatment with chemotherapy. Initial serum HMGB1 levels were significantly higher than HMGB1concentrations in control dogs and the levels in W2, W6 and W12. HMGB1-W1 concentrations were lower in dogs achieving complete remission than that in the single dog with partial remission. The ratio W12/W6 exhibited significant influence on remission duration. In these dogs with lymphoma, serum HMGB1 was elevated in comparison with that in controls. Initial serum HMGB1 level and its modulation during treatment may possess prognostic value.

Unique protein expression signatures of survival time in kidney renal clear cell carcinoma through a pan-cancer screening.

PubMed

Han, Guangchun; Zhao, Wei; Song, Xiaofeng; Kwok-Shing Ng, Patrick; Karam, Jose A; Jonasch, Eric; Mills, Gordon B; Zhao, Zhongming; Ding, Zhiyong; Jia, Peilin

2017-10-03

In 2016, it is estimated that there will be 62,700 new cases of kidney cancer in the United States, and 14,240 patients will die from the disease. Because the incidence of kidney renal clear cell carcinoma (KIRC), the most common type of kidney cancer, is expected to continue to increase in the US, there is an urgent need to find effective diagnostic biomarkers for KIRC that could help earlier detection of and customized treatment strategies for the disease. Accordingly, in this study we systematically investigated KIRC's prognostic biomarkers for survival using the reverse phase protein array (RPPA) data and the high throughput sequencing data from The Cancer Genome Atlas (TCGA). With comprehensive data available in TCGA, we systematically screened protein expression based survival biomarkers in 10 major cancer types, among which KIRC presented many protein prognostic biomarkers of survival time. This is in agreement with a previous report that expression level changes (mRNAs, microRNA and protein) may have a better performance for prognosis of KIRC. In this study, we also identified 52 prognostic genes for KIRC, many of which are involved in cell-cycle and cancer signaling, as well as 15 tumor-stage-specific prognostic biomarkers. Notably, we found fewer prognostic biomarkers for early-stage than for late-stage KIRC. Four biomarkers (the RPPA protein IDs: FASN, ACC1, Cyclin_B1 and Rad51) were found to be prognostic for survival based on both protein and mRNA expression data. Through pan-cancer screening, we found that many protein biomarkers were prognostic for patients' survival in KIRC. Stage-specific survival biomarkers in KIRC were also identified. Our study indicated that these protein biomarkers might have potential clinical value in terms of predicting survival in KIRC patients and developing individualized treatment strategies. Importantly, we found many biomarkers in KIRC at both the mRNA expression level and the protein expression level. These biomarkers shared a significant overlap, indicating that they were technically replicable.

Selection for inpatient rehabilitation after acute stroke: a systematic review of the literature.

PubMed

Hakkennes, Sharon J; Brock, Kim; Hill, Keith D

2011-12-01

To identify patient-related factors that have been found to correlate with functional outcomes post acute stroke to guide clinical decision making with regard to rehabilitation admission after acute stroke. We systematically searched the scientific literature between 1966 and January 2010. The primary source of studies was the electronic databases Medline, CINAHL, and Embase. The search was supplemented with citation tracking. Two reviewers independently applied the inclusion criteria to identify relevant articles from the citations obtained through the literature search. Eligible studies included systematic reviews of prognostic indicators, studies of prognostic indicators of acute discharge disposition, and studies of rehabilitation admission criteria after acute stroke. Of the 8895 studies identified, 83 articles, representing 79 studies, were included in the review. One reviewer extracted the data relating to the participants, prognostic indicators, and outcomes. A second reviewer independently checked data extracted with disagreement resolved by a third reviewer. Quality of included studies was assessed for internal and external validity. Of the 79 studies, 26 were systematic reviews of prognostic indicators of functional level and/or discharge disposition, 48 were studies of prognostic indicators of acute discharge disposition, and 6 were studies of rehabilitation selection criteria. The methodologic quality of the included studies was generally poor. Age, cognition, functional level after stroke, and, to a lesser extent, continence were found to have a consistent association with outcome across all 3 research areas. In addition, stroke severity was also associated with acute discharge disposition, final discharge disposition, and functional level. Sex and side of stroke appeared to have no association across all 3 of the research areas. This review highlights a number of important prognostic indicators and rehabilitation selection criteria that may assist clinicians in improving selection procedures and standardizing access to inpatient rehabilitation after stroke, although the quality of many studies is low. Further high quality studies and reviews of prognostic indicators and clinician decision making with regards to rehabilitation acceptance are required. Copyright © 2011 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Preoperative serum C-reactive protein levels and post-operative lymph node ratio are important predictors of survival after pancreaticoduodenectomy for pancreatic ductal adenocarcinoma.

PubMed

Sanjay, Pandanaboyana; de Figueiredo, Rodrigo S; Leaver, Heather; Ogston, Simon; Kulli, Christoph; Polignano, Francesco M; Tait, Iain S

2012-03-10

There is paucity of data on the prognostic value of pre-operative inflammatory response and post-operative lymph node ratio on patient survival after pancreatic-head resection for pancreatic ductal adenocarcinoma. To evaluate the role of the preoperative inflammatory response and postoperative pathology criteria to identify predictive and/or prognostic variables for pancreatic ductal adenocarcinoma. All patients who underwent pancreaticoduodenectomy for pancreatic ductal adenocarcinoma between 2002 and 2008 were reviewed retrospectively. The following impacts on patient survival were assessed: i) preoperative serum CRP levels, white cell count, neutrophil count, neutrophil/lymphocyte ratio, lymphocyte count, platelet/lymphocyte ratio; and ii) post-operative pathology criteria including lymph node status and lymph node ratio. Fifty-one patients underwent potentially curative resection for pancreatic ductal adenocarcinoma during the study period. An elevated preoperative CRP level (greater than 3 mg/L) was found to be a significant adverse prognostic factor (P=0.015) predicting a poor survival, whereas white cell count (P=0.278), neutrophil count (P=0.850), neutrophil/lymphocyte ratio (P=0.272), platelet/lymphocyte ratio (P=0.532) and lymphocyte count (P=0.721) were not significant prognosticators at univariate analysis. Presence of metastatic lymph nodes did not adversely affect survival (P=0.050), however a raised lymph node ratio predicted poor survival at univariate analysis (P<0.001). The preoperative serum CRP level retained significance at multivariate analysis (P=0.011), together with lymph node ratio (P<0.001) and tumour size (greater than 2 cm; P=0.008). A pre-operative elevated serum CRP level and raised post-operative lymph node ratio represent significant independent prognostic factors that predict poor prognosis in patients undergoing curative resection for pancreatic ductal adenocarcinoma. There is potential for future neo-adjuvant and adjuvant treatment strategies in pancreatic cancer to be tailored based on preoperative and postoperative factors that predict a poor survival.

Impact of history of heart failure on diagnostic and prognostic value of BNP: results from the B-type Natriuretic Peptide for Acute Shortness of Breath Evaluation (BASEL) study.

PubMed

Boldanova, Tujana; Noveanu, Markus; Breidthardt, Tobias; Potocki, Mihael; Reichlin, Tobias; Taegtmeyer, Anne; Christ, Michael; Laule, Kirsten; Stelzig, Claudia; Mueller, Christian

2010-07-23

This study aimed to examine the influence of history of heart failure (HF) on circulating levels, diagnostic accuracy and prognostic value of B-type natriuretic peptide (BNP) in patients presenting with all cause dyspnea at the emergency department. BNP has been shown to be very helpful in diagnosis and prognosis of HF. Due to chronically elevated cardiac filling pressures, patients with a history of HF might have higher BNP levels and therefore diagnostic and prognostic properties of BNP may be affected. We analyzed circulating levels, diagnostic accuracy and prognostic value of BNP in 388 patients without a previous history of HF and compared these to data to 64 patients with a history of HF included in the B-type Natriuretic Peptide for Acute Shortness of Breath Evaluation (BASEL) Study. Baseline BNP levels were higher in patients with a history of HF (median 814 pg/ml [353-1300 pg/ml] vs. 216 pg/ml [45-801 pg/ml], p<0.001). Diagnostic accuracy of BNP to identify HF was comparable in patients with (AUC=0.804; 95% CI 0.628-0.980) and in patients without history of HF (AUC=0.883; 95% CI 0.848-0.919, p=0.389). Prognostic ability of BNP to predict one-year mortality was lower in overall patients with history of HF (AUC=0.458; 95%CI 0.294-0.622) compared to patients without history of HF (AUC=0.710; 95% CI 0.653-0.768, p<0.05). In patients with history of HF, BNP levels retain diagnostic accuracy. Ability to predict one-year mortality was decreased in unselected patients, but not in patients with acute HF-induced dyspnea. Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.

Preoperative prognostic factors for mortality in peptic ulcer perforation: a systematic review.

PubMed

Møller, Morten Hylander; Adamsen, Sven; Thomsen, Reimar Wernich; Møller, Ann Merete

2010-08-01

Mortality and morbidity following perforated peptic ulcer (PPU) is substantial and probably related to the development of sepsis. During the last three decades a large number of preoperative prognostic factors in patients with PPU have been examined. The aim of this systematic review was to summarize available evidence on these prognostic factors. MEDLINE (January 1966 to June 2009), EMBASE (January 1980 to June 2009), and the Cochrane Library (Issue 3, 2009) were screened for studies reporting preoperative prognostic factors for mortality in patients with PPU. The methodological quality of the included studies was assessed. Summary relative risks with 95% confidence intervals for the identified prognostic factors were calculated and presented as Forest plots. Fifty prognostic studies with 37 prognostic factors comprising a total of 29,782 patients were included in the review. The overall methodological quality was acceptable, yet only two-thirds of the studies provided confounder adjusted estimates. The studies provided strong evidence for an association of older age, comorbidity, and use of NSAIDs or steroids with mortality. Shock upon admission, preoperative metabolic acidosis, tachycardia, acute renal failure, low serum albumin level, high American Society of Anaesthesiologists score, and preoperative delay >24 h were associated with poor prognosis. In patients with PPU, a number of negative prognostic factors can be identified prior to surgery, and many of these seem to be related to presence of the sepsis syndrome.

Prognostic significance of FAM83D gene expression across human cancer types

DOE PAGES

Walian, Peter J.; Hang, Bo; Mao, Jian-Hua

2015-12-15

The family with sequence similarity 83, member D (FAM83D) gene has been proposed as a new prognostic marker for breast cancer. In this work, we further evaluate the prognostic significance of FAM83D expression in different breast cancer subtypes using a meta-analysis. Patients with higher FAM83D mRNA levels have significantly decreased overall and metastatic relapse-free survival, particularly in the group of patients with ER-positive, or luminal subtype tumors. We also assessed FAM83D alterations and its prognostic significance across 22 human cancer types using The Cancer Genome Atlas (TCGA). FAM83D is frequently gained in the majority of human cancer types, resulting inmore » the elevated expression of FAM83D. Higher levels of FAM83D mRNA expression are significantly associated with decreased overall survival in several cancer types. Finally, we demonstrate that TP53 mutation in human cancers is coupled to a significant increase in the expression of FAM83D, and that a higher level of FAM83D expression is positively correlated with an increase in genome instability in many cancer types. These results identify FAM83D as a potential novel oncogene across multiple human cancer types.« less

Prognostic significance of Glasgow prognostic score in patients undergoing esophagectomy for esophageal squamous cell carcinoma.

PubMed

Feng, Ji-Feng; Zhao, Qiang; Chen, Qi-Xun

2014-01-01

Recent studies have revealed that Glasgow prognostic score (GPS), an inflammation-based prognostic score, is inversely related to prognosis in a variety of cancers; high levels of GPS is associated with poor prognosis. However, few studies regarding GPS in esophageal cancer (EC) are available. The aim of this study was to determine whether the GPS is useful for predicting cancer-specific survival (CSS) of patients for esophageal squamous cell carcinoma (ESCC). The GPS was calculated on the basis of admission data as follows: Patients with elevated C-reactive protein (CRP) level (>10 mg/L) and hypoalbuminemia (<35 g/L) were assigned to GPS2. Patients with one or no abnormal value were assigned to GPS1 or GPS0, respectively. Our study showed that GPS was associated with tumor size, depth of invasion, and nodal metastasis (P<0.001). In addition, there was a negative correlation between the serum CRP and albumin (r=-0.412, P<0.001). The 5-year CSS in patients with GPS0, GPS1, and GPS2 were 60.8%, 34.7% and 10.7%, respectively (P<0.001). Multivariate analysis showed that GPS was a significant predictor of CSS. GPS1-2 had a hazard ratio (HR) of 2.399 [95% confidence interval (CI): 1.805-3.190] for 1-year CSS (P<0.001) and 1.907 (95% CI: 1.608-2.262) for 5-year CSS (P<0.001). High levels of GPS is associated with tumor progression. GPS can be considered as an independent prognostic factor in patients who underwent esophagectomy for ESCC.

Pretreatment 18F-FDG PET Textural Features in Locally Advanced Non-Small Cell Lung Cancer: Secondary Analysis of ACRIN 6668/RTOG 0235.

PubMed

Ohri, Nitin; Duan, Fenghai; Snyder, Bradley S; Wei, Bo; Machtay, Mitchell; Alavi, Abass; Siegel, Barry A; Johnson, Douglas W; Bradley, Jeffrey D; DeNittis, Albert; Werner-Wasik, Maria; El Naqa, Issam

2016-06-01

In a secondary analysis of American College of Radiology Imaging Network (ACRIN) 6668/RTOG 0235, high pretreatment metabolic tumor volume (MTV) on (18)F-FDG PET was found to be a poor prognostic factor for patients treated with chemoradiotherapy for locally advanced non-small cell lung cancer (NSCLC). Here we utilize the same dataset to explore whether heterogeneity metrics based on PET textural features can provide additional prognostic information. Patients with locally advanced NSCLC underwent (18)F-FDG PET prior to treatment. A gradient-based segmentation tool was used to contour each patient's primary tumor. MTV, maximum SUV, and 43 textural features were extracted for each tumor. To address overfitting and high collinearity among PET features, the least absolute shrinkage and selection operator (LASSO) method was applied to identify features that were independent predictors of overall survival (OS) after adjusting for MTV. Recursive binary partitioning in a conditional inference framework was utilized to identify optimal thresholds. Kaplan-Meier curves and log-rank testing were used to compare outcomes among patient groups. Two hundred one patients met inclusion criteria. The LASSO procedure identified 1 textural feature (SumMean) as an independent predictor of OS. The optimal cutpoint for MTV was 93.3 cm(3), and the optimal SumMean cutpoint for tumors above 93.3 cm(3) was 0.018. This grouped patients into three categories: low tumor MTV (n = 155; median OS, 22.6 mo), high tumor MTV and high SumMean (n = 23; median OS, 20.0 mo), and high tumor MTV and low SumMean (n = 23; median OS, 6.2 mo; log-rank P < 0.001). We have described an appropriate methodology to evaluate the prognostic value of textural PET features in the context of established prognostic factors. We have also identified a promising feature that may have prognostic value in locally advanced NSCLC patients with large tumors who are treated with chemoradiotherapy. Validation studies are warranted. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Pretreatment 18F-FDG PET Textural Features in Locally Advanced Non–Small Cell Lung Cancer: Secondary Analysis of ACRIN 6668/RTOG 0235

PubMed Central

Ohri, Nitin; Duan, Fenghai; Snyder, Bradley S.; Wei, Bo; Machtay, Mitchell; Alavi, Abass; Siegel, Barry A.; Johnson, Douglas W.; Bradley, Jeffrey D.; DeNittis, Albert; Werner-Wasik, Maria; El Naqa, Issam

2016-01-01

In a secondary analysis of American College of Radiology Imaging Network (ACRIN) 6668/RTOG 0235, high pretreatment metabolic tumor volume (MTV) on 18F-FDG PET was found to be a poor prognostic factor for patients treated with chemoradiotherapy for locally advanced non–small cell lung cancer (NSCLC). Here we utilize the same dataset to explore whether heterogeneity metrics based on PET textural features can provide additional prognostic information. Methods Patients with locally advanced NSCLC underwent 18F-FDG PET prior to treatment. A gradient-based segmentation tool was used to contour each patient’s primary tumor. MTV, maximum SUV, and 43 textural features were extracted for each tumor. To address over-fitting and high collinearity among PET features, the least absolute shrinkage and selection operator (LASSO) method was applied to identify features that were independent predictors of overall survival (OS) after adjusting for MTV. Recursive binary partitioning in a conditional inference framework was utilized to identify optimal thresholds. Kaplan–Meier curves and log-rank testing were used to compare outcomes among patient groups. Results Two hundred one patients met inclusion criteria. The LASSO procedure identified 1 textural feature (SumMean) as an independent predictor of OS. The optimal cutpoint for MTV was 93.3 cm3, and the optimal Sum-Mean cutpoint for tumors above 93.3 cm3 was 0.018. This grouped patients into three categories: low tumor MTV (n = 155; median OS, 22.6 mo), high tumor MTV and high SumMean (n = 23; median OS, 20.0 mo), and high tumor MTV and low SumMean (n = 23; median OS, 6.2 mo; log-rank P < 0.001). Conclusion We have described an appropriate methodology to evaluate the prognostic value of textural PET features in the context of established prognostic factors. We have also identified a promising feature that may have prognostic value in locally advanced NSCLC patients with large tumors who are treated with chemoradiotherapy. Validation studies are warranted. PMID:26912429

Prediction of survival benefits from progression-free survival benefits in advanced non-small-cell lung cancer: evidence from a meta-analysis of 2334 patients from 5 randomised trials

PubMed Central

Laporte, Silvy; Squifflet, Pierre; Baroux, Noémie; Fossella, Frank; Georgoulias, Vassilis; Pujol, Jean-Louis; Douillard, Jean-Yves; Kudoh, Shinzohy; Pignon, Jean-Pierre; Quinaux, Emmanuel; Buyse, Marc

2013-01-01

Objectives To investigate whether progression-free survival (PFS) can be considered a surrogate endpoint for overall survival (OS) in advanced non-small-cell lung cancer (NSCLC). Design Meta-analysis of individual patient data from randomised trials. Setting Five randomised controlled trials comparing docetaxel-based chemotherapy with vinorelbine-based chemotherapy for the first-line treatment of NSCLC. Participants 2331 patients with advanced NSCLC. Primary and secondary outcome measures Surrogacy of PFS for OS was assessed through the association between these endpoints and between the treatment effects on these endpoints. The surrogate threshold effect was the minimum treatment effect on PFS required to predict a non-zero treatment effect on OS. Results The median follow-up of patients still alive was 23.4 months. Median OS was 10 months and median PFS was 5.5 months. The treatment effects on PFS and OS were correlated, whether using centres (R²=0.62, 95% CI 0.52 to 0.72) or prognostic strata (R²=0.72, 95% CI 0.60 to 0.84) as units of analysis. The surrogate threshold effect was a PFS hazard ratio (HR) of 0.49 using centres or 0.53 using prognostic strata. Conclusions These analyses provide only modest support for considering PFS as an acceptable surrogate for OS in patients with advanced NSCLC. Only treatments that have a major impact on PFS (risk reduction of at least 50%) would be expected to also have a significant effect on OS. Whether these results also apply to targeted therapies is an open question that requires independent evaluation. PMID:23485717

Ambrisentan response in connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) - A subgroup analysis of the ARIES-E clinical trial.

PubMed

Fischer, Aryeh; Denton, Christopher P; Matucci-Cerinic, Marco; Gillies, Hunter; Blair, Christiana; Tislow, James; Nathan, Steven D

2016-08-01

Pulmonary arterial hypertension (PAH) is a condition which may lead to right ventricular failure and early mortality and is an important complication in patients with connective tissue disease (CTD). Previously, the endothelin A selective receptor antagonist, ambrisentan, demonstrated efficacy and safety in treating patients with PAH due to WHO Group I etiologies. These analyses describe the 3-year efficacy and safety of ambrisentan in patients specifically with CTD associated PAH (CTD-PAH). Patients with CTD-PAH participating in the ARIES-1 and -2 clinical trials and their long-term extension were evaluated. Efficacy evaluations including 6-min walk distance (6MWD), clinical worsening, and survival were collected at routine study visits. Additional analyses of 6MWD categorical (30 m) breakpoints were conducted to determine any relationship between 6MWD and a prognostic threshold for survival. 124 patients with CTD-PAH were evaluated. 62.6%, 57.3%, and 58.2% of CTD-PAH patients treated with ambrisentan exhibited increases in 6MWD at 1-, 2-, and 3- years respectively. At 3 years, 64% of patients were free from clinical worsening and 76% of patients were still alive (Kaplan-Meier estimates). Identified factors holding prognostic relevance for survival include: baseline functional class, CTD-PAH subgroup, patient sex, improvement in 6MWD ≥30 m over the first 12 weeks of treatment, the most recent 6MWD, and a 6MWD absolute threshold of 222 m. These first analyses of the 3-year treatment of CTD-PAH patients with ambrisentan revealed fewer clinical worsening events and improved survival compared to historical controls. Key exercise parameters were also identified which appear important in guiding treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Merkel cell carcinoma: histopathologic and prognostic features according to the immunohistochemical expression of Merkel cell polyomavirus large T antigen correlated with viral load.

PubMed

Leroux-Kozal, Valérie; Lévêque, Nicolas; Brodard, Véronique; Lesage, Candice; Dudez, Oriane; Makeieff, Marc; Kanagaratnam, Lukshe; Diebold, Marie-Danièle

2015-03-01

Merkel cell carcinoma (MCC) is a neuroendocrine skin malignancy frequently associated with Merkel cell polyomavirus (MCPyV), which is suspected to be oncogenic. In a series of MCC patients, we compared clinical, histopathologic, and prognostic features according to the expression of viral large T antigen (LTA) correlated with viral load. We evaluated the LTA expression by immunohistochemistry using CM2B4 antibody and quantified viral load by real-time polymerase chain reaction. We analyzed formalin-fixed, paraffin-embedded (FFPE) tissue samples (n = 36) and corresponding fresh-frozen biopsies when available (n = 12), of the primary tumor and/or metastasis from 24 patients. MCPyV was detected in 88% and 58% of MCC patients by real-time polymerase chain reaction and immunohistochemistry, respectively. The relevance of viral load measurements was demonstrated by the strong consistency of viral load level between FFPE and corresponding frozen tissues as well as between primary tumor and metastases. From FFPE samples, 2 MCC subgroups were distinguished based on a viral load threshold defined by the positivity of CM2B4 immunostaining. In the LTA-negative subgroup with no or low viral load (nonsignificant), tumor cells showed more anisokaryosis (P = .01), and a solar elastosis around the tumor was more frequently observed (P = .03). LTA-positive MCCs with significant viral load had a lower proliferation index (P = .03) and a longer survival of corresponding patients (P = .008). Depending on MCPyV involvement, 2 MCC subgroups can be distinguished on histopathologic criteria, and the CM2B4 antibody is able to differentiate them reliably. Furthermore, the presence of a significant viral load in tumors is predictive of better prognosis. Copyright © 2015 Elsevier Inc. All rights reserved.

Stability of radiomic features in CT perfusion maps

NASA Astrophysics Data System (ADS)

Bogowicz, M.; Riesterer, O.; Bundschuh, R. A.; Veit-Haibach, P.; Hüllner, M.; Studer, G.; Stieb, S.; Glatz, S.; Pruschy, M.; Guckenberger, M.; Tanadini-Lang, S.

2016-12-01

This study aimed to identify a set of stable radiomic parameters in CT perfusion (CTP) maps with respect to CTP calculation factors and image discretization, as an input for future prognostic models for local tumor response to chemo-radiotherapy. Pre-treatment CTP images of eleven patients with oropharyngeal carcinoma and eleven patients with non-small cell lung cancer (NSCLC) were analyzed. 315 radiomic parameters were studied per perfusion map (blood volume, blood flow and mean transit time). Radiomics robustness was investigated regarding the potentially standardizable (image discretization method, Hounsfield unit (HU) threshold, voxel size and temporal resolution) and non-standardizable (artery contouring and noise threshold) perfusion calculation factors using the intraclass correlation (ICC). To gain added value for our model radiomic parameters correlated with tumor volume, a well-known predictive factor for local tumor response to chemo-radiotherapy, were excluded from the analysis. The remaining stable radiomic parameters were grouped according to inter-parameter Spearman correlations and for each group the parameter with the highest ICC was included in the final set. The acceptance level was 0.9 and 0.7 for the ICC and correlation, respectively. The image discretization method using fixed number of bins or fixed intervals gave a similar number of stable radiomic parameters (around 40%). The potentially standardizable factors introduced more variability into radiomic parameters than the non-standardizable ones with 56-98% and 43-58% instability rates, respectively. The highest variability was observed for voxel size (instability rate  >97% for both patient cohorts). Without standardization of CTP calculation factors none of the studied radiomic parameters were stable. After standardization with respect to non-standardizable factors ten radiomic parameters were stable for both patient cohorts after correction for inter-parameter correlations. Voxel size, image discretization, HU threshold and temporal resolution have to be standardized to build a reliable predictive model based on CTP radiomics analysis.

Prognostic value of the MicroRNA regulators Dicer and Drosha in non-small-cell lung cancer: co-expression of Drosha and miR-126 predicts poor survival.

PubMed

Lønvik, Kenneth; Sørbye, Sveinung W; Nilsen, Marit N; Paulssen, Ruth H

2014-01-01

Dicer and Drosha are important enzymes for processing microRNAs. Recent studies have exhibited possible links between expression of different miRNAs, levels of miRNA processing enzymes, and cancer prognosis. We have investigated the prognostic impact of Dicer and Drosha and their correlation with miR-126 expression in a large cohort of non-small cell lung cancer (NSCLC) patients. We aimed to find patient groups within the cohort that might have an advantage of receiving adjunctive therapies. Dicer expression in the cytoplasm and Drosha expression in the nucleus were evaluated by manual immunohistochemistry of tissue microarrays (TMAs), including tumor tissue samples from 335 patients with resected stages I to IIIA NSCLC. In addition, in situ hybridizations of TMAs for visualization of miR-126 were performed. Kaplan-Meier analysis was performed, and the log-rank test via SPSS v.22 was used for estimating significance levels. In patients with normal performance status (ECOG = 0, n = 197), high Dicer expression entailed a significantly better prognosis than low Dicer expression (P = 0.024). Dicer had no significant prognostic value in patients with reduced performance status (ECOG = 1-2, n = 138). High Drosha expression was significantly correlated with high levels of the microRNA 126 (miR-126) (P = 0.004). Drosha/miR-126 co-expression had a significant negative impact on the disease-specific survival (DSS) rate (P < 0.001). Multivariate analyses revealed that the interaction Dicer*Histology (P = 0.049) and Drosha/miR-126 co-expression (P = 0.033) were independent prognostic factors. In NSCLC patients with normal performance status, Dicer is a positive prognostic factor. The importance of Drosha as a prognostic factor in our material seems to be related to miR-126 and possibly other microRNAs.

Neuromagnetic Index of Hemispheric Asymmetry Prognosticating the Outcome of Sudden Hearing Loss

PubMed Central

Li, Lieber Po-Hung; Shiao, An-Suey; Chen, Kuang-Chao; Lee, Po-Lei; Niddam, David M.; Chang, Shyue-Yih; Hsieh, Jen-Chuen

2012-01-01

The longitudinal relationship between central plastic changes and clinical presentations of peripheral hearing impairment remains unknown. Previously, we reported a unique plastic pattern of “healthy-side dominance” in acute unilateral idiopathic sudden sensorineural hearing loss (ISSNHL). This study aimed to explore whether such hemispheric asymmetry bears any prognostic relevance to ISSNHL along the disease course. Using magnetoencephalography (MEG), inter-hemispheric differences in peak dipole amplitude and latency of N100m to monaural tones were evaluated in 21 controls and 21 ISSNHL patients at two stages: initial and fixed stage (1 month later). Dynamics/Prognostication of hemispheric asymmetry were assessed by the interplay between hearing level/hearing gain and ipsilateral/contralateral ratio (I/C) of N100m latency and amplitude. Healthy-side dominance of N100m amplitude was observed in ISSNHL initially. The pattern changed with disease process. There is a strong correlation between the hearing level at the fixed stage and initial I/Camplitude on affected-ear stimulation in ISSNHL. The optimal cut-off value with the best prognostication effect for the hearing improvement at the fixed stage was an initial I/Clatency on affected-ear stimulation of 1.34 (between subgroups of complete and partial recovery) and an initial I/Clatency on healthy-ear stimulation of 0.76 (between subgroups of partial and no recovery), respectively. This study suggested that a dynamic process of central auditory plasticity can be induced by peripheral lesions. The hemispheric asymmetry at the initial stage bears an excellent prognostic potential for the treatment outcomes and hearing level at the fixed stage in ISSNHL. Our study demonstrated that such brain signature of central auditory plasticity in terms of both N100m latency and amplitude at defined time can serve as a prognostication predictor for ISSNHL. Further studies are needed to explore the long-term temporal scenario of auditory hemispheric asymmetry and to get better psychoacoustic correlates of pathological hemispheric asymmetry in ISSNHL. PMID:22532839

Homoarginine—A prognostic indicator in adolescents and adults with complex congenital heart disease?

PubMed Central

Mueller, Marieke; Meinitzer, Andreas; Maerz, Winfried; Dschietzig, Thomas

2017-01-01

Background Homoarginine (hArg) has been shown to be of prognostic value in patients with chronic left heart failure. The present study aims to assess the clinical utility and prognostic value of hArg levels in patients with complex congenital heart disease (CHD). Methods Plasma hArg levels were measured in 143 patients with complex CHD and compared to clinical status, echocardiographic and laboratory parameters as well as the occurrence of adverse cardiac events. Results Median hArg levels were 1.5 μmol/l in CHD patients as compared to 1.70 μmol/l in healthy controls (p = 0.051). Median hArg levels were lowest in patients with Fontan palliation (1.27 μmol/l) and Eisenmenger physiology (0.99 μmol/l) and decreased with the severity of adverse cardiac events with lowest values found in patients prior to death or overt heart failure (0.89 μmol/l). According to ROC analysis, the most important predictors of adverse cardiac events were hArg levels (AUC 0.837, p<0.001, CI 0.726–0.947), NYHA class (AUC 0.800, p<0.001, CI 0.672–0.928) and NT-proBNP levels (AUC 0.780, p<0.001, CI 0.669–0.891). The occurrence of overt heart failure or death due to progressive heart failure were best predicted by NYHA class (AUC 0.945, p<0.001, CI 0.898–0.992), hArg levels (AUC 0.911, p<0.001, CI 0.850–0.971) and NT-proBNP levels (AUC 0.877, p<0.001, CI 0.791–0.962), respectively. Conclusion In patients with complex CHD, hArg levels can predict adverse cardiac events as reliably as or even better than NT-proBNP levels and thus might be of prognostic value in this subset of patients. PMID:28886170

High-level mRNA quantification of proliferation marker pKi-67 is correlated with favorable prognosis in colorectal carcinoma.

PubMed

Ihmann, Thomas; Liu, Jian; Schwabe, Wolfgang; Häusler, Peter; Behnke, Detlev; Bruch, Hans-Peter; Broll, Rainer; Windhövel, Ute; Duchrow, Michael

2004-12-01

The present study retrospectively examines the expression of pKi-67 mRNA and protein in colorectal carcinoma and their correlation to the outcome of patients. Immunohistochemistry and quantitative RT-PCR were used to analyze the expression of pKi-67 in 43 archival specimens of patients with curatively resected primary colorectal carcinoma, who were not treated with neo-adjuvant therapy. We determined a median pKi-67 (MIB-1) labeling index of 31.3% (range 10.3-66.4%), and a mean mRNA level of 0.1769 (DeltaC(T): range 0.01-0.69); indices and levels did not correlate. High pKi-67 mRNA DeltaC(T) values were associated with a significantly favorable prognosis, while pKi-67 labeling indices were not correlated to prognostic outcome. A multivariate analysis of clinical and biological factors indicated that tumor stage (UICC) and pKi-67 mRNA expression level were independent prognostic factors. Quantitatively determined pKi-67 mRNA can be a good and new prognostic indicator for primary resected colorectal carcinoma.

Validation of serum amyloid α as an independent biomarker for progression-free and overall survival in metastatic renal cell cancer patients.

PubMed

Vermaat, Joost S; Gerritse, Frank L; van der Veldt, Astrid A; Roessingh, Wijnand M; Niers, Tatjana M; Oosting, Sjoukje F; Sleijfer, Stefan; Roodhart, Jeanine M; Beijnen, Jos H; Schellens, Jan H; Gietema, Jourik A; Boven, Epie; Richel, Dick J; Haanen, John B; Voest, Emile E

2012-10-01

We recently identified apolipoprotein A2 (ApoA2) and serum amyloid α (SAA) as independent prognosticators in metastatic renal cell carcinoma (mRCC) patients, thereby improving the accuracy of the Memorial-Sloan Kettering Cancer Center (MSKCC) model. Validate these results prospectively in a separate cohort of mRCC patients treated with tyrosine kinase inhibitors (TKIs). For training we used 114 interferon-treated mRCC patients (inclusion 2001-2006). For validation we studied 151 TKI-treated mRCC patients (inclusion 2003-2009). Using Cox proportional hazards regression analysis, SAA and ApoA2 were associated with progression-free survival (PFS) and overall survival (OS). In 72 TKI-treated patients, SAA levels were analyzed longitudinally as a potential early marker for treatment effect. Baseline ApoA2 and SAA levels significantly predicted PFS and OS in the training and validation cohorts. Multivariate analysis identified SAA in both separate patient sets as a robust and independent prognosticator for PFS and OS. In contrast to our previous findings, ApoA2 interacted with SAA in the validation cohort and did not contribute to a better predictive accuracy than SAA alone and was therefore excluded from further analysis. According to the tertiles of SAA levels, patients were categorized in three risk groups, demonstrating accurate risk prognostication. SAA as a single biomarker showed equal prognostic accuracy when compared with the multifactorial MSKCC risk mode. Using receiver operating characteristic analysis, SAA levels >71 ng/ml were designated as the optimal cut-off value in the training cohort, which was confirmed for its significant sensitivity and specificity in the validation cohort. Applying SAA >71 ng/ml as an additional risk factor significantly improved the predictive accuracy of the MSKCC model in both independent cohorts. Changes in SAA levels after 6-8 wk of TKI treatment had no value in predicting treatment outcome. SAA but not ApoA2 was shown to be a robust and independent prognosticator for PFS and OS in mRCC patients. When incorporated in the MSKCC model, SAA showed additional prognostic value for patient management. Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Lymph node ratio predicts disease-specific survival in melanoma patients.

PubMed

Xing, Yan; Badgwell, Brian D; Ross, Merrick I; Gershenwald, Jeffrey E; Lee, Jeffrey E; Mansfield, Paul F; Lucci, Anthony; Cormier, Janice N

2009-06-01

The objectives of this analysis were to compare various measures associated with lymph node (LN) dissection and to identify threshold values associated with disease-specific survival (DSS) outcomes in patients with melanoma. Patients with lymph node-positive melanoma who underwent therapeutic LN dissection of the neck, axilla, and inguinal region were identified from the SEER database (1988-2005). We performed Cox multivariate analyses to determine the impact of the total number of LNs removed, number of negative LNs removed, and LN ratio on DSS. Multivariate cut-point analyses were conducted for each anatomic region to identify the threshold values associated with the largest improvement in DSS. The LN ratio was significantly associated with DSS for all LN regions. The LN ratio thresholds resulting in the greatest difference in 5-year DSS were .07, .13, and .18 for neck, axillary, and inguinal regions, respectively, corresponding to 15, 8, and 6 LNs removed per positive lymph node. After adjustment for other clinicopathologic factors, the hazard ratios (HRs) were .53 (95% confidence interval [CI], .40 to .71) in the neck, .52 (95% CI, .42 to .65) in the axillary, and .47 (95% CI, .36 to .61) in the inguinal regions for patients who met the LN ratio threshold. Among the prognostic factors examined, LN ratio was the best indicator of the extent of LN dissection, regardless of anatomic nodal region. These data provide evidence-based guidelines for defining adequate LN dissections in melanoma patients. (c) 2009 American Cancer Society.

Serum level of CD26 predicts time to first treatment in early B-chronic lymphocytic leukemia.

PubMed

Molica, Stefano; Digiesi, Giovanna; Mirabelli, Rosanna; Cutrona, Giovanna; Antenucci, Anna; Molica, Matteo; Giannarelli, Diana; Sperduti, Isabella; Morabito, Fortunato; Neri, Antonino; Baldini, Luca; Ferrarini, Manlio

2009-09-01

We analyzed the correlation between well-established biological parameters of prognostic relevance in B-cell chronic lymphocytic leukemia (CLL) [i.e. mutational status of the immunoglobulin heavy chain variable region (IgV(H)), ZAP-70- and CD38-expression] and serum levels of CD26 (dipeptidyl peptidase IV, DPP IV) by evaluating the impact of these variables on the time to first treatment (TFT) in a series of 69 previously untreated Binet stage A B-cell CLL patients. By using a commercial ELISA we found that with exception of a borderline significance for ZAP-70 (P = 0.07) and CD38 (P = 0.08), circulating levels of CD26 did not correlate with either Rai substages (P = 0.520) or other biomarker [beta2-microglobulin (P = 0.933), LDH (P = 0.101), mutational status of IgV(H) (P = 0.320)]. Maximally selected log-rank statistic plots identified a CD26 serum concentration of 371 ng/mL as the best cut-off. This threshold allowed the identification of two subsets of patients with CD26 serum levels higher and lower that 371 ng/mL respectively, whose clinical outcome was different with respect to TFT (i.e. 46% and 71% at 5 yr respectively; P = 0.005). Along with higher serum levels of CD26, the univariate Cox proportional hazard model identified absence of mutation in IgV(H) (P < 0.0001) as predictor of shorter TFT. As in multivariate analysis all these parameters maintained their discriminating power (mutational status of IgV(H,)P < 0.0001; soluble CD26, P = 0.02) their combined effect on clinical outcome was assessed. When three groups were considered: (1) Low-risk group (n = 31), patients with concordant IgVH(mut) and low level of soluble CD26; (2) intermediate risk group (n = 26), patients with discordant pattern; (3) high-risk group (n = 12), patients with concordant IgVH(unmut) and high level of soluble CD26, differences in the TFT were statistically significant, with a TFT at 5 yr of respectively 88%, 51% and 43% (P < 0.0001). Our results indicate that in early B-cell CLL biological profile including among other parameters soluble CD26 may provide a useful insight into the complex interrelationship of prognostic variables. Furthermore, CD26 along with mutational status of IgV(H) can be adequately used to predict clinical behavior of patients with low risk disease.

Prognostic Significance of Serum Alkaline Phosphatase Level in Osteosarcoma: A Meta-Analysis of Published Data.

PubMed

Ren, Hai-Yong; Sun, Ling-Ling; Li, Heng-Yuan; Ye, Zhao-Ming

2015-01-01

Serum alkaline phosphatase (SALP) is commonly elevated in osteosarcoma patients. A number of studies have investigated the prognostic role of SALP level in patients with osteosarcoma but yielded inconsistent results. Systematic computerized searches were performed in PubMed, Embase, and Web of Science databases for relevant original articles. The pooled hazard ratios (HRs) and relative risks (RRs) with corresponding confidence intervals (CIs) were calculated to assess the prognostic value of SALP level. Finally, 21 studies comprising 3228 patients were included. Overall, the pooled HRs of SALP suggested that elevated level had an unfavorable impact on osteosarcoma patients' overall survival (OS) (HR = 1.82; 95% CI: 1.61-2.06; p < 0.001) and event-free survival (EFS) (HR = 1.97; 95% CI: 1.61-2.42; p < 0.001). Combined RRs of SALP indicated that elevated level was associated with presence of metastasis at diagnosis (RR = 5.55; 95% CI: 1.61-9.49; p = 0.006). No significantly different results were obtained after stratified by variables of age range, cancer stage, sample size, and geographic region. This meta-analysis demonstrated that high SALP level is significantly associated with poor OS or EFS rate and presence of metastasis at diagnosis. SALP level is a convenient and effective biomarker of prognosis for osteosarcoma.

Alpha-fetoprotein as a prognostic marker in acute liver failure: a pilot study.

PubMed

Varshney, Anshul; Gupta, Rohit; Verma, Sanjiv K; Ahmad, Sohaib

2017-07-01

Prognostic markers of acute liver failure (ALF) are based on clinical, laboratory or radiological parameters. Most of the biochemical markers are based on hepatic degeneration. We studied the impact of serial serum alpha-fetoprotein (AFP) levels, a marker of liver regeneration, on the outcome of the patients with ALF. AFP levels were estimated on days 1 and 3 of hospitalisation of 32 patients with ALF and the ratio (AFP day3/day1) was calculated. All subjects were categorised as group A (expired) or group B (survived). The AFP ratio was 0.84  +  0.15 in group A (n = 20) versus 1.55  +  0.70 in group B (n = 10); P < 0.001. However, the absolute initial AFP values were not associated with the outcome, favourable or unfavourable. We conclude that AFP levels change dynamically during ALF and have the potential to be used as a predictor of outcome in isolation or in combination with well-established prognostic markers.

The Prognostic Value of Epithelial Membrane Protein 1 (EMP-1) in Patients with Laryngeal Carcinoma

PubMed Central

Liu, Chang; Wei, Xiaojun; Li, Feng; Wang, Li; Ruan, Xinjian; Jia, Jia; Zhang, Xia

2017-01-01

Background In the present study, we aimed to investigate the prognostic value of epithelial membrane protein 1 (EMP-1) gene in patients diagnosed with laryngeal carcinoma (LC). Material/Methods Patients who were pathologically diagnosed with LC were enrolled in the present study. The expression levels of EMP-1 in tumor tissues and corresponding normal tissues collected from the LC patients were detected by semi-reverse transcriptase polymerase chain reaction (semi-RT-PCR). Chi-square analysis was used to evaluate the relationship between EMP-1 expression level and clinical characteristics. Survival analysis for the study population was analyzed by Kaplan-Meier method with log rank test. Additionally, Cox regression model was applied to evaluate the prognostic value of EMP-1 in LC patients. Results 106 LC patients, including 55 men and 51 women, were enrolled in the present study. Semi-RT-PCR demonstrated that the expression level of EMP-1 was decreased in tumor tissues, compared with adjacent normal tissues (p<0.001). Moreover, the level was significantly associated with lymph node metastasis, histological grade, and clinical stage (p<0.05 for all). In addition, low levels of EMP-1 was significantly correlated with poor survival rate (log rank test, p=0.020). Cox regression analysis indicated that EMP-1 was an independent marker for LC prognosis (HR=2.755, 95% CI=1.123–6.760, p=0.027). Conclusions The abnormal expression of EMP-1 may be associated with progression of LC and the gene may act as a prognostic marker for LC. PMID:28779068

The Prognostic Value of Epithelial Membrane Protein 1 (EMP-1) in Patients with Laryngeal Carcinoma.

PubMed

Liu, Chang; Wei, Xiaojun; Li, Feng; Wang, Li; Ruan, Xinjian; Jia, Jia; Zhang, Xia

2017-08-05

BACKGROUND In the present study, we aimed to investigate the prognostic value of epithelial membrane protein 1 (EMP-1) gene in patients diagnosed with laryngeal carcinoma (LC). MATERIAL AND METHODS Patients who were pathologically diagnosed with LC were enrolled in the present study. The expression levels of EMP-1 in tumor tissues and corresponding normal tissues collected from the LC patients were detected by semi-reverse transcriptase polymerase chain reaction (semi-RT-PCR). Chi-square analysis was used to evaluate the relationship between EMP-1 expression level and clinical characteristics. Survival analysis for the study population was analyzed by Kaplan-Meier method with log rank test. Additionally, Cox regression model was applied to evaluate the prognostic value of EMP-1 in LC patients. RESULTS 106 LC patients, including 55 men and 51 women, were enrolled in the present study. Semi-RT-PCR demonstrated that the expression level of EMP-1 was decreased in tumor tissues, compared with adjacent normal tissues (p<0.001). Moreover, the level was significantly associated with lymph node metastasis, histological grade, and clinical stage (p<0.05 for all). In addition, low levels of EMP-1 was significantly correlated with poor survival rate (log rank test, p=0.020). Cox regression analysis indicated that EMP-1 was an independent marker for LC prognosis (HR=2.755, 95% CI=1.123-6.760, p=0.027). CONCLUSIONS The abnormal expression of EMP-1 may be associated with progression of LC and the gene may act as a prognostic marker for LC.

[Molecular characterization of breast cancer in clinical practice].

PubMed

Zemmouri, Y; De Croze, D; Vincent Salomon, A; Rouzier, R; Bonneau, C

2016-05-01

Breast cancer involves various types of tumors. The objective of this review was to provide a summary of the main methods currently available in clinical practice to characterize breast cancers at a molecular level and to discuss their prognostic and predictive values. Hormonal receptors expression and the HER2 status are prognostic markers and can also predict the response to targeted therapies. Their analysis through immunohistochemistry is systematical. Ki67 is an effective prognostic marker, but its reliability is debated because of its low reproducibility between laboratories and between pathologists. Commercial genomic signatures are all considered valid prognostic tools and may guide physicians to make therapeutic choices. These signatures are costly and should therefore be restricted to situations in which the use of chemotherapy remains equivocal. Copyright © 2016. Published by Elsevier SAS.

Combination of neurofilament heavy chain and complement c3 as CSF biomarkers for ALS

PubMed Central

Ganesalingam, Jeban; An, Jiyan; Shaw, Christopher E; Shaw, Gerry; Lacomis, David; Bowser, Robert

2011-01-01

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive and ultimately fatal neurodegenerative disease with an average survival of 3 years from symptom onset. Rapid and conclusive early diagnosis is essential if interventions with disease-modifying therapies are to be successful. Cytoskeletal modification and inflammation are known to occur during the pathogenesis of ALS. We measured levels of cytoskeletal proteins and inflammatory markers in the cerebrospinal fluid (CSF) of ALS, disease controls and healthy subjects. We determined threshold values for each protein that provided the optimal sensitivity and specificity for ALS within a training set, as determined by receiver operating characteristic (ROC) analysis. Interestingly, the optimal assay was a ratio of the levels for phosphorylated neurofilament heavy chain and complement C3 (pNFH/C3). We next applied this assay to a separate test set of CSF samples to verify our results. Overall, the predictive pNFH/C3 ratio identified ALS with 87.3% sensitivity and 94.6% specificity in a total of 71 ALS subjects, 52 disease control subjects and 40 healthy subjects. In addition, the level of CSF pNFH correlated with survival of ALS patients. We also detected increased pNFH in the plasma of ALS patients and observed a correlation between CSF and plasma pNFH levels within the same subjects. These findings support large-scale prospective biomarker studies to determine the clinical utility of diagnostic and prognostic signatures in ALS. PMID:21418221

Serum soluble E-cadherin is a potential prognostic marker in esophageal squamous cell carcinoma.

PubMed

Chung, Y; Law, S; Kwong, D L W; Luk, J M

2011-01-01

E-cadherin is a well-documented tumor suppressor with downregulated expression in many cancer types. Upon proteolytic cleavage, a soluble form of 80-kDa degradation fragment, known as soluble E-cadherin (s-Ecad), is present in circulation; its level in sera of cancer patients is significantly associated with metastasis, recurrence, and prognosis in some malignancies. The present study investigated the association of s-Ecad with clinicopathological characteristics of patients with esophageal squamous cell carcinoma (ESCC) and its prognostic significance. A cohort of 97 patients who underwent surgery alone (n= 56) or neoadjuvant chemoradiation therapy and surgery (CRT) (n= 41) was recruited for this study. Serum samples were collected at operation (surgery group) and pre- and post-CRT treatment (CRT group) for measurement of s-Ecad protein by enzyme linked immunosorbent assay. Serum s-Ecad levels were correlated with clinicopathological parameters as well as survival. Univariate analysis showed no significant relationship between serum s-Ecad level and clinicopathological parameters for all sets of samples. Survival analysis showed that in patients who had surgical resection only, those with s-Ecad levels equal to or below the median value survived significantly longer than those with levels above the median (median survival 25.6 vs. 14.1 months, P= 0.012). Multivariate analysis showed that pathological N stage, M stage, R category, and serum s-Ecad level were significant independent prognostic factors for ESCC patients who underwent surgery only. The hazard ratio for s-Ecad was 1.104 (95% CI: 1.026-1.187) and P= 0.008. Serum s-Ecad was detected in ESCC patients and its potential as an independent prognostic marker requires further investigation. © 2010 Copyright the Authors. Journal compilation © 2010, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.

Metastatic Spinal Cord Compression from Non-Small-Cell Lung Cancer Treated with Surgery and Adjuvant Therapies: A Retrospective Analysis of Outcomes and Prognostic Factors in 116 Patients.

PubMed

Tang, Yu; Qu, Jintao; Wu, Juan; Li, Song; Zhou, Yue; Xiao, Jianru

2015-09-02

Metastatic spinal cord compression is a disastrous consequence of non-small-cell lung cancer (NSCLC). There have been few studies of the outcomes or prognostic factors in patients with metastatic spinal cord compression from NSCLC treated with surgery and adjuvant therapies. From 2002 to 2013, 116 patients with metastatic spinal cord compression from NSCLC treated with surgery and adjuvant therapies were enrolled in this retrospective analysis. Kaplan-Meier methods and Cox regression analysis were used to estimate overall survival and identify prognostic factors for survival. Multivariate analysis suggested that the Eastern Cooperative Oncology Group performance status (ECOG-PS), preoperative and postoperative Frankel scores, postoperative adjuvant radiation therapy, and target therapy were independent prognostic factors. Ninety patients died at a median of twelve months (range, three to forty-seven months) postoperatively, and twenty-six patients were still alive at the time of final follow-up (at a median of fifteen months [range, five to fifty-four months]). The complete disappearance of deficits in spinal cord function after surgery was the most robust predictor of survival. Adjuvant radiation therapy and target therapy were also associated with a better prognosis. Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence. Copyright © 2015 by The Journal of Bone and Joint Surgery, Incorporated.

MicroRNA expression at diagnosis adds relevant prognostic information to molecular categorization in patients with intermediate-risk cytogenetic acute myeloid leukemia.

PubMed

Díaz-Beyá, M; Brunet, S; Nomdedéu, J; Tejero, R; Díaz, T; Pratcorona, M; Tormo, M; Ribera, J M; Escoda, L; Duarte, R; Gallardo, D; Heras, I; Queipo de Llano, M P; Bargay, J; Monzo, M; Sierra, J; Navarro, A; Esteve, J

2014-04-01

Acute myeloid leukemia (AML) is a heterogeneous disease, and optimal treatment varies according to cytogenetic risk factors and molecular markers. Several studies have demonstrated the prognostic importance of microRNAs (miRNAs) in AML. Here we report a potential association between miRNA expression and clinical outcome in 238 intermediate-risk cytogenetic AML (IR-AML) patients from 16 institutions in the CETLAM cooperative group. We first profiled 670 miRNAs in a subset of 85 IR-AML patients from a single institution and identified 10 outcome-related miRNAs. We then validated these 10 miRNAs by individual assays in the total cohort and confirmed the prognostic impact of 4 miRNAs. High levels of miR-196b and miR-644 were independently associated with shorter overall survival, and low levels of miR-135a and miR-409-3p with a higher risk of relapse. Interestingly, miR-135a and miR-409-3p maintained their independent prognostic value within the unfavorable molecular subcategory (wild-type NPM1 and CEBPA and/or FLT3-ITD), and miR-644 retained its value within the favorable molecular subcategory. miR-409-3p, miR-135a, miR-196b and mir-644 arose as prognostic markers for IR-AML, both overall and within specific molecular subgroups.

Causes and prognostic factors for early death in patients with acute promyelocytic leukemia treated with single-agent arsenic trioxide.

PubMed

Hou, Jinxiao; Wang, Shuye; Zhang, Yingmei; Fan, Dachuan; Li, Haitao; Yang, Yiju; Ge, Fei; Hou, Wenyi; Fu, Jinyue; Wang, Ping; Zhao, Hongli; Sun, Jiayue; Yang, Kunpeng; Zhou, Jin; Li, Xiaoxia

2017-12-01

Early death (ED) is one of the most critical issues involved in the current care of patients with acute promyelocytic leukemia (APL). Factors identified as independent predictors of ED varied among published studies. We retrospectively analyzed the incidence, causes, and prognostic factors of ED in a series of 216 patients with newly diagnosed APL who received arsenic trioxide (ATO) as induction therapy. Multivariate logistic regression analysis was used to determine the association of clinical factors with overall ED, hemorrhagic ED, death within 7 days, and death within 8-30 days. In total, 35 EDs (16.2%) occurred that were caused by hemorrhage, differentiation syndrome (DS), infection, and other causes, in order of prevalence. The independent prognostic factors for overall ED and death within 8-30 days were the same and included serum creatinine level, Eastern Cooperative Oncology Group (ECOG) score, sex, and fibrinogen level. The risk factors for hemorrhagic ED and death within 7 days were similar and included serum creatinine level, ECOG score, and white blood cell count, while hemorrhagic ED was also associated with D-dimer. Our findings revealed a high rate of ED, and the causes of ED were similar to those among patients who received ATRA-based therapy. Increased creatinine level was the most powerful predictor, and an ECOG score greater than 2 was another strong prognostic factor for all four types of ED.

Prognostics for Ground Support Systems: Case Study on Pneumatic Valves

NASA Technical Reports Server (NTRS)

Daigle, Matthew; Goebel, Kai

2011-01-01

Prognostics technologies determine the health (or damage) state of a component or sub-system, and make end of life (EOL) and remaining useful life (RUL) predictions. Such information enables system operators to make informed maintenance decisions and streamline operational and mission-level activities. We develop a model-based prognostics methodology for pneumatic valves used in ground support equipment for cryogenic propellant loading operations. These valves are used to control the flow of propellant, so failures may have a significant impact on launch availability. Therefore, correctly predicting when valves will fail enables timely maintenance that avoids launch delays and aborts. The approach utilizes mathematical models describing the underlying physics of valve degradation, and, employing the particle filtering algorithm for joint state-parameter estimation, determines the health state of the valve and the rate of damage progression, from which EOL and RUL predictions are made. We develop a prototype user interface for valve prognostics, and demonstrate the prognostics approach using historical pneumatic valve data from the Space Shuttle refueling system.

Significance of serum CA125 and TPS antigen levels for determination of overall survival after three chemotherapy courses in ovarian cancer patients during long-term follow-up.

PubMed

van Dalen, A; Favier, J; Hallensleben, E; Burges, A; Stieber, P; de Bruijn, H W A; Fink, D; Ferrero, A; McGing, P; Harlozinska, A; Kainz, Ch; Markowska, J; Molina, R; Sturgeon, C; Bowman, A; Einarsson, R; Goike, H

2009-01-01

To evaluate the prognostic significance for overall survival rate for the marker combination TPS and CA125 in ovarian cancer patients after three chemotherapy courses during long-term clinical follow-up. The overall survival of 212 (out of 213) ovarian cancer patients (FIGO Stages I-IV) was analyzed in a prospective multicenter study during a 10-year clinical follow-up by univariate and multivariate analysis. In patients with ovarian cancer FIGO Stage I (34 patients) or FIGO Stage II (30 patients) disease, the univariate and multivariate analysis of the 10-year overall survival data showed that CA125 and TPS serum levels were not independent prognostic factors. In the FIGO Stage III group (112 patients), the 10-year overall survival was 15.2%; while in the FIGO Stage IV group (36 patients) a 10-year overall survival of 5.6% was seen. Here, the tumor markers CA125 and TPS levels were significant prognostic factors in both univariate and multivariate analysis (p < 0.0001). In a combined FIGO Stage III + FIGO Stage IV group (60 patients with optimal debulking surgery), multivariate analysis demonstrated that CA125 and TPS levels were independent prognostic factors. For patients in this combined FIGO Stage III + IV group having both markers below respective discrimination level, 35.3% survived for more than ten years, as opposed to patients having one marker above the discrimination level where the 10-year survival was reduced to 10% of the patients. For patients showing both markers above the respective discrimination level, none of the patients survived for the 10-year follow-up time. In FIGO III and IV ovarian cancer patients, only patients with CA 125 and TPS markers below the discrimination level after three chemotherapy courses indicated a favorable prognosis. Patients with an elevated level of CA 125 or TPS or both markers after three chemotherapy courses showed unfavorable prognosis.

Neutrophil gelatinase‐associated lipocalin level is a prognostic factor for survival in rat and human chronic liver diseases

PubMed Central

Yoshikawa, Kyoko; Iwasa, Motoh; Kojima, Shinichi; Yoshizawa, Naohiko; Tempaku, Mina; Sugimoto, Ryosuke; Yamamoto, Norihiko; Sugimoto, Kazushi; Kobayashi, Yoshinao; Hasegawa, Hiroshi; Takei, Yoshiyuki

2017-01-01

Chronic liver disease patients often have complications, such as hepatocellular carcinoma (HCC) and acute bacterial infection. Model for end‐stage liver disease and Child‐Pugh scores are useful prognostic factors for chronic liver diseases but not for all chronic conditions, such as HCC. Our investigative aim targeted the prognostic abilities of neutrophil gelatinase‐associated lipocalin (NGAL) in rat and human chronic liver diseases. Blood NGAL levels were measured by enzyme‐linked immunosorbent assay in rats with cirrhosis and 96 patients with chronic liver disease and HCC. We examined the correlation between blood NGAL levels and liver functions as well as survival. In our rat model, liver NGAL expression was assessed by immunostaining, real‐time quantitative polymerase chain reaction, and immunoblot. In rats with cirrhosis, blood NGAL levels were continuously and significantly elevated in the deceased group and were significantly correlated with liver functions. Liver NGAL, toll‐like receptor 4, and interleukin‐6 levels were increased in the deceased group compared to the survival group. Blood NGAL levels were significantly correlated with liver NGAL levels, indicating blood NGAL was derived from the liver. In patients with chronic liver disease, blood NGAL levels were associated with liver function and renal function. Blood NGAL levels were significantly increased in patients with chronic liver disease with HCC compared to without HCC. For the survival group, 38 out of 96 patients were dead in the average follow‐up period of 9.9 months. The patients with blood NGAL ≤119 ng/mL had significantly longer rates of survival compared to patients with blood NGAL >119 ng/mL. Conclusion: Blood NGAL predicts the survival rate in rat and human chronic liver diseases. Our findings suggest blood NGAL may be prognostic of survival in chronic liver diseases complicated by HCC. (Hepatology Communications 2017;1:946–956) PMID:29404502

[Prognostic value of first fasting glucose measurement compared with admission glucose level in patients with acute coronary syndrome].

PubMed

Vivas, David; García-Rubira, Juan C; González-Ferrer, Juan J; Núñez-Gil, Iván; del Prado, Náyade; Fernández-Ortiz, Antonio; Macaya, Carlos

2008-05-01

The admission plasma glucose (APG) level is a recognized prognostic factor in patients with acute coronary syndrome (ACS). However, little is known about the prognostic value of the first fasting plasma glucose (FPG) measurement. The aim of this study was to determine the prognostic value of the first FPG measurement relative to that of the APG level in patients with ACS. The study involved 547 consecutive patients who were admitted to our center with a diagnosis of ACS in 2006. Patients were divided into three groups according to their first FPG or APG level (i.e., <126 mg/dL, 126-200 mg/dL, or >200 mg/dL). The primary endpoint was the combined outcome of death or reinfarction during hospitalization. The primary endpoint was observed in 46 patients, 25 of whom died. Patients in this group were older, were more often diabetics or smokers, more often had had a prior myocardial infarction, were in a higher admission Killip class, showed more than one vessel disease on catheterization, had a lower left ventricular ejection fraction, and had higher admission creatinine, APG, and first FPG levels. Multivariate analysis, adjusted for previously identified factors, revealed that the first FPG level was an independent risk factor for death or reinfarction (126-200 mg/dL, odds ratio [OR]=5.26; 95% confidence interval [CI], 1.09-25.45; >200 mg/dL, OR=6.66; 95% CI, 2.05-21.63), but that the APG level was not (126-200 mg/dL, OR=0.84; 95% CI, 0.63-1.05; >200 mg/dL, OR=1.14; 95% CI, 0.29-4.51). The first FPG level was found to be a better predictor of an adverse outcome (i.e., death or reinfarction) during hospitalization in ACS patients than the APG level.

Repeatability of pleural adenosine deaminase measurements in diagnostic evaluation of pleural effusions.

PubMed

Kotsiou, Ourania S; Tzortzi, Panagiota; Beta, Rafailia A A; Kyritsis, Athanasios; Gourgoulianis, Konstantinos I

2018-06-01

A follow-up thoracentesis is proposed in suspected atypical tuberculosis cases. The study aimed to define the variability of pleural ADA values across repeated thoracenteses in different types of pleural effusions (PEs) and to evaluate whether ADA variance, in regard to the cutoff value of 40 U/L, affected final diagnosis. A total of 131 patients with PEs of various etiologies underwent three repeated thoracenteses. ADA values were subsequently estimated. 82% and 55% of patients had greater than 10% and 20% deviation from the highest ADA value, respectively. From those patients who had a variance of 20%, 36% had only increasing ADA values, while 19% had only decreasing values. Considering the cutoff value of 40 U/L, only in two cases, ADA decreased below this threshold, which concerned a man with tuberculous pleurisy and a woman with lymphoma both in the course of treatment. Furthermore, only in two cases with rising values, ADA finally exceeded the cutoff limit, which concerned a man with rheumatoid pleurisy and a man with tuberculous pleurisy. Surprisingly, malignant PEs (MPEs) showed a higher percentage of increasing values compared to all other exudates that did not, however, exceed the threshold. The determination of pleural ADA levels is a reproducible method for rapid tuberculosis diagnosis. The detected measurement deviations do not appear to affect final diagnosis. In specific situations, repeated ADA measurements may be valuable in directing further diagnostic evaluation. More investigation is needed to elucidate the possible prognostic significance of the increasing trend in ADA values in MPEs. © 2017 Wiley Periodicals, Inc.

Electrically evoked compound action potential amplitude growth functions and HiResolution programming levels in pediatric CII implant subjects.

PubMed

Eisen, Marc D; Franck, Kevin H

2004-12-01

To characterize the amplitude growth functions of the electrically evoked compound action potential (ECAP) in pediatric subjects implanted with the Clarion HiFocus electrode array with respect to electrode position and the presence or absence of a Silastic positioner. Electrophysiologic growth function data are compared with HiResolution (HiRes) psychophysical programming levels. ECAP growth functions were measured for all electrodes along the implant's array in 16 pediatric subjects. Nine of the patients were implanted with a Silastic positioner, whereas seven had no positioner. ECAP thresholds and growth function slopes were calculated. Fifteen of the 16 patients had psychophysical threshold and maximum comfort levels available. Programming levels and ECAP thresholds were compared within and among the subjects. ECAP thresholds showed variability among patients, ranging from 178 to 920 nA at 32 musec pulse width. ECAP thresholds did not depend on electrode position along the cochlea but were lower in the presence of the Silastic positioner (p < 0.001). Thresholds determined with the masker-probe versus the alternating polarity paradigms revealed moderate (r = 0.76) correlation. Growth function slopes also showed considerable variation among patients. Unlike thresholds, slopes decreased from apical to basal cochlear locations (p < 0.001) but showed no difference between the absence and presence of the positioner. Programming levels in HiRes were correlated with ECAP threshold levels. When ECAP thresholds were adjusted for each patient by the difference between M level and ECAP threshold at electrode 9, however, overall correlation between the two measurements was excellent (r = 0.98, N = 224). In pediatric subjects with the Clarion HiFocus electrode, ECAP growth function thresholds appear to decrease with the presence of the Silastic positioner but are unaffected by electrode position along the array. Growth function slope, however, depends on electrode position along the array but not on the presence of the positioner. ECAP programming levels can reliably predict stimulus intensities within the patients' dynamic ranges, but considerable variability is seen between ECAP thresholds and HiRes programming levels.

Inflammation-based prognostic score and number of lymph node metastases are independent prognostic factors in esophageal squamous cell carcinoma.

PubMed

Kobayashi, Takashi; Teruya, Masanori; Kishiki, Tomokazu; Kaneko, Susumu; Endo, Daisuke; Takenaka, Yoshiharu; Miki, Kenji; Kobayashi, Kaoru; Morita, Koji

2010-08-01

Few studies have investigated whether the Glasgow Prognostic Score (GPS), an inflammation-based prognostic score, is useful for postoperative prognosis of esophageal squamous cell carcinoma. GPS was calculated on the basis of admission data as follows: patients with elevated C-reactive protein level (>10 mg/l) and hypoalbuminemia (<35 g/l) were assigned to GPS2. Patients with one or no abnormal value were assigned to GPS1 or GPS0. A new scoring system was constructed using independent prognostic variables and was evaluated on whether it could be used to dictate the choice of clinical options. 65 patients with esophageal squamous cell carcinoma were enrolled. GPS and the number of lymph node metastases were found to be independent prognostic variables. The scoring system comprising GPS and the number of lymph node metastases was found to be effective in the prediction of a long-term outcome (p < 0.0001). Preoperative GPS may be useful for postoperative prognosis of patients with esophageal squamous cell carcinoma. GPS and the number of lymph node metastases could be used to identify a subgroup of patients with esophageal squamous cell carcinoma who are eligible for radical resection but show poor prognosis.

Multiple Score Comparison: a network meta-analysis approach to comparison and external validation of prognostic scores.

PubMed

Haile, Sarah R; Guerra, Beniamino; Soriano, Joan B; Puhan, Milo A

2017-12-21

Prediction models and prognostic scores have been increasingly popular in both clinical practice and clinical research settings, for example to aid in risk-based decision making or control for confounding. In many medical fields, a large number of prognostic scores are available, but practitioners may find it difficult to choose between them due to lack of external validation as well as lack of comparisons between them. Borrowing methodology from network meta-analysis, we describe an approach to Multiple Score Comparison meta-analysis (MSC) which permits concurrent external validation and comparisons of prognostic scores using individual patient data (IPD) arising from a large-scale international collaboration. We describe the challenges in adapting network meta-analysis to the MSC setting, for instance the need to explicitly include correlations between the scores on a cohort level, and how to deal with many multi-score studies. We propose first using IPD to make cohort-level aggregate discrimination or calibration scores, comparing all to a common comparator. Then, standard network meta-analysis techniques can be applied, taking care to consider correlation structures in cohorts with multiple scores. Transitivity, consistency and heterogeneity are also examined. We provide a clinical application, comparing prognostic scores for 3-year mortality in patients with chronic obstructive pulmonary disease using data from a large-scale collaborative initiative. We focus on the discriminative properties of the prognostic scores. Our results show clear differences in performance, with ADO and eBODE showing higher discrimination with respect to mortality than other considered scores. The assumptions of transitivity and local and global consistency were not violated. Heterogeneity was small. We applied a network meta-analytic methodology to externally validate and concurrently compare the prognostic properties of clinical scores. Our large-scale external validation indicates that the scores with the best discriminative properties to predict 3 year mortality in patients with COPD are ADO and eBODE.

Prognostic Role of Phospho-STAT3 in Patients with Cancers of the Digestive System: A Systematic Review and Meta-Analysis.

PubMed

Li, Mu-xing; Bi, Xin-yu; Huang, Zhen; Zhao, Jian-jun; Han, Yue; Li, Zhi-Yu; Zhang, Ye-fan; Li, Yuan; Chen, Xiao; Hu, Xu-hui; Zhao, Hong; Cai, Jian-qiang

2015-01-01

The definite prognostic role of p-STAT3 has not been well defined. We performed a meta-analysis evaluating the prognostic role of p-STAT3 expression in patients with digestive system cancers. We searched the available articles reporting the prognostic value of p-STAT3 in patients with cancers of the digestive system, mainly including colorectal cancer, gastric cancer, hepatocellular carcinoma, esophagus cancer and pancreatic cancer. The pooled hazard ratios (HRs) with 95 % confidence intervals (95 % CIs) of overall survival (OS) and disease-free survival (DFS) were used to assess the prognostic role of p-STAT3 expression level in cancer tissues. And the association between p-STAT3 expression and clinicopathological characteristics was evaluated. A total of 22 studies with 3585 patients were finally enrolled in the meta-analysis. The results showed that elevated p-STAT3 expression level predicted inferior OS (HR = 1.809, 95% CI: 1.442-2.270, P < 0.001) and DFS (HR = 1.481, 95% CI: 1.028-2.133, P = 0.035) in patients with malignant cancers of the digestive system. Increased expression of p-STAT3 is significantly related with tumor cell differentiation (Odds ratio (OR) = 1.895, 95% CI: 1.364-2.632, P < 0.001) and lymph node metastases (OR = 2.108, 95% CI: 1.104-4.024, P = 0.024). Sensitivity analysis suggested that the pooled HR was stable and omitting a single study did not change the significance of the pooled HR. Funnel plots and Egger's tests revealed there was no significant publication bias in the meta-analysis. Phospho-STAT3 might be a prognostic factor of patients with digestive system cancers. More well designed studies with adequate follow-up are needed to gain a thorough understanding of the prognostic role of p-STAT3.

Prognostic Biomarkers Used for Localised Prostate Cancer Management: A Systematic Review.

PubMed

Lamy, Pierre-Jean; Allory, Yves; Gauchez, Anne-Sophie; Asselain, Bernard; Beuzeboc, Philippe; de Cremoux, Patricia; Fontugne, Jacqueline; Georges, Agnès; Hennequin, Christophe; Lehmann-Che, Jacqueline; Massard, Christophe; Millet, Ingrid; Murez, Thibaut; Schlageter, Marie-Hélène; Rouvière, Olivier; Kassab-Chahmi, Diana; Rozet, François; Descotes, Jean-Luc; Rébillard, Xavier

2017-03-07

Prostate cancer stratification is based on tumour size, pretreatment PSA level, and Gleason score, but it remains imperfect. Current research focuses on the discovery and validation of novel prognostic biomarkers to improve the identification of patients at risk of aggressive cancer or of tumour relapse. This systematic review by the Intergroupe Coopérateur Francophone de Recherche en Onco-urologie (ICFuro) analysed new evidence on the analytical validity and clinical validity and utility of six prognostic biomarkers (PHI, 4Kscore, MiPS, GPS, Prolaris, Decipher). All available data for the six biomarkers published between January 2002 and April 2015 were systematically searched and reviewed. The main endpoints were aggressive prostate cancer prediction, additional value compared to classical prognostic parameters, and clinical benefit for patients with localised prostate cancer. The preanalytical and analytical validations were heterogeneous for all tests and often not adequate for the molecular signatures. Each biomarker was studied for specific indications (candidates for a first or second biopsy, and potential candidates for active surveillance, radical prostatectomy, or adjuvant treatment) for which the level of evidence (LOE) was variable. PHI and 4Kscore were the biomarkers with the highest LOE for discriminating aggressive and indolent tumours in different indications. Blood biomarkers (PHI and 4Kscore) have the highest LOE for the prediction of more aggressive prostate cancer and could help clinicians to manage patients with localised prostate cancer. The other biomarkers show a potential prognostic value; however, they should be evaluated in additional studies to confirm their clinical validity. We reviewed studies assessing the value of six prognostic biomarkers for prostate cancer. On the basis of the available evidence, some biomarkers could help in discriminating between aggressive and non-aggressive tumours with an additional value compared to the prognostic parameters currently used by clinicians. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Gastric lymphomas in Turkey. Analysis of prognostic factors with special emphasis on flow cytometric DNA content.

PubMed

Aydin, Z D; Barista, I; Canpinar, H; Sungur, A; Tekuzman, G

2000-07-01

In contrast to DNA ploidy, to the authors' knowledge the prognostic significance of S-phase fraction (SPF) in gastric lymphomas has not been determined. In the current study, the prognostic significance of various parameters including SPF and DNA aneuploidy were analyzed and some distinct epidemiologic and biologic features of gastric lymphomas in Turkey were found. A series of 78 gastric lymphoma patients followed at Hacettepe University is reported. DNA flow cytometry was performed for 34 patients. The influence of various parameters on survival was investigated with the log rank test. The Cox proportional hazards model was fitted to identify independent prognostic factors. The median age of the patients was 50 years. There was no correlation between patient age and tumor grade. DNA content analysis revealed 4 of the 34 cases to be aneuploid with DNA index values < 1.0. The mean SPF was 33.5%. In the univariate analysis, surgical resection of the tumor, modified Ann Arbor stage, performance status, response to first-line chemotherapy, lactate dehydrogenase (LDH) level, and SPF were important prognostic factors for disease free survival (DFS). The same parameters, excluding LDH level, were important for determining overall survival (OS). In the multivariate analysis, surgical resection of the tumor, disease stage, performance status, and age were found to be important prognostic factors for OS. To the authors' knowledge the current study is the first to demonstrate the prognostic significance of SPF in gastric lymphomas. The distinguishing features of Turkish gastric lymphoma patients are 1) DNA indices of aneuploid cases that all are < 1.0, which is a unique feature; 2) a lower percentage of aneuploid cases; 3) a higher SPF; 4) a younger age distribution; and 5) lack of an age-grade correlation. The authors conclude that gastric lymphomas in Turkey have distinct biologic and epidemiologic characteristics. Copyright 2000 American Cancer Society.

The prognostic value of the systemic inflammatory score in patients with unresectable metastatic colorectal cancer.

PubMed

Shibutani, Masatsune; Maeda, Kiyoshi; Nagahara, Hisashi; Fukuoka, Tatsunari; Matsutani, Shinji; Kimura, Kenjiro; Amano, Ryosuke; Hirakawa, Kosei; Ohira, Masaichi

2018-07-01

Inflammation has been widely recognized as a contributor to cancer progression and several inflammatory markers have been reported as associated with the clinical outcomes in patients with various types of cancer. Recently, a novel inflammatory marker, the systemic inflammatory score (SIS), which is based on a combination of the lymphocyte-to-monocyte ratio (LMR) and the serum albumin concentration has been reported as a useful prognostic marker. The aim of the present study was to assess the prognostic value of the SIS in patients with unresectable metastatic colorectal cancer (mCRC). The retrospective cohort study included 160 patients who underwent combination chemotherapy for unresectable mCRC between January 2008 and December 2016. The SIS was used to classify the patients into three groups based on their LMR and the serum albumin concentration. Patients with high-LMR and high serum albumin level were given a score of 0; patients with low-LMR or low serum albumin level were given a score of 1; patients with low-LMR and low serum albumin level were given a score of 2. There were significant differences in the overall survival among the three SIS groups and the SIS was an independent prognostic factor for the overall survival. Although the SIS was significantly associated with the overall survival rate even when using the original cut-off values, the SIS according to the new cut-off values had a more accurate prognostic value. The present study determined that the SIS was a useful biomarker for predicting the survival outcomes in patients with unresectable mCRC, although the optimum cut-off value of the SIS according to the patients' background needs to be examined in further studies.

Bimodality of intratumor Ki67 expression is an independent prognostic factor of overall survival in patients with invasive breast carcinoma.

PubMed

Laurinavicius, Arvydas; Plancoulaine, Benoit; Rasmusson, Allan; Besusparis, Justinas; Augulis, Renaldas; Meskauskas, Raimundas; Herlin, Paulette; Laurinaviciene, Aida; Abdelhadi Muftah, Abir A; Miligy, Islam; Aleskandarany, Mohammed; Rakha, Emad A; Green, Andrew R; Ellis, Ian O

2016-04-01

Proliferative activity, assessed by Ki67 immunohistochemistry (IHC), is an established prognostic and predictive biomarker of breast cancer (BC). However, it remains under-utilized due to lack of standardized robust measurement methodologies and significant intratumor heterogeneity of expression. A recently proposed methodology for IHC biomarker assessment in whole slide images (WSI), based on systematic subsampling of tissue information extracted by digital image analysis (DIA) into hexagonal tiling arrays, enables computation of a comprehensive set of Ki67 indicators, including intratumor variability. In this study, the tiling methodology was applied to assess Ki67 expression in WSI of 152 surgically removed Ki67-stained (on full-face sections) BC specimens and to test which, if any, Ki67 indicators can predict overall survival (OS). Visual Ki67 IHC estimates and conventional clinico-pathologic parameters were also included in the study. Analysis revealed linearly independent intrinsic factors of the Ki67 IHC variance: proliferation (level of expression), disordered texture (entropy), tumor size and Nottingham Prognostic Index, bimodality, and correlation. All visual and DIA-generated indicators of the level of Ki67 expression provided significant cutoff values as single predictors of OS. However, only bimodality indicators (Ashman's D, in particular) were independent predictors of OS in the context of hormone receptor and HER2 status. From this, we conclude that spatial heterogeneity of proliferative tumor activity, measured by DIA of Ki67 IHC expression and analyzed by the hexagonal tiling approach, can serve as an independent prognostic indicator of OS in BC patients that outperforms the prognostic power of the level of proliferative activity.

An elevated serum beta-2-microglobulin level is an adverse prognostic factor for overall survival in patients with early-stage Hodgkin disease.

PubMed

Chronowski, Gregory M; Wilder, Richard B; Tucker, Susan L; Ha, Chul S; Sarris, Andreas H; Hagemeister, Fredrick B; Barista, Ibrahim; Hess, Mark A; Cabanillas, Fernando; Cox, James D

2002-12-15

The relative importance of prognostic factors in patients with early-stage Hodgkin disease remains controversial. The purpose of this study was to evaluate prognostic factors among patients who received chemotherapy before radiotherapy. From 1987 to 1995, 217 consecutive patients ranging in age from 16 to 88 years (median, 28 years) with Ann Arbor Stage I (n = 55) or II (n = 162) Hodgkin disease underwent chemotherapy before radiotherapy at a single center. Most were treated on prospective studies. Patients received a median of three cycles of induction chemotherapy. Mitoxantrone, vincristine, vinblastine, and prednisone (NOVP), doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), mechlorethamine, vincristine, procarbazine, and prednisone (MOPP), cyclophosphamide, vinblastine, procarbazine, prednisone, doxorubicin, bleomycin, dacarbazine, and CCNU (CVPP/ABDIC), or other chemotherapeutic regimens were given to 160, 18, 15, 10, and 14 patients, respectively. The median radiotherapy dose was 40 Gy. Serum beta-2-microglobulin (beta-2M) levels ranged from 1.0 to 4.1 mg/L (median, 1.7 mg/L; upper limit of normal, 2.0 mg/L). We studied univariate and multivariate associations between survival and the following clinical features: serum beta-2M level above 1.25 times the upper limit of normal (n = 12), male gender (n = 113), hypoalbuminemia (n = 11), and bulky mediastinal disease (n = 94). Follow-up of surviving patients ranged from 0.9 to 13.4 years (median, 6.6 years) and 92% were observed for 3.0 or more years. Nineteen patients have died. Only elevation of the serum beta-2M level was an independent adverse prognostic factor for overall survival (P = 0.0009). The prognostic significance of a simple, widely available, and inexpensive blood test, beta-2M, has not been studied routinely in patients with Hodgkin disease and should be tested prospectively in large, cooperative group trials. Copyright 2002 American Cancer Society.DOI 10.1002/cncr.10998

Entropy-Based Adaptive Nuclear Texture Features are Independent Prognostic Markers in a Total Population of Uterine Sarcomas

PubMed Central

Nielsen, Birgitte; Hveem, Tarjei Sveinsgjerd; Kildal, Wanja; Abeler, Vera M; Kristensen, Gunnar B; Albregtsen, Fritz; Danielsen, Håvard E; Rohde, Gustavo K

2015-01-01

Nuclear texture analysis measures the spatial arrangement of the pixel gray levels in a digitized microscopic nuclear image and is a promising quantitative tool for prognosis of cancer. The aim of this study was to evaluate the prognostic value of entropy-based adaptive nuclear texture features in a total population of 354 uterine sarcomas. Isolated nuclei (monolayers) were prepared from 50 µm tissue sections and stained with Feulgen-Schiff. Local gray level entropy was measured within small windows of each nuclear image and stored in gray level entropy matrices, and two superior adaptive texture features were calculated from each matrix. The 5-year crude survival was significantly higher (P < 0.001) for patients with high texture feature values (72%) than for patients with low feature values (36%). When combining DNA ploidy classification (diploid/nondiploid) and texture (high/low feature value), the patients could be stratified into three risk groups with 5-year crude survival of 77, 57, and 34% (Hazard Ratios (HR) of 1, 2.3, and 4.1, P < 0.001). Entropy-based adaptive nuclear texture was an independent prognostic marker for crude survival in multivariate analysis including relevant clinicopathological features (HR = 2.1, P = 0.001), and should therefore be considered as a potential prognostic marker in uterine sarcomas. © The Authors. Published 2014 International Society for Advancement of Cytometry PMID:25483227

Prognostic Value of Ultrasound Grading Systems in Prenatally Diagnosed Unilateral Urinary Tract Dilatation.

PubMed

Scalabre, Aurélien; Demède, Delphine; Gaillard, Ségolène; Pracros, Jean-Pierre; Mouriquand, Pierre; Mure, Pierre-Yves

2017-04-01

We compared the prognostic value of anteroposterior intrasinus diameter of the renal pelvis, urinary tract dilatation and the Society for Fetal Urology grading system in children with prenatally diagnosed unilateral urinary tract dilatation. All newborns with prenatally diagnosed unilateral urinary tract dilatation, normal bladder and anteroposterior intrasinus diameter 10 mm or greater on the first postnatal ultrasonography were prospectively enrolled from January 2011 to February 2015. Indications for surgery were recurrent febrile urinary tract infections and/or decrease of relative renal function more than 10% on serial isotope studies and/or increasing anteroposterior intrasinus diameter greater than 20% on serial ultrasounds. Sensitivity, specificity and ROC curves were calculated to evaluate the accuracy of anteroposterior intrasinus diameter, urinary tract dilatation and Society for Fetal Urology grading system in determining which children would need surgery within 24 months. A total of 57 males and 13 females were included. Of the patients 33 required surgery at a median age of 5 months (IQR 3.8 to 6.4). Urinary tract dilatation remained stable in 14 cases and decreased in 23 with a median followup of 42 months (IQR 25 to 67). Anteroposterior intrasinus diameter, urinary tract dilatation and Society for Fetal Urology scores were all correlated with the need for surgery. Anteroposterior intrasinus diameter with a threshold of 20 mm had the best prognostic value, with a sensitivity of 81.8% and a specificity of 91.7%. Our study confirms that the prognostic value was comparable between anteroposterior intrasinus diameter of the renal pelvis, urinary tract dilatation and Society for Fetal Urology grading system in newborns with prenatally diagnosed unilateral urinary tract dilatation. Anteroposterior intrasinus diameter and abnormal parenchymal thickness are the most important ultrasound criteria to identify children at risk for requiring surgery. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Six-minute walk test and cardiopulmonary exercise testing in patients with chronic heart failure: a comparative analysis on clinical and prognostic insights.

PubMed

Guazzi, Marco; Dickstein, Kenneth; Vicenzi, Marco; Arena, Ross

2009-11-01

The six-minute walk test (6MWT) and cardiopulmonary exercise testing (CPET) are the 2 testing modalities most broadly used for assessing functional limitation in patients with heart failure (HF). A comprehensive comparison on clinical and prognostic validity of the 2 techniques has not been performed and is the aim of the present investigation. Two hundred fifty-three patients diagnosed with systolic (n=211) or diastolic (n=42) HF (age: 61.9+/-10.1 years; New York Heart Association Class: 2.2+/-0.78) underwent a 6MWT and a symptom-limited CPET evaluation and were prospectively followed up. During the 4-year tracking period, there were 43 cardiac-related deaths with an annual cardiac mortality rate of 8.7%. The 6MWT distance correlated with CPET-derived variables (ie, peak Vo(2), Vo(2) at anaerobic threshold, and Ve/Vco(2) slope) and was significantly reduced in proportion with lower peak Vo(2) and higher Ve/Vco(2) slope classes and presence of an exercise oscillatory breathing (EOB) pattern (P<0.01). However, no significant differences were observed in distance covered between survivors and nonsurvivors (353.2+/-95.8 m versus 338.5+/-76.4 m; P=NS). At univariate and multivariate Cox proportional analyses, the association of the 6MWT distance with survival was not significant either as a continuous or dicotomized variable (< or =300 m). Conversely, CPET-derived variables emerged as prognostic with the strongest association found for EOB (systolic HF) and Ve/Vco(2) slope (entire population with HF and patients with a 6MWT< or =300 m). The 6MWT is confirmed to be a simple and reliable first-line test for quantification of exercise intolerance in patients with HF. However, there is no supportive evidence for its use as a prognostic marker in alternative to or in conjunction with CPET-derived variables.

Analysis of overall survival in a large multiethnic cohort reveals absolute neutrophil count of 1,100 as a novel prognostic cutoff in African Americans

PubMed Central

Mantzaris, Ioannis; Yu, Yiting; Msaouel, Pavlos; Lam, Anthony P.; Janakiram, Murali; Friedman, Ellen W.; Steidl, Ulrich; Verma, Amit K.

2016-01-01

Although absolute neutrophil counts (ANC) below 1.5x103/uL are used to define neutropenia as a marker of increased susceptibility to infections, their relationship with survival has not been examined. Since low counts trigger extensive investigations, determining prognostic cutoffs especially for different ethnicities and races is critical. A multiethnic cohort of 27,760 subjects, 65 years old and above, was utilized to evaluate the association of neutropenia with overall survival in different ethnicities and races. The mean ANC was 4.6±1.51x103/uL in non-Hispanic whites, 3.6±1.57x103/uL in non-Hispanic blacks and 4.3±1.54x103/uL in Hispanics (p<0.001). An ANC below 1.5x103/uL was associated with significantly shorter overall survival among whites (HR 1.74; 95% CI 1.18 - 2.58; p<0.001), but not in blacks (HR 0.89; 95% CI 0.86 - 1.17; p=0.40) or Hispanics (HR 1.04; 95% CI 0.76 - 1.46; p=0.82), after adjustment for age, sex, comorbidities, anemia and thrombocytopenia. Using Cox regression multivariable models, an ANC below 1.1x103/uL in blacks was found to be associated with increased mortality (HR 1.86; 95%CI 1.21 - 2.87; p<0.01). We found no association between neutropenia and mortality at any ANC cutoff in elderly Hispanics. In conclusion, neutropenia was found to be an independent prognostic variable in the elderly, when determined in race-specific manner. Most importantly, a cutoff of 1.1x103 neutrophils/uL may be a more prognostically relevant marker in elderly blacks and could serve as a novel threshold for further evaluation and intervention in this population. PMID:27144332

1 H MR spectroscopy in cervical carcinoma using external phase array body coil at 3.0 Tesla: Prediction of poor prognostic human papillomavirus genotypes.

PubMed

Lin, Gigin; Lai, Chyong-Huey; Tsai, Shang-Yueh; Lin, Yu-Chun; Huang, Yu-Ting; Wu, Ren-Chin; Yang, Lan-Yan; Lu, Hsin-Ying; Chao, Angel; Wang, Chiun-Chieh; Ng, Koon-Kwan; Ng, Shu-Hang; Chou, Hung-Hsueh; Yen, Tzu-Chen; Hung, Ji-Hong

2017-03-01

To assess the clinical value of proton ( 1 H) MR spectroscopy in cervical carcinomas, in the prediction of poor prognostic human papillomavirus (HPV) genotypes as well as persistent disease following concurrent chemoradiotherapy (CCRT). 1 H MR spectroscopy using external phase array coil was performed in 52 consecutive cervical cancer patients at 3 Tesla (T). Poor prognostic HPV genotypes (alpha-7 species or absence of HPV infection) and persistent cervical carcinoma after CCRT were recorded. Statistical significance was calculated with the Mann-Whitney two-sided nonparametric test and areas under the receiver operating characteristics curve (AUC) analysis. A 4.3-fold (P = 0.032) increased level of methyl resonance at 0.9 ppm was found in the poor prognostic HPV genotypes, mainly attributed to the presence of HPV18, with a sensitivity of 75%, a specificity of 81%, and an AUC of 0.76. Poor prognostic HPV genotypes were more frequently observed in patients with adeno-/adenosquamous carcinoma (Chi-square, P < 0.0001). In prediction of the four patients with persistent disease after CCRT, elevated methyl resonance demonstrated a sensitivity of 100%, a specificity of 74%, and an AUC of 0.82. 1 H MR spectroscopy at 3T can be used to depict the elevated lipid resonance levels in cervical carcinomas, as well as help to predict the poor prognostic HPV genotypes and persistent disease following CCRT. Further large studies with longer follow up times are warranted to validate our initial findings. 1 J. Magn. Reson. Imaging 2017;45:899-907. © 2016 International Society for Magnetic Resonance in Medicine.

Combined evaluation of the FAS cell surface death receptor and CD8+ tumor infiltrating lymphocytes as a prognostic biomarker in breast cancer

PubMed Central

Blok, Erik J.; van den Bulk, Jitske; Dekker-Ensink, N. Geeske; Derr, Remco; Kanters, Corné; Bastiaannet, Esther; Kroep, Judith R.; van de Velde, Cornelis J.H.; Kuppen, Peter J.K.

2017-01-01

Multiple studies showed the prognostic capacities of tumor-infiltrating lymphocytes (TILs) in triple-negative breast cancer (TNBC), but not in other subtypes. We evaluated tumor expression of FAS, a key receptor in T-cell mediated apoptosis, as possible explanation for this differential prognostic value of TILs. Furthermore, we evaluated the prognostic relevance of FAS, both as an independent biomarker and in relation to CD8-positive T-cell presence. The study cohort consisted of 667 breast cancer patients treated in the LUMC between 1997 and 2009. FAS expression was determined using immunohistochemistry and the percentage of FAS-positive tumor cells was quantified. Furthermore, the number of CD8-positive infiltrating cells was determined, and its prognostic relevance was associated to FAS-expression using stratified survival analysis. In TNBC, FAS was averagely expressed in 49% of tumor cells, whereas ER-positive subtypes showed an average Fas expression of 16-20%. In the entire cohort, FAS was identified as significant prognostic marker for recurrence (adjusted HR 0.53, 95% CI 0.36-0.77) and borderline significant marker for overall survival (adjusted HR 0.72, 95% CI 0.52-1.01). Upon stratification for FAS-expression, CD8+ TILs were only prognostic at high levels (above median) of FAS expression in ER-negative disease. In summary, FAS was identified as an independent prognostic marker for recurrence free survival in breast cancer, with large variation in expression by receptor subtypes. Interestingly, the prognostic effect of CD8+ TILs in ER-negative disease was only valid for tumors with a high FAS expression. PMID:28121628

Combined evaluation of the FAS cell surface death receptor and CD8+ tumor infiltrating lymphocytes as a prognostic biomarker in breast cancer.

PubMed

Blok, Erik J; van den Bulk, Jitske; Dekker-Ensink, N Geeske; Derr, Remco; Kanters, Corné; Bastiaannet, Esther; Kroep, Judith R; van de Velde, Cornelis J H; Kuppen, Peter J K

2017-02-28

Multiple studies showed the prognostic capacities of tumor-infiltrating lymphocytes (TILs) in triple-negative breast cancer (TNBC), but not in other subtypes. We evaluated tumor expression of FAS, a key receptor in T-cell mediated apoptosis, as possible explanation for this differential prognostic value of TILs. Furthermore, we evaluated the prognostic relevance of FAS, both as an independent biomarker and in relation to CD8-positive T-cell presence. The study cohort consisted of 667 breast cancer patients treated in the LUMC between 1997 and 2009. FAS expression was determined using immunohistochemistry and the percentage of FAS-positive tumor cells was quantified. Furthermore, the number of CD8-positive infiltrating cells was determined, and its prognostic relevance was associated to FAS-expression using stratified survival analysis. In TNBC, FAS was averagely expressed in 49% of tumor cells, whereas ER-positive subtypes showed an average Fas expression of 16-20%. In the entire cohort, FAS was identified as significant prognostic marker for recurrence (adjusted HR 0.53, 95% CI 0.36-0.77) and borderline significant marker for overall survival (adjusted HR 0.72, 95% CI 0.52-1.01). Upon stratification for FAS-expression, CD8+ TILs were only prognostic at high levels (above median) of FAS expression in ER-negative disease. In summary, FAS was identified as an independent prognostic marker for recurrence free survival in breast cancer, with large variation in expression by receptor subtypes. Interestingly, the prognostic effect of CD8+ TILs in ER-negative disease was only valid for tumors with a high FAS expression.

Clinical implications of six inflammatory biomarkers as prognostic indicators in Ewing sarcoma

PubMed Central

Li, Yong-Jiang; Yang, Xi; Zhang, Wen-Biao; Yi, Cheng; Wang, Feng; Li, Ping

2017-01-01

Cancer-related systemic inflammation responses have been correlated with cancer development and progression. The prognostic significance of several inflammatory indicators, including neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), Glasgow Prognostic Score (GPS), C-reactive protein to albumin ratio (CRP/Alb ratio), lymphocyte–monocyte ratio (LMR), and neutrophil–platelet score (NPS), were found to be correlated with prognosis in several cancers. However, the prognostic role of these inflammatory biomarkers in Ewing sarcoma has not been evaluated. This study enrolled 122 Ewing patients. Receiver operating characteristic (ROC) analysis was generated to determine optimal cutoff values; areas under the curves (AUCs) were assessed to show the discriminatory ability of the biomarkers; Kaplan–Meier analysis was conducted to plot the survival curves; and Cox multivariate survival analysis was performed to identify independent prognostic factors. The optimal cutoff values of CRP/Alb ratio, NLR, PLR, and LMR were 0.225, 2.38, 131, and 4.41, respectively. CRP/Alb ratio had a significantly larger AUC than NLR, PLR, LMR, and NPS. Higher levels of CRP/Alb ratio (hazard ratio [HR] 2.41, P=0.005), GPS (HR 2.27, P=0.006), NLR (HR 2.07, P=0.013), and PLR (HR 1.85, P=0.032) were significantly correlated with poor prognosis. As the biomarkers had internal correlations, only the CRP/Alb ratio was involved in the multivariate Cox analysis and remained an independent prognostic indicator. The study demonstrated that CRP/Alb ratio, GPS, and NLR were effective prognostic indicators for patients with Ewing sarcoma, and the CRP/Alb ratio was the most robust prognostic indicator with a discriminatory ability superior to that of the other indicators; however, PLR, LMR, and NPS may not be suitable as prognostic indicators in Ewing sarcoma. PMID:29033609

GAS PHOTOTUBE CIRCUIT

DOEpatents

Richardson, J.H.

1958-03-01

This patent pertains to electronic circuits for measuring the intensity of light and is especially concerned with measurement between preset light thresholds. Such a circuit has application in connection with devices for reading-out information stored on punch cards or tapes where the cards and tapes are translucent. By the novel arrangement of this invention thc sensitivity of a gas phototube is maintained at a low value when the light intensity is below a first threshold level. If the light level rises above the first threshold level, the tube is rendered highly sensitive and an output signal will vary in proportion to the light intensity change. When the light level decreases below a second threshold level, the gas phototube is automatically rendered highly insensitive. Each of these threshold points is adjustable.

Potential Biomarkers of Fat Loss as a Feature of Cancer Cachexia.

PubMed

Ebadi, Maryam; Mazurak, Vera C

2015-01-01

Fat loss is associated with shorter survival and reduced quality of life in cancer patients. Effective intervention for fat loss in cachexia requires identification of the condition using prognostic biomarkers for early detection and prevention of further depletion. No biomarkers of fat mass alterations have been defined for application to the neoplastic state. Several inflammatory cytokines have been implicated in mediating fat loss associated with cachexia; however, plasma levels may not relate to adipose atrophy. Zinc-α2-glycoprotein may be a local catabolic mediator within adipose tissue rather than serving as a plasma biomarker of fat loss. Plasma glycerol and leptin associate with adipose tissue atrophy and mass, respectively; however, no study has evaluated their potential as a prognostic biomarker of cachexia-associated fat loss. This review confirms the need for further studies to identify valid prognostic biomarkers to identify loss of fat based on changes in plasma levels of biomarkers.

The role of copeptin as a diagnostic and prognostic biomarker for risk stratification in the emergency department

PubMed Central

2012-01-01

The hypothalamic-pituitary-adrenal axis is activated in response to stress. One of the activated hypothalamic hormones is arginine vasopressin, a hormone involved in hemodynamics and osmoregulation. Copeptin, the C-terminal part of the arginine vasopressin precursor peptide, is a sensitive and stable surrogate marker for arginine vasopressin release. Measurement of copeptin levels has been shown to be useful in a variety of clinical scenarios, particularly as a prognostic marker in patients with acute diseases such as lower respiratory tract infection, heart disease and stroke. The measurement of copeptin levels may provide crucial information for risk stratification in a variety of clinical situations. As such, the emergency department appears to be the ideal setting for its potential use. This review summarizes the recent progress towards determining the prognostic and diagnostic value of copeptin in the emergency department. PMID:22264220

Influence of fatiguing noise on auditory evoked responses to stimuli of various levels in a beluga whale, Delphinapterus leucas.

PubMed

Popov, Vladimir V; Sysueva, Evgeniya V; Nechaev, Dmitry I; Rozhnov, Viatcheslav V; Supin, Alexander Ya

2017-03-15

The negative impact of man-made noise on the hearing of odontocetes has attracted considerable recent attention. In the majority of studies, permanent or temporary reductions in sensitivity, known as permanent or temporary threshold shift (PTS or TTS, respectively), have been investigated. In the present study, the effects of a fatiguing sound on the hearing of a beluga whale, Delphinapterus leucas , within a wide range of levels of test signals was investigated. The fatiguing noise was half-octave band-limited noise centered at 32 kHz. Post-exposure effects of this noise on the evoked responses to test stimuli (rhythmic pip trains with a 45-kHz center frequency) at various levels (from threshold to 60 dB above threshold) were measured. For baseline (pre-exposure) responses, the magnitude-versus-level function featured a segment of steep magnitude dependence on level (up to 30 dB above threshold) that was followed by a plateau segment that featured little dependence on level (30 to 55 dB above threshold). Post-exposure, the function shifted upward along the level scale. The shift was 23 dB at the threshold and up to 33 dB at the supra-threshold level. Owing to the plateau in the magnitude-versus-level function, post-exposure suppression of responses depended on the stimulus level such that higher levels corresponded to less suppression. The experimental data may be modeled based on the compressive non-linearity of the cochlea. According to the model, post-exposure responses of the cochlea to high-level stimuli are minimally suppressed compared with the pre-exposure responses, despite a substantially increased threshold. © 2017. Published by The Company of Biologists Ltd.

40 CFR Table Jj-1 to Subpart Jj of... - Animal Population Threshold Level Below Which Facilities Are Not Required To Report Emissions...

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 22 2012-07-01 2012-07-01 false Animal Population Threshold Level... Subpart JJ of Part 98—Animal Population Threshold Level Below Which Facilities Are Not Required To Report...,200 Swine 34,100 Poultry: Layers 723,600 Broilers 38,160,000 Turkeys 7,710,000 1 The threshold head...

Prognostic grouping of metastatic prostate cancer using conventional pretreatment prognostic factors.

PubMed

Mikkola, Arto; Aro, Jussi; Rannikko, Sakari; Ruutu, Mirja

2009-01-01

To develop three prognostic groups for disease specific mortality based on the binary classified pretreatment variables age, haemoglobin concentration (Hb), erythrocyte sedimentation rate (ESR), alkaline phosphatase (ALP), prostate-specific antigen (PSA), plasma testosterone and estradiol level in hormonally treated patients with metastatic prostate cancer (PCa). The present study comprised 200 Finnprostate 6 study patients, but data on all variables were not known for every patient. The patients were divided into three prognostic risk groups (Rgs) using the prognostically best set of pretreatment variables. The best set was found by backward stepwise selection and the effect of every excluded variable on the binary classification cut-off points of the remaining variables was checked and corrected when needed. The best group of variables was ALP, PSA, ESR and age. All data were known in 142 patients. Patients were given one risk point each for ALP > 180 U/l (normal value 60-275 U/l), PSA > 35 microg/l, ESR > 80 mm/h and age < 60 years. Three risk groups were formed: Rg-a (0-1 risk points), Rg-b (2 risk points) and Rg-c (3-4 risk points). The risk of death from PCa increased statistically significantly with advancing prognostic group. Patients with metastatic PCa can be divided into three statistically significantly different prognostic risk groups for PCa-specific mortality by using the binary classified pretreatment variables ALP, PSA, ESR and age.

Emphasizing Malleability in the Biology of Depression: Durable Effects on Perceived Agency and Prognostic Pessimism

PubMed Central

Lebowitz, Matthew S.; Ahn, Woo-kyoung

2015-01-01

Biological attributions for depression, which are currently ascendant, can lead to prognostic pessimism—the perception that symptoms are relatively immutable and unlikely to abate (Kvaale, Haslam, & Gottdiener, 2013; Lebowitz, Ahn, & Nolen-Hoeksema, 2013). Among symptomatic individuals, this may have important clinical ramifications, as reduced confidence in one’s own ability to overcome depression carries the risk of becoming a self-fulfilling prophecy. Previous research (Lebowitz, Ahn, et al., 2013) has demonstrated that educational interventions teaching symptomatic individuals about how the effects of genetic and neurobiological factors involved in depression are malleable and can be modified by experiences and environmental factors can reduce prognostic pessimism. While previous research demonstrated such effects only in the immediate term, the present research extends these findings by testing whether such benefits persist six weeks after the intervention. Indeed, among individuals who initially considered biological factors to play a major role in influencing their levels of depression, exposure to malleability-focused psychoeducation reduced levels of depression-related prognostic pessimism and stronger belief in their ability to regulate their moods. Critically, this benefit persisted six weeks after the intervention. Clinical implications of the findings are discussed. PMID:26112398

Identification of Serum Periostin as a Potential Diagnostic and Prognostic Marker for Colorectal Cancer.

PubMed

Dong, Dong; Zhang, Lufang; Jia, Li; Ji, Wei; Wang, Zhiyong; Ren, Li; Niu, Ruifang; Zhou, Yunli

2018-06-01

Periostin (POSTN) plays an important role in numerous cancers, especially in gastrointestinal malignancy. The objective of this study was to investigate the diagnostic and prognostic role of serum POSTN in colorectal cancer (CRC). Serum periostin, together with CEA, CA19.9, CA72.4, and CA242 levels were measured in samples from 108 patients with CRC and 56 healthy controls, and their correlation with clinical characteristics was further analyzed. Receiver operating curves (ROC), Kaplan-Meier curves, and log-rank analyses were used to evaluate diagnostic and prognostic significance. Serum POSTN levels were significantly higher in patients with CRC compared with healthy controls (p < 0.0001) and associated with clinical stages (p < 0.001). ROC analysis revealed that POSTN was a biomarker comparable to CEA, CA19.9, and CA72.4 to distinguish all CRC from healthy controls (AUC = 0.75). Moreover, POSTN retained its diagnostic ability for CEA-negative (AUC = 0.69) and CA19.9-negative CRC patients (AUC = 0.71). Survival analysis revealed that patients with lower serum POSTN had longer overall survival than those with high serum POSTN (p = 0.0146). Serum POSTN might be a novel diagnostic and prognostic biomarker for patients with CRC.

Incorporating genomic, transcriptomic and clinical data: a prognostic and stem cell-like MYC and PRC imbalance in high-risk neuroblastoma.

PubMed

Yang, Xinan Holly; Tang, Fangming; Shin, Jisu; Cunningham, John M

2017-10-03

Previous studies suggested that cancer cells possess traits reminiscent of the biological mechanisms ascribed to normal embryonic stem cells (ESCs) regulated by MYC and Polycomb repressive complex 2 (PRC2). Several poorly differentiated adult tumors showed preferentially high expression levels in targets of MYC, coincident with low expression levels in targets of PRC2. This paper will reveal this ESC-like cancer signature in high-risk neuroblastoma (HR-NB), the most common extracranial solid tumor in children. We systematically assembled genomic variants, gene expression changes, priori knowledge of gene functions, and clinical outcomes to identify prognostic multigene signatures. First, we assigned a new, individualized prognostic index using the relative expressions between the poor- and good-outcome signature genes. We then characterized HR-NB aggressiveness beyond these prognostic multigene signatures through the imbalanced effects of MYC and PRC2 signaling. We further analyzed Retinoic acid (RA)-induced HR-NB cells to model tumor cell differentiation. Finally, we performed in vitro validation on ZFHX3, a cell differentiation marker silenced by PRC2, and compared cell morphology changes before and after blocking PRC2 in HR-NB cells. A significant concurrence existed between exons with verified variants and genes showing MYCN-dependent expression in HR-NB. From these biomarker candidates, we identified two novel prognostic gene-set pairs with multi-scale oncogenic defects. Intriguingly, MYC targets over-represented an unfavorable component of the identified prognostic signatures while PRC2 targets over-represented a favorable component. The cell cycle arrest and neuronal differentiation marker ZFHX3 was identified as one of PRC2-silenced tumor suppressor candidates. Blocking PRC2 reduced tumor cell growth and increased the mRNA expression levels of ZFHX3 in an early treatment stage. This hypothesis-driven systems bioinformatics work offered novel insights into the PRC2-mediated tumor cell growth and differentiation in neuroblastoma, which may exert oncogenic effects together with MYC regulation. Our results propose a prognostic effect of imbalanced MYC and PRC2 moderations in pediatric HR-NB for the first time. This study demonstrates an incorporation of genomic landscapes and transcriptomic profiles into the hypothesis-driven precision prognosis and biomarker discovery. The application of this approach to neuroblastoma, as well as other cancer more broadly, could contribute to reduced relapse and mortality rates in the long term.

δ-aminolevulinic acid–induced protoporphyrin IX concentration correlates with histopathologic markers of malignancy in human gliomas: the need for quantitative fluorescence-guided resection to identify regions of increasing malignancy

PubMed Central

Valdés, Pablo A.; Kim, Anthony; Brantsch, Marco; Niu, Carolyn; Moses, Ziev B.; Tosteson, Tor D.; Wilson, Brian C.; Paulsen, Keith D.; Roberts, David W.; Harris, Brent T.

2011-01-01

Extent of resection is a major goal and prognostic factor in the treatment of gliomas. In this study we evaluate whether quantitative ex vivo tissue measurements of δ-aminolevulinic acid–induced protoporphyrin IX (PpIX) identify regions of increasing malignancy in low- and high-grade gliomas beyond the capabilities of current fluorescence imaging in patients undergoing fluorescence-guided resection (FGR). Surgical specimens were collected from 133 biopsies in 23 patients and processed for ex vivo neuropathological analysis: PpIX fluorimetry to measure PpIX concentrations (CPpIX) and Ki-67 immunohistochemistry to assess tissue proliferation. Samples displaying visible levels of fluorescence showed significantly higher levels of CPpIX and tissue proliferation. CPpIX was strongly correlated with histopathological score (nonparametric) and tissue proliferation (parametric), such that increasing levels of CPpIX were identified with regions of increasing malignancy. Furthermore, a large percentage of tumor-positive biopsy sites (∼40%) that were not visibly fluorescent under the operating microscope had levels of CPpIX greater than 0.1 µg/mL, which indicates that significant PpIX accumulation exists below the detection threshold of current fluorescence imaging. Although PpIX fluorescence is recognized as a visual biomarker for neurosurgical resection guidance, these data show that it is quantitatively related at the microscopic level to increasing malignancy in both low- and high-grade gliomas. This work suggests a need for improved PpIX fluorescence detection technologies to achieve better sensitivity and quantification of PpIX in tissue during surgery. PMID:21798847

Pretreatment TG/HDL-C Ratio Is Superior to Triacylglycerol Level as an Independent Prognostic Factor for the Survival of Triple Negative Breast Cancer Patients.

PubMed

Dai, Danian; Chen, Bo; Wang, Bin; Tang, Hailin; Li, Xing; Zhao, Zhiping; Li, Xuan; Xie, Xiaoming; Wei, Weidong

2016-01-01

Previous studies have reported that the triacylglycerol (TG) level and high-density lipoprotein cholesterol (HDL-C) are connected with breast cancer. However, the prognostic utility of the TG level and the TG/HDL-C ratio (THR) as conventional biomarkers in patients with triple negative breast cancer (TNBC) has not been elucidated. In this research, we investigate and compare the predictive value of the pretreatment serum TG level and THR in TNBC patients. We evaluated 221 patients with TNBC who had pretreatment conventional blood biochemical examinations and calculated the THR. Univariate and multivariate logistic regression analyses were used to assess the effect of the TG level and the THR on overall survival (OS) and disease-free survival (DFS). The optimal cutoff values of the TG level and the THR were determined to be 0.935 mmol/L and 0.600, respectively. As shown in a Kaplan-Meier analysis, TNBC patients with a high TG level and THR had shorter OS and DFS than patients in the low-level groups ( p < 0.05). The multivariate analysis suggested that the pretreatment THR level is an independent prognostic factor of OS (HR: 1.935; 95%CI: 1.032-3.629; p = 0.040) in TNBC patients. In conclusion, our data indicate that a high THR is an independent predictor and is superior to the TG level for predicting poor clinical outcomes in TNBC patients.

Proposal and validation of prognostic scoring systems for IgG and IgA monoclonal gammopathies of undetermined significance.

PubMed

Rossi, Francesca; Petrucci, Maria Teresa; Guffanti, Andrea; Marcheselli, Luigi; Rossi, Davide; Callea, Vincenzo; Vincenzo, Federico; De Muro, Marianna; Baraldi, Alessandra; Villani, Oreste; Musto, Pellegrino; Bacigalupo, Andrea; Gaidano, Gianluca; Avvisati, Giuseppe; Goldaniga, Maria; Depaoli, Lorenzo; Baldini, Luca

2009-07-01

The presenting clinico-hematologic features of 1,283 patients with IgG and IgA monoclonal gammopathies of undetermined significance (MGUS) were correlated with the frequency of evolution into multiple myeloma (MM). Two IgG MGUS populations were evaluated: a training sample (553 patients) and a test sample (378 patients); the IgA MGUS population consisted of 352 patients. Forty-seven of the 553 training group patients and 22 of 378 test group IgG patients developed MM after a median follow-up of 6.7 and 3.6 years, respectively. Multivariate analysis showed that serum monoclonal component (MC) levels of < or =1.5 g/dL, the absence of light-chain proteinuria and normal serum polyclonal immunoglobulin levels defined a prognostically favorable subset of patients, and could be used to stratify the patients into three groups at different 10-year risk of evolution (hazard ratio, 1.0, 5.04, 11.2; P < 0.001). This scoring system was validated in the test sample. Thirty of the 352 IgA patients developed MM after a median follow-up of 4.8 years, and multivariate analysis showed that hemoglobin levels of <12.5 g/dL and reduced serum polyclonal immunoglobulin correlated with progression. A pooled statistical analysis of all of the patients confirmed the validity of Mayo Clinic risk model showing that IgA class, serum MC levels, and light-chain proteinuria are the most important variables correlated with disease progression. Using simple variables, we validated a prognostic model for IgG MGUS. Among the IgA cases, the possible prognostic role of hemoglobin emerged in addition to a decrease in normal immunoglobulin levels.

Luteinizing Hormone and Testosterone Levels during Acute Phase of Severe Traumatic Brain Injury: Prognostic Implications for Adult Male Patients

PubMed Central

Hohl, Alexandre; Zanela, Fernando Areas; Ghisi, Gabriela; Ronsoni, Marcelo Fernando; Diaz, Alexandre Paim; Schwarzbold, Marcelo Liborio; Dafre, Alcir Luiz; Reddi, Benjamin; Lin, Kátia; Pizzol, Felipe Dal; Walz, Roger

2018-01-01

Traumatic brain injury (TBI) is a worldwide core public health problem affecting mostly young male subjects. An alarming increase in incidence has turned TBI into a leading cause of morbidity and mortality in young adults as well as a tremendous resource burden on the health and welfare sector. Hormone dysfunction is highly prevalent during the acute phase of severe TBI. In particular, investigation of the luteinizing hormone (LH) and testosterone levels during the acute phase of severe TBI in male has identified a high incidence of low testosterone levels in male patients (36.5–100%) but the prognostic significance of which remains controversial. Two independent studies showed that normal or elevated levels of LH levels earlier during hospitalization are significantly associated with higher mortality/morbidity. The association between LH levels and prognosis was independent of other predictive variables such as neuroimaging, admission Glasgow coma scale, and pupillary reaction. The possible mechanisms underlying this association and further research directions in this field are discussed. Overall, current data suggest that LH levels during the acute phase of TBI might contribute to accurate prognostication and further prospective multicentric studies are required to develop more sophisticated predictive models incorporating biomarkers such as LH in the quest for accurate outcome prediction following TBI. Moreover, the potential therapeutic benefits of modulating LH during the acute phase of TBI warrant investigation. PMID:29487565

Prognostic Significance of Serum Alkaline Phosphatase Level in Osteosarcoma: A Meta-Analysis of Published Data

PubMed Central

Ren, Hai-Yong; Sun, Ling-Ling; Li, Heng-Yuan; Ye, Zhao-Ming

2015-01-01

Background. Serum alkaline phosphatase (SALP) is commonly elevated in osteosarcoma patients. A number of studies have investigated the prognostic role of SALP level in patients with osteosarcoma but yielded inconsistent results. Method. Systematic computerized searches were performed in PubMed, Embase, and Web of Science databases for relevant original articles. The pooled hazard ratios (HRs) and relative risks (RRs) with corresponding confidence intervals (CIs) were calculated to assess the prognostic value of SALP level. Results. Finally, 21 studies comprising 3228 patients were included. Overall, the pooled HRs of SALP suggested that elevated level had an unfavorable impact on osteosarcoma patients' overall survival (OS) (HR = 1.82; 95% CI: 1.61–2.06; p < 0.001) and event-free survival (EFS) (HR = 1.97; 95% CI: 1.61–2.42; p < 0.001). Combined RRs of SALP indicated that elevated level was associated with presence of metastasis at diagnosis (RR = 5.55; 95% CI: 1.61–9.49; p = 0.006). No significantly different results were obtained after stratified by variables of age range, cancer stage, sample size, and geographic region. Conclusion. This meta-analysis demonstrated that high SALP level is significantly associated with poor OS or EFS rate and presence of metastasis at diagnosis. SALP level is a convenient and effective biomarker of prognosis for osteosarcoma. PMID:26618165

Evaluation of serum uric acid levels in normal pregnant Nigerian women.

PubMed

Nwagha, U I; Ejezie, F E; Iyare, E E

2009-03-01

Hypertensive disorders in pregnancy are common in our environment. The aetiology is unknown and the prognostic indicators of the severity of maternal and fetal complications are variable. The level of uric acid, which is one of the prognostic indicators, is altered in normal pregnancy and as pregnancy advances. Base line values are thus extremely important to enable reasonable prognostic assessment in hypertensive pregnancies. To determine levels of serum uric acid during normal pregnancy in University of Nigeria Teaching Hospital (UNTH) Enugu. settings and methods: Sixty- five pregnant and 65 non-pregnant women with age range 20-38 years were recruited. The pregnant women were in their second and third trimesters, attending antenatal clinic at the University of Nigeria Teaching Hospital Enugu. Serum levels of uric acid were determined for the entire subjects. The serum uric acid levels were significantly lower in the pregnant women than in controls (P < 0.001). 0.15 +/- 0.03 mmol/L in the second trimester, 0.14 +/- 0.02 mmol/L in the third trimester and 0.29 +/- 0.04 mmoL for control. The low levels in pregnancy and as pregnancy progresses should be taken into consideration when monitoring hypertensive disorders in pregnancy using serum uric acid. Thus levels that are within normal for non pregnant population may indeed be an indication for intervention in pregnancies complicated by preeclampsia.

Prognostic Value of Serum Caspase-Cleaved Cytokeratin-18 Levels before Liver Transplantation for One-Year Survival of Patients with Hepatocellular Carcinoma

PubMed Central

Lorente, Leonardo; Rodriguez, Sergio T.; Sanz, Pablo; Pérez-Cejas, Antonia; Padilla, Javier; Díaz, Dácil; González, Antonio; Martín, María M.; Jiménez, Alejandro; Barrera, Manuel A.

2016-01-01

Cytokeratin (CK)-18 is the major intermediate filament protein in the liver and during hepatocyte apoptosis is cleaved by the action of caspases; the resulting fragments are released into the blood as caspase-cleaved cytokeratin (CCCK)-18. Higher circulating levels of CCCK-18 have been found in patients with hepatocellular carcinoma (HCC) than in healthy controls and than in cirrhotic patients. However, it is unknown whether serum CCCK-18 levels before liver transplantation (LT) in patients with HCC could be used as a prognostic biomarker of one-year survival, and this was the objective of our study with 135 patients. At one year after LT, non-survivors showed higher serum CCCK-18 levels than survivors (p = 0.001). On binary logistic regression analysis, serum CCCK-18 levels >384 U/L were associated with death at one year (odds ratio = 19.801; 95% confidence interval = 5.301–73.972; p < 0.001) after controlling for deceased donor age. The area under the receiver operating characteristic (ROC) curve of serum CCCK-18 levels to predict death at one year was 77% (95% CI = 69%–84%; p < 0.001). The new finding of our study was that serum levels of CCCK-18 before LT in patients with HCC could be used as prognostic biomarker of survival. PMID:27618033

Prognostic value of tissue-type plasminogen activator (tPA) and its complex with the type-1 inhibitor (PAI-1) in breast cancer

PubMed Central

Witte, J H de; Sweep, C G J; Klijn, J G M; Grebenschikov, N; Peters, H A; Look, M P; Tienoven, ThH van; Heuvel, J J T M; Vries, J Bolt-De; Benraad, ThJ; Foekens, J A

1999-01-01

The prognostic value of tissue-type plasminogen activator (tPA) measured in samples derived from 865 patients with primary breast cancer using a recently developed enzyme-linked immunosorbent assay (ELISA) was evaluated. Since the assay could easily be adapted to the assessment of the complex of tPA with its type-1 inhibitor (PAI-1), it was investigated whether the tPA:PAI-1 complex also provides prognostic information. To this end, cytosolic extracts and corresponding detergent extracts of 100 000 g pellets obtained after ultracentrifugation when preparing the cytosolic fractions for routine steroid hormone receptor determination were assayed. Statistically significant correlations were found between the cytosolic levels and those determined in the pellet extracts (Spearman correlation coefficient rs = 0.75, P < 0.001 for tPA and r = 0.50, P < 0.001 for tPA:PAI-1 complex). In both Cox univariate and multivariate analysis elevated levels of (total) tPA determined in the pellet extracts, but not in cytosols, were associated with prolonged relapse-free (RFS) and overall survival (OS). In contrast, high levels of the tPA:PAI-1 complex measured in cytosols, but not in the pellet extracts, were associated with a poor RFS and OS. The prognostic information provided by the cytosolic tPA:PAI-1 complex was comparable to that provided by cytosolic (total) PAI-1. Furthermore, the estimated levels of free, uncomplexed tPA and PAI-1, in cytosols and in pellet extracts, were related to patient prognosis in a similar way as the (total) levels of tPA and PAI-1 respectively. Determination of specific forms of components of the plasminogen activation system, i.e. tPA:PAI-1 complex and free, uncomplexed tPA and/or PAI-1, may be considered a useful adjunct to the analyses of the separate components (tPA and/or PAI-1) and provide valuable additional prognostic information with respect to survival of breast cancer patients. © 1999 Cancer Research Campaign PMID:10390010

Methods for automatic trigger threshold adjustment

DOEpatents

Welch, Benjamin J; Partridge, Michael E

2014-03-18

Methods are presented for adjusting trigger threshold values to compensate for drift in the quiescent level of a signal monitored for initiating a data recording event, thereby avoiding false triggering conditions. Initial threshold values are periodically adjusted by re-measuring the quiescent signal level, and adjusting the threshold values by an offset computation based upon the measured quiescent signal level drift. Re-computation of the trigger threshold values can be implemented on time based or counter based criteria. Additionally, a qualification width counter can be utilized to implement a requirement that a trigger threshold criterion be met a given number of times prior to initiating a data recording event, further reducing the possibility of a false triggering situation.

The impact of cochlear fine structure on hearing thresholds and DPOAE levels

NASA Astrophysics Data System (ADS)

Lee, Jungmee; Long, Glenis; Talmadge, Carrick L.

2004-05-01

Although otoacoustic emissions (OAE) are used as clinical and research tools, the correlation between OAE behavioral estimates of hearing status is not large. In normal-hearing individuals, the level of OAEs can vary as much as 30 dB when the frequency is changed less than 5%. These pseudoperiodic variations of OAE level with frequency are known as fine structure. Hearing thresholds measured with high-frequency resolution reveals a similar (up to 15 dB) fine structure. We examine the impact of OAE and threshold fine structures on the prediction of auditory thresholds from OAE levels. Distortion product otoacoustic emissions (DPOAEs) were measured with sweeping primary tones. Psychoacoustic detection thresholds were measured using pure tones, sweep tones, FM tones, and narrow-band noise. Sweep DPOAE and narrow-band threshold estimates provide estimates that are less influenced by cochlear fine structure and should lead to a higher correlation between OAE levels and psychoacoustic thresholds. [Research supported by PSC CUNY, NIDCD, National Institute on Disability and Rehabilitation Research in U.S. Department of Education, and The Ministry of Education in Korea.

Wisteria floribunda Agglutinin and Its Reactive-Glycan-Carrying Prostate-Specific Antigen as a Novel Diagnostic and Prognostic Marker of Prostate Cancer

PubMed Central

Hagiwara, Kazuhisa; Tobisawa, Yuki; Kaya, Takatoshi; Kaneko, Tomonori; Hatakeyama, Shingo; Mori, Kazuyuki; Hashimoto, Yasuhiro; Koie, Takuya; Suda, Yoshihiko; Ohyama, Chikara; Yoneyama, Tohru

2017-01-01

Wisteria floribunda agglutinin (WFA) preferably binds to LacdiNAc glycans, and its reactivity is associated with tumor progression. The aim of this study to examine whether the serum LacdiNAc carrying prostate-specific antigen–glycosylation isomer (PSA-Gi) and WFA-reactivity of tumor tissue can be applied as a diagnostic and prognostic marker of prostate cancer (PCa). Between 2007 and 2016, serum PSA-Gi levels before prostate biopsy (Pbx) were measured in 184 biopsy-proven benign prostatic hyperplasia patients and 244 PCa patients using an automated lectin-antibody immunoassay. WFA-reactivity on tumor was analyzed in 260 radical prostatectomy (RP) patients. Diagnostic and prognostic performance of serum PSA-Gi was evaluated using area under the receiver-operator characteristic curve (AUC). Prognostic performance of WFA-reactivity on tumor was evaluated via Cox proportional hazards regression analysis and nomogram. The AUC of serum PSA-Gi detecting PCa and predicting Pbx Grade Group (GG) 3 and GG ≥ 3 after RP was much higher than those of conventional PSA. Multivariate analysis showed that WFA-reactivity on prostate tumor was an independent risk factor of PSA recurrence. The nomogram was a strong model for predicting PSA-free survival provability with a c-index ≥0.7. Serum PSA-Gi levels and WFA-reactivity on prostate tumor may be a novel diagnostic and pre- and post-operative prognostic biomarkers of PCa, respectively. PMID:28134773

Wisteria floribunda Agglutinin and Its Reactive-Glycan-Carrying Prostate-Specific Antigen as a Novel Diagnostic and Prognostic Marker of Prostate Cancer.

PubMed

Hagiwara, Kazuhisa; Tobisawa, Yuki; Kaya, Takatoshi; Kaneko, Tomonori; Hatakeyama, Shingo; Mori, Kazuyuki; Hashimoto, Yasuhiro; Koie, Takuya; Suda, Yoshihiko; Ohyama, Chikara; Yoneyama, Tohru

2017-01-26

Wisteria floribunda agglutinin (WFA) preferably binds to LacdiNAc glycans, and its reactivity is associated with tumor progression. The aim of this study to examine whether the serum LacdiNAc carrying prostate-specific antigen-glycosylation isomer (PSA-Gi) and WFA-reactivity of tumor tissue can be applied as a diagnostic and prognostic marker of prostate cancer (PCa). Between 2007 and 2016, serum PSA-Gi levels before prostate biopsy (Pbx) were measured in 184 biopsy-proven benign prostatic hyperplasia patients and 244 PCa patients using an automated lectin-antibody immunoassay. WFA-reactivity on tumor was analyzed in 260 radical prostatectomy (RP) patients. Diagnostic and prognostic performance of serum PSA-Gi was evaluated using area under the receiver-operator characteristic curve (AUC). Prognostic performance of WFA-reactivity on tumor was evaluated via Cox proportional hazards regression analysis and nomogram. The AUC of serum PSA-Gi detecting PCa and predicting Pbx Grade Group (GG) 3 and GG ≥ 3 after RP was much higher than those of conventional PSA. Multivariate analysis showed that WFA-reactivity on prostate tumor was an independent risk factor of PSA recurrence. The nomogram was a strong model for predicting PSA-free survival provability with a c -index ≥0.7. Serum PSA-Gi levels and WFA-reactivity on prostate tumor may be a novel diagnostic and pre- and post-operative prognostic biomarkers of PCa, respectively.

Prognostic factors in patients with metastatic spinal cord compression secondary to melanoma: a systematic review.

PubMed

Hadden, Nicholas J; McIntosh, Jerome R D; Jay, Samuel; Whittaker, Paula J

2018-02-01

Melanoma is one of the most common primary tumours associated with metastatic spinal cord compression (MSCC). The aim of this review is to identify prognostic factors specifically for MSCC secondary to melanoma. A systematic search of literature was performed in MEDLINE, Embase and the Cochrane Library to identify studies reporting prognostic factors for patients with MSCC secondary to melanoma. Two studies, involving a total of 39 patients, fulfilled the inclusion criteria. The variables associated with increased survival were receiving postoperative radiotherapy, receiving chemotherapy, perioperative lactate dehydrogenase level less than or equal to 8.0 µkat/l, preoperative haemoglobin level more than 11.5 mg/dl, an interval of 4 or more years between melanoma diagnosis and skeletal metastasis, absence of further skeletal metastases, absence of visceral metastases, Eastern Cooperative Oncology Group Performance Status of 2 or less, two or fewer involved vertebrae, being ambulatory preradiotherapy and an interval of more than 7 days between developing motor deficits and radiotherapy. The variables associated with good functional outcome were slow development of motor dysfunction, good performance status and being ambulatory before radiotherapy. The most important prognostic factors for survival are Eastern Cooperative Oncology Group Performance Status of 2 or less and absence of visceral metastases. There is a lack of studies looking specifically at prognostic factors for patients with MSCC secondary to melanoma, and the number of patients involved in the existing studies is small.

Variable selection under multiple imputation using the bootstrap in a prognostic study

PubMed Central

Heymans, Martijn W; van Buuren, Stef; Knol, Dirk L; van Mechelen, Willem; de Vet, Henrica CW

2007-01-01

Background Missing data is a challenging problem in many prognostic studies. Multiple imputation (MI) accounts for imputation uncertainty that allows for adequate statistical testing. We developed and tested a methodology combining MI with bootstrapping techniques for studying prognostic variable selection. Method In our prospective cohort study we merged data from three different randomized controlled trials (RCTs) to assess prognostic variables for chronicity of low back pain. Among the outcome and prognostic variables data were missing in the range of 0 and 48.1%. We used four methods to investigate the influence of respectively sampling and imputation variation: MI only, bootstrap only, and two methods that combine MI and bootstrapping. Variables were selected based on the inclusion frequency of each prognostic variable, i.e. the proportion of times that the variable appeared in the model. The discriminative and calibrative abilities of prognostic models developed by the four methods were assessed at different inclusion levels. Results We found that the effect of imputation variation on the inclusion frequency was larger than the effect of sampling variation. When MI and bootstrapping were combined at the range of 0% (full model) to 90% of variable selection, bootstrap corrected c-index values of 0.70 to 0.71 and slope values of 0.64 to 0.86 were found. Conclusion We recommend to account for both imputation and sampling variation in sets of missing data. The new procedure of combining MI with bootstrapping for variable selection, results in multivariable prognostic models with good performance and is therefore attractive to apply on data sets with missing values. PMID:17629912

lncRNA co-expression network model for the prognostic analysis of acute myeloid leukemia

PubMed Central

Pan, Jia-Qi; Zhang, Yan-Qing; Wang, Jing-Hua; Xu, Ping; Wang, Wei

2017-01-01

Acute myeloid leukemia (AML) is a highly heterogeneous hematologic malignancy with great variability of prognostic behaviors. Previous studies have reported that long non-coding RNAs (lncRNAs) play an important role in AML and may thus be used as potential prognostic biomarkers. However, thus use of lncRNAs as prognostic biomarkers in AML and their detailed mechanisms of action in this disease have not yet been well characterized. For this purpose, in the present study, the expression levels of lncRNAs and mRNAs were calculated using the RNA-seq V2 data for AML, following which a lncRNA-lncRNA co-expression network (LLCN) was constructed. This revealed a total of 8 AML prognosis-related lncRNA modules were identified, which displayed a significant correlation with patient survival (p≤0.05). Subsequently, a prognosis-related lncRNA module pathway network was constructed to interpret the functional mechanism of the prognostic modules in AML. The results indicated that these prognostic modules were involved in the AML pathway, chemokine signaling pathway and WNT signaling pathway, all of which play important roles in AML. Furthermore, the investigation of lncRNAs in these prognostic modules suggested that an lncRNA (ZNF571-AS1) may be involved in AML via the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway by regulating KIT and STAT5. The results of the present study not only provide potential lncRNA modules as prognostic biomarkers, but also provide further insight into the molecular mechanisms of action of lncRNAs. PMID:28204819

Prognostic Importance of Sex-Specific Cardiac Troponin T 99(th) Percentiles in Suspected Acute Coronary Syndrome.

PubMed

Eggers, Kai M; Jernberg, Tomas; Lindahl, Bertil

2016-08-01

Cardiac troponin levels differ between the sexes, with higher values commonly seen in men. The use of sex-specific troponin thresholds is, thus, subject of an ongoing debate. We assessed whether sex-specific cardiac troponin T (cTnT) 99(th) percentiles would improve risk prediction in patients admitted to Swedish coronary care units due to suspected acute coronary syndrome. In this retrospective register-based study (48,250 patients), we investigated the prediction of all-cause mortality and the composite of cardiovascular death or nonfatal myocardial infarction within 1 year using the single 99(th) cTnT percentile (>14 ng/L) or sex-specific cTnT 99(th) percentiles (>16/9 ng/L). A total of 1078 men (3.0%) with cTnT 15-16 ng/L and 1854 women (8.4%) with cTnT 10-14 ng/L would have been reclassified regarding their cTnT status by the means of sex-specific 99(th) percentiles. The prevalence of cardiovascular risk factors and crude event rates increased across higher cTnT strata in both men and women. Multivariable-adjusted Cox models, however, did not demonstrate better risk prediction by sex-specific 99(th) percentiles. Assessing cTnT as a continuous variable demonstrated an increase in multivariable-adjusted risk starting at levels around 10-12 ng/L in both men and women. We found no evidence supporting the use of sex-specific cTnT 99(th) percentiles in men and women admitted because of suspected acute coronary syndrome. This likely depends on sex-specific differences in disease mechanisms associated with small cTnT elevations. From a pragmatic perspective, a single cTnT cutoff slightly below 14 ng/L seems to be preferable as a threshold for medical decision-making. Copyright © 2016 Elsevier Inc. All rights reserved.

Associations between tooth loss and prognostic biomarkers and the risk for cardiovascular events in patients with stable coronary heart disease.

PubMed

Vedin, Ola; Hagström, Emil; Östlund, Ollie; Avezum, Alvaro; Budaj, Andrzej; Flather, Marcus D; Harrington, Robert A; Koenig, Wolfgang; Soffer, Joseph; Siegbahn, Agneta; Steg, Philippe Gabriel; Stewart, Ralph A H; Wallentin, Lars; White, Harvey D; Held, Claes

2017-10-15

Underlying mechanisms behind the hypothesized relationship between periodontal disease (PD) and coronary heart disease (CHD) have been insufficiently explored. We evaluated associations between self-reported tooth loss- a marker of PD- and prognostic biomarkers in 15,456 (97%) patients with stable CHD in the global STABILITY trial. Baseline blood samples were obtained and patients reported their number of teeth according to the following tooth loss levels: "26-32 (All)" [lowest level], "20-25", "15-19", "1-14", and "No Teeth" [highest level]. Linear and Cox regression models assessed associations between tooth loss levels and biomarker levels, and the relationship between tooth loss levels and outcomes, respectively. After multivariable adjustment, the relative biomarker increase between the highest and the lowest tooth loss level was: high-sensitivity C-reactive protein 1.21 (95% confidence interval, 1.14-1.29), interleukin 6 1.14 (1.10-1.18), lipoprotein-associated phospholipase A 2 activity 1.05 (1.03-1.06), growth differentiation factor 15 1.11 (1.08-1.14), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) 1.18 (1.11-1.25). No association was detected for high-sensitivity troponin T 1.02 (0.98-1.05). Some attenuation of the relationship between tooth loss and outcomes resulted from the addition of biomarkers to the multivariable analysis, of which NT-proBNP had the biggest impact. A graded and independent association between tooth loss and several prognostic biomarkers was observed, suggesting that tooth loss and its underlying mechanisms may be involved in multiple pathophysiological pathways also implicated in the development and prognosis of CHD. The association between tooth loss and cardiovascular death and stroke persisted despite comprehensive adjustment including prognostic biomarkers. www.clinicaltrials.gov; NCT00799903. Copyright © 2017 Elsevier B.V. All rights reserved.

NCCN-IPI score-independent prognostic potential of pretreatment uric acid levels for clinical outcome of diffuse large B-cell lymphoma patients

PubMed Central

Prochazka, Katharina T; Melchardt, Thomas; Posch, Florian; Schlick, Konstantin; Deutsch, Alexander; Beham-Schmid, Christine; Weiss, Lukas; Gary, Thomas; Neureiter, Daniel; Klieser, Eckhard; Greil, Richard; Neumeister, Peter; Egle, Alexander; Pichler, Martin

2016-01-01

Background: Blood-based parameters are gaining increasing interest as potential prognostic biomarkers in patients with diffuse large B-cell lymphoma (DLBCL). The aim of this study was to comprehensively evaluate the prognostic significance of pretreatment plasma uric acid levels in patients with newly diagnosed DLBCL. Methods: The clinical course of 539 DLBCL patients, diagnosed and treated between 2004 and 2013 at two Austrian high-volume centres with rituximab-based immunochemotherapy was evaluated retrospectively. The prognostic influence of uric acid on overall survival (OS) and progression-free survival (PFS) were studied including multi-state modelling, and analysis of conditional survival. Results: Five-year OS and PFS were 50.4% (95% CI: 39.2–60.6) and 44.0% (33.4–54.0) in patients with uric acid levels above the 75th percentile of the uric acid distribution (Q3, cut-off: 6.8 mg dl−1), and 66.2% (60.4–71.5) and 59.6% (53.7–65.0%) in patients with lower levels (log-rank P=0.002 and P=0.0045, respectively). In univariable time-to-event analysis, elevated uric acid levels were associated with a worse PFS (hazard ratio (HR) per 1 log increase in uric acid 1.47, 95% CI: 1.10–1.97, P=0.009) and a worse OS (HR=1.60, 95% CI: 1.16–2.19, P=0.004). These associations prevailed upon multivariable adjustment for the NCCN-IPI score. Uric acid levels significantly improved the predictive performance of the R-IPI and NCCN-IPI scores, and in multi-state analysis, it emerged as a highly significant predictor of an increased risk of death without developing recurrence (transition-HR=4.47, 95% CI: 2.17–9.23, P<0.0001). Conclusions: We demonstrate that elevated uric acid levels predict poor long-term outcomes in DLBCL patients beyond the NCCN-IPI risk index. PMID:27764838

Treatment selection for patients with ductal carcinoma in situ (DCIS) of the breast using the University of Southern California/Van Nuys (USC/VNPI) prognostic index.

PubMed

Silverstein, Melvin J; Lagios, Michael D

2015-01-01

The University of Southern California/Van Nuys Prognostic Index (USC/VNPI) is an algorithm that quantifies five measurable prognostic factors known to be important in predicting local recurrence in conservatively treated patients with ductal carcinoma in situ (DCIS) (tumor size, margin width, nuclear grade, age, and comedonecrosis). With five times as many patients since originally developed, sufficient numbers now exist for analysis by individual scores rather than groups of scores. To achieve a local recurrence rate of less than 20% at 12 years, these data support excision alone for all patients scoring 4, 5, or 6 and patients who score 7 but have margin widths ≥3 mm. Excision plus RT achieves the less than 20% local recurrence threshold at 12 years for patients who score 7 and have margins <3 mm, patients who score 8 and have margins ≥3 mm, and for patients who score 9 and have margins ≥5 mm. Mastectomy is required for patients who score 8 and have margins <3 mm, who score 9 and have margins <5 mm and for all patients who score 10, 11, or 12 to keep the local recurrence rate less than 20% at 12 years. DCIS is a highly favorable disease. There is no difference in mortality rate regardless of which treatment is chosen. The USC/VNPI is a numeric tool that can be used to aid the treatment decision-making process. © 2015 Wiley Periodicals, Inc.

Serum level of uric acid, partly secreted from the failing heart, is a prognostic marker in patients with congestive heart failure.

PubMed

Sakai, Hiroshi; Tsutamoto, Takayoshi; Tsutsui, Takashi; Tanaka, Toshinari; Ishikawa, Chitose; Horie, Minoru

2006-08-01

A recent study suggested that xanthine oxidase is activated in congestive heart failure (CHF). However, whether uric acid (UA) is secreted from the failing heart remains unknown, so it is currently unclear whether serum UA can provide prognostic information independent of brain natriuretic peptide (BNP). Serum UA was measured in the aortic root (AO) and the coronary sinus (CS) of 74 patients with CHF. The serum UA level was significantly higher in the CS than in the AO. The transcardiac gradient of UA (CS-AO) increased with the severity of CHF, inversely correlated with left ventricular ejection fraction (LVEF) and positively correlated with left ventricular end-diastolic volume index. The plasma levels of norepinephrine, BNP, UA, and LVEF were monitored prospectively in 150 CHF patients for a mean follow-up of 3 years. High plasma levels of UA (p<0.001) and BNP (p<0.001) were shown by multivariate stepwise analysis to be independent predictors of mortality. High plasma UA level, partly secreted from the failing heart, is a prognostic predictor independent of BNP in patients with CHF. Monitoring a combination of BNP and UA may be useful for the management of patients with CHF.

How to conduct a high-quality original study on a diagnostic research topic.

PubMed

Yao, Xiaomei; Vella, Emily

2017-09-01

As health research methodologists and journal reviewers, we noticed that the methodological rigor of many publications on diagnostic or prognostic topics in the medical literature could be improved. We present a concise and clear series of reviews to help clinicians and health researchers to master the basic key components of how to conduct a high-quality original study or systematic review on a diagnostic or prognostic research topic from a methodological perspective. This is the first review of the series, which focuses on how to conduct a high-quality diagnostic study. We are introducing four aspects: clarifying the objectives; generating an appropriate research question; planning the study design; and reporting and analyzing data. This review highlights that diagnostic test accuracy outcomes are surrogates for patient outcomes, a diagnostic test has three roles, the "PIRO" components should be included in a diagnostic research question, a new study should be registered, multiple index tests can be compared in one study, and prevalence affects test accuracy outcomes. This review also emphasizes reporting any thresholds, calculating sample size, and performing a two-by-three table to calculate diagnostic outcomes. Copyright © 2017 Elsevier Ltd. All rights reserved.

The prognostic impact of clinical and CT parameters in patients with pontine hemorrhage.

PubMed

Dziewas, Rainer; Kremer, Marion; Lüdemann, Peter; Nabavi, Darius G; Dräger, Bianca; Ringelstein, Bernd

2003-01-01

In patients with pontine hemorrhage (PH), an accurate prognostic assessment is critical for establishing a reasonable therapeutic approach. The initial clinical symptoms and computed tomography (CT) features were analyzed with multivariate regression analysis in 39 consecutive patients with PH. PHs were classified into three types: (1) large paramedian, (2) basal or basotegmental and (3) lateral tegmental, and the hematomas' diameters were measured. The patients' outcome was evaluated. Twenty-seven patients (69%) died and 12 (31%) survived for more than 1 year after PH. The symptom most predictive of death was coma on admission. The large paramedian type of PH predicted a poor prognosis, whereas the lateral tegmental type was associated with a favorable outcome. The transverse hematoma diameter was also related to outcome, with the threshold value found to be 20 mm. We conclude that PH outcome can be estimated best by combining the CT parameters 'large paramedian PH' and 'transverse diameter >/=20 mm' with the clinical variable 'coma on admission'. Survival is unlikely if all 3 features are present, whereas survival may be expected if only 1 or none of these features is found. Copyright 2003 S. Karger AG, Basel

Adaptive Multi-scale Prognostics and Health Management for Smart Manufacturing Systems

PubMed Central

Choo, Benjamin Y.; Adams, Stephen C.; Weiss, Brian A.; Marvel, Jeremy A.; Beling, Peter A.

2017-01-01

The Adaptive Multi-scale Prognostics and Health Management (AM-PHM) is a methodology designed to enable PHM in smart manufacturing systems. In application, PHM information is not yet fully utilized in higher-level decision-making in manufacturing systems. AM-PHM leverages and integrates lower-level PHM information such as from a machine or component with hierarchical relationships across the component, machine, work cell, and assembly line levels in a manufacturing system. The AM-PHM methodology enables the creation of actionable prognostic and diagnostic intelligence up and down the manufacturing process hierarchy. Decisions are then made with the knowledge of the current and projected health state of the system at decision points along the nodes of the hierarchical structure. To overcome the issue of exponential explosion of complexity associated with describing a large manufacturing system, the AM-PHM methodology takes a hierarchical Markov Decision Process (MDP) approach into describing the system and solving for an optimized policy. A description of the AM-PHM methodology is followed by a simulated industry-inspired example to demonstrate the effectiveness of AM-PHM. PMID:28736651

Diagnostic and prognostic significance of receptor-binding cancer antigen expressed on SiSo cells in lung-cancer-associated pleural effusion.

PubMed

Yang, Jian; Zhu, Ying; Wu, Liangquan; Zhu, Wenyan; Zhang, Xiuwei; Yang, Yang; Xu, Chunhua

2018-01-01

This study aimed to evaluate the diagnostic and prognostic value of pleural effusion levels of soluble receptor-binding cancer antigen expressed on SiSo cells (sRCAS1) in lung cancer patients with malignant pleural effusion (MPE). Pleural effusion samples were collected from 78 patients with MPE, and from 48 patients with benign pleural effusion (BPE). Pleural effusion sRCAS1 concentrations were measured by enzyme-linked immunosorbent assay. MPE has significantly higher sRCAS1 levels than that of BPE (P < .01). With a cutoff value of 18.7 U/mL, sRCAS1 showed a good diagnostic performance for MPE. Univariate and multivariate analysis indicated that elevated sRCAS1 levels were an independent predictor of overall survival (OS) and disease-free survival (DFS). Kaplan-Meier survival curves further confirmed that patients with high sRCAS1 have shorter DFS and OS (P = .026 and P = .032, respectively). In conclusion, measurement of sRCAS1 might be a useful diagnostic and prognostic marker for MPE. © 2016 John Wiley & Sons Ltd.

Impact of preoperative levels of hemoglobin and albumin on the survival of pancreatic carcinoma.

PubMed

Ruiz-Tovar, J; Martín-Pérez, E; Fernández-Contreras, M E; Reguero-Callejas, M E; Gamallo-Amat, C

2010-11-01

Pancreatic cancer presents the worst survival rates of all neoplasms. Surgical resection is the only potentially curative treatment, but is associated with high complication rates and outcome is bad even in those resected cases. Therefore, candidates amenable for resection must be carefully selected. Identification of prognostic factors preoperatively may help to improve the treatment of these patients, focusing on individually management based on the expected response. We perform a retrospective study of 59 patients with histological diagnosis of pancreatic carcinoma between 1999 and 2003, looking for possible prognostic factors. We analyze 59 patients, 32 males and 27 females with a mean age of 63.8 years. All the patients were operated, performing palliative surgery in 32% and tumoral resection in 68%, including pancreaticoduodenectomies in 51% and distal pancreatectomy in 17%. Median global survival was 14 months (Range 1-110).We observed that preoperative levels of hemoglobin under 12 g/dl (p = 0.0006) and serum albumina under 2.8 g/dl (p = 0.021) are associated with worse survival. Preoperative levels of hemoglobin and serum albumina may be prognostic indicators in pancreatic cancer.

Why Does Threshold Level Change in Transcranial Motor-evoked Potentials During Surgery for Supratentorial Lesions?

PubMed

Abboud, Tammam; Huckhagel, Torge; Stork, Jan-Henrich; Hamel, Wolfgang; Schwarz, Cindy; Vettorazzi, Eik; Westphal, Manfred; Martens, Tobias

2017-10-01

Rising threshold level during monitoring of motor-evoked potentials (MEP) using transcranial electrical stimulation (TES) has been described without damage to the motor pathway in the cranial surgery, suggesting the need for monitoring of affected and unaffected hemisphere. We aimed to determine the factors that lead to a change in threshold level and to establish reliable criteria for adjusting stimulation intensity during surgery for supratentorial lesions. Between October 2014 and October 2015, TES-MEP were performed in 143 patients during surgery for unilateral supratentorial lesions in motor-eloquent brain areas. All procedures were performed under general anesthesia using a strict protocol to maintain stable blood pressure. MEP were evaluated bilaterally to assess the percentage increase in threshold level, which was considered significant if it exceeded 20% on the contralateral side beyond the percentage increase on the ipsilateral side. Patients who developed a postoperative motor deficit were excluded. Volume of subdural air was measured on postoperative magnetic resonance imaging. Logistic regression was performed to identify factors associated with the intraoperative recorded changes in threshold level. A total of 123 patients were included in the study. On the affected side, 82 patients (66.7%) showed an increase in threshold level, which ranged from 2% to 48% and 41 patients (33.3%) did not show any change. The difference to the unaffected side was under 20% in all patients. The recorded range of changes in the systolic and mean pressure did not exceed 20 mm Hg in any of the patients. Pneumocephalus was detected on postoperative magnetic resonance imaging scans in 87 patients (70.7%) and 81 of them (93.1%) had an intraoperative increase in threshold level on either sides. Pneumocephalus was the only factor associated with an increase in threshold level on the affected side (P<0.001), while each of pneumocephalus and length of the procedure correlated with a change in threshold level on the unaffected side (P<0.001 and 0.032, respectively). Pneumocephalus was the only factor associated with increase in threshold level during MEP monitoring without damaging motor pathway. Threshold level on the affected side can rise up to 48% without being predictive of postoperative paresis, as long as the difference between the increased threshold of the affected and unaffected side is within 20%. Changes in systolic or mean blood pressure within a range of 20 mm Hg do not seem to influence intraoperative MEP.

A Novel Independent Survival Predictor in Pulmonary Embolism: Prognostic Nutritional Index.

PubMed

Hayıroğlu, Mert İlker; Keskin, Muhammed; Keskin, Taha; Uzun, Ahmet Okan; Altay, Servet; Kaya, Adnan; Öz, Ahmet; Çinier, Göksel; Güvenç, Tolga Sinan; Kozan, Ömer

2018-05-01

The prognostic impact of nutritional status in patients with pulmonary embolism (PE) is poorly understood. A well-accepted nutritional status parameter, prognostic nutritional index (PNI), which was first demonstrated to be valuable in patients with cancer and gastrointestinal surgery, was introduced to patients with PE. Our aim was to evaluate the predictive value of PNI in outcomes of patients with PE. We evaluated the in-hospital and long-term (53.8 ± 5.4 months) prognostic impact of PNI on 251 patients with PE. During a median follow-up of 53.8 ± 5.4 months, 27 (11.6%) patients died in hospital course and 31 (13.4%) died in out-of-hospital course. The patients with lower PNI had significantly higher in-hospital and long-term mortality. The Cox proportional hazard analyses showed that PNI was associated with an increased risk of all-cause death for both unadjusted model and adjusted for all covariates. Our study demonstrated that PNI, calculated based on serum albumin level and lymphocyte count, is an independent prognostic factor for mortality in patients with PE.

Newly identified poor prognostic factors for adult T-cell leukemia-lymphoma treated with allogeneic hematopoietic stem cell transplantation.

PubMed

Tokunaga, Masahito; Uto, Hirofumi; Takeuchi, Shogo; Nakano, Nobuaki; Kubota, Ayumu; Tokunaga, Mayumi; Takatsuka, Yoshifusa; Seto, Masao; Ido, Akio; Utsunomiya, Atae

2017-01-01

To explore pre-transplantation prognostic factors for adult T-cell leukemia-lymphoma (ATL), we retrospectively analyzed allogeneic hematopoietic stem cell transplantation (allo-HSCT) in 70 patients at our institute (63 acute type and seven lymphoma type patients). Forty-five patients died after HSCT and the three-year overall survival (OS) rate was 35.2%. By univariate analysis, the adverse prognostic factors for OS were performance status ≥2, hematopoietic cell transplantation-specific comorbidity index (HCT-CI) score ≥3, European Group for Blood and Marrow Transplantation (EBMT) risk score ≥5, HSCT from an HLA-mismatched donor, serum soluble interleukin-2 receptor (sIL-2R) level ≥10,000 U/mL, lymphocyte count ≥4000/μL, and hemoglobin <9 g/dL at the time of HSCT. EBMT risk score and sIL-2R were identified as significant adverse prognostic factors using multivariate analysis. This analysis clearly demonstrates for the first time that HCT-CI and EBMT risk scores are reliable prognostic factors for ATL patients receiving allo-HSCT.

Which type of leader do I support in step-level public good dilemmas? The roles of level of threshold and trust.

PubMed

De Cremer, David

2007-02-01

The present research examined the moderating effect of the level of threshold on people's preferences for different leader types in step-level public good dilemmas. It was assumed that the primary focus of people in step-level public good dilemmas is to make sure that the group surpasses the threshold. Consequently, when the level of threshold is difficult to reach people are expected to provide more support for and cooperate with a leader that monitors and controls the contributions made toward the public good. However, if the threshold is easy to surpass people will focus more on whether the obtained public good or bonus will be distributed according to agreements, suggesting that people will provide more support to and cooperate with a leader that monitors and controls the distribution of the bonus. These predictions were confirmed across two experiments using a step-level public good paradigm with a dichotomous (Study 1) and a continuous (Study 2) contribution choice. Moreover, the results also revealed that perceptions of trust accounted, in part, for the effect of level of threshold on people's leadership preferences.

Growth differentiation factor 15, a marker of oxidative stress and inflammation, for risk assessment in patients with atrial fibrillation: insights from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial.

PubMed

Wallentin, Lars; Hijazi, Ziad; Andersson, Ulrika; Alexander, John H; De Caterina, Raffaele; Hanna, Michael; Horowitz, John D; Hylek, Elaine M; Lopes, Renato D; Asberg, Signild; Granger, Christopher B; Siegbahn, Agneta

2014-11-18

Growth differentiation factor 15 (GDF-15), high-sensitivity troponin, and N-terminal pro-brain natriuretic peptide levels are predictive of death and cardiovascular events in healthy elderly subjects, patients with acute coronary syndrome, and patients with heart failure. High-sensitivity troponin I and N-terminal pro-brain natriuretic peptide are also prognostic in patients with atrial fibrillation. We evaluated the prognostic value of GDF-15 alone and in addition to clinical characteristics and other biomarkers in patients with atrial fibrillation. The Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial randomized 18 201 patients with atrial fibrillation to apixaban or warfarin. Biomarkers were measured at randomization in 14 798 patients. Efficacy and safety outcomes during 1.9 years of follow-up were compared across quartiles of GDF-15 by use of Cox analyses adjusted for clinical characteristics, randomized treatment, and other biomarkers. The GDF-15 level showed a median of 1383 ng/L (interquartile range, 977-2052 ng/L). Annual rates of stroke or systemic embolism ranged from 0.9% to 2.03% (P<0.001); of major bleeding, from 1.22% to 4.53% (P<0.001); and of mortality, from 1.34% to 7.19% (P<0.001) in the lowest compared with the highest GDF-15 quartile. The prognostic information provided by GDF-15 was independent of clinical characteristics and clinical risk scores. Adjustment for the other cardiac biomarkers attenuated the prognostic value for stroke, whereas the prognostic value for mortality and major bleeding remained. Apixaban consistently reduced stroke, mortality, and bleeding, regardless of GDF-15 levels. GDF-15 is a risk factor for major bleeding, mortality, and stroke in atrial fibrillation. The prognostic value for major bleeding and death remained even in the presence of N-terminal pro-brain natriuretic peptide and high-sensitivity troponin I. http://www.clinicaltrials.gov. Unique identifier: NCT00412984. © 2014 American Heart Association, Inc.

Net reclassification index at event rate: properties and relationships.

PubMed

Pencina, Michael J; Steyerberg, Ewout W; D'Agostino, Ralph B

2017-12-10

The net reclassification improvement (NRI) is an attractively simple summary measure quantifying improvement in performance because of addition of new risk marker(s) to a prediction model. Originally proposed for settings with well-established classification thresholds, it quickly extended into applications with no thresholds in common use. Here we aim to explore properties of the NRI at event rate. We express this NRI as a difference in performance measures for the new versus old model and show that the quantity underlying this difference is related to several global as well as decision analytic measures of model performance. It maximizes the relative utility (standardized net benefit) across all classification thresholds and can be viewed as the Kolmogorov-Smirnov distance between the distributions of risk among events and non-events. It can be expressed as a special case of the continuous NRI, measuring reclassification from the 'null' model with no predictors. It is also a criterion based on the value of information and quantifies the reduction in expected regret for a given regret function, casting the NRI at event rate as a measure of incremental reduction in expected regret. More generally, we find it informative to present plots of standardized net benefit/relative utility for the new versus old model across the domain of classification thresholds. Then, these plots can be summarized with their maximum values, and the increment in model performance can be described by the NRI at event rate. We provide theoretical examples and a clinical application on the evaluation of prognostic biomarkers for atrial fibrillation. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Proposed Lymph Node Staging System Using the International Consensus Guidelines for Lymph Node Levels Is Predictive for Nasopharyngeal Carcinoma Patients From Endemic Areas Treated With Intensity Modulated Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Wen-Fei; Sun, Ying; Mao, Yan-Ping

2013-06-01

Purpose: To propose a lymph node (N) staging system for nasopharyngeal carcinoma (NPC) based on the International Consensus Guidelines for lymph node (LN) levels and MRI-determined nodal variables. Methods and Materials: The MRI scans and medical records of 749 NPC patients receiving intensity modulated radiation therapy with or without chemotherapy were retrospectively reviewed. The prognostic significance of nodal level, laterality, maximal axial diameter, extracapsular spread, necrosis, and Union for International Cancer Control/American Joint Committee on Cancer (UICC/AJCC) size criteria were analyzed. Results: Nodal level and laterality were the only independent prognostic factors for distant failure and disease failure in multivariatemore » analysis. Compared with unilateral levels Ib, II, III, and/or Va involvement (hazard ratio [HR] 1), retropharyngeal lymph node involvement alone had a similar prognostic value (HR 0.71; 95% confidence interval [CI] 0.43-1.17; P=.17), whereas bilateral levels Ib, II, III, and/or Va involvement (HR 1.65; 95% CI 1.06-2.58; P=.03) and levels IV, Vb, and/or supraclavicular fossa involvement (HR 3.47; 95% CI 1.92-6.29; P<.01) both significantly increased the HR for distant failure. Thus we propose that the N category criteria could be revised as follows: N0, no regional LN metastasis; N1, retropharyngeal lymph node involvement, and/or unilateral levels Ib, II, III, and/or Va involvement; N2, bilateral levels Ib, II, III, and/or Va involvement; N3, levels IV, Vb, and/or supraclavicular fossa involvement. Compared with the 7th edition of the UICC/AJCC criteria, the proposed N staging system provides a more satisfactory distinction between the HRs for regional failure, distant failure, and disease failure in each N category. Conclusions: The proposed N staging system defined by the International Consensus Guidelines and laterality is predictive and practical. However, because of no measurements of the maximal nodal diameter on MRI slices, the prognostic significance of LN size needs further evaluation.« less

Towards Prognostics of Electrolytic Capacitors

NASA Technical Reports Server (NTRS)

Celaya, Jose R.; Kulkarni, Chetan; Biswas, Gautam; Goegel, Kai

2011-01-01

A remaining useful life prediction algorithm and degradation model for electrolytic capacitors is presented. Electrolytic capacitors are used in several applications ranging from power supplies on critical avionics equipment to power drivers for electro-mechanical actuators. These devices are known for their low reliability and given their criticality in electronics subsystems they are a good candidate for component level prognostics and health management research. Prognostics provides a way to assess remaining useful life of a capacitor based on its current state of health and its anticipated future usage and operational conditions. In particular, experimental results of an accelerated aging test under electrical stresses are presented. The capacitors used in this test form the basis for a remaining life prediction algorithm where a model of the degradation process is suggested. This preliminary remaining life prediction algorithm serves as a demonstration of how prognostics methodologies could be used for electrolytic capacitors.

Prognostics and Health Management of Wind Turbines: Current Status and Future Opportunities

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sheng, Shuangwen

Prognostics and health management is not a new concept. It has been used in relatively mature industries, such as aviation and electronics, to help improve operation and maintenance (O&M) practices. In the wind industry, prognostics and health management is relatively new. The level for both wind industry applications and research and development (R&D) has increased in recent years because of its potential for reducing O&M cost of wind power, especially for turbines installed offshore. The majority of wind industry application efforts has been focused on diagnosis based on various sensing and feature extraction techniques. For R&D, activities are being conductedmore » in almost all areas of a typical prognostics and health management framework (i.e., sensing, data collection, feature extraction, diagnosis, prognosis, and maintenance scheduling). This presentation provides an overview of the current status of wind turbine prognostics and health management that focuses on drivetrain condition monitoring through vibration, oil debris, and oil condition analysis techniques. It also discusses turbine component health diagnosis through data mining and modeling based on supervisory control and data acquisition system data. Finally, it provides a brief survey of R&D activities for wind turbine prognostics and health management, along with future opportunities.« less

Assessing the cost effectiveness of using prognostic biomarkers with decision models: case study in prioritising patients waiting for coronary artery surgery

PubMed Central

Henriksson, Martin; Palmer, Stephen; Chen, Ruoling; Damant, Jacqueline; Fitzpatrick, Natalie K; Abrams, Keith; Hingorani, Aroon D; Stenestrand, Ulf; Janzon, Magnus; Feder, Gene; Keogh, Bruce; Shipley, Martin J; Kaski, Juan-Carlos; Timmis, Adam; Sculpher, Mark

2010-01-01

Objective To determine the effectiveness and cost effectiveness of using information from circulating biomarkers to inform the prioritisation process of patients with stable angina awaiting coronary artery bypass graft surgery. Design Decision analytical model comparing four prioritisation strategies without biomarkers (no formal prioritisation, two urgency scores, and a risk score) and three strategies based on a risk score using biomarkers: a routinely assessed biomarker (estimated glomerular filtration rate), a novel biomarker (C reactive protein), or both. The order in which to perform coronary artery bypass grafting in a cohort of patients was determined by each prioritisation strategy, and mean lifetime costs and quality adjusted life years (QALYs) were compared. Data sources Swedish Coronary Angiography and Angioplasty Registry (9935 patients with stable angina awaiting coronary artery bypass grafting and then followed up for cardiovascular events after the procedure for 3.8 years), and meta-analyses of prognostic effects (relative risks) of biomarkers. Results The observed risk of cardiovascular events while on the waiting list for coronary artery bypass grafting was 3 per 10 000 patients per day within the first 90 days (184 events in 9935 patients). Using a cost effectiveness threshold of £20 000-£30 000 (€22 000-€33 000; $32 000-$48 000) per additional QALY, a prioritisation strategy using a risk score with estimated glomerular filtration rate was the most cost effective strategy (cost per additional QALY was <£410 compared with the Ontario urgency score). The impact on population health of implementing this strategy was 800 QALYs per 100 000 patients at an additional cost of £245 000 to the National Health Service. The prioritisation strategy using a risk score with C reactive protein was associated with lower QALYs and higher costs compared with a risk score using estimated glomerular filtration rate. Conclusion Evaluating the cost effectiveness of prognostic biomarkers is important even when effects at an individual level are small. Formal prioritisation of patients awaiting coronary artery bypass grafting using a routinely assessed biomarker (estimated glomerular filtration rate) along with simple, routinely collected clinical information was cost effective. Prioritisation strategies based on the prognostic information conferred by C reactive protein, which is not currently measured in this context, or a combination of C reactive protein and estimated glomerular filtration rate, is unlikely to be cost effective. The widespread practice of using only implicit or informal means of clinically ordering the waiting list may be harmful and should be replaced with formal prioritisation approaches. PMID:20085988

Clinical value of circulating endothelial cell levels in metastatic colorectal cancer patients treated with first-line chemotherapy and bevacizumab.

PubMed

Malka, D; Boige, V; Jacques, N; Vimond, N; Adenis, A; Boucher, E; Pierga, J Y; Conroy, T; Chauffert, B; François, E; Guichard, P; Galais, M P; Cvitkovic, F; Ducreux, M; Farace, F

2012-04-01

We investigated whether circulating endothelial cells (CECs) predict clinical outcome of first-line chemotherapy and bevacizumab in metastatic colorectal cancer (mCRC) patients. In a substudy of the randomized phase II FNCLCC ACCORD 13/0503 trial, CECs (CD45- CD31+ CD146+ 7-amino-actinomycin- cells) were enumerated in 99 patients by four-color flow cytometry at baseline and after one cycle of treatment. We correlated CEC levels with objective response rate (ORR), 6-month progression-free survival (PFS) rate (primary end point of the trial), PFS, and overall survival (OS). Multivariate analyses of potential prognostic factors, including CEC counts and Köhne score, were carried out. By multivariate analysis, high baseline CEC levels were the only independent prognostic factor for 6-month PFS rate (P < 0.01) and were independently associated with worse PFS (P = 0.02). High CEC levels after one cycle were the only independent prognostic factor for ORR (P = 0.03). High CEC levels at both time points independently predicted worse ORR (P = 0.025), 6-month PFS rate (P = 0.007), and PFS (P = 0.02). Köhne score was the only variable associated with OS. CEC levels at baseline and after one treatment cycle may independently predict ORR and PFS in mCRC patients starting first-line bevacizumab and chemotherapy.

Hematologic and biochemical characteristics of stranded green sea turtles.

PubMed

March, Duane T; Vinette-Herrin, Kimberly; Peters, Andrew; Ariel, Ellen; Blyde, David; Hayward, Doug; Christidis, Les; Kelaher, Brendan P

2018-05-01

To improve understanding of pathophysiologic processes occurring in green sea turtles ( Chelonia mydas) stranded along the east coast of Australia, we retrospectively examined the hematologic and biochemical blood parameters of 127 green turtles admitted to 2 rehabilitation facilities, Dolphin Marine Magic (DMM) and Taronga Zoo (TZ), between 2002 and 2016. The predominant size class presented was small immature animals (SIM), comprising 88% and 69% of admissions to DMM and TZ, respectively. Significant differences in blood profiles were noted between facility, size, and outcome. Elevated levels of aspartate aminotransferase (AST) and heterophils were poor prognostic indicators in animals from TZ, but not DMM. SIM animals at both institutions had lower protein levels than large older (LO) animals. SIM animals at DMM also had lower hematocrit and monocyte concentration; SIM animals at TZ had lower heterophil counts. Urea was measured for 27 SIM animals from TZ, but the urea-to-uric acid ratio was not prognostically useful. Strong correlations were seen between AST and glutamate dehydrogenase (GDH; r = 0.68) and uric acid and bile acids ( r = 0.72) in the 45 SIM animals from DMM in which additional analytes were measured. χ 2 contingency tests showed that the most recently published reference intervals were not prognostically useful. A paired t-test showed that protein levels rose and heterophil numbers fell in the 15 SIM animals from TZ during the rehabilitation process. Our results indicate that further work is required to identify reliable prognostic biomarkers for green turtles.

Serum-circulating miRNAs predict neuroblastoma progression in mouse model of high-risk metastatic disease.

PubMed

Ramraj, Satish Kumar; Aravindan, Sheeja; Somasundaram, Dinesh Babu; Herman, Terence S; Natarajan, Mohan; Aravindan, Natarajan

2016-04-05

Circulating miRNAs have momentous clinical relevance as prognostic biomarkers and in the progression of solid tumors. Recognizing novel candidates of neuroblastoma-specific circulating miRNAs would allow us to identify potential prognostic biomarkers that could predict the switch from favorable to high-risk metastatic neuroblastoma (HR-NB). Utilizing mouse models of favorable and HR-NB and whole miRnome profiling, we identified high serum levels of 34 and low levels of 46 miRNAs in animals with HR-NB. Preferential sequence homology exclusion of mouse miRNAs identified 25 (11 increased; 14 decreased) human-specific prognostic marker candidates, of which, 21 were unique to HR-NB. miRNA QPCR validated miRnome profile. Target analysis defined the candidate miRNAs' signal transduction flow-through and demonstrated their converged roles in tumor progression. miRNA silencing studies verified the function of select miRNAs on the translation of at least 14 target proteins. Expressions of critical targets that correlate tumor progression in tissue of multifarious organs identify the orchestration of HR-NB. Significant (>10 fold) increase in serum levels of miR-381, miR-548h, and miR-580 identify them as potential prognostic markers for neuroblastoma progression. For the first time, we identified serum-circulating miRNAs that predict the switch from favorable to HR-NB and, further imply that these miRNAs could play a functional role in tumor progression.

Prognostic value of lncRNAs in lung carcinoma: a meta-analysis.

PubMed

Fan, Fan; Zhu, Zhengqiu; Gao, Chao; Liu, Yun; Wang, Baoqing; Wang, Ziquan; Feng, Jifeng

2017-10-10

Many different long non-coding RNAs (lncRNAs) have been reported to be abnormally expressed in lung carcinoma and may thus serve as prognostic biomarkers for this disease. We conducted this meta-analysis, which included a total of 30 studies identified via searches of PubMed, Embase, Medline, and Web of Science and included 2912 patients from China (28), Germany (1), and Japan (1), to investigate the prognostic value of different lncRNAs in lung carcinoma. The results revealed that lncRNA transcription levels were significantly associated with overall survival in lung cancer patients (HR:1.46, 95% CI: 1.16-1.83, P = 0.000). However, lncRNA transcription levels were not associated with progression-free survival (PFS) (HR: 1.55, 95% CI: 0.50-4.80, P = 0.449). Further analysis showed that high lncRNA transcription levels were significantly associated with tumour-node-metastasis (TNM) stage (III/IV vs I/II: RR = 1.339, 95% CI: 1.046-1.716, P = 0.012), lymph node metastasis (positive vs negative: RR = 1.442, 95% CI: 1.103-1.885, P = 0.007), and distant metastasis (yes vs no: RR = 3.187,95% CI: 1.393-7.294, P = 0.006). Taken together, the results of our present meta-analysis revealed that lncRNAs may be useful prognostic markers for lung carcinoma and may also have value as biomarkers for TNM stage, lymph node metastasis and distant metastasis.

Prognostic value of lncRNAs in lung carcinoma: a meta-analysis

PubMed Central

Fan, Fan; Zhu, Zhengqiu; Gao, Chao; Liu, Yun; Wang, Baoqing; Wang, Ziquan; Feng, Jifeng

2017-01-01

Many different long non-coding RNAs (lncRNAs) have been reported to be abnormally expressed in lung carcinoma and may thus serve as prognostic biomarkers for this disease. We conducted this meta-analysis, which included a total of 30 studies identified via searches of PubMed, Embase, Medline, and Web of Science and included 2912 patients from China (28), Germany (1), and Japan (1), to investigate the prognostic value of different lncRNAs in lung carcinoma. The results revealed that lncRNA transcription levels were significantly associated with overall survival in lung cancer patients (HR:1.46, 95% CI: 1.16–1.83, P = 0.000). However, lncRNA transcription levels were not associated with progression-free survival (PFS) (HR: 1.55, 95% CI: 0.50–4.80, P = 0.449). Further analysis showed that high lncRNA transcription levels were significantly associated with tumour-node-metastasis (TNM) stage (III/IV vs I/II: RR = 1.339, 95% CI: 1.046–1.716, P = 0.012), lymph node metastasis (positive vs negative: RR = 1.442, 95% CI: 1.103–1.885, P = 0.007), and distant metastasis (yes vs no: RR = 3.187,95% CI: 1.393–7.294, P = 0.006). Taken together, the results of our present meta-analysis revealed that lncRNAs may be useful prognostic markers for lung carcinoma and may also have value as biomarkers for TNM stage, lymph node metastasis and distant metastasis. PMID:29137343

The Relationship between the Behavioral Hearing Thresholds and Maximum Bilirubin Levels at Birth in Children with a History of Neonatal Hyperbilirubinemia

PubMed Central

Panahi, Rasool; Jafari, Zahra; Sheibanizade, Abdoreza; Salehi, Masoud; Esteghamati, Abdoreza; Hasani, Sara

2013-01-01

Introduction: Neonatal hyperbilirubinemia is one of the most important factors affecting the auditory system and can cause sensorineural hearing loss. This study investigated the relationship between behavioral hearing thresholds in children with a history of jaundice and the maximum level of bilirubin concentration in the blood. Materials and Methods: This study was performed on 18 children with a mean age of 5.6 years and with a history of neonatal hyperbilirubinemia. Behavioral hearing thresholds, transient evoked emissions and brainstem evoked responses were evaluated in all children. Results: Six children (33.3%) had normal hearing thresholds and the remaining (66.7%) had some degree of hearing loss. There was no significant relationship (r=-0.28, P=0.09) between the mean total bilirubin levels and behavioral hearing thresholds in all samples. A transient evoked emission was seen only in children with normal hearing thresholds however in eight cases brainstem evoked responses had not detected. Conclusion: Increased blood levels of bilirubin at the neonatal period were potentially one of the causes of hearing loss. There was a lack of a direct relationship between neonatal bilirubin levels and the average hearing thresholds which emphasizes on the necessity of monitoring the various amounts of bilirubin levels. PMID:24303432

Comparison of image segmentation of lungs using methods: connected threshold, neighborhood connected, and threshold level set segmentation

NASA Astrophysics Data System (ADS)

Amanda, A. R.; Widita, R.

2016-03-01

The aim of this research is to compare some image segmentation methods for lungs based on performance evaluation parameter (Mean Square Error (MSE) and Peak Signal Noise to Ratio (PSNR)). In this study, the methods compared were connected threshold, neighborhood connected, and the threshold level set segmentation on the image of the lungs. These three methods require one important parameter, i.e the threshold. The threshold interval was obtained from the histogram of the original image. The software used to segment the image here was InsightToolkit-4.7.0 (ITK). This research used 5 lung images to be analyzed. Then, the results were compared using the performance evaluation parameter determined by using MATLAB. The segmentation method is said to have a good quality if it has the smallest MSE value and the highest PSNR. The results show that four sample images match the criteria of connected threshold, while one sample refers to the threshold level set segmentation. Therefore, it can be concluded that connected threshold method is better than the other two methods for these cases.

Safety limit warning levels for the avoidance of excessive sound amplification to protect against further hearing loss.

PubMed

Johnson, Earl E

2017-11-01

To determine safe output sound pressure levels (SPL) for sound amplification devices to preserve hearing sensitivity after usage. A mathematical model consisting of the Modified Power Law (MPL) (Humes & Jesteadt, 1991 ) combined with equations for predicting temporary threshold shift (TTS) and subsequent permanent threshold shift (PTS) (Macrae, 1994b ) was used to determine safe output SPL. The study involves no new human subject measurements of loudness tolerance or threshold shifts. PTS was determined by the MPL model for 234 audiograms and the SPL output recommended by four different validated prescription recommendations for hearing aids. PTS can, on rare occasion, occur as a result of SPL delivered by hearing aids at modern day prescription recommendations. The trading relationship of safe output SPL, decibel hearing level (dB HL) threshold, and PTS was captured with algebraic expressions. Better hearing thresholds lowered the safe output SPL and higher thresholds raised the safe output SPL. Safe output SPL can consider the magnitude of unaided hearing loss. For devices not set to prescriptive levels, limiting the output SPL below the safe levels identified should protect against threshold worsening as a result of long-term usage.

Underwater temporary threshold shift in pinnipeds: effects of noise level and duration.

PubMed

Kastak, David; Southall, Brandon L; Schusterman, Ronald J; Kastak, Colleen Reichmuth

2005-11-01

Behavioral psychophysical techniques were used to evaluate the residual effects of underwater noise on the hearing sensitivity of three pinnipeds: a California sea lion (Zalophus californianus), a harbor seal (Phoca vitulina), and a northern elephant seal (Mirounga angustirostris). Temporary threshold shift (TTS), defined as the difference between auditory thresholds obtained before and after noise exposure, was assessed. The subjects were exposed to octave-band noise centered at 2500 Hz at two sound pressure levels: 80 and 95 dB SL (re: auditory threshold at 2500 Hz). Noise exposure durations were 22, 25, and 50 min. Threshold shifts were assessed at 2500 and 3530 Hz. Mean threshold shifts ranged from 2.9-12.2 dB. Full recovery of auditory sensitivity occurred within 24 h of noise exposure. Control sequences, comprising sham noise exposures, did not result in significant mean threshold shifts for any subject. Threshold shift magnitudes increased with increasing noise sound exposure level (SEL) for two of the three subjects. The results underscore the importance of including sound exposure metrics (incorporating sound pressure level and exposure duration) in order to fully assess the effects of noise on marine mammal hearing.

Prognostic and predictive potential molecular biomarkers in colon cancer.

PubMed

Nastase, A; Pâslaru, L; Niculescu, A M; Ionescu, M; Dumitraşcu, T; Herlea, V; Dima, S; Gheorghe, C; Lazar, V; Popescu, I

2011-01-01

An important objective in nowadays research is the discovery of new biomarkers that can detect colon tumours in early stages and indicate with accuracy the status of the disease. The aim of our study was to identify potential biomarkers for colon cancer onset and progression. We assessed gene expression profiles of a list of 10 candidate genes (MMP-1, MMP-3, MMP-7, DEFA 1, DEFA-5, DEFA-6, IL-8, CXCL-1, SPP-1, CTHRC-1) by quantitative real time PCR in triplets of colonic mucosa (normal, adenoma, tumoral tissue) collected from the same patient during surgery for a group of 20 patients. Additionally we performed immunohistochemistry for DEFA1-3 and SPP1. We remarked that DEFA5 and DEFA6 are key factors in adenoma formation (p<0.05). MMP7 is important in the transition from a benign to a malignant status (p <0.01) and further in metastasis being a prognostic indicator for tumor transformation and for the metastatic potential of cancer cells. IL8, irrespective of tumor stage, has a high mRNA level in adenocarcinoma (p< 0.05). The level of expression for SPP1 is correlated with tumor level. We suggest that high levels of DEFAS, DEFA6 (key elements in adenoma formation), MMP7 (marker of colon cancer onset and progression to metastasis), SPP1 (marker of progression) and IL8 could be used to diagnose an early stage colon cancer and to evaluate the prognostic of progression for colon tumors. Further, if DEFA5 and DEFA6 level of expression are low but MMP7, SPP1 and IL8 level are high we could point out that the transition from adenoma to adenocarcinoma had already occurred. Thus, DEFA5, DEFA6, MMP7, IL8 and SPP1 consist in a valuable panel of biomarkers, whose detection can be used in early detection and progressive disease and also in prognostic of colon cancer.

Stapedotomy in osteogenesis imperfecta: a prospective study of 32 consecutive cases.

PubMed

Vincent, Robert; Wegner, Inge; Stegeman, Inge; Grolman, Wilko

2014-12-01

To prospectively evaluate hearing outcomes in patients with osteogenesis imperfecta undergoing primary stapes surgery and to isolate prognostic factors for success. A nonrandomized, open, prospective case series. A tertiary referral center. Twenty-five consecutive patients who underwent 32 primary stapedotomies for osteogenesis imperfecta with evidence of stapes fixation and available postoperative pure-tone audiometry. Primary stapedotomy with vein graft interposition and reconstruction with a regular Teflon piston or bucket handle-type piston. Preoperative and postoperative audiometric evaluation using conventional 4-frequency (0.5, 1, 2, and 4 kHz) audiometry. Air-conduction thresholds, bone-conduction thresholds, and air-bone gap were measured. The overall audiometric results as well as the results of audiometric evaluation at 3 months and at least 1 year after surgery were used. Overall, postoperative air-bone gap closure to within 10 dB was achieved in 88% of cases. Mean (standard deviation) gain in air-conduction threshold was 22 (9.4) dB for the entire case series, and mean (standard deviation) air-bone gap closure was 22 (9.0) dB. Backward multivariate logistic regression showed that a model with preoperative air-bone gap closure and intraoperatively established incus length accurately predicts success after primary stapes surgery. Stapes surgery is a feasible and safe treatment option in patients with osteogenesis imperfecta. Success is associated with preoperative air-bone gap and intraoperatively established incus length.

Prognostic utility of serum CRP levels in combination with CURB-65 in patients with clinically suspected sepsis: a decision curve analysis.

PubMed

Yamamoto, Shungo; Yamazaki, Shin; Shimizu, Tsunehiro; Takeshima, Taro; Fukuma, Shingo; Yamamoto, Yosuke; Tochitani, Kentaro; Tsuchido, Yasuhiro; Shinohara, Koh; Fukuhara, Shunichi

2015-04-28

The prognostic utility of serum C reactive protein (CRP) alone in sepsis is controversial. We used decision curve analysis (DCA) to evaluate the clinical usefulness of combining serum CRP levels with the CUBR-65 score in patients with suspected sepsis. Retrospective cohort study. Emergency department (ED) of an urban teaching hospital in Japan. Consecutive ED patients over 15 years of age who were admitted to the hospital after having a blood culture taken in the ED between 1 January 2010 and 31 December 2012. 30-day in-hospital mortality. Data from 1262 patients were analysed for score evaluation. The 30-day in-hospital mortality was 8.4%. Multivariable analysis showed that serum CRP ≥150 mg/L was an independent predictor of death (adjusted OR 2.0; 95% CI 1.3 to 3.1). We compared the predictive performance of CURB-65 with the performance of a modified CURB-65 with that included CRP (≥150 mg/L) to quantify the clinical usefulness of combining serum CRP with CURB-65. The areas under the receiver operating characteristics curves of CURB-65 and a modified CURB-65 were 0.76 (95% CI 0.72 to 0.80) and 0.77 (95% CI 0.72 to 0.81), respectively. Both models had good calibration for mortality and were useful among threshold probabilities from 0% to 30%. However, while incorporating CRP into CURB-65 yielded a significant category-free net reclassification improvement of 0.387 (95% CI 0.193 to 0.582) and integrated discrimination improvement of 0.015 (95% CI 0.004 to 0.027), DCA showed that CURB-65 and the modified CURB-65 score had comparable net benefits for prediction of mortality. Measurement of serum CRP added limited clinical usefulness to CURB-65 in predicting mortality in patients with clinically suspected sepsis, regardless of the source. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Robust Intratumor Partitioning to Identify High-Risk Subregions in Lung Cancer: A Pilot Study.

PubMed

Wu, Jia; Gensheimer, Michael F; Dong, Xinzhe; Rubin, Daniel L; Napel, Sandy; Diehn, Maximilian; Loo, Billy W; Li, Ruijiang

2016-08-01

To develop an intratumor partitioning framework for identifying high-risk subregions from (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) and computed tomography (CT) imaging and to test whether tumor burden associated with the high-risk subregions is prognostic of outcomes in lung cancer. In this institutional review board-approved retrospective study, we analyzed the pretreatment FDG-PET and CT scans of 44 lung cancer patients treated with radiation therapy. A novel, intratumor partitioning method was developed, based on a 2-stage clustering process: first at the patient level, each tumor was over-segmented into many superpixels by k-means clustering of integrated PET and CT images; next, tumor subregions were identified by merging previously defined superpixels via population-level hierarchical clustering. The volume associated with each of the subregions was evaluated using Kaplan-Meier analysis regarding its prognostic capability in predicting overall survival (OS) and out-of-field progression (OFP). Three spatially distinct subregions were identified within each tumor that were highly robust to uncertainty in PET/CT co-registration. Among these, the volume of the most metabolically active and metabolically heterogeneous solid component of the tumor was predictive of OS and OFP on the entire cohort, with a concordance index or CI of 0.66-0.67. When restricting the analysis to patients with stage III disease (n=32), the same subregion achieved an even higher CI of 0.75 (hazard ratio 3.93, log-rank P=.002) for predicting OS, and a CI of 0.76 (hazard ratio 4.84, log-rank P=.002) for predicting OFP. In comparison, conventional imaging markers, including tumor volume, maximum standardized uptake value, and metabolic tumor volume using threshold of 50% standardized uptake value maximum, were not predictive of OS or OFP, with CI mostly below 0.60 (log-rank P>.05). We propose a robust intratumor partitioning method to identify clinically relevant, high-risk subregions in lung cancer. We envision that this approach will be applicable to identifying useful imaging biomarkers in many cancer types. Copyright © 2016 Elsevier Inc. All rights reserved.

Robust Intratumor Partitioning to Identify High-Risk Subregions in Lung Cancer: A Pilot Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Jia; Gensheimer, Michael F.; Dong, Xinzhe

2016-08-01

Purpose: To develop an intratumor partitioning framework for identifying high-risk subregions from {sup 18}F-fluorodeoxyglucose positron emission tomography (FDG-PET) and computed tomography (CT) imaging and to test whether tumor burden associated with the high-risk subregions is prognostic of outcomes in lung cancer. Methods and Materials: In this institutional review board–approved retrospective study, we analyzed the pretreatment FDG-PET and CT scans of 44 lung cancer patients treated with radiation therapy. A novel, intratumor partitioning method was developed, based on a 2-stage clustering process: first at the patient level, each tumor was over-segmented into many superpixels by k-means clustering of integrated PET andmore » CT images; next, tumor subregions were identified by merging previously defined superpixels via population-level hierarchical clustering. The volume associated with each of the subregions was evaluated using Kaplan-Meier analysis regarding its prognostic capability in predicting overall survival (OS) and out-of-field progression (OFP). Results: Three spatially distinct subregions were identified within each tumor that were highly robust to uncertainty in PET/CT co-registration. Among these, the volume of the most metabolically active and metabolically heterogeneous solid component of the tumor was predictive of OS and OFP on the entire cohort, with a concordance index or CI of 0.66-0.67. When restricting the analysis to patients with stage III disease (n=32), the same subregion achieved an even higher CI of 0.75 (hazard ratio 3.93, log-rank P=.002) for predicting OS, and a CI of 0.76 (hazard ratio 4.84, log-rank P=.002) for predicting OFP. In comparison, conventional imaging markers, including tumor volume, maximum standardized uptake value, and metabolic tumor volume using threshold of 50% standardized uptake value maximum, were not predictive of OS or OFP, with CI mostly below 0.60 (log-rank P>.05). Conclusion: We propose a robust intratumor partitioning method to identify clinically relevant, high-risk subregions in lung cancer. We envision that this approach will be applicable to identifying useful imaging biomarkers in many cancer types.« less

Frequency-specific hearing outcomes in pediatric type I tympanoplasty.

PubMed

Kent, David T; Kitsko, Dennis J; Wine, Todd; Chi, David H

2014-02-01

Middle ear disease is the primary cause of hearing loss in children and has a significant impact on language development and academic performance. Multiple prognostic factors have previously been examined, but there is little published data regarding frequency-specific hearing outcomes. To examine the relationship between type I tympanoplasty in a pediatric population and frequency-specific hearing changes, as well as the relationship between several prognostic factors and graft retention. Retrospective medical chart review (February 2006 to October 2011) of 492 consecutive pediatric otolaryngology patients undergoing type I tympanoplasty for tympanic membrane (TM) perforation of any etiology at a tertiary-care pediatric otolaryngology practice. Type I tympanoplasty. Preoperative and postoperative audiometric data were collected for patients undergoing successful TM repair. It was hypothesized before data collection that conductive hearing would improve at all frequencies with no significant change in sensorineural hearing. Data collected included air conduction at 250 to 8000 Hz, speech reception thresholds, bone conduction at 500 to 4000 Hz, and air-bone gap at 500 to 4000 Hz. Demographic data obtained included sex, age, size, mechanism, location of perforation, and operative repair technique. Of 492 patients, 320 were excluded; results were thus examined for 172 patients. Surgery was successful for 73.8% of patients. Perforation size was significantly associated with repair success (mean [SD] surgical success rate of 38.6% [15.3%] vs surgical failure rate of 31.4% [15.0%]; P < .01); however, mean (SD) age (9.02 [3.89] years [surgical success] vs 8.52 [3.43] years [surgical failure]; P > .05) and repair technique (medial [73.08%] vs lateral [76.47%] graft success; P > .99) were not. Air conduction significantly improved from 250 to 2000 Hz (P < .001), did not significantly improve at 4000 Hz (P = .08), and there was a nonsignificant decline at 8000 Hz (P = .12). Speech reception threshold significantly improved (20 vs 15 dB; P < .001). This large review found an association of TM perforation size with surgical success and an improvement in speech reception threshold, air conduction at 250 to 2000 Hz, air-bone gap at 500 to 2000 Hz, and worsening bone conduction at 4000 Hz. Patients with high-frequency hearing loss due to TM perforation should not anticipate significant recovery from type I tympanoplasty. Hearing loss at higher frequencies may require postoperative hearing rehabilitation.

Initial Assessment and Resuscitation in Nonvariceal Upper Gastrointestinal Bleeding.

PubMed

Simon, Tracey G; Travis, Anne C; Saltzman, John R

2015-07-01

Acute nonvariceal upper gastrointestinal bleeding remains an important cause of hospital admission with an associated mortality of 2-14%. Initial patient evaluation includes rapid hemodynamic assessment, large-bore intravenous catheter insertion and volume resuscitation. A hemoglobin transfusion threshold of 7 g/dL is recommended, and packed red blood cell transfusion may be necessary to restore intravascular volume and improve tissue perfusion. Patients should be risk stratified into low- and high-risk categories, using validated prognostic scoring systems such as the Glasgow-Blatchford, AIMS65 or Rockall scores. Effective early management of acute, nonvariceal upper gastrointestinal hemorrhage is critical for improving patient outcomes. Copyright © 2015 Elsevier Inc. All rights reserved.

A Self-Aware Machine Platform in Manufacturing Shop Floor Utilizing MTConnect Data

DTIC Science & Technology

2014-10-02

condition monitoring , and equipment time to failure prediction in manufacturing 1 ANNUAL CONFERENCE OF THE PROGNOSTICS AND HEALTH MANAGEMENT SOCIETY 2014 589...Component Level Health Monitoring and Prediction One of the characteristics of a self-aware machine is to be able to detect its components...the annual conference of the prognostics and health management society. Filzmoser, P., Garrett, R. G., & Reimann, C . (2005). Mul- tivariate outlier

Neues "Francais fondamental?" Das Europa-Projekt "Un niveau seuil." (A New "Francais fondamental?" The European Project "A Threshold Level").

ERIC Educational Resources Information Center

Raasch, Albert

1978-01-01

The project "Threshold Level," initiated by the Council of Europe in 1976, is compared with "Francais fondamental," comparing their aims and their differences. Offered as an interim statement, the article leaves open the question of whether Francais fondamental should be replaced by the the Threshold Level. (IFS/WGA)

Reliability of the method of levels for determining cutaneous temperature sensitivity

NASA Astrophysics Data System (ADS)

Jakovljević, Miroljub; Mekjavić, Igor B.

2012-09-01

Determination of the thermal thresholds is used clinically for evaluation of peripheral nervous system function. The aim of this study was to evaluate reliability of the method of levels performed with a new, low cost device for determining cutaneous temperature sensitivity. Nineteen male subjects were included in the study. Thermal thresholds were tested on the right side at the volar surface of mid-forearm, lateral surface of mid-upper arm and front area of mid-thigh. Thermal testing was carried out by the method of levels with an initial temperature step of 2°C. Variability of thermal thresholds was expressed by means of the ratio between the second and the first testing, coefficient of variation (CV), coefficient of repeatability (CR), intraclass correlation coefficient (ICC), mean difference between sessions (S1-S2diff), standard error of measurement (SEM) and minimally detectable change (MDC). There were no statistically significant changes between sessions for warm or cold thresholds, or between warm and cold thresholds. Within-subject CVs were acceptable. The CR estimates for warm thresholds ranged from 0.74°C to 1.06°C and from 0.67°C to 1.07°C for cold thresholds. The ICC values for intra-rater reliability ranged from 0.41 to 0.72 for warm thresholds and from 0.67 to 0.84 for cold thresholds. S1-S2diff ranged from -0.15°C to 0.07°C for warm thresholds, and from -0.08°C to 0.07°C for cold thresholds. SEM ranged from 0.26°C to 0.38°C for warm thresholds, and from 0.23°C to 0.38°C for cold thresholds. Estimated MDC values were between 0.60°C and 0.88°C for warm thresholds, and 0.53°C and 0.88°C for cold thresholds. The method of levels for determining cutaneous temperature sensitivity has acceptable reliability.

Prostate-Specific Antigen at 4 to 5 Years After Low-Dose-Rate Prostate Brachytherapy Is a Strong Predictor of Disease-Free Survival

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lo, Andrea C.; Department of Surgery, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia; Morris, W. James, E-mail: JMorris@bccancer.bc.ca

2014-01-01

Purpose: To determine (1) the prognostic utility of prostate-specific antigen (PSA) concentration at 45 to 60 months (48mPSA) after low-dose-rate prostate brachytherapy (LDR-PB); (2) the predictors of 48mPSA; and (3) the prognostic utility of directional trends between PSA levels at 24, 36, and 48 months after LDR-PB. Methods and Materials: Between 1998 and 2008, 2223 patients with low- and intermediate-risk prostate cancer received LDR-PB monotherapy. A cohort of 1434 of these patients was identified with a documented 48mPSA and no evidence of disease relapse prior to the 48mPSA. In addition, a subset of this cohort (n=585) was identified with ≥72more » months of follow-up and documented PSA values at both 24 and 36 months after implantation. Results: Median follow-up time was 76 months. Eight-year Kaplan-Meier disease-free survival (DFS) rates were 100% vs 73.4% for patients with 48mPSA ≤0.2 vs those with >0.2 ng/mL; 99.1% versus 53.8% for a 48mPSA threshold of ≤0.4 versus >0.4 ng/mL, respectively; and 97.3% versus 0% for a threshold of ≤1.0 versus >1.0 ng/mL, respectively. On multivariate analysis, the only factor predictive of DFS was 48mPSA (P<.0001). On subset analysis (n=585), 29 patients had a PSA rise (defined as >0.2 ng/mL) between 24 and 36 months, 24 patients had a rise between 36 and 48 months, and 11 patients had rises over both intervals. Failure rates in these patients were 52%, 79%, and 100%, respectively. On multivariate analysis, initial PSA, androgen deprivation therapy, and dose to 90% of the prostate significantly correlated with 48mPSA but together accounted for only ∼5% of its total variance. Conclusions: The 48mPSA after LDR-PB is highly predictive of long-term DFS. Patients with 48mPSA ≤0.4 ng/mL had a <1% risk of disease relapse at 8 years, whereas all patients with 48mPSA >1.0 ng/mL relapsed. Consecutive PSA rises of >0.2 ng/mL from 24 to 36 months and from 36 to 48 months were also highly predictive of subsequent failure.« less

The lincRNA HOTAIRM1, located in the HOXA genomic region, is expressed in acute myeloid leukemia, impacts prognosis in patients in the intermediate-risk cytogenetic category, and is associated with a distinctive microRNA signature

PubMed Central

Díaz-Beyá, Marina; Brunet, Salut; Nomdedéu, Josep; Pratcorona, Marta; Cordeiro, Anna; Gallardo, David; Escoda, Lourdes; Tormo, Mar; Heras, Inmaculada; Ribera, Josep Maria; Duarte, Rafael; de Llano, María Paz Queipo; Bargay, Joan; Sampol, Antonia; Nomdedeu, Mertixell; Risueño, Ruth M.; Hoyos, Montserrat; Sierra, Jorge; Monzo, Mariano; Navarro, Alfons; Esteve, Jordi

2015-01-01

Long non-coding RNAs (lncRNAs) are deregulated in several tumors, although their role in acute myeloid leukemia (AML) is mostly unknown. We have examined the expression of the lncRNA HOX antisense intergenic RNA myeloid 1 (HOTAIRM1) in 241 AML patients. We have correlated HOTAIRM1 expression with a miRNA expression profile. We have also analyzed the prognostic value of HOTAIRM1 expression in 215 intermediate-risk AML (IR-AML) patients. The lowest expression level was observed in acute promyelocytic leukemia (P < 0.001) and the highest in t(6;9) AML (P = 0.005). In 215 IR-AML patients, high HOTAIRM1 expression was independently associated with shorter overall survival (OR:2.04;P = 0.001), shorter leukemia-free survival (OR:2.56; P < 0.001) and a higher cumulative incidence of relapse (OR:1.67; P = 0.046). Moreover, HOTAIRM1 maintained its independent prognostic value within the favorable molecular subgroup (OR: 3.43; P = 0.009). Interestingly, HOTAIRM1 was overexpressed in NPM1-mutated AML (P < 0.001) and within this group retained its prognostic value (OR: 2.21; P = 0.01). Moreover, HOTAIRM1 expression was associated with a specific 33- microRNA signature that included miR-196b (P < 0.001). miR-196b is located in the HOX genomic region and has previously been reported to have an independent prognostic value in AML. miR-196b and HOTAIRM1 in combination as a prognostic factor can classify patients as high-, intermediate-, or low-risk (5-year OS: 24% vs 42% vs 70%; P = 0.004). Determination of HOTAIRM1 level at diagnosis provided relevant prognostic information in IR-AML and allowed refinement of risk stratification based on common molecular markers. The prognostic information provided by HOTAIRM1 was strengthened when combined with miR-196b expression. Furthermore, HOTAIRM1 correlated with a 33-miRNA signature. PMID:26436590

High Pretreatment Plasma D-dimer Levels Are Associated With Poor Prognosis in Patients With Ovarian Cancer Independently of Venous Thromboembolism and Tumor Extension.

PubMed

Sakurai, Manabu; Satoh, Toyomi; Matsumoto, Koji; Michikami, Hiroo; Nakamura, Yuko; Nakao, Sari; Ochi, Hiroyuki; Onuki, Mamiko; Minaguchi, Takeo; Yoshikawa, Hiroyuki

2015-05-01

Elevated plasma D-dimer (DD) is associated with decreased survival among patients with breast, lung, and colon cancers. The present study clarifies the prognostic significance of pretreatment plasma DD levels in patients with epithelial ovarian cancer (EOC). We investigated pretreatment DD levels and other variables for overall survival using univariate and multivariate analyses in 134 consecutive patients with EOC stages II to IV who were initially treated between November 2004 and December 2010. The median follow-up period was 53 (7-106) months. Univariate analysis significantly associated elevated pretreatment DD (≥2.0 μg/mL) levels to poor 5-year overall survival rates irrespective of previously treated venous thromboembolism (72.2% vs 52.6%, P = 0.039). Cancer antigen 125 levels of 200 U/mL or higher (P = 0.011), distant metastases (P = 0.0004), residual tumors (P < 0.0001), and International Federation of Gynecology and Obstetrics stage III/IV (P = 0.0033) were also poor prognostic factors. Multivariate analysis independently associated DD levels of 2.0 μg/mL or higher (P = 0.041), distant metastases (P = 0.013), and residual tumors (P < 0.0001) with poor overall survival. High pretreatment DD levels are associated with poor overall survival in patients with EOC independently of venous thromboembolism and tumor extension and might comprise a promising prognostic biomarker for patients with EOC.

Elevated tumor and serum levels of the hypoxia-associated protein osteopontin are associated with prognosis for soft tissue sarcoma patients.

PubMed

Bache, Matthias; Kappler, Matthias; Wichmann, Henri; Rot, Swetlana; Hahnel, Antje; Greither, Thomas; Said, Harun M; Kotzsch, Matthias; Würl, Peter; Taubert, Helge; Vordermark, Dirk

2010-04-08

Osteopontin (OPN) overexpression is correlated with a poor prognosis for tumor patients. However, only a few studies investigated the prognostic impact of expression of OPN in soft tissue sarcomas (STS) yet. This study is based on tumor and serum samples from 93 adult STS patients. We investigated OPN protein levels in serum (n = 86) and tumor tissue (n = 80) by ELISA and OPN mRNA levels in tumor tissue (n = 68) by quantitative real-time PCR. No correlation was found between OPN levels in serum and tumor tissue. Moreover, an elevated OPN protein level in the serum was significantly associated with clinical parameters such as higher stage (p = 0.004), higher grade (p = 0.003), subtype (p = 0.002) and larger tumor size (p = 0.03). OPN protein levels in the tumor tissue were associated with higher stage (p = 0.06), higher grade (p = 0.003), subtype (p = 0.07) and an increased rate of relapse (p = 0.02). In addition, using a Cox's proportional hazards regression model, we found that an elevated OPN protein level in the serum and tumor tissue extracts is a significant negative prognostic factor for patients with STS. The relative risks of tumor-related death were 2.2 (p < 0.05) and 3.7 (p = 0.01), respectively. Our data suggest OPN protein in serum as well as in tumor tissue extracts is an important prognostic factor for soft tissue sarcoma patients.

The influence of metabolic syndrome and diabetes mellitus on the N-terminal pro-B-type natriuretic peptide level and its prognostic performance in patients with coronary artery disease.

PubMed

Huang, Fang-Yang; Peng, Yong; Deng, Xue-Xue; Huang, Bao-Tao; Xia, Tian-Li; Gui, Yi-Yue; Liu, Rui-Shuang; Yang, Yong; Pu, Xiao-Bo; Chen, Shi-Jian; Chen, Fei; Zhu, Ye; Chen, Mao

2017-03-01

Our aim was to investigate whether the presence of metabolic syndrome (MetS) and diabetes mellitus (DM) influenced the N-terminal pro-B-type natriuretic peptide (NT-proBNP) level and its prognostic performance in coronary artery disease (CAD). The present study enrolled a total of 1638 CAD patients. Multivariate regression analyses were carried out to relate NT-proBNP to metabolic components, nondiabetic MetS, DM, and MetS score. Furthermore, we examined the prognostic performance of NT-proBNP in patients with non-MetS, nondiabetic MetS, and DM. NT-proBNP levels correlated inversely with BMI (β=-0.11, P=0.003) and correlated positively with fasting glucose (β=0.12, P=0.001). There were no significant relationships of NT-proBNP with other metabolic parameters. Compared with non-MetS, the presence of DM significantly increased NT-proBNP levels (P=0.004), whereas nondiabetic MetS did not influence NT-proBNP levels (P=0.954). During the median follow-up of 21 months, 109 all-cause deaths occurred. NT-proBNP levels independently predicted all-cause deaths irrespective of the presence of nondiabetic MetS and DM (Pinteraction=0.43). DM, but not nondiabetic MetS, is associated with higher NT-proBNP levels. NT-proBNP can still predict death in patients with CAD, even with the confounding effect of MetS and diabetes.

Implications of infiltrating immune cells within bone marrow of patients with diffuse large B-cell lymphoma.

PubMed

Jeong, Juhyeon; Oh, Eun Ji; Yang, Woo Ick; Kim, Soo Jeong; Yoon, Sun Och

2017-06-01

The implications of infiltrating immune cells, especially T cells and macrophages, in the bone marrow (BM) microenvironment of patients with diffuse large B-cell lymphoma (DLBCL) have rarely been studied. We aimed to investigate the significance of infiltrating immune cells in the BM microenvironment as a prognostic factor for DLBCL patients. Using the initial pretreatment BM biopsy obtained from 198 DLBCL patients, we semiquantitatively evaluated CD3+ T cells, CD8+ T cells, and CD163+ macrophages that infiltrate into the paratrabecular and interstitial areas of BM by immunohistochemistry and analyzed their clinicopathological and prognostic implications. Levels of infiltrating CD3+ T cells, CD8+ T cells, and CD163+ macrophages were significantly higher in BM with DLBCL involvement (BMI-positive group) than in that without DLBCL involvement (BMI-negative group). Infiltration of CD8+ T cells significantly increased in cases with advanced Ann Arbor stage, elevated lactate dehydrogenase level, extranodal site involvement ≥2 sites, higher Eastern Cooperative Oncology Group performance status, and higher International Prognostic Index (IPI) risk. High levels of CD3+ T cells were significantly associated with age ≤60, and high levels of CD163+ macrophages were associated with advanced Ann Arbor stage and higher IPI risk. High infiltration of CD8+ T cells was significantly related to inferior overall and recurrence-free survival rate, even in the BMI-negative group. High infiltration of CD8+ T cells within the pretreatment BM was related to poor prognosis, and might be a useful prognostic factor of DLBCL patients. Therefore, evaluation of CD8+ T cells is helpful for predicting prognosis in initial pretreatment BM biopsy of DLBCL patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Serum biomarkers of bone metabolism in castration-resistant prostate cancer patients with skeletal metastases: results from SWOG 0421.

PubMed

Lara, Primo N; Ely, Benjamin; Quinn, David I; Mack, Philip C; Tangen, Catherine; Gertz, Erik; Twardowski, Przemyslaw W; Goldkorn, Amir; Hussain, Maha; Vogelzang, Nicholas J; Thompson, Ian M; Van Loan, Marta D

2014-04-01

Prior studies suggest that elevated markers of bone turnover are prognostic for poor survival in castration-resistant prostate cancer (CRPC). The predictive role of these markers relative to bone-targeted therapy is unknown. We prospectively evaluated the prognostic and predictive value of bone biomarkers in sera from CRPC patients treated on a placebo-controlled phase III trial of docetaxel with or without the bone targeted endothelin-A receptor antagonist atrasentan (SWOG S0421). Markers for bone resorption (N-telopeptide and pyridinoline) and formation (C-terminal collagen propeptide and bone alkaline phosphatase) were assayed in pretreatment and serial sera. Cox proportional hazards regression models were fit for overall survival. Models were fit with main effects for marker levels and with/without terms for marker-treatment interaction, adjusted for clinical variables, to assess the prognostic and predictive value of atrasentan. Analysis was adjusted for multiple comparisons. Two-sided P values were calculated using the Wald test. Sera from 778 patients were analyzed. Elevated baseline levels of each of the markers were associated with worse survival (P < .001). Increasing marker levels by week nine of therapy were also associated with subsequent poor survival (P < .001). Patients with the highest marker levels (upper 25th percentile for all markers) not only had a poor prognosis (hazard ratio [HR] = 4.3; 95% confidence interval [CI] = 2.41 to 7.65; P < .001) but also had a survival benefit from atrasentan (HR = 0.33; 95% CI = 0.15 to 0.71; median survival = 13 [atrasentan] vs 5 months [placebo]; P interaction = .005). Serum bone metabolism markers have statistically significant independent prognostic value in CRPC. Importantly, a small group of patients (6%) with highly elevated markers of bone turnover appear to preferentially benefit from atrasentan therapy.

Statistical evaluation of surrogate endpoints with examples from cancer clinical trials.

PubMed

Buyse, Marc; Molenberghs, Geert; Paoletti, Xavier; Oba, Koji; Alonso, Ariel; Van der Elst, Wim; Burzykowski, Tomasz

2016-01-01

A surrogate endpoint is intended to replace a clinical endpoint for the evaluation of new treatments when it can be measured more cheaply, more conveniently, more frequently, or earlier than that clinical endpoint. A surrogate endpoint is expected to predict clinical benefit, harm, or lack of these. Besides the biological plausibility of a surrogate, a quantitative assessment of the strength of evidence for surrogacy requires the demonstration of the prognostic value of the surrogate for the clinical outcome, and evidence that treatment effects on the surrogate reliably predict treatment effects on the clinical outcome. We focus on these two conditions, and outline the statistical approaches that have been proposed to assess the extent to which these conditions are fulfilled. When data are available from a single trial, one can assess the "individual level association" between the surrogate and the true endpoint. When data are available from several trials, one can additionally assess the "trial level association" between the treatment effect on the surrogate and the treatment effect on the true endpoint. In the latter case, the "surrogate threshold effect" can be estimated as the minimum effect on the surrogate endpoint that predicts a statistically significant effect on the clinical endpoint. All these concepts are discussed in the context of randomized clinical trials in oncology, and illustrated with two meta-analyses in gastric cancer. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

[Work-related COPD].

PubMed

Fell, Anne Kristin Møller; Aasen, Tor Olav Brøvig; Kongerud, Johny

2014-11-01

Work-related COPD occurs as a result of exposure to harmful particles and gases/fumes in the workplace, including among non-smokers. The objective of this article is to present more recent findings on the correlation between occupational exposure and COPD. In addition, we review diagnostic and prognostic considerations and the potential for prevention. We have undertaken literature searches in Medline and EMBASE for the period May 2009 - July 2014. Studies without any measurements of pulmonary function or references to occupational exposure were excluded. We have also included three prospective studies on pulmonary function and occupational exposure that were not indexed with the search terms used for obstructive pulmonary disease. Three population studies and eight studies that described a specific industry or sector were included. Recent studies detect an association between exposure and an increased risk of COPD in the construction industry, metallurgical smelting, cement production and the textile industry. In other respects, the findings from previous review studies are confirmed. Exposure to a number of organic and inorganic particles and fumes in the workplace may cause COPD even at prevailing levels of exposure. Doctors should inquire about such exposure in cases of suspected and established COPD and should have a low threshold for referral to occupational health assessment.

Plasma serotonin level is a predictor for recurrence and poor prognosis in colorectal cancer patients.

PubMed

Xia, Yan; Wang, Dawei; Zhang, Nan; Wang, Zhihao; Pang, Li

2018-02-01

To investigate the prognostic value of plasma serotonin levels in colorectal cancer (CRC). Preoperative plasma serotonin levels of 150 healthy control (HC) cases, 150 benign colorectal polyp (BCP) cases, and 176 CRC cases were determined using radioimmunoassay assay. Serotonin levels were compared between HC, BCP, and CRC cases, and those in CRC patients were related to 5-year outcome. Plasma serotonin levels were markedly higher in CRC patients than in either HCs or BCP cases. An elevated serotonin level was significantly associated with advanced tumor node metastasis. Receiver operating characteristic curve analysis showed that the level of serotonin had a high predictive value for disease recurrence and mortality. Multivariate analysis revealed that high serotonin level was significantly associated with poor recurrence-free survival and overall survival. Our results suggest that a high peri-operative plasma serotonin level is useful as a prognostic biomarker for CRC recurrence and poor survival. © 2017 Wiley Periodicals, Inc.

Prognostic relevance of Fédération Nationale des Centres de Lutte Contre le Cancer grade and MDM2 amplification levels in dedifferentiated liposarcoma: a study of 50 cases.

PubMed

Jour, George; Gullet, Ashley; Liu, Mingdong; Hoch, Benjamin L

2015-01-01

Dedifferentiated liposarcoma represents a form of liposarcoma composed of a non-lipogenic sarcoma associated with well-differentiated liposarcoma. The prognostic significance of histological grading of the dedifferentiated component remains to be elucidated due to vague grading criteria employed in previous studies. Molecular markers of tumor behavior, including amplification levels of murine double minute-2 (MDM2) and cyclin-dependent kinase-4 (CDK4) genes, have been explored in a limited number of cases. Here we investigate whether 'Fédération Nationale des Centres de Lutte Contre le Cancer' (FNCLCC) grade and MDM2 gene amplification levels have prognostic value in dedifferentiated liposarcoma in terms of local recurrence and disease-specific survival. Fifty cases were retrieved, reviewed and FNCLCC grade was scored for the dedifferentiated component. Testing for MDM2 gene amplification was performed by fluorescence in situ hybridization. Amplification was categorized as high level (≥20 copies) and as low level (<20 copies). Follow-up data was obtained through chart review. Log-rank test and Cox proportional hazard models were used to determine the effect of grade and level of MDM2 amplification on outcomes. Our series includes 50 patients (male n=28, female n=22) with an average age of 63 years (range, 28-88) and a median follow-up of 28 months (range, 2-120). Tumors were graded as grade 1 (6%), grade 2 (58%), and grade 3 (36%). When adjusted for age, sex, site, tumor size, and margin status, grade 3 patients had a higher recurrence rate than grades 1 and 2 (HR=2.07, 95% CI: 1.24, 7.62; P=0.015). Patients with high-level MDM2 amplification had higher recurrence rate on univariate analysis (P=0.028), but not on multivariate analysis (HR=1.69, 95% CI: 0.73, 3.94; P=0.221). FNCLCC grade 3 dedifferentiation confers a worse prognosis in dedifferentiated liposarcoma in terms of local recurrence. MDM2 amplification level remains a useful diagnostic tool in dedifferentiated liposarcoma, but has no prognostic value in terms of local recurrence.

Calnexin, an ER stress-induced protein, is a prognostic marker and potential therapeutic target in colorectal cancer.

PubMed

Ryan, Deborah; Carberry, Steven; Murphy, Áine C; Lindner, Andreas U; Fay, Joanna; Hector, Suzanne; McCawley, Niamh; Bacon, Orna; Concannon, Caoimhin G; Kay, Elaine W; McNamara, Deborah A; Prehn, Jochen H M

2016-07-01

Colorectal cancer (CRC) is a leading cause of cancer mortality in the Western world and commonly treated with genotoxic chemotherapy. Stress in the endoplasmic reticulum (ER) was implicated to contribute to chemotherapeutic resistance. Hence, ER stress related protein may be of prognostic or therapeutic significance. The expression levels of ER stress proteins calnexin, calreticulin, GRP78 and GRP94 were determined in n = 23 Stage II and III colon cancer fresh frozen tumour and matched normal tissue samples. Data were validated in a cohort of n = 11 rectal cancer patients treated with radiochemotherapy in the neoadjuvant setting. The calnexin gene was silenced using siRNA in HCT116 cells. There were no increased levels of ER stress proteins in tumour compared to matched normal tissue samples in Stage II or III CRC. However, increased calnexin protein levels were predictive of poor clinical outcome in the patient cohort. Data were validated in the rectal cancer cohort treated in the neoadjuvant setting. Calnexin gene-silencing significantly reduced cell survival and increased cancer cell susceptibility to 5FU chemotherapy. Increased tumour protein levels of calnexin may be of prognostic significance in CRC, and calnexin may represent a potential target for future therapies.

Biomarkers improve mortality prediction by prognostic scales in community-acquired pneumonia.

PubMed

Menéndez, R; Martínez, R; Reyes, S; Mensa, J; Filella, X; Marcos, M A; Martínez, A; Esquinas, C; Ramirez, P; Torres, A

2009-07-01

Prognostic scales provide a useful tool to predict mortality in community-acquired pneumonia (CAP). However, the inflammatory response of the host, crucial in resolution and outcome, is not included in the prognostic scales. The aim of this study was to investigate whether information about the initial inflammatory cytokine profile and markers increases the accuracy of prognostic scales to predict 30-day mortality. To this aim, a prospective cohort study in two tertiary care hospitals was designed. Procalcitonin (PCT), C-reactive protein (CRP) and the systemic cytokines tumour necrosis factor alpha (TNFalpha) and interleukins IL6, IL8 and IL10 were measured at admission. Initial severity was assessed by PSI (Pneumonia Severity Index), CURB65 (Confusion, Urea nitrogen, Respiratory rate, Blood pressure, > or = 65 years of age) and CRB65 (Confusion, Respiratory rate, Blood pressure, > or = 65 years of age) scales. A total of 453 hospitalised CAP patients were included. The 36 patients who died (7.8%) had significantly increased levels of IL6, IL8, PCT and CRP. In regression logistic analyses, high levels of CRP and IL6 showed an independent predictive value for predicting 30-day mortality, after adjustment for prognostic scales. Adding CRP to PSI significantly increased the area under the receiver operating characteristic curve (AUC) from 0.80 to 0.85, that of CURB65 from 0.82 to 0.85 and that of CRB65 from 0.79 to 0.85. Adding IL6 or PCT values to CRP did not significantly increase the AUC of any scale. When using two scales (PSI and CURB65/CRB65) and CRP simultaneously the AUC was 0.88. Adding CRP levels to PSI, CURB65 and CRB65 scales improves the 30-day mortality prediction. The highest predictive value is reached with a combination of two scales and CRP. Further validation of that improvement is needed.

Adaptive Multi-scale PHM for Robotic Assembly Processes

PubMed Central

Choo, Benjamin Y.; Beling, Peter A.; LaViers, Amy E.; Marvel, Jeremy A.; Weiss, Brian A.

2017-01-01

Adaptive multiscale prognostics and health management (AM-PHM) is a methodology designed to support PHM in smart manufacturing systems. As a rule, PHM information is not used in high-level decision-making in manufacturing systems. AM-PHM leverages and integrates component-level PHM information with hierarchical relationships across the component, machine, work cell, and production line levels in a manufacturing system. The AM-PHM methodology enables the creation of actionable prognostic and diagnostic intelligence up and down the manufacturing process hierarchy. Decisions are made with the knowledge of the current and projected health state of the system at decision points along the nodes of the hierarchical structure. A description of the AM-PHM methodology with a simulated canonical robotic assembly process is presented. PMID:28664161

Salicylate-induced changes in auditory thresholds of adolescent and adult rats.

PubMed

Brennan, J F; Brown, C A; Jastreboff, P J

1996-01-01

Shifts in auditory intensity thresholds after salicylate administration were examined in postweanling and adult pigmented rats at frequencies ranging from 1 to 35 kHz. A total of 132 subjects from both age levels were tested under two-way active avoidance or one-way active avoidance paradigms. Estimated thresholds were inferred from behavioral responses to presentations of descending and ascending series of intensities for each test frequency value. Reliable threshold estimates were found under both avoidance conditioning methods, and compared to controls, subjects at both age levels showed threshold shifts at selective higher frequency values after salicylate injection, and the extent of shifts was related to salicylate dose level.

Three-level sampler having automated thresholds

NASA Technical Reports Server (NTRS)

Jurgens, R. F.

1976-01-01

A three-level sampler is described that has its thresholds controlled automatically so as to track changes in the statistics of the random process being sampled. In particular, the mean value is removed and the ratio of the standard deviation of the random process to the threshold is maintained constant. The system is configured in such a manner that slow drifts in the level comparators and digital-to-analog converters are also removed. The ratio of the standard deviation to threshold level may be chosen within the constraints of the ratios of two integers N and M. These may be chosen to minimize the quantizing noise of the sampled process.

Plasma level of cardiotrophin-1 as a prognostic predictor in patients with chronic heart failure.

PubMed

Tsutamoto, Takayoshi; Asai, Shigeru; Tanaka, Toshinari; Sakai, Hiroshi; Nishiyama, Keizo; Fujii, Masanori; Yamamoto, Takashi; Ohnishi, Masato; Wada, Atsuyuki; Saito, Yoshihiko; Horie, Minoru

2007-10-01

Cardiotrophin-1 (CT-1) is a member of the interleukin (IL-6) family of cytokines and is increased in patients with chronic heart failure (CHF). To evaluate the prognostic role of CT-1 in patients with CHF. We measured the plasma levels of CT-1, brain natriuretic peptide (BNP), and IL-6 in 125 patients with CHF. Patients were monitored for a mean follow-up period of 2.9 years. Plasma levels of CT-1 increased with severity of CHF. There was a significant negative correlation between plasma CT-1 and left ventricular ejection fraction. There was a significant correlation between plasma CT-1 and log IL-6. During the follow-up period, 37 patients died. High plasma levels of CT-1, BNP, and IL-6 were independent predictors of mortality on stepwise multivariate analysis. The hazard ratio for mortality in patients with plasma BNP>170 pg/mL and CT-1>658 fmol/mL was 2.48 (95% confidence interval, 1.217-5.060) compared to those with plasma BNP>170 pg/mL and CT-1<658 fmol/mL (p=0.0124). These findings indicate that plasma CT-1 measurement provides additional prognostic information and that combined levels of CT-1 and BNP are more accurate at predicting mortality in patients with CHF than either marker alone.

[Neck lymphatic metastasis, surgical methods and prognosis in early tongue squamous cell carcinoma].

PubMed

Wang, L S; Zhou, F T; Han, C B; He, X P; Zhang, Z X

2018-02-09

Objective: To investigate the different pattern of neck lymph node metastasis, the choice of surgical methods and prognosis in early tongue squamous cell carcinoma. Methods: A total of 157 patients with early oral tongue squamous cell carcinoma were included in this study. Statistical analysis was performed to identify the pattern of lymph node metastasis, to determine the best surgical procedure and to analyze the prognosis. Results: The occurrence of cervical lymph node metastasis rate was 31%(48/157). Neck lymphatic metastasis was significantly related to tumor size ( P= 0.026) and histology differentiation type ( P= 0.022). The rate of metastasis was highest in level Ⅱ [33% (16/48)]. In level Ⅳ, the incidence of lymph node metastasis was 5%(7/157), and there was no skip metastases. The possibility of level Ⅳ metastasis was higher, when level Ⅱ ( P= 0.000) or Ⅲ ( P= 0.000) involved. The differentiation tumor recurrence, neck lymphatic metastasis and adjuvant radiotherapy were prognostic factors ( P< 0.05). Multivariate analyses revealed histology differentiation type, neck lymphatic metastases and adjuvant radiotherapy were the independent prognostic factors. Conclusions: Neck lymphatic metastasis rate is high in early tongue squamous cell carcinoma, simultaneous glossectomy and neck dissection should be performed. Level Ⅳ metastasis rate is extremely low, so supraomohyoid neck dissection is sufficient for most of the time. The histology differentiation type, neck lymphatic metastasis and adjuvant radiotherapy are independent prognostic factors.

WE-E-17A-05: Complementary Prognostic Value of CT and 18F-FDG PET Non-Small Cell Lung Cancer Tumor Heterogeneity Features Quantified Through Texture Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Desseroit, M; Cheze Le Rest, C; Tixier, F

2014-06-15

Purpose: Previous studies have shown that CT or 18F-FDG PET intratumor heterogeneity features computed using texture analysis may have prognostic value in Non-Small Cell Lung Cancer (NSCLC), but have been mostly investigated separately. The purpose of this study was to evaluate the potential added value with respect to prognosis regarding the combination of non-enhanced CT and 18F-FDG PET heterogeneity textural features on primary NSCLC tumors. Methods: One hundred patients with non-metastatic NSCLC (stage I–III), treated with surgery and/or (chemo)radiotherapy, that underwent staging 18F-FDG PET/CT images, were retrospectively included. Morphological tumor volumes were semi-automatically delineated on non-enhanced CT using 3D SlicerTM.more » Metabolically active tumor volumes (MATV) were automatically delineated on PET using the Fuzzy Locally Adaptive Bayesian (FLAB) method. Intratumoral tissue density and FDG uptake heterogeneities were quantified using texture parameters calculated from co-occurrence, difference, and run-length matrices. In addition to these textural features, first order histogram-derived metrics were computed on the whole morphological CT tumor volume, as well as on sub-volumes corresponding to fine, medium or coarse textures determined through various levels of LoG-filtering. Association with survival regarding all extracted features was assessed using Cox regression for both univariate and multivariate analysis. Results: Several PET and CT heterogeneity features were prognostic factors of overall survival in the univariate analysis. CT histogram-derived kurtosis and uniformity, as well as Low Grey-level High Run Emphasis (LGHRE), and PET local entropy were independent prognostic factors. Combined with stage and MATV, they led to a powerful prognostic model (p<0.0001), with median survival of 49 vs. 12.6 months and a hazard ratio of 3.5. Conclusion: Intratumoral heterogeneity quantified through textural features extracted from both CT and FDG PET images have complementary and independent prognostic value in NSCLC.« less

Re-evaluation of DNA Index as a Prognostic Factor in Children with Precursor B Cell Acute Lymphoblastic Leukemia.

PubMed

Noh, O Kyu; Park, Se Jin; Park, Hyeon Jin; Ju, HeeYoung; Han, Seung Hyon; Jung, Hyun Joo; Park, Jun Eun

2017-09-01

We aimed to investigate the prognostic value of DNA index (DI) in children with precursor B cell acute lymphoblastic lymphoma (pre-B ALL). From January 2003 to December 2014, 72 children diagnosed with pre-B ALL were analyzed. We analyzed the prognostic value of DI and its relations with other prognostic factors. The DI cut-point of 1.16 did not discriminate significantly the groups between high and low survivals (DI≥1.16 versus <1.16; 5-year OS, 90.5% vs. 82.8%, p =0.665). We explored the survivals according to the level of DI (<1.00, 1.00, 1.01-1.30, 1.31-1.60, 1.61-1.90, and >1.90), and the survival of children with a DI between 1.00-1.90 were significantly higher than that of children with DI of <1.00 or >1.90 (5-year OS, 90.6% vs. 50.0%, p <0.001). The DI of 1.16 was not a significant cut-point discriminating the risk group in children with pre-B ALL. However, the DI divided by specific ranges of values remained an independent prognostic factor. Further studies are warranted to re-evaluate the prognostic value and cut-point of DI in children treated with recent treatment protocols. © 2017 by the Association of Clinical Scientists, Inc.

Nutritional prognostic scores in patients with hilar cholangiocarcinoma treated by percutaneous transhepatic biliary stenting combined with 125I seed intracavitary irradiation: A retrospective observational study.

PubMed

Cui, Peiyuan; Pang, Qing; Wang, Yong; Qian, Zhen; Hu, Xiaosi; Wang, Wei; Li, Zongkuang; Zhou, Lei; Man, Zhongran; Yang, Song; Jin, Hao; Liu, Huichun

2018-06-01

We mainly aimed to preliminarily explore the prognostic values of nutrition-based prognostic scores in patients with advanced hilar cholangiocarcinoma (HCCA).We retrospectively analyzed 73 cases of HCCA, who underwent percutaneous transhepatic biliary stenting (PTBS) combined with I seed intracavitary irradiation from November 2012 to April 2017 in our department. The postoperative changes of total bilirubin (TBIL), direct bilirubin (DBIL), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and albumin (ALB) were observed. The preoperative clinical data were collected to calculate the nutrition-based scores, including controlling nutritional status (CONUT), C-reactive protein/albumin ratio (CAR), and prognostic nutritional index (PNI). Kaplan-Meier curve and Cox regression model were used for overall survival (OS) analyses.The serum levels of TBIL, DBIL, ALT, AST, and ALP significantly reduced, and ALB significantly increased at 1 month and 3 months postoperatively. The median survival time of the cohort was 12 months and the 1-year survival rate was 53.1%. Univariate analysis revealed that the statistically significant factors related to OS were CA19-9, TBIL, ALB, CONUT, and PNI. Multivariate analysis further identified CA19-9, CONUT, and PNI as independent prognostic factors.Nutrition-based prognostic scores, CONUT and PNI in particular, can be used as predictors of survival in unresectable HCCA.

A Model-based Prognostics Methodology for Electrolytic Capacitors Based on Electrical Overstress Accelerated Aging

NASA Technical Reports Server (NTRS)

Celaya, Jose; Kulkarni, Chetan; Biswas, Gautam; Saha, Sankalita; Goebel, Kai

2011-01-01

A remaining useful life prediction methodology for electrolytic capacitors is presented. This methodology is based on the Kalman filter framework and an empirical degradation model. Electrolytic capacitors are used in several applications ranging from power supplies on critical avionics equipment to power drivers for electro-mechanical actuators. These devices are known for their comparatively low reliability and given their criticality in electronics subsystems they are a good candidate for component level prognostics and health management. Prognostics provides a way to assess remaining useful life of a capacitor based on its current state of health and its anticipated future usage and operational conditions. We present here also, experimental results of an accelerated aging test under electrical stresses. The data obtained in this test form the basis for a remaining life prediction algorithm where a model of the degradation process is suggested. This preliminary remaining life prediction algorithm serves as a demonstration of how prognostics methodologies could be used for electrolytic capacitors. In addition, the use degradation progression data from accelerated aging, provides an avenue for validation of applications of the Kalman filter based prognostics methods typically used for remaining useful life predictions in other applications.

Towards A Model-Based Prognostics Methodology for Electrolytic Capacitors: A Case Study Based on Electrical Overstress Accelerated Aging

NASA Technical Reports Server (NTRS)

Celaya, Jose R.; Kulkarni, Chetan S.; Biswas, Gautam; Goebel, Kai

2012-01-01

A remaining useful life prediction methodology for electrolytic capacitors is presented. This methodology is based on the Kalman filter framework and an empirical degradation model. Electrolytic capacitors are used in several applications ranging from power supplies on critical avionics equipment to power drivers for electro-mechanical actuators. These devices are known for their comparatively low reliability and given their criticality in electronics subsystems they are a good candidate for component level prognostics and health management. Prognostics provides a way to assess remaining useful life of a capacitor based on its current state of health and its anticipated future usage and operational conditions. We present here also, experimental results of an accelerated aging test under electrical stresses. The data obtained in this test form the basis for a remaining life prediction algorithm where a model of the degradation process is suggested. This preliminary remaining life prediction algorithm serves as a demonstration of how prognostics methodologies could be used for electrolytic capacitors. In addition, the use degradation progression data from accelerated aging, provides an avenue for validation of applications of the Kalman filter based prognostics methods typically used for remaining useful life predictions in other applications.

The prognostic reliability of intracranial pressure monitoring and MRI data in severe traumatic brain injury.

PubMed

Woischneck, Dieter; Kapapa, Thomas

2017-02-01

The predictive quality of intracranial pressure (ICP) monitoring has for many years been a matter of debate. We correlate ICP data comparing MRI data with the outcome after severe traumatic brain injury to evaluate their prognostic potency. This study compares the results of ICP monitoring, MRI, coma duration and outcome according to Glasgow Outcome Scale obtained in 32 patients having suffered severe TBI. Level of significance was set to p≤0.05 in statistical tests. The MRI results were closely correlated with coma duration and Glasgow Outcome Scale, but the ICP measurements were not. With the exception of severe, bipontine lesions, there is no other region of the brain in which increased evidence of traumatogenic lesions emerges as the intracranial pressure rises. Just bipontine lesions that proof to be infaust correlate with elevated ICP values. ICP monitoring does not allow individual prognostic conclusions to be made. Implantation of an intracranial pressure sensor alone for making a prognostic estimate is not advisable. The use of intracranial pressure measurements in the retrospective appraisal of disease progress is highly problematic. However, MRI diagnostic in patients with severe TBI improves prognostic potency of clinical parameters. Copyright © 2016 Elsevier Inc. All rights reserved.

Systematic review of renal carcinoma prognostic factors.

PubMed

Lorente, D; Trilla, E; Meseguer, A; Planas, J; Placer, J; Celma, A; Salvador, C; Regis, L; Morote, J

2017-05-01

The natural history of renal cell carcinoma is heterogeneous. Some scenarios can be found in terms of clinical presentation, clinical evolution or type of recurrence (local/metastatic). The aim of this publication is to analyze the most important prognostic factors published in the literature. A literature review ob published papers was performed using the Pubmed, from first Motzer's classification published in 1999 to 2015, according to PRISMA declaration. Search was done using the following keywords: kidney neoplasm, kidney cancer, renal cell carcinoma, prognostic factors, mortality, survival and disease progression. Papers were classified according to level of evidence, the number of patients included and the type of study performed. The evolution in the knowledge of molecular pathways related to renal oncogenesis and the new targeted therapies has left to remain obsolete the old prognostic models. It's necessary to perform a continuous review to actualize nomograms and to adapt them to the new scenarios. Is necessary to perform a proper external validation of existing prognostic factors using prospective and multicentric studies to add them into the daily urologist clinical practice. Copyright © 2016 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

[Correlation analysis of hearing level and soft palate movement after palatoplasty].

PubMed

Lou, Qun; Ma, Xiaoran; Ma, Lian; Luo, Yi; Zhu, Hongping; Zhou, Zhibo

2015-10-01

To explore the relationship between hearing level and soft palate movement after palatoplasty and to verify the importance of recovery of soft palate movement function for improving the middle ear function as well as reducing the hearing loss. A total of 64 non-syndromic cleft palate patients were selected and the lateral cephalometric radiographs were taken. The patients hearing level was evaluated by the pure tone hearing threshold examination. This study also analyzed the correlation between hearing threshold of the patients after palatoplasty and the soft palate elevation angle and velopharyngeal rate respectively. Kendall correlation analysis revealed that the correlation coefficient between hearing threshold and the soft palate elevation angle after palatoplasty was -0.339 (r = -0.339, P < 0.01).The correlation showed a negative correlation. The hearing threshold decreased as the soft palate elevation angle increased. After palatoplasty, the correlation coefficient between the hearing threshold and the rate of velopharyngeal closure was -0.277 (r = -0.277, P < 0.01). The correlation showed a negative correlation. While, The hearing threshold decreased with the increase of velopharyngeal closure rate. The hearing threshold was correlated with soft palate elevation angle and velpharyngeal closure rate. The movement of soft palate and velopharyngeal closure function after palatoplasty both have impact on patient hearing level. In terms of the influence level, the movement of soft palate has a higher level of impact on patient hearing level than velopharygeal closure function.

Assessment of Data and Knowledge Fusion Strategies for Diagnostics and Prognostics

DTIC Science & Technology

2001-04-05

prognostic technologies has proven effective in reducing false alarm rates, increasing confidence levels in early fault detection , and predicting time...or better than the sum of the parts. Specific to health management, this means reduced uncertainty in current condition assessment reduced (improving...achieve time synchronous averaged vibration features. Semmm Amy -U....1A MreN T.g 4 Id F~As- Anomaly DEtection Figure 1 - Fusion Application Areas At a

Contemporary approach to neurologic prognostication of coma after cardiac arrest.

PubMed

Ben-Hamouda, Nawfel; Taccone, Fabio S; Rossetti, Andrea O; Oddo, Mauro

2014-11-01

Coma after cardiac arrest (CA) is an important cause of admission to the ICU. Prognosis of post-CA coma has significantly improved over the past decade, particularly because of aggressive postresuscitation care and the use of therapeutic targeted temperature management (TTM). TTM and sedatives used to maintain controlled cooling might delay neurologic reflexes and reduce the accuracy of clinical examination. In the early ICU phase, patients' good recovery may often be indistinguishable (based on neurologic examination alone) from patients who eventually will have a poor prognosis. Prognostication of post-CA coma, therefore, has evolved toward a multimodal approach that combines neurologic examination with EEG and evoked potentials. Blood biomarkers (eg, neuron-specific enolase [NSE] and soluble 100-β protein) are useful complements for coma prognostication; however, results vary among commercial laboratory assays, and applying one single cutoff level (eg, > 33 μg/L for NSE) for poor prognostication is not recommended. Neuroimaging, mainly diffusion MRI, is emerging as a promising tool for prognostication, but its precise role needs further study before it can be widely used. This multimodal approach might reduce false-positive rates of poor prognosis, thereby providing optimal prognostication of comatose CA survivors. The aim of this review is to summarize studies and the principal tools presently available for outcome prediction and to describe a practical approach to the multimodal prognostication of coma after CA, with a particular focus on neuromonitoring tools. We also propose an algorithm for the optimal use of such multimodal tools during the early ICU phase of post-CA coma.

Molecular Pathways: Extracting Medical Knowledge from High Throughput Genomic Data

PubMed Central

Goldstein, Theodore; Paull, Evan O.; Ellis, Matthew J.; Stuart, Joshua M.

2013-01-01

High-throughput genomic data that measures RNA expression, DNA copy number, mutation status and protein levels provide us with insights into the molecular pathway structure of cancer. Genomic lesions (amplifications, deletions, mutations) and epigenetic modifications disrupt biochemical cellular pathways. While the number of possible lesions is vast, different genomic alterations may result in concordant expression and pathway activities, producing common tumor subtypes that share similar phenotypic outcomes. How can these data be translated into medical knowledge that provides prognostic and predictive information? First generation mRNA expression signatures such as Genomic Health's Oncotype DX already provide prognostic information, but do not provide therapeutic guidance beyond the current standard of care – which is often inadequate in high-risk patients. Rather than building molecular signatures based on gene expression levels, evidence is growing that signatures based on higher-level quantities such as from genetic pathways may provide important prognostic and diagnostic cues. We provide examples of how activities for molecular entities can be predicted from pathway analysis and how the composite of all such activities, referred to here as the “activitome,” help connect genomic events to clinical factors in order to predict the drivers of poor outcome. PMID:23430023

The Threshold Level--For Schools?

ERIC Educational Resources Information Center

Lauerbach, Gerda

1979-01-01

Comments on the document "Threshold Level for Modern Language Learning Schools" (J. A. Van Ek, Strasbourg, 1976) and its appropriateness as a description of learning goals for the first years of foreign language teaching. Criticizes particularly the "reduced learning" concept, on which the threshold projects are based. (IFS/WGA)

Plasma Mesothelin as a Novel Diagnostic and Prognostic Biomarker in Colorectal Cancer

PubMed Central

Li, Shuwei; Xie, Lisheng; He, Lei; Fan, Zhimin; Xu, Junhua; Xu, Kaili; Zhu, Lingjun; Ma, Gaoxiang; Du, Mulong; Chu, Haiyan; Zhang, Zhengdong; Ni, Min; Wang, Meilin

2017-01-01

Objective Mesothelin is a cell surface protein and overexpressed in many cancers. However, the potential value of mesothelin as plasma biomarker in colorectal cancer has not been explored. The purpose of this study was to identify whether plasma mesothelin is a suitable diagnostic and prognostic biomarker for colorectal cancer. Methods We performed a two-stage case-control study to evaluate plasma mesothelin levels in colorectal cancer using enzyme-linked immunosorbent assay (ELISA). Preoperative and postoperative plasma were collected to examine the level changes influenced by surgery. Receiver operating characteristic (ROC) curves were applied to identify the diagnostic value of plasma mesothelin. We also conducted univariate Kaplan-Meier survival analysis and Cox regression analysis of patients with survival information. Results We found that the plasma mesothelin levels in colorectal cancer patients were significantly higher than that in the controls (P < 0.001) with an AUC value of 0.690 (95% CI = 0.625 to 0.752). Individuals with lower mesothelin level had a longer survival time (adjusted HR = 4.43, 95% CI = 1.93-10.15, P < 0.001). Furthermore, Patients had slightly decreased mesothelin levels in postoperative plasma than preoperative plasma, although the alteration was not statistically significant (P = 0.052). Conclusion Our findings highlight the correlative relationship between plasma mesothelin levels and the presence and progression of colorectal cancer. Plasma mesothelin may be a potential diagnostic and, or prognostic biomarker for colorectal cancer. PMID:28638449

Partial Oxygen Pressure Affects the Expression of Prognostic Biomarkers HIF-1 Alpha, Ki67, and CK20 in the Microenvironment of Colorectal Cancer Tissue.

PubMed

Zhang, Lirong; Hu, Yu; Xi, Ning; Song, Jie; Huang, Wenjing; Song, Shanshan; Liu, Yiting; Liu, Xianying; Xie, Yingjun

2016-01-01

Hypoxia is prognostically important in colorectal cancer (CRC) therapy. Partial oxygen pressure (pO 2 ) is an important parameter of hypoxia. The correlation between pO 2 levels and expression levels of prognostic biomarkers was measured in CRC tissues. Human CRC tissues were collected and pO 2 levels were measured by OxyLite. Three methods for tissue fixation were compared, including formalin, Finefix, and Finefix-plus-microwave. Immunohistochemistry (IHC) staining was conducted by using the avidin-biotin complex technique for detecting the antibodies to hypoxia inducible factor-1 (HIF-1) alpha, cytokeratin 20 (CK20), and cell proliferation factor Ki67. The levels of pO 2 were negatively associated with the size of CRC tissues. Finefix-plus-microwave fixation has the potential to replace formalin. Additionally, microwave treatment improved Finefix performance in tissue fixation and protein preservation. The percentage of positive cells and gray values of HIF-1 alpha, CK20, and Ki67 were associated with CRC development ( P < 0.05). The levels of pO 2 were positively related with the gray values of Ki67 and negatively related with the values of HIF-1 alpha and CK20 ( P < 0.05). Thus, the levels of microenvironmental pO 2 affect the expression of predictive biomarkers HIF-1 alpha, CK20, and Ki67 in the development of CRC tissues.

Prognostic factors of whiplash-associated disorders: a systematic review of prospective cohort studies.

PubMed

Scholten-Peeters, Gwendolijne G M; Verhagen, Arianne P; Bekkering, Geertruida E; van der Windt, Daniëlle A W M; Barnsley, Les; Oostendorp, Rob A B; Hendriks, Erik J M

2003-07-01

We present a systematic review of prospective cohort studies. Our aim was to assess prognostic factors associated with functional recovery of patients with whiplash injuries. The failure of some patients to recover following whiplash injury has been linked to a number of prognostic factors. However, there is some inconsistency in the literature and there have been no systematic attempts to analyze the level of evidence for prognostic factors in whiplash recovery. Studies were selected for inclusion following a comprehensive search of MEDLINE, EMBASE, CINAHL, the database of the Dutch Institute of Allied Health Professions up until April 2002 and hand searches of the reference lists of retrieved articles. Studies were selected if the objective was to assess prognostic factors associated with recovery; the design was a prospective cohort study; the study population included at least an identifiable subgroup of patients suffering from a whiplash injury; and the paper was a full report published in English, German, French or Dutch. The methodological quality was independently assessed by two reviewers. A study was considered to be of 'high quality' if it satisfied at least 50% of the maximum available quality score. Two independent reviewers extracted data and the association between prognostic factors and functional recovery was calculated in terms of risk estimates. Fifty papers reporting on twenty-nine cohorts were included in the review. Twelve cohorts were considered to be of 'high quality'. Because of the heterogeneity of patient selection, type of prognostic factors and outcome measures, no statistical pooling was able to be performed. Strong evidence was found for high initial pain intensity being an adverse prognostic factor. There was strong evidence that for older age, female gender, high acute psychological response, angular deformity of the neck, rear-end collision, and compensation not being associated with an adverse prognosis. Several physical (e.g. restricted range of motion, high number of complaints), psychosocial (previous psychological problems), neuropsychosocial factors (nervousness), crash related (e.g. accident on highway) and treatment related factors (need to resume physiotherapy) showed limited prognostic value for functional recovery. High initial pain intensity is an important predictor for delayed functional recovery for patients with whiplash injury. Often mentioned factors like age, gender and compensation do not seem to be of prognostic value. Scientific information about prognostic factors can guide physicians or other care providers to direct treatment and to probably prevent chronicity.

Prediction of new brain metastases after radiosurgery: validation and analysis of performance of a multi-institutional nomogram.

PubMed

Ayala-Peacock, Diandra N; Attia, Albert; Braunstein, Steve E; Ahluwalia, Manmeet S; Hepel, Jaroslaw; Chung, Caroline; Contessa, Joseph; McTyre, Emory; Peiffer, Ann M; Lucas, John T; Isom, Scott; Pajewski, Nicholas M; Kotecha, Rupesh; Stavas, Mark J; Page, Brandi R; Kleinberg, Lawrence; Shen, Colette; Taylor, Robert B; Onyeuku, Nasarachi E; Hyde, Andrew T; Gorovets, Daniel; Chao, Samuel T; Corso, Christopher; Ruiz, Jimmy; Watabe, Kounosuke; Tatter, Stephen B; Zadeh, Gelareh; Chiang, Veronica L S; Fiveash, John B; Chan, Michael D

2017-11-01

Stereotactic radiosurgery (SRS) without whole brain radiotherapy (WBRT) for brain metastases can avoid WBRT toxicities, but with risk of subsequent distant brain failure (DBF). Sole use of number of metastases to triage patients may be an unrefined method. Data on 1354 patients treated with SRS monotherapy from 2000 to 2013 for new brain metastases was collected across eight academic centers. The cohort was divided into training and validation datasets and a prognostic model was developed for time to DBF. We then evaluated the discrimination and calibration of the model within the validation dataset, and confirmed its performance with an independent contemporary cohort. Number of metastases (≥8, HR 3.53 p = 0.0001), minimum margin dose (HR 1.07 p = 0.0033), and melanoma histology (HR 1.45, p = 0.0187) were associated with DBF. A prognostic index derived from the training dataset exhibited ability to discriminate patients' DBF risk within the validation dataset (c-index = 0.631) and Heller's explained relative risk (HERR) = 0.173 (SE = 0.048). Absolute number of metastases was evaluated for its ability to predict DBF in the derivation and validation datasets, and was inferior to the nomogram. A nomogram high-risk threshold yielding a 2.1-fold increased need for early WBRT was identified. Nomogram values also correlated to number of brain metastases at time of failure (r = 0.38, p < 0.0001). We present a multi-institutionally validated prognostic model and nomogram to predict risk of DBF and guide risk-stratification of patients who are appropriate candidates for radiosurgery versus upfront WBRT.

Hospital type- and volume-outcome relationships in esophageal cancer patients receiving non-surgical treatments.

PubMed

Hsu, Po-Kuei; Chen, Hui-Shan; Wang, Bing-Yen; Wu, Shiao-Chi; Liu, Chao-Yu; Shih, Chih-Hsun; Liu, Chia-Chuan

2015-01-28

To study the "hospital type-outcome" and "volume-outcome" relationships in patients with esophageal cancer who receive non-surgical treatments. A total of 6106 patients with esophageal cancer diagnosed between 2008 and 2011 were identified from a national population-based cancer registry in Taiwan. The hospital types were defined as medical center and non-medical center. The threshold for high-volume hospitals was based on a median volume of 225 cases between 2008 and 2011 (annual volume, >56 cases) or an upper quartile (>75%) volume of 377 cases (annual volume>94 cases). Cox regression analyses were used to determine the effects of hospital type and volume outcome on patient survival. A total of 3955 non-surgically treated patients were included in the survival analysis. In the unadjusted analysis, the significant prognostic factors included cT, cN, cM stage, hospital type and hospital volume (annual volume, >94 vs ≤94). The 1- and 3-year overall survival rates in the non-medical centers (36.2% and 13.2%, respectively) were significantly higher than those in the medical centers (33.5% and 11.3%, respectively; P=0.027). The 1- and 3-year overall survival rates in hospitals with an annual volume of ≤94 (35.3% and 12.6%, respectively) were significantly higher than those with an annual volume of >94 (31.1% and 9.4%, respectively; P=0.001). However, in the multivariate analysis, the hospital type was not statistically significant. Only cT, cN, and cM stages and hospital volume (annual volume>94 vs ≤94) were independent prognostic factors. Whether the treatment occurs in medical centers is not a significant prognostic factor. High-volume hospitals were not associated with better survival rates compared with low-volume hospitals.

Survivin gene levels in the peripheral blood of patients with gastric cancer independently predict survival

PubMed Central

2009-01-01

Background The detection of circulating tumor cells (CTC) is considered a promising tool for improving risk stratification in patients with solid tumors. We investigated on whether the expression of CTC related genes adds any prognostic power to the TNM staging system in patients with gastric carcinoma. Methods Seventy patients with TNM stage I to IV gastric carcinoma were retrospectively enrolled. Peripheral blood samples were tested by means of quantitative real time PCR (qrtPCR) for the expression of four CTC related genes: carcinoembryonic antigen (CEA), cytokeratin-19 (CK19), vascular endothelial growth factor (VEGF) and Survivin (BIRC5). Results Gene expression of Survivin, CK19, CEA and VEGF was higher than in normal controls in 98.6%, 97.1%, 42.9% and 38.6% of cases, respectively, suggesting a potential diagnostic value of both Survivin and CK19. At multivariable survival analysis, TNM staging and Survivin mRNA levels were retained as independent prognostic factors, demonstrating that Survivin expression in the peripheral blood adds prognostic information to the TNM system. In contrast with previously published data, the transcript abundance of CEA, CK19 and VEGF was not associated with patients' clinical outcome. Conclusions Gene expression levels of Survivin add significant prognostic value to the current TNM staging system. The validation of these findings in larger prospective and multicentric series might lead to the implementation of this biomarker in the routine clinical setting in order to optimize risk stratification and ultimately personalize the therapeutic management of these patients. PMID:20028510

Computed Tomography Aortic Valve Calcium Scoring in Patients With Aortic Stenosis.

PubMed

Pawade, Tania; Clavel, Marie-Annick; Tribouilloy, Christophe; Dreyfus, Julien; Mathieu, Tiffany; Tastet, Lionel; Renard, Cedric; Gun, Mesut; Jenkins, William Steven Arthur; Macron, Laurent; Sechrist, Jacob W; Lacomis, Joan M; Nguyen, Virginia; Galian Gay, Laura; Cuéllar Calabria, Hug; Ntalas, Ioannis; Cartlidge, Timothy Robert Graham; Prendergast, Bernard; Rajani, Ronak; Evangelista, Arturo; Cavalcante, João L; Newby, David E; Pibarot, Philippe; Messika Zeitoun, David; Dweck, Marc R

2018-03-01

Computed tomography aortic valve calcium scoring (CT-AVC) holds promise for the assessment of patients with aortic stenosis (AS). We sought to establish the clinical utility of CT-AVC in an international multicenter cohort of patients. Patients with AS who underwent ECG-gated CT-AVC within 3 months of echocardiography were entered into an international, multicenter, observational registry. Optimal CT-AVC thresholds for diagnosing severe AS were determined in patients with concordant echocardiographic assessments, before being used to arbitrate disease severity in those with discordant measurements. In patients with long-term follow-up, we assessed whether CT-AVC thresholds predicted aortic valve replacement and death. In 918 patients from 8 centers (age, 77±10 years; 60% men; peak velocity, 3.88±0.90 m/s), 708 (77%) patients had concordant echocardiographic assessments, in whom CT-AVC provided excellent discrimination for severe AS (C statistic: women 0.92, men 0.89). Our optimal sex-specific CT-AVC thresholds (women 1377 Agatston unit and men 2062 Agatston unit) were nearly identical to those previously reported (women 1274 Agatston unit and men 2065 Agatston unit). Clinical outcomes were available in 215 patients (follow-up 1029 [126-2251] days). Sex-specific CT-AVC thresholds independently predicted aortic valve replacement and death (hazard ratio, 3.90 [95% confidence interval, 2.19-6.78]; P <0.001) after adjustment for age, sex, peak velocity, and aortic valve area. Among 210 (23%) patients with discordant echocardiographic assessments, there was considerable heterogeneity in CT-AVC scores, which again were an independent predictor of clinical outcomes (hazard ratio, 3.67 [95% confidence interval, 1.39-9.73]; P =0.010). Sex-specific CT-AVC thresholds accurately identify severe AS and provide powerful prognostic information. These findings support their integration into routine clinical practice. URL: http://www.clinicaltrials.gov. Unique identifiers: NCT01358513, NCT02132026, NCT00338676, NCT00647088, NCT01679431. © 2018 American Heart Association, Inc.

Thermal QST Phenotypes Associated with Response to Lumbar Epidural Steroid Injections: A Pilot Study.

PubMed

Maher, Dermot P; Ding, Weihua; Singh, Sarabdeep; Opalacz, Arissa; Fishman, Claire; Houghton, Mary; Ahmed, Shihab; Chen, Lucy; Mao, Jianren; Zhang, Yi

2017-08-01

Response to lumbar epidural steroid injection in lumbar radicular pain varies. The purpose of this study is to characterize the changes in quantitative sensory testing (QST) phenotypes of subjects and compare the QST characteristics in patients who do respond to treatment of radicular pain with a lumbar epidural steroid injection (ESI). Prospective, observational pilot study. Outpatient pain center. Twenty subjects with a lower extremity (LE) radicular pain who were scheduled to have an ESI were recruited. At the visit prior to and four weeks following an ESI, subjects underwent QST measurements of both the affected LE and the contralateral unaffected UE. Following an ESI, nine subjects reported a greater than 30% reduction in radicular pain and 11 reported a less than 30% reduction in radicular pain. Subjects who had less than 30% pain reduction response (nonresponders) to an ESI had increased pre-injection warm sensation threshold (37.30 °C, SD = 2.51 vs 40.39, SD = 3.36, P = 0.03) and heat pain threshold (47.22 °C, SD = 1.38, vs 48.83 °C, SD = 2.10, P = 0.04). Further, the nonresponders also showed increased pre-injection warm sensation threshold as measured in the difference of warm sensation detection threshold difference in the affected limb and the unaffected arm (2.68 °C, SD = 2.92 vs 5.67 °C, SD = 3.22, P  = 0.045). Other QST parameters were not affected. The results show that the nonresponders to ESIs have increased detection threshold to heat pain and warm sensation, suggesting that a preexisting dysfunction in the C fibers in this group of subjects who can be detected by QST. Such altered QST characteristics may prognosticate the response to ESIs. © 2017 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Matrix metalloproteinases in cancer: their value as diagnostic and prognostic markers and therapeutic targets.

PubMed

Hadler-Olsen, Elin; Winberg, Jan-Olof; Uhlin-Hansen, Lars

2013-08-01

Biomarkers are used as tools in cancer diagnostics and in treatment stratification. In most cancers, there are increased levels of one or several members of the matrix metalloproteinases (MMPs). This is a family of proteolytic enzymes that are involved in many phases of cancer progression, including angiogenesis, invasiveness, and metastasis. It has therefore been expected that MMPs could serve as both diagnostic and prognostic markers in cancer patients, but despite a huge number of studies, it has been difficult to establish MMPs as cancer biomarkers. In the present paper, we assess some of the challenges associated with MMP research as well as putative reasons for the conflicting data on the value of these enzymes as diagnostic and prognostic markers in cancer patients. We also review the prognostic value of a number of MMPs in patients with lung, colorectal, breast, and prostate cancers. The review also discusses MMPs as potential target molecules for therapeutic agents and new strategies for development of such drugs.

Chromatic Perceptual Learning but No Category Effects without Linguistic Input.

PubMed

Grandison, Alexandra; Sowden, Paul T; Drivonikou, Vicky G; Notman, Leslie A; Alexander, Iona; Davies, Ian R L

2016-01-01

Perceptual learning involves an improvement in perceptual judgment with practice, which is often specific to stimulus or task factors. Perceptual learning has been shown on a range of visual tasks but very little research has explored chromatic perceptual learning. Here, we use two low level perceptual threshold tasks and a supra-threshold target detection task to assess chromatic perceptual learning and category effects. Experiment 1 investigates whether chromatic thresholds reduce as a result of training and at what level of analysis learning effects occur. Experiment 2 explores the effect of category training on chromatic thresholds, whether training of this nature is category specific and whether it can induce categorical responding. Experiment 3 investigates the effect of category training on a higher level, lateralized target detection task, previously found to be sensitive to category effects. The findings indicate that performance on a perceptual threshold task improves following training but improvements do not transfer across retinal location or hue. Therefore, chromatic perceptual learning is category specific and can occur at relatively early stages of visual analysis. Additionally, category training does not induce category effects on a low level perceptual threshold task, as indicated by comparable discrimination thresholds at the newly learned hue boundary and adjacent test points. However, category training does induce emerging category effects on a supra-threshold target detection task. Whilst chromatic perceptual learning is possible, learnt category effects appear to be a product of left hemisphere processing, and may require the input of higher level linguistic coding processes in order to manifest.

Cell-Free DNA in Metastatic Colorectal Cancer: A Systematic Review and Meta-Analysis.

PubMed

Spindler, Karen-Lise G; Boysen, Anders K; Pallisgård, Niels; Johansen, Julia S; Tabernero, Josep; Sørensen, Morten M; Jensen, Benny V; Hansen, Torben F; Sefrioui, David; Andersen, Rikke F; Brandslund, Ivan; Jakobsen, Anders

2017-09-01

Circulating DNA can be detected and quantified in the blood of cancer patients and used for detection of tumor-specific genetic alterations. The clinical utility has been intensively investigated for the past 10 years. The majority of reports focus on analyzing the clinical potential of tumor-specific mutations, whereas the use of total cell-free DNA (cfDNA) quantification is somehow controversial and sparsely described in the literature, but holds important clinical information in itself. The purpose of the present report was to present a systematic review and meta-analysis of the prognostic value of total cfDNA in patients with metastatic colorectal cancer (mCRC) treated with chemotherapy. In addition, we report on the overall performance of cfDNA as source for KRAS mutation detection. A systematic literature search of PubMed and Embase was performed by two independent investigators. Eligibility criteria were (a) total cfDNA analysis, (b) mCRC, and (c) prognostic value during palliative treatment. The preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines were followed, and meta-analysis applied on both aggregate data extraction and individual patients' data. Ten eligible cohorts were identified, including a total of 1,076 patients. Seven studies used quantitative polymerase chain reaction methods, two BEAMing [beads, emulsification, amplification, and magnetics] technology, and one study digital droplet polymerase chain reaction. The baseline levels of cfDNA was similar in the presented studies, and all studies reported a clear prognostic value in favor of patients with lowest levels of baseline cfDNA. A meta-analysis revealed a combined estimate of favorable overall survival hazard ratio (HR) in patients with levels below the median cfDNA (HR = 2.39, 95% confidence interval 2.03-2.82, p  < .0001). The total cfDNA levels are high in patients with mCRC and bear strong prognostic information, which should be tested prospectively by using a predefined cut-off value based on normal values in healthy cohorts. Finally, the potential use of cfDNA for detection of tumor-specific mutations was emphasized in a large individual patients' data meta-analysis. Reliable prognostic markers could help to guide patients and treating physicians regarding the relevance and choice of systemic therapy. Small fragments of circulating cell-free DNA (cfDNA) can be measured in a simple blood sample. This report presents the first meta-analysis of the prognostic value of total cfDNA measurement in patients with metastatic colorectal cancer. Data from 1,076 patients confirmed that patients with the lowest pre-treatment levels of cfDNA had a significantly higher chance of longer survival than those with higher levels. Cell-free DNA analysis can also be used for detection of tumor-specific mutations, and hold potential as a valuable tool in colorectal cancer treatment. © AlphaMed Press 2017.

On the expected discounted penalty functions for two classes of risk processes under a threshold dividend strategy

NASA Astrophysics Data System (ADS)

Lu, Zhaoyang; Xu, Wei; Sun, Decai; Han, Weiguo

2009-10-01

In this paper, the discounted penalty (Gerber-Shiu) functions for a risk model involving two independent classes of insurance risks under a threshold dividend strategy are developed. We also assume that the two claim number processes are independent Poisson and generalized Erlang (2) processes, respectively. When the surplus is above this threshold level, dividends are paid at a constant rate that does not exceed the premium rate. Two systems of integro-differential equations for discounted penalty functions are derived, based on whether the surplus is above this threshold level. Laplace transformations of the discounted penalty functions when the surplus is below the threshold level are obtained. And we also derive a system of renewal equations satisfied by the discounted penalty function with initial surplus above the threshold strategy via the Dickson-Hipp operator. Finally, analytical solutions of the two systems of integro-differential equations are presented.

20 CFR 404.1641 - Standards of performance.

Code of Federal Regulations, 2010 CFR

2010-04-01

.... (a) General. The performance standards include both a target level of performance and a threshold level of performance for the State agency. The target level represents a level of performance that we and the States will work to attain in the future. The threshold level is the minimum acceptable level...

20 CFR 416.1041 - Standards of performance.

Code of Federal Regulations, 2010 CFR

2010-04-01

... performance. (a) General. The performance standards include both a target level of performance and a threshold level of performance for the State agency. The target level represents a level of performance that we and the States will work to attain in the future. The threshold level is the minimum acceptable level...

Clinicopathologic and prognostic significance of C-reactive protein/albumin ratio in patients with solid tumors: an updated systemic review and meta-analysis.

PubMed

Wu, Jiayuan; Tan, Wenkai; Chen, Lin; Huang, Zhe; Mai, Shao

2018-03-02

C-reactive protein/albumin ratio (CAR) was originally used as a novel inflammation-based prognostic score in predicting outcomes in septic patients. Recently, more and more studies have reported the prognostic value of pretreatment CAR in solid tumors. However, the results remain controversial rather than conclusive. We conducted a meta-analysis based on 24 studies with 10203 patients to explore the relationship between CAR and survival outcomes in patients with solid tumors. The correlation between CAR and clinicopathological parameters was also assessed. Hazard ratio (HR) or odds ratio (OR) with its 95% confidence interval (CI) was applied to be the effect size estimate. The overall results showed that elevated CAR was associated with shorter overall survival (OS) (including 23 studies and 10067 patients) and poorer disease-free survival (DFS) (including 6 studies and 2904 patients). Significant associations between high CAR level and poor OS were also found in the subgroup analyses of study region, cancer type, primary treatment, clinical stage, cut-off selection, sample size, and cut-off value. Moreover, subgroup analyses demonstrated that study region, primary treatment, clinical stage, sample size, and cut-off value did not alter the prognostic value of CAR for DFS. Furthermore, elevated CAR was correlated with certain phenotypes of tumor aggressiveness, such as poor histological grade, serious clinical stage, advanced tumor depth, positive lymph node metastasis, and positive distant metastasis. Together, our meta-analysis suggests that elevated level of serum CAR predicts worse survival and unfavorable clinical characteristics in cancer patients, and CAR may serve as an effective prognostic factor for solid tumors.

Prognostic Value of Soluble Death Receptor Ligands in Patients with Transitional Cell Carcinoma of Bladder.

PubMed

Ben Bahria-Sediki, Islem; Chebil, Mohamed; Sampaio, Carla; Martel-Frachet, Véronique; Cherif, Mohamed; Zermani, Rachida; Rammeh, Soumaya; Ben Ammar Gaaied, Amel; Bettaieb, Ali

2018-05-02

The activation of Fas/Fas ligand (FasL) and DR4-DR5/tumor necrosis factor-related-apoptosis-inducing ligand (TRAIL) pathways in cancer cells triggers apoptosis. The objective of this study was to investigate the prognostic value of soluble FasL (sFasL) and soluble (sTRAIL) in the serum of patients with bladder cancer. The sFasL and sTRAIL levels in the sera of patients with bladder cancer or healthy donors were determined using the enzyme-linked immunosorbent assay. Micro-culture tetrazolium viability assay and Western blot were used to analyze cell cytotoxicity and death receptors protein expression respectively. Whether no difference in sTRAIL levels was seen between patients and controls, the level of sFasL was higher in patients than that in healthy donors. According to, sFasL level was the highest in the serum of patients with superficial stage or low- and medium-grade cancer. Moreover, sFasL in patients with superficial noninvasive bladder tumors or low- and medium-grade cancers was higher than that in patients with invasive carcinomas and high-grade cancers. Patients with high levels of sFasL survive longer than those with low levels, probably related to the cytotoxic potential of FasL preserved in its soluble form. The data suggest that monitoring the level of sFasL and its cytotoxic activity could be a prognostic marker in the follow-up of patients with bladder cancer. © 2018 S. Karger AG, Basel.

The prognostic significance of preoperative serum cancer antigen 15-3 levels in endometrial carcinomas

PubMed Central

Tas, Emre E.; Yavuz, Ayse F.

2017-01-01

Objectives: To determine the associations between serum cancer antigen 15-3 levels and prognostic factors in patients with endometrial carcinomas. Additionally, we investigated the clinical utility of serum cancer antigen 15-3 levels in the selection of low-risk patients with endometrioid type, tumor size <2 cm, myometrial invasion ≤50%, and histological grade 1-2. Methods: Ninety-six patients, who were surgically staged at Ankara Yildirim Beyazit University, Ankara, Turkey, between 2007 and 2016, were retrospectively analyzed. Demographic, clinical, and surgical characteristics were retrieved from the patients’ hospital records. A p<0.05 was considered significant. Results: Fifteen patients had advanced (≥Stage II) disease, 14 patients had Type 2 histology, 20 patients had Grade 3 tumors, 23 patients had lymphovascular space invasion, and 10 patients had positive lymph node involvement. Serum cancer antigen 15-3 levels were significantly higher in patients with advanced (≥Stage II) disease, Type 2 histology, Grade 3 tumors, lymp°hovascular space invasion, and positive lymph node involvement (p<0.05). Serum cancer antigen 15-3 levels were also significantly correlated with tumor size (p=0.006). Serum cancer antigen 15-3 levels were significantly lower (95% confidence interval: 0.57−0.79; p=0.03) in low-risk patients compared to other endometrial carcinoma patients. A cutoff of 25.0 IU/mL was used to identify high-risk patients with a specificity of 100%. Conclusion: Serum cancer antigen 15-3 levels significantly correlated with prognostic factors and were a useful diagnostic tool for endometrial carcinomas. PMID:29114696

Cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) in the treatment of stage IE/IIE extranodal natural killer/T cell lymphoma, nasal type: 13-year follow-up in 135 patients.

PubMed

Wang, Liang; Xia, Zhong-jun; Huang, Hui-qiang; Lu, Yue; Zhang, Yu-jing

2012-11-01

We conducted a retrospective study of 135 patients of stage IE/IIE extranodal natural killer/T cell lymphoma, nasal type (ENKTL) treated with CHOP as induction chemotherapy to find some valuable prognostic factors and analyze the usefulness of International Prognostic Index (IPI) and Korean Prognostic Index (KPI) in predicting prognosis. Most of the patients were in the low-risk group (IPI score 0-1). Complete remission (CR) after induction chemotherapy was achieved in 31.8 % of the patients, which increased to 69.6 % after radiotherapy. The 2-, 5-, and 10-year overall survival (OS) rates were 60, 48, and 43 %, respectively. Patients with better performance status (ECOG 0-1), normal serum LDH level, without local invasiveness, low KPI scores, and IPI score of 0 had significantly better overall survival (P < 0.05) in univariate analysis. Using multivariate analysis, we identified serum LDH level, ECOG PS score and local invasiveness to be independent prognostic factors. In conclusion, ENKTL is an aggressive lymphoma that shows heterogeneity. The IPI and KPI score systems should be improved further to classify patients into different groups, and should be validated in larger prospective trials. Due to the multi-drug resistance mechanism of ENKTL, CHOP is no longer the state of art and novel drugs should be incorporated into future treatments.

Integrated analysis of DNA methylation, immunohistochemistry and mRNA expression, data identifies a Methylation Expression Index (MEI) robustly associated with survival of ER-positive breast cancer patients

PubMed Central

Garcia-Closas, Montserrat; Davis, Sean; Meltzer, Paul; Lissowska, Jolanta; Horne, Hisani N.; Sherman, Mark E.; Lee, Maxwell

2015-01-01

Identification of prognostic gene expression signatures may enable improved decisions about management of breast cancer. To identify a prognostic signature for breast cancer, we performed DNA methylation profiling and identified methylation markers that were associated with expression of ER, PR, HER2, CK5/6 and EGFR proteins. Methylation markers that were correlated with corresponding mRNA expression levels were identified using 208 invasive tumors from a population-based case-control study conducted in Poland. Using this approach, we defined the Methylation Expression Index (MEI) signature that was based on a weighted sum of mRNA levels of 57 genes. Classification of cases as low or high MEI scores were related to survival using Cox regression models. In the Polish study, women with ER-positive low MEI cancers had reduced survival at a median of 5.20 years of follow-up, HR=2.85 95%CI=1.25-6.47. Low MEI was also related to decreased survival in four independent datasets totaling over 2500 ER-positive breast cancers. These results suggest that integrated analysis of tumor expression markers, DNA methylation, and mRNA data can be an important approach for identifying breast cancer prognostic signatures. Prospective assessment of MEI along with other prognostic signatures should be evaluated in future studies. PMID:25773928

Comparison of the performances of copeptin and multiple biomarkers in long-term prognosis of severe traumatic brain injury.

PubMed

Zhang, Zu-Yong; Zhang, Li-Xin; Dong, Xiao-Qiao; Yu, Wen-Hua; Du, Quan; Yang, Ding-Bo; Shen, Yong-Feng; Wang, Hao; Zhu, Qiang; Che, Zhi-Hao; Liu, Qun-Jie; Jiang, Li; Du, Yuan-Feng

2014-10-01

Enhanced blood levels of copeptin correlate with poor clinical outcomes after acute critical illness. This study aimed to compare the prognostic performances of plasma concentrations of copeptin and other biomarkers like myelin basic protein, glial fibrillary astrocyte protein, S100B, neuron-specific enolase, phosphorylated axonal neurofilament subunit H, Tau and ubiquitin carboxyl-terminal hydrolase L1 in severe traumatic brain injury. We recruited 102 healthy controls and 102 acute patients with severe traumatic brain injury. Plasma concentrations of these biomarkers were determined using enzyme-linked immunosorbent assay. Their prognostic predictive performances of 6-month mortality and unfavorable outcome (Glasgow Outcome Scale score of 1-3) were compared. Plasma concentrations of these biomarkers were statistically significantly higher in all patients than in healthy controls, in non-survivors than in survivors and in patients with unfavorable outcome than with favorable outcome. Areas under receiver operating characteristic curves of plasma concentrations of these biomarkers were similar to those of Glasgow Coma Scale score for prognostic prediction. Except plasma copeptin concentration, other biomarkers concentrations in plasma did not statistically significantly improve prognostic predictive value of Glasgow Coma Scale score. Copeptin levels may be a useful tool to predict long-term clinical outcomes after severe traumatic brain injury and have a potential to assist clinicians. Copyright © 2014 Elsevier Inc. All rights reserved.

A Novel UAV Electric Propulsion Testbed for Diagnostics and Prognostics

NASA Technical Reports Server (NTRS)

Gorospe, George E., Jr.; Kulkarni, Chetan S.

2017-01-01

This paper presents a novel hardware-in-the-loop (HIL) testbed for systems level diagnostics and prognostics of an electric propulsion system used in UAVs (unmanned aerial vehicle). Referencing the all electric, Edge 540T aircraft used in science and research by NASA Langley Flight Research Center, the HIL testbed includes an identical propulsion system, consisting of motors, speed controllers and batteries. Isolated under a controlled laboratory environment, the propulsion system has been instrumented for advanced diagnostics and prognostics. To produce flight like loading on the system a slave motor is coupled to the motor under test (MUT) and provides variable mechanical resistance, and the capability of introducing nondestructive mechanical wear-like frictional loads on the system. This testbed enables the verification of mathematical models of each component of the propulsion system, the repeatable generation of flight-like loads on the system for fault analysis, test-to-failure scenarios, and the development of advanced system level diagnostics and prognostics methods. The capabilities of the testbed are extended through the integration of a LabVIEW-based client for the Live Virtual Constructive Distributed Environment (LVCDC) Gateway which enables both the publishing of generated data for remotely located observers and prognosers and the synchronization the testbed propulsion system with vehicles in the air. The developed HIL testbed gives researchers easy access to a scientifically relevant portion of the aircraft without the overhead and dangers encountered during actual flight.

Determinants and Prognostic Significance of Hematoma Sedimentation Levels in Acute Intracerebral Hemorrhage.

PubMed

Sato, Shoichiro; Delcourt, Candice; Zhang, Shihong; Arima, Hisatomi; Heeley, Emma; Zheng, Danni; Al-Shahi Salman, Rustam; Stapf, Christian; Tzourio, Christophe; Robinson, Thompson; Lindley, Richard I; Chalmers, John; Anderson, Craig S

2016-01-01

This study aimed at identifying the determinants and prognostic significance of a sedimentation level (fluid-blood level) in the hematoma among patients with acute intracerebral hemorrhage (ICH) who participated in the main Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2). Post-hoc analysis of the INTERACT2 dataset, a randomized controlled trial of patients with acute ICH with elevated systolic blood pressure (SBP), randomly assigned to intensive (target SBP <140 mm Hg) or guideline-based (<180 mm Hg) BP management. Patients with a sedimentation level at baseline assessment on CT, and modified Rankin Scale score at 90-day, were included in these analyses. Factors associated with a sedimentation level and its significance in relation to 90-day clinical outcomes were assessed in univariable and multivariable logistic regression models. Of 2,065 participants, 19 (1%) had sedimentation level on baseline CT, which was independently associated with warfarin use (p = 0.006) and lobar ICH (p = 0.025). Sedimentation level was also associated with death or major disability at 90-day in both crude (84 vs. 53%; p = 0.014) and multivariable analyses adjusted for age, gender, Chinese region, warfarin use, baseline National Institutes of Health Stroke Scale score, onset to CT time, volume and location of ICH, intraventricular extension, and randomized intensive BP lowering (OR 3.94, 95% CI 1.01-15.37; p = 0.049). The presence of hematoma sedimentation level on baseline CT is associated with warfarin use and lobar location of ICH, and predicts a worse outcome. Although uncommon, sedimentation level is an easily detectable prognostic factor in acute ICH. © 2015 S. Karger AG, Basel.

25-Hydroxyvitamin D and TSH as Risk Factors or Prognostic Markers in Thyroid Carcinoma

PubMed Central

Danilovic, Debora Lucia Seguro; Ferraz-de-Souza, Bruno; Fabri, Amanda Wictky; Santana, Nathalie Oliveira; Kulcsar, Marco Aurelio; Cernea, Claudio Roberto; Marui, Suemi; Hoff, Ana Oliveira

2016-01-01

Objective The increasing incidence of thyroid nodules demands identification of risk factors for malignant disease. Several studies suggested the association of higher TSH levels with cancer, but influence of 25-hydroxyvitamin D (25OHD) is controversial. This study aimed to identify the relationship of thyroid cancer with higher TSH levels and hypovitaminosis D and to evaluate their influence on prognostic characteristics of papillary thyroid carcinomas (PTC). Methods We retrospectively evaluated 433 patients submitted to thyroidectomy for thyroid nodules. Patients were categorized according to quartiles of TSH and 25OHD levels. Clinicopathological features were analyzed. Results Subjects with thyroid carcinomas were more frequently male and younger compared to those with benign disease. Their median TSH levels were higher and adjusted odds-ratio (OR) for cancer in the highest-quartile of TSH (> 2.4 mUI/mL) was 2.36 (1.36–4.09). Although vitamin D deficiency/insufficiency was prevalent in our cohort (84%), no significant differences in 25OHD levels or quartile distribution were observed between benign and malignant cases. Among 187 patients with PTC, analyses of prognostic features revealed increased risk of lymph nodes metastases for subjects with highest-quartile TSH levels (OR = 3.7, p = 0.029). Decreased 25OHD levels were not overtly associated with poor prognosis in PTC. Conclusions In this cross-sectional cohort, higher TSH levels increased the risk of cancer in thyroid nodules and influenced its prognosis, particularly favoring lymph nodes metastases. On the other hand, no association was found between 25OHD levels and thyroid carcinoma risk or prognosis, suggesting that serum 25OHD determination may not contribute to risk assessment workup of thyroid nodules. PMID:27737011

Empirically defining rapid response to intensive treatment to maximize prognostic utility for bulimia nervosa and purging disorder.

PubMed

MacDonald, Danielle E; Trottier, Kathryn; McFarlane, Traci; Olmsted, Marion P

2015-05-01

Rapid response (RR) to eating disorder treatment has been reliably identified as a predictor of post-treatment and sustained remission, but its definition has varied widely. Although signal detection methods have been used to empirically define RR thresholds in outpatient settings, RR to intensive treatment has not been investigated. This study investigated the optimal definition of RR to day hospital treatment for bulimia nervosa and purging disorder. Participants were 158 patients who completed ≥6 weeks of day hospital treatment. Receiver operating characteristic (ROC) analysis was used to create four definitions of RR that could differentiate between remission and nonremission at the end of treatment. Definitions were based on binge/vomit episode frequency or percent reduction from pre-treatment, during either the first four or first two weeks of treatment. All definitions were associated with higher remission rates in rapid compared to nonrapid responders. Only one definition (i.e., ≤3 episodes in the first four weeks of treatment) predicted sustained remission (versus relapse) at 6- and 12-month follow-up. These findings provide an empirically derived definition of RR to intensive eating disorder treatment, and provide further evidence that early change is an important prognostic indicator. Copyright © 2015 Elsevier Ltd. All rights reserved.

Criteria predictive of limb viability at 1 year in patients with chronic severe ischemia--TcPO2 and demographic parameters.

PubMed

Chomard, D; Habault, P; Eveno, D; Le Lamer, S; Ledemeney, M; Haon, C

2000-09-01

Following an earlier study, the investigators sought to identify and define objective prognostic criteria of viability at 1 year of a limb with severe chronic ischemia. A study was undertaken in 116 patients (118 limbs) (74 men and 42 women), with a mean age of 71.9 years for men and 81.6 years for women. Static transcutaneous oxygen pressure (TcPO2) was measured with a verticalization sensitization test and inhalation of oxygen on JO and viability of the limb noted 1 year later. Logistic analysis was made of 13 oximetry parameters and two demographic parameters (age and gender). Results were analyzed in absolute terms and by tissue oxygenation ratio (TOR) (ratio between absolute TcPO2 at the foot and at a chest reference electrode). Six factors appeared to be prognostic factors of limb viability at 1 year, statistically significant at 6% according to threshold values: age, verticalization TcPO2, TcPO2 after 1 minute's inhalation of oxygen, TcPO2 after 4 minutes' inhalation of oxygen, and slope of TcPO2 and slope of TOR between 1 and 4 minutes' inhalation. A 1 year viability index integrating these criteria is suggested.

The Prognostic Role of Ventilatory Inefficiency and Exercise Capacity in Idiopathic Pulmonary Fibrosis.

PubMed

Vainshelboim, Baruch; Oliveira, Jose; Fox, Benjamin Daniel; Kramer, Mordechai Reuven

2016-08-01

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and fatal interstitial lung disease associated with poor prognosis and limited effective treatment options. Reliable predictors of outcome in daily clinical practice are needed to determine high-risk patients for urgent lung transplantation referral. This study aimed to identify practical prognostic predictors of mortality using cardiopulmonary exercise testing (CPET) in IPF subjects. Thirty-four subjects with IPF (22 men and 12 women), median age 68 (range 50-81) y were prospectively studied. At baseline, all subjects were assessed with CPET and were followed up for 40 months from baseline. Receiver operating characteristic curve analysis was conducted to determine cut-off points of CPET variables for mortality, Cox regression analysis for survival using a log-rank test, and hazard ratio for death using a Wald test. Peak work rate <62 watts (P = .005), peak V̇O2 ≤13.8 mL/kg/min (P = .031), tidal volume reserve ≤0.48 L/breath (P = .010), minute ventilation to carbon dioxide (V̇E)/V̇CO2 ) ratio at the anaerobic threshold >34 (P = .02), and V̇E)/V̇O2 nadir >34 (P = .002) were detected as cut-off points associated with mortality. Non-survivor subjects were characterized by higher dyspnea levels, the presence of pulmonary hypertension assessed by echocardiography, pronounced inefficient ventilatory pattern, lower exercise capacity, and more severe desaturation during physical exertion. By the end of the study, 11 subjects (7 women and 4 men) died. Overall mean survival was 60%, 33.7 months (95% CI 30.2-37.2). This study provides simple, practical, and novel cut-off points for CPET as predictors of prognosis to identify high-risk IPF subjects. Impairment in exercise capacity and abnormal ventilatory responses during CPET were associated with poorer survival in IPF subjects. The findings suggest considering the use of CPET for IPF risk stratification and prediction of prognosis. (ClinicalTrials.gov registration NCT01499745.). Copyright © 2016 by Daedalus Enterprises.

Elevation of cardiac troponin I during non-exertional heat-related illnesses in the context of a heatwave

PubMed Central

2010-01-01

Introduction The prognostic value of cardiac troponin I (cTnI) in patients having a heat-related illness during a heat wave has been poorly documented. Methods In a post hoc analysis, we evaluated 514 patients admitted to emergency departments during the August 2003 heat wave in Paris, having a core temperature >38.5°C and who had analysis of cTnI levels. cTnI was considered as normal, moderately elevated (abnormality threshold to 1.5 ng.mL-1), or severely elevated (>1.5 ng.mL-1). Patients were classified according to our previously described risk score (high, intermediate, and low-risk of death). Results Mean age was 84 ± 12 years, mean body temperature 40.3 ± 1.2°C. cTnI was moderately elevated in 165 (32%) and severely elevated in 97 (19%) patients. One-year survival was significantly decreased in patients with moderate or severe increase in cTnI (24 and 46% vs 58%, all P < 0.05). Using logistic regression, four independent variables were associated with an elevated cTnI: previous coronary artery disease, Glasgow coma scale <12, serum creatinine >120 μmol.L-1, and heart rate >110 bpm. Using Cox regression, only severely elevated cTnI was an independent prognostic factor (hazard ratio 1.93, 95% confidence interval 1.35 to 2.77) when risk score was taken into account. One-year survival was decreased in patients with elevated cTnI only in high risk patients (17 vs 31%, P = 0.04). Conclusions cTnI is frequently elevated in patients with non-exertional heat-related illnesses during a heat wave and is an independent risk factor only in high risk patients where severe increase (>1.5 ng.mL-1) indicates severe myocardial damage. PMID:20507603

Prolonged noise exposure-induced auditory threshold shifts in rats

PubMed Central

Chen, Guang-Di; Decker, Brandon; Muthaiah, Vijaya Prakash Krishnan; Sheppard, Adam; Salvi, Richard

2014-01-01

Noise-induced hearing loss (NIHL) initially increases with exposure duration, but eventually reaches an asymptotic threshold shift (ATS) once the exposure duration exceeds 18-24 h. Equations for predicting the ATS have been developed for several species, but not for rats, even though this species is extensively used in noise exposure research. To fill this void, we exposed rats to narrowband noise (NBN, 16-20 kHz) for 5 weeks starting at 80 dB SPL in the first week and then increasing the level by 6 dB per week to a final level of 104 dB SPL. Auditory brainstem responses (ABR) were recorded before, during, and following the exposure to determine the amount of hearing loss. The noise induced threshold shift to continuous long-term exposure, defined as compound threshold shift (CTS), within and above 16-20 kHz increased with noise level at the rate of 1.82 dB threshold shift per dB of noise level (NL) above a critical level (C) of 77.2 dB SPL i.e. CTS = 1.82(NL-77.2). The normalized amplitude of the largest ABR peak measured at 100 dB SPL decreased at the rate of 3.1% per dB of NL above the critical level of 76.9 dB SPL, i.e., %ABR Reduction = 3.1%(NL-76.9). ABR thresholds measured >30 days post-exposure only partially recovered resulting in a permanent threshold shift of 30-40 dB along with severe hair cell loss in the basal, high-frequency region of the cochlea. In the rat, CTS increases with noise level with a slope similar to humans and chinchillas. The critical level (C) in the rat is similar to that of humans, but higher than that of chinchillas. PMID:25219503

Diagnostic Dilemma for Low Viremia with Significant Fibrosis; Is HBV DNA Threshold Level a Good Indicator for Predicting Liver Damage?

PubMed

Yenilmez, Ercan; Çetinkaya, Rıza Aytaç; Tural, Ersin

2018-05-04

The most important difficulties about management of hepatitis B are still determining the liver damage and the right time to start antiviral therapy. To reveal the role of hepatitis B virus DNA threshold level for prediction of liver fibrosis and inflammation in young-aged hepatitis B e antigen negative chronic hepatitis B patients. Diagnostic accuracy study. A total of 273 hepatitis B e antigen negative young chronic hepatitis B patients with any hepatitis B virus DNA levels between 2008 and 2016, who had liver biopsy after at least 6 months follow up period, enrolled in this retrospective study. We created two groups as case and control, cases with hepatitis B virus DNA levels below 2.000 IU/mL and controls with hepatitis B virus DNA levels over 2.000 IU/mL. Having histological activity index ≥4 or/and fibrosis scores ≥2 were defined as significant histological abnormality. Then, we analyzed the relationship between these groups. We showed that significant fibrosis may occur in one third of young chronic hepatitis B patients with low viremia (30.2%, n=42/139 in cases, %55.2, n=74/134 in controls). Among the 42 cases with low viremia and significant fibrosis, 21.4% had alanine aminotransferase level between 40-59 U/L, 42.8% had alanine aminotransferase level between 60-79 U/L, and 35.7% had alanine aminotransferase level over 80 U/L. There was weak correlation between hepatitis B virus DNA threshold level and fibrosis score (p=0.000, rho=0.253). The optimum serum hepatitis B virus DNA threshold level in our study for predicting significant fibrosis was 1293 IU/mL (p=0.00, AUC: 0.657±0.034). The optimum alanine aminotransferase threshold level for predicting significant histological activity index and fibrosis was 64.5 and 59.5 U/L, respectively. The sensitivity and the specificity of 1293 vs 2000 IU/mL hepatitis B virus DNA threshold with 60 U/L alanine aminotransferase threshold level for predicting F≥2 fibrosis score were similar (sensitivity: 0.43 and 0.38, respectively; specificity: 0.76 and 0.77, respectively). Significant fibrosis may occur even in young cases with low viremia. It is not possible to define a single threshold hepatitis B virus DNA level for differentiating inactive carriers from patients with hepatitis B e antigen-negative chronic hepatitis. Diagnostic accuracy of hepatitis B virus DNA with alanine aminotransferase thresholds for the prediction of significant fibrosis is weak.

[Decrease and asymmetry in taste perception in patients with nerve trunk damage].

PubMed

Nikulina, V A; Kokin, G S; Morozov, I S

1995-01-01

The purpose of this article was the gustatory perception state study (NaCl solution perception) in patients with one-sided damages of branchial plexus as well as of radial, facial and ulnar nervous trunks. The decrease of gustatory perception was observed in 78 (70.3%) cases, while the lack of such alterations in 33 (29.7%) patients. The gustatory perception disturbances (increase of the absolute threshold on the ipsilateral tongue's half) took place in 82.2% and 69.6% at right and left limbs damages respectively. The results presented testified the strengthening of normally existing asymmetry in gustatory perception especially in patients with left-sided denervation. The degree of gustatory perception restoration may serve as a prognostic test at surgery of such patients.

Audiovestibular consequences of congenital cytomegalovirus infection.

PubMed

Teissier, N; Bernard, S; Quesnel, S; Van Den Abbeele, T

2016-12-01

Congenital cytomegalovirus (CMV) infection is the second most frequent cause of mental retardation and sensorineural hearing loss, after genetic factors. Recently, pediatric forensic and fetopathological studies have led to progress in understanding the pathophysiological mechanisms underlying the various neurosensory sequelae. Thanks to the identification of certain prognostic factors of hearing loss, therapeutic protocols based on antiviral molecules are now proposed for target populations. This treatment has shown efficacy in limiting hearing threshold deterioration and even, in some cases, seems to provide partial recovery of hearing in symptomatic congenitally infected CMV neonates. However, optimal treatment duration and administration modalities are not clearly defined. This article reviews recent data concerning audiovestibular sequelae and their management in children congenitally infected by CMV. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

[Copeptin and ischemia modified albumin in early diagnosis and prognosis of myocardial damage in acute organic phosphorus pesticide poisoning].

PubMed

Li, Jing; Zhang, Jianjun; Li, Na; Li, Jia; Liu, Juan; Liu, Qian

2015-03-01

To assess the value of combined detection of copeptin and ischemia modified albumin (IMA) in early diagnosis and prognostic evaluation of myocardial damage in patients with acute organic phosphorus pesticide poisoning (AOPP). A total of 126 AOPP patients were examined for blood copepin and IMA levels and myocardial injury markers within 1 h after admission. Copeptin and IMA levels significantly increased in patients with AOPP compared with those in the control subjects. Copeptin and IMA levels were significantly higher in severe AOPP cases than in mild to moderate cases (P<0.05). Logistic regression analysis showed that increased copeptin and IMA levels and severe complications of AOPP were associated with an increased risk of cardiovascular events. Early detection of copeptin and IMA levels has important clinical value in early diagnosis and prognostic evaluation of myocardial damage in patients with AOPP, and their levels are positively correlated with the severity of the condition.

Serum leptin level and waist-to-hip ratio (WHR) predict the overall survival of metastatic breast cancer (MBC) patients treated with aromatase inhibitors (AIs).

PubMed

Artac, Mehmet; Bozcuk, Hakan; Kiyici, Aysel; Eren, Orhan Onder; Boruban, Melih Cem; Ozdogan, Mustafa

2013-04-01

Our objective was to determine whether serum leptin levels and obesity-related factors could affect outcome for metastatic breast cancer (MBC) patients treated with aromatase inhibitors (AIs). Sixty MBC patients treated with first line hormonal therapy were enrolled in this study. Median age was 51 years (range 28-75). Median leptin level was 19400 pg/ml (1970-91900) and estradiol level 29.6 pg/ml (4.0-181.9). Factors associated with overall survival in univariate analysis were age and waist-to-hip ratio (WHR), whereas only WHR retained significance in the multivariate analysis. However, no factor was associated with progression-free survival. However, WHR was found to be a significant prognostic marker only if the leptin level was ≥19400 pg/ml (HR = 0.38; 95% CI: 0.16-0.91). This study suggests that serum leptin levels and WHR together may serve as potential prognostic markers in MBC patients treated with AIs.

Prognostic factors in canine appendicular osteosarcoma – a meta-analysis

PubMed Central

2012-01-01

Background Appendicular osteosarcoma is the most common malignant primary canine bone tumor. When treated by amputation or tumor removal alone, median survival times (MST) do not exceed 5 months, with the majority of dogs suffering from metastatic disease. This period can be extended with adequate local intervention and adjuvant chemotherapy, which has become common practice. Several prognostic factors have been reported in many different studies, e.g. age, breed, weight, sex, neuter status, location of tumor, serum alkaline phosphatase (SALP), bone alkaline phosphatase (BALP), infection, percentage of bone length affected, histological grade or histological subtype of tumor. Most of these factors are, however, only reported as confounding factors in larger studies. Insight in truly significant prognostic factors at time of diagnosis may contribute to tailoring adjuvant therapy for individual dogs suffering from osteosarcoma. The objective of this study was to systematically review the prognostic factors that are described for canine appendicular osteosarcoma and validate their scientific importance. Results A literature review was performed on selected studies and eligible data were extracted. Meta-analyses were done for two of the three selected possible prognostic factors (SALP and location), looking at both survival time (ST) and disease free interval (DFI). The third factor (age) was studied in a qualitative manner. Both elevated SALP level and the (proximal) humerus as location of the primary tumor are significant negative prognostic factors for both ST and DFI in dogs with appendicular osteosarcoma. Increasing age was associated with shorter ST and DFI, however, was not statistically significant because information of this factor was available in only a limited number of papers. Conclusions Elevated SALP and proximal humeral location are significant negative prognosticators for canine osteosarcoma. PMID:22587466

Prognostic factors in canine appendicular osteosarcoma - a meta-analysis.

PubMed

Boerman, Ilse; Selvarajah, Gayathri T; Nielen, Mirjam; Kirpensteijn, Jolle

2012-05-15

Appendicular osteosarcoma is the most common malignant primary canine bone tumor. When treated by amputation or tumor removal alone, median survival times (MST) do not exceed 5 months, with the majority of dogs suffering from metastatic disease. This period can be extended with adequate local intervention and adjuvant chemotherapy, which has become common practice. Several prognostic factors have been reported in many different studies, e.g. age, breed, weight, sex, neuter status, location of tumor, serum alkaline phosphatase (SALP), bone alkaline phosphatase (BALP), infection, percentage of bone length affected, histological grade or histological subtype of tumor. Most of these factors are, however, only reported as confounding factors in larger studies. Insight in truly significant prognostic factors at time of diagnosis may contribute to tailoring adjuvant therapy for individual dogs suffering from osteosarcoma. The objective of this study was to systematically review the prognostic factors that are described for canine appendicular osteosarcoma and validate their scientific importance. A literature review was performed on selected studies and eligible data were extracted. Meta-analyses were done for two of the three selected possible prognostic factors (SALP and location), looking at both survival time (ST) and disease free interval (DFI). The third factor (age) was studied in a qualitative manner. Both elevated SALP level and the (proximal) humerus as location of the primary tumor are significant negative prognostic factors for both ST and DFI in dogs with appendicular osteosarcoma. Increasing age was associated with shorter ST and DFI, however, was not statistically significant because information of this factor was available in only a limited number of papers. Elevated SALP and proximal humeral location are significant negative prognosticators for canine osteosarcoma.

The importance of histopathological and clinical variables in predicting the evolution of colon cancer.

PubMed

Diculescu, Mircea; Iacob, Răzvan; Iacob, Speranţa; Croitoru, Adina; Becheanu, Gabriel; Popeneciu, Valentin

2002-09-01

It has been a consensus that prognostic factors should always be taken into account before planning treatment in colorectal cancer. A 5 year prospective study was conducted, in order to assess the importance of several histopathological and clinical prognostic variables in the prediction of evolution in colon cancer. Some of the factors included in the analysis are still subject to dispute by different authors. 46 of 53 screened patients qualified to enter the study and underwent a potentially curative resection of the tumor, followed, when necessary, by adjuvant chemotherapy. Univariate and multivariate analyses were carried out in order to identify independent prognostic indicators. The endpoint of the study was considered the recurrence of the tumor or the detection of metastases. 65.2% of the patients had a good evolution during the follow up period. Multivariate survival analysis performed by Cox proportional hazard model identified 3 independent prognostic factors: Dukes stage (p = 0.00002), the grade of differentiation (p = 0.0009) and the weight loss index, representing the weight loss of the patient divided by the number of months when it was actually lost (p = 0.02). Age under 40 years, sex, microscopic aspect of the tumor, tumor location, anemia degree were not identified by our analysis as having prognostic importance. Histopathological factors continue to be the most valuable source of information regarding the possible evolution of patients with colorectal cancer. Individual clinical symptoms or biological parameters such as erytrocyte sedimentation rate or hemoglobin level are of little or no prognostic value. More research is required relating to the impact of a performance status index (which could include also weight loss index) as another reliable prognostic variable.

Distress Due to Prognostic Uncertainty in Palliative Care: Frequency, Distribution, and Outcomes among Hospitalized Patients with Advanced Cancer.

PubMed

Gramling, Robert; Stanek, Susan; Han, Paul K J; Duberstein, Paul; Quill, Tim E; Temel, Jennifer S; Alexander, Stewart C; Anderson, Wendy G; Ladwig, Susan; Norton, Sally A

2018-03-01

Prognostic uncertainty is common in advanced cancer and frequently addressed during palliative care consultation, yet we know little about its impact on quality of life (QOL). We describe the prevalence and distribution of distress due to prognostic uncertainty among hospitalized patients with advanced cancer before palliative care consultation. We evaluate the association between this type of distress and overall QOL before and after palliative care consultation. Observational cohort study. Hospitalized patients with advanced cancer who receive a palliative care consultation at two geographically distant academic medical centers. At the time of enrollment, before palliative care consultation, we asked participants: "Over the past two days, how much have you been bothered by uncertainty about what to expect from the course of your illness?" (Not at all/Slightly/Moderately/Quite a Bit/Extremely). We defined responses of "Quite a bit" and "Extremely" to be indicative of substantial distress. Two hundred thirty-six participants completed the baseline assessment. Seventy-seven percent reported being at least moderately bothered by prognostic uncertainty and half reported substantial distress. Compared with others, those who were distressed by prognostic uncertainty (118/236) reported poorer overall QOL before palliative care consultation (mean QOL 3.8 out of 10 vs. 5.3 out of 10, p = < 0.001) and greater improvement in QOL following consultation (Adjusted difference in mean QOL change = 1.1; 95% confidence interval = 0.2, 2.0). Prognostic uncertainty is a prevalent source of distress among hospitalized patients with advanced cancer at the time of initial palliative care consultation. Distress from prognostic uncertainty is associated with lower levels of preconsultation QOL and with greater pre-post consultation improvement in the QOL.

Evaluation of prognostic factors in liver-limited metastatic colorectal cancer: a preplanned analysis of the FIRE-1 trial

PubMed Central

Giessen, C; Fischer von Weikersthal, L; Laubender, R P; Stintzing, S; Modest, D P; Schalhorn, A; Schulz, C; Heinemann, V

2013-01-01

Background: Liver-limited disease (LLD) denotes a specific subgroup of metastatic colorectal cancer (mCRC) patients. Patients and Methods: A total of 479 patients with unresectable mCRC from an irinotecan-based randomised phase III trial were evaluated. Patients with LLD and non-LLD and hepatic resection were differentiated. Based on baseline patient characteristic, prognostic factors for hepatic resection were evaluated. Furthermore, prognostic factors for median overall survival (OS) were estimated via Cox regression in LLD patients. Results: Secondary liver resection was performed in 38 out of 479 patients (resection rate: 7.9%). Prognostic factors for hepatic resection were LLD, lactate dehydrogenase (LDH), node-negative primary, alkaline phosphatase (AP) and Karnofsky performance status (PS). Median OS was significantly increased after hepatic resection (48 months), whereas OS in LLD (17 months) and non-LLD (19 months) was comparable in non-resected patients. With the inapplicability of Koehne's risk classification in LLD patients, a new score based on only the independent prognostic factors LDH and white blood cell (WBC) provided markedly improved information on the outcome. Conclusion: Patients undergoing hepatic resection showed favourable long-term survival, whereas non-resected LLD patients and non-LLD patients did not differ with regard to progression-free survival and OS. The LDH levels and WBC count were confirmed as prognostic factors and provide a useful and simple score for OS-related risk stratification also in LLD. PMID:23963138

Prognosis: the "missing link" within the CanMEDS competency framework.

PubMed

Maida, Vincent; Cheon, Paul M

2014-05-13

The concept of prognosis dates back to antiquity. Quantum advances in diagnostics and therapeutics have relegated this once highly valued core competency to an almost negligible role in modern medical practice. Medical curricula are devoid of teaching opportunities focused on prognosis. This void is driven by a corresponding relative dearth within physician competency frameworks. This study aims to assess the level of content related to prognosis within CanMEDS (Canadian Medical Education Directives for Specialists), a leading and prototypical physician competency framework. A quantitative content analysis of CanMEDS competency framework was carried out to measure the extent of this deficiency. Foxit Reader 5.1 (Foxit Corporation), a keyword scanning software, was used to assess the CanMEDS 2005 framework documents of 29 physician specialties and 37 subspecialties across the seven physician roles (medical expert, communicator, collaborator, manager, health advocate, scholar, and professional). The keywords used in the search included prognosis, prognostic, prognosticate, and prognostication. Of the 29 specialties six (20.7%) contained at least one citation of the keyword "prognosis", and one (3.4%) contained one citation of the keyword "prognostic". Of the 37 subspecialties, sixteen (43.2%) contained at least one citation of the keyword "prognosis", and three (8.1%) contained at least one citation of the keyword "prognostic". The terms "prognosticate" and "prognostication" were completely absent from all CanMEDS 2005 documents. Overall, the combined citations for "prognosis" and "prognostic" were linked with the following competency roles: Medical Expert (80.3%), Scholar (11.5%), and Communicator (8.2%). Given the fundamental and foundational importance of prognosis within medical practice, it is recommended that physicians develop appropriate attitudes, skills and knowledge related to the formulation and communication of prognosis. The deficiencies within CanMEDS, demonstrated by this study, should be addressed in advance of the launch of its updated version in 2015.

Comparisons between detection threshold and loudness perception for individual cochlear implant channels

PubMed Central

Bierer, Julie Arenberg; Nye, Amberly D

2014-01-01

Objective The objective of the present study, performed in cochlear implant listeners, was to examine how the level of current required to detect single-channel electrical pulse trains relates to loudness perception on the same channel. The working hypothesis was that channels with relatively high thresholds, when measured with a focused current pattern, interface poorly to the auditory nerve. For such channels a smaller dynamic range between perceptual threshold and the most comfortable loudness would result, in part, from a greater sensitivity to changes in electrical field spread compared to low-threshold channels. The narrower range of comfortable listening levels may have important implications for speech perception. Design Data were collected from eight, adult cochlear implant listeners implanted with the HiRes90k cochlear implant (Advanced Bionics Corp.). The partial tripolar (pTP) electrode configuration, consisting of one intracochlear active electrode, two flanking electrodes carrying a fraction (σ) of the return current, and an extracochlear ground, was used for stimulation. Single-channel detection thresholds and most comfortable listening levels were acquired using the most focused pTP configuration possible (σ ≥ 0.8) to identify three channels for further testing – those with the highest, median, and lowest thresholds – for each subject. Threshold, equal-loudness contours (at 50% of the monopolar dynamic range), and loudness growth functions were measured for each of these three test channels using various partial tripolar fractions. Results For all test channels, thresholds increased as the electrode configuration became more focused. The rate of increase with the focusing parameter σ was greatest for the high-threshold channel compared to the median- and low-threshold channels. The 50% equal-loudness contours exhibited similar rates of increase in level across test channels and subjects. Additionally, test channels with the highest thresholds had the narrowest dynamic ranges (for σ ≥ 0.5) and steepest growth of loudness functions for all electrode configurations. Conclusions Together with previous studies using focused stimulation, the results suggest that auditory responses to electrical stimuli at both threshold and suprathreshold current levels are not uniform across the electrode array of individual cochlear implant listeners. Specifically, the steeper growth of loudness and thus smaller dynamic ranges observed for high-threshold channels are consistent with a degraded electrode-neuron interface, which could stem from lower numbers of functioning auditory neurons or a relatively large distance between the neurons and electrodes. These findings may have potential implications for how stimulation levels are set during the clinical mapping procedure, particularly for speech-processing strategies that use focused electrical fields. PMID:25036146

High expressions of LDHA and AMPK as prognostic biomarkers for breast cancer.

PubMed

Huang, Xiaojia; Li, Xing; Xie, Xinhua; Ye, Feng; Chen, Bo; Song, Cailu; Tang, Hailin; Xie, Xiaoming

2016-12-01

The purpose of this study was to investigate the potential correlation between lactate dehydrogenase A (LDHA) and AMP-activated protein kinase (AMPK) and their clinicopathologic significance in breast cancer. Western blot and qRT-PCR were used to detect the expression levels of LDHA and AMPK in eight breast cancer lines and eight breast cancer tissues. In addition, LDHA and AMPK were detected by immunohistochemistry (IHC) using breast cancer tissue microarrays (TMAs) of 112 patients. The association between LDHA and AMPK expression levels was statistically analyzed. So were the prognostic roles and clinicopathologic significances in breast cancer. The expression levels of LDHA and AMPK were relatively higher in triple-negative breast cancer (TNBC) cell lines than in non-triple-negative breast cancer (NTNBC) cell lines. LDHA and AMPK were also further up-regulated in TNBC tissues than in NTNBC tissues. Correlation analysis showed a positive correlation between LDHA and AMPK expression levels. Expression of LDHA and AMPK were significantly correlated with TNM stage, distant metastasis, Ki67 status and survival outcomes of patients. Patients with both positive expression of LDHA and AMPK showed shorter overall survival (OS) and disease-free survival (DFS). These findings improve our understanding of the expression pattern of LDHA and AMPK in breast cancer and clarify the role of LDHA and AMPK as promising prognostic biomarkers for breast cancer. Copyright © 2016. Published by Elsevier Ltd.

Prognostic significance of pretreatment plasma fibrinogen level in patients with digestive system tumors: a meta-analysis.

PubMed

Ji, Rui; Ren, Qian; Bai, Suyang; Wang, Yuping; Zhou, Yongning

2018-06-01

High pretreatment levels of plasma fibrinogen have been widely reported to be a potential predictor of prognosis in digestive system tumors; however, the conclusions are not consistent. Therefore, we performed a meta-analysis to comprehensively assess the prognostic roles of high pretreatment plasma fibrinogen levels in digestive system tumors. We searched for eligible studies in the PubMed, Embase, and Web of Science electronic databases for publications from the database inception to 1 September 2017. The endpoints of interest included overall survival, disease-free survival, and recurrence-free survival. We investigated the relationship between fibrinogenemia and overall survival in colorectal cancer (10 studies), gastric cancer (6), pancreatic cancer (6), hepatocellular carcinoma (7), and esophageal squamous cell carcinoma (10); the pooled results indicated that fibrinogenemia was significantly related to a worse overall survival (hazard ratio (HR) 1.73; 95% confidence interval (CI) 1.52, 1.97; P <0.001; HR 1.71; 95% CI 1.28, 2.28; P <0.001; HR 1.57; 95% CI 1.13, 2.17; P = 0.007; HR 1.89; 95% CI 1.57, 2.27; P <0.001, and HR 1.67; 95% CI 1.35, 2.07; P <0.001). Taken together, an increased pretreatment plasma fibrinogen level was related to worse survival in digestive system tumors, indicating that it could be a useful prognostic marker in these types of tumors.

SLP-2 overexpression could serve as a prognostic factor in node positive and HER2 negative breast cancer.

PubMed

Cao, Wenfeng; Zhang, Bin; Li, Jin; Liu, Yanxue; Liu, Zhihua; Sun, Baocun

2011-12-01

This study aimed to evaluate the utility as a prognostic factor of SLP-2 on the outcome of breast cancer patients. We performed immunohistochemical analysis to examine the SLP-2 expression in a large panel of invasive breast cancer samples. Of the 496 samples, 261 showed overexpression of SLP-2. Importantly, there were significant associations between SLP-2 overexpression and tumour size (p = 0.002), lymph node/distant metastases, clinical stage (p < 0.001), HER2/neu expression (p = 0.003). In addition, there were obvious differences in levels of SLP-2 expression within four molecular subtypes of breast cancer (p = 0.011). High level SLP-2 expression was shown in tumour samples of HER2 and luminal B subtypes, and low level SLP-2 expression was shown in luminal A and triple negative subtypes, suggesting that overexpression of SLP-2 was closely correlated with HER2/neu expression, and that both SLP-2 and HER2/neu can play a role in lymph node/distant metastases of breast cancers. Thus lymph node status, HER2/neu and SLP-2 high-level expression can act as independent prognostic factors. There is an obvious link between SLP-2 and HER2/neu expression. Overexpression of SLP-2 is associated with poorer total survival, especially in lymph node positive coupled with HER2/neu negative patients.

Embedded diagnostic, prognostic, and health management system and method for a humanoid robot

NASA Technical Reports Server (NTRS)

Barajas, Leandro G. (Inventor); Strawser, Philip A (Inventor); Sanders, Adam M (Inventor); Reiland, Matthew J (Inventor)

2013-01-01

A robotic system includes a humanoid robot with multiple compliant joints, each moveable using one or more of the actuators, and having sensors for measuring control and feedback data. A distributed controller controls the joints and other integrated system components over multiple high-speed communication networks. Diagnostic, prognostic, and health management (DPHM) modules are embedded within the robot at the various control levels. Each DPHM module measures, controls, and records DPHM data for the respective control level/connected device in a location that is accessible over the networks or via an external device. A method of controlling the robot includes embedding a plurality of the DPHM modules within multiple control levels of the distributed controller, using the DPHM modules to measure DPHM data within each of the control levels, and recording the DPHM data in a location that is accessible over at least one of the high-speed communication networks.

Chromatic Perceptual Learning but No Category Effects without Linguistic Input

PubMed Central

Grandison, Alexandra; Sowden, Paul T.; Drivonikou, Vicky G.; Notman, Leslie A.; Alexander, Iona; Davies, Ian R. L.

2016-01-01

Perceptual learning involves an improvement in perceptual judgment with practice, which is often specific to stimulus or task factors. Perceptual learning has been shown on a range of visual tasks but very little research has explored chromatic perceptual learning. Here, we use two low level perceptual threshold tasks and a supra-threshold target detection task to assess chromatic perceptual learning and category effects. Experiment 1 investigates whether chromatic thresholds reduce as a result of training and at what level of analysis learning effects occur. Experiment 2 explores the effect of category training on chromatic thresholds, whether training of this nature is category specific and whether it can induce categorical responding. Experiment 3 investigates the effect of category training on a higher level, lateralized target detection task, previously found to be sensitive to category effects. The findings indicate that performance on a perceptual threshold task improves following training but improvements do not transfer across retinal location or hue. Therefore, chromatic perceptual learning is category specific and can occur at relatively early stages of visual analysis. Additionally, category training does not induce category effects on a low level perceptual threshold task, as indicated by comparable discrimination thresholds at the newly learned hue boundary and adjacent test points. However, category training does induce emerging category effects on a supra-threshold target detection task. Whilst chromatic perceptual learning is possible, learnt category effects appear to be a product of left hemisphere processing, and may require the input of higher level linguistic coding processes in order to manifest. PMID:27252669

Very high levels of soluble CD30 recognize the patients with classical Hodgkin's lymphoma retaining a very poor prognosis.

PubMed

Visco, Carlo; Nadali, Gianpaolo; Vassilakopoulos, Theodoros P; Bonfante, Valeria; Viviani, Simonetta; Gianni, Alessandro M; Federico, Massimo; Luminari, Stefano; Peethambaram, Prema; Witzig, Thomas E; Pangalis, Gerassimos; Cabanillas, Fernando; Medeiros, L Jeffrey; Sarris, Andreas H; Pizzolo, Giovanni

2006-11-01

To evaluate the prognostic role of pretreatment serum levels of soluble CD30 (sCD30) in patients with advanced stage classical Hodgkin's lymphoma (cHL) treated with adriamycin, bleomycin, vinblastine, and dacarbazine or equivalent regimens. We identified 321 previously untreated patients with cHL who presented to the participating centers between 1985 and 2002, and had serum samples available for the determination of sCD30 levels. With a median follow-up of 72 months, the actuarial 5-year overall survival was 82%, and failure-free survival (FFS) was 71%. The median serum level of sCD30 was 65 U/mL (range: 1-2230), and was significantly higher (P < 0.0001) when compared with a group of 113 healthy controls (4 U/mL, range: 0-20). Increasing level of sCD30 was associated with a continuous worsening of FFS and OS, and patients with sCD30 >or=200 U/mL had a 5-year FFS of 39%. With multivariate analysis, sCD30, Ann Arbor stage, and lactic acid dehydrogenase were significant independent factors in terms of FFS. The association of the above-mentioned three independent prognostic variables could discriminate 22% of patients with 5-year FFS of 40%. Our data confirm the independent prognostic role of sCD30 in identifying the patients with high risk of treatment failure, and show that its association with other variables can recognize patients with FFS considerably lower than 50%.

Alcohol and cigarette consumption predict mortality in patients with head and neck cancer: a pooled analysis within the International Head and Neck Cancer Epidemiology (INHANCE) Consortium

PubMed Central

Giraldi, L; Leoncini, E; Pastorino, R; Wünsch-Filho, V; de Carvalho, M; Lopez, R; Cadoni, G; Arzani, D; Petrelli, L; Bosetti, C; La Vecchia, C; Garavello, W; Polesel, J; Serraino, D; Simonato, L; Canova, C; Richiardi, L; Boffetta, P; Hashibe, M; Lee, Y C A; Boccia, S

2017-01-01

Abstract Background This study evaluated whether demographics, pre-diagnosis lifestyle habits and clinical data are associated with the overall survival (OS) and head and neck cancer (HNC)-specific survival in patients with HNC. Patients and methods We conducted a pooled analysis, including 4759 HNC patients from five studies within the International Head and Neck Cancer Epidemiology (INHANCE) Consortium. Cox proportional hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) were estimated including terms reported significantly associated with the survival in the univariate analysis. Results Five-year OS was 51.4% for all HNC sites combined: 50.3% for oral cavity, 41.1% for oropharynx, 35.0% for hypopharynx and 63.9% for larynx. When we considered HNC-specific survival, 5-year survival rates were 57.4% for all HNC combined: 54.6% for oral cavity, 45.4% for oropharynx, 37.1% for hypopharynx and 72.3% for larynx. Older ages at diagnosis and advanced tumour staging were unfavourable predictors of OS and HNC-specific survival. In laryngeal cancer, low educational level was an unfavourable prognostic factor for OS (HR = 2.54, 95% CI 1.01–6.38, for high school or lower versus college graduate), and status and intensity of alcohol drinking were prognostic factors both of the OS (current drinkers HR = 1.73, 95% CI 1.16–2.58) and HNC-specific survival (current drinkers HR = 2.11, 95% CI 1.22–3.66). In oropharyngeal cancer, smoking status was an independent prognostic factors for OS. Smoking intensity (>20 cigarettes/day HR = 1.41, 95% CI 1.03–1.92) was also an independent prognostic factor for OS in patients with cancer of the oral cavity. Conclusions OS and HNC-specific survival differ among HNC sites. Pre-diagnosis cigarette smoking is a prognostic factor of the OS for patients with cancer of the oral cavity and oropharynx, whereas pre-diagnosis alcohol drinking is a prognostic factor of OS and HNC-specific survival for patients with cancer of the larynx. Low educational level is an unfavourable prognostic factor for OS in laryngeal cancer patients. PMID:28945835

Rate of Decline of Ferritin in Patients with Hemophagocytic Lymphohistiocytosis as a Prognostic Variable for Mortality

PubMed Central

Lin, Tiffany F.; Ferlic-Stark, Laura L.; Allen, Carl E.; Kozinetz, Claudia A.; McClain, Kenneth L.

2012-01-01

Hemophagocytic lymphohistiocytosis (HLH) is difficult to diagnose and treat. Highly elevated ferritin is strongly associated with HLH and levels may provide a prognostic marker. A comprehensive review of ferritin data from our patients during treatment was analyzed with respect to mortality. A patient was 17 times more likely to die when percent ferritin decrease was less than 50% as compared to a 96% or greater decrease as indicated with multivariate logistic modeling. Higher maximum ferritin levels in the first 3 weeks also contributed to the odds of death (OR=5.6;90%CI=1.2-24.9). Regular ferritin measurements may be useful predicting outcomes in HLH patients. PMID:20842751

Thermal detection thresholds in 5-year-old preterm born children; IQ does matter.

PubMed

de Graaf, Joke; Valkenburg, Abraham J; Tibboel, Dick; van Dijk, Monique

2012-07-01

Experiencing pain at newborn age may have consequences on one's somatosensory perception later in life. Children's perception for cold and warm stimuli may be determined with the Thermal Sensory Analyzer (TSA) device by two different methods. This pilot study in 5-year-old children born preterm aimed at establishing whether the TSA method of limits, which is dependent of reaction time, and the method of levels, which is independent of reaction time, would yield different cold and warm detection thresholds. The second aim was to establish possible associations between intellectual ability and the detection thresholds obtained with either method. A convenience sample was drawn from the participants in an ongoing 5-year follow-up study of a randomized controlled trial on effects of morphine during mechanical ventilation. Thresholds were assessed using both methods and statistically compared. Possible associations between the child's intelligence quotient (IQ) and threshold levels were analyzed. The method of levels yielded more sensitive thresholds than did the method of limits, i.e. mean (SD) cold detection thresholds: 30.3 (1.4) versus 28.4 (1.7) (Cohen'sd=1.2, P=0.001) and warm detection thresholds; 33.9 (1.9) versus 35.6 (2.1) (Cohen's d=0.8, P=0.04). IQ was statistically significantly associated only with the detection thresholds obtained with the method of limits (cold: r=0.64, warm: r=-0.52). The TSA method of levels, is to be preferred over the method of limits in 5-year-old preterm born children, as it establishes more sensitive detection thresholds and is independent of IQ. Copyright © 2011 Elsevier Ltd. All rights reserved.

Oxidation of RyR2 Has a Biphasic Effect on the Threshold for Store Overload-Induced Calcium Release.

PubMed

Waddell, Helen M M; Zhang, Joe Z; Hoeksema, Katie J; McLachlan, Julia J; McLay, Janet C; Jones, Peter P

2016-06-07

At the single-channel level, oxidation of the cardiac ryanodine receptor (RyR2) is known to activate and inhibit the channel depending on the level of oxidation. However, the mechanisms through which these changes alter the activity of RyR2 in a cellular setting are poorly understood. In this study, we determined the effect of oxidation on a common form of RyR2 regulation; store overload-induced Ca(2+) release (SOICR). We found that oxidation resulted in concentration and time-dependent changes in the activation threshold for SOICR. Low concentrations of the oxidant H2O2 resulted in a decrease in the threshold for SOICR, which led to an increase in SOICR events. However, higher concentrations of H2O2, or prolonged exposure, reversed these changes and led to an increase in the threshold for SOICR. This increase in the threshold for SOICR in most cells was to such an extent that it led to the complete inhibition of SOICR. Acute exposure to high concentrations of H2O2 led to an initial decrease and then increase in the threshold for SOICR. In the majority of cells the increased threshold could not be reversed by the application of the reducing agent dithiothreitol. Therefore, our data suggest that low levels of RyR2 oxidation increase the channel activity by decreasing the threshold for SOICR, whereas high levels of RyR2 oxidation irreversibly increase the threshold for SOICR leading to an inhibition of RyR2. Combined, this indicates that oxidation regulates RyR2 by the same mechanism as phosphorylation, methylxanthines, and mutations, via changes in the threshold for SOICR. Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Can quantitative sensory testing predict responses to analgesic treatment?

PubMed

Grosen, K; Fischer, I W D; Olesen, A E; Drewes, A M

2013-10-01

The role of quantitative sensory testing (QST) in prediction of analgesic effect in humans is scarcely investigated. This updated review assesses the effectiveness in predicting analgesic effects in healthy volunteers, surgical patients and patients with chronic pain. A systematic review of English written, peer-reviewed articles was conducted using PubMed and Embase (1980-2013). Additional studies were identified by chain searching. Search terms included 'quantitative sensory testing', 'sensory testing' and 'analgesics'. Studies on the relationship between QST and response to analgesic treatment in human adults were included. Appraisal of the methodological quality of the included studies was based on evaluative criteria for prognostic studies. Fourteen studies (including 720 individuals) met the inclusion criteria. Significant correlations were observed between responses to analgesics and several QST parameters including (1) heat pain threshold in experimental human pain, (2) electrical and heat pain thresholds, pressure pain tolerance and suprathreshold heat pain in surgical patients, and (3) electrical and heat pain threshold and conditioned pain modulation in patients with chronic pain. Heterogeneity among studies was observed especially with regard to application of QST and type and use of analgesics. Although promising, the current evidence is not sufficiently robust to recommend the use of any specific QST parameter in predicting analgesic response. Future studies should focus on a range of different experimental pain modalities rather than a single static pain stimulation paradigm. © 2013 European Federation of International Association for the Study of Pain Chapters.

20 CFR 418.2105 - What is the threshold?

Code of Federal Regulations, 2012 CFR

2012-04-01

... 20 Employees' Benefits 2 2012-04-01 2012-04-01 false What is the threshold? 418.2105 Section 418... Adjustment Amount § 418.2105 What is the threshold? (a) The threshold is a level of modified adjusted gross... years 2011 through and including 2019, the modified adjusted gross income threshold is $85,000 for...

20 CFR 418.1105 - What is the threshold?

Code of Federal Regulations, 2012 CFR

2012-04-01

... 20 Employees' Benefits 2 2012-04-01 2012-04-01 false What is the threshold? 418.1105 Section 418... What is the threshold? (a) The threshold is a level of modified adjusted gross income above which the... gross income threshold is $80,000 for individuals with a Federal income tax filing status of single...

Prognostic impact of mRNA levels of osteopontin splice variants in soft tissue sarcoma patients.

PubMed

Hahnel, Antje; Wichmann, Henri; Greither, Thomas; Kappler, Matthias; Würl, Peter; Kotzsch, Matthias; Taubert, Helge; Vordermark, Dirk; Bache, Matthias

2012-04-02

It is well known that osteopontin (OPN) plays an important role in tumor progression and that a high OPN expression level in several tumor entities correlates with poor prognosis in cancer patients. However, little is known about the prognostic relevance of the OPN mRNA splice variants. We analyzed the mRNA expression levels of different OPN splice variants in tumor tissue of 124 soft tissue sarcoma (STS) patients. Quantitative real-time PCR (qRT-PCR) was used to analyze the mRNA expression level of three OPN splice variants (OPN-a, -b and -c). The multivariate Cox's proportional hazard regression model revealed that high mRNA expression levels of OPN splice variants are significantly associated with poor prognosis in STS patients (n = 124). Women (n = 68) with high mRNA expression levels of OPN-a and OPN-b have an especially elevated risk of tumor-related death (OPN-a: RR = 3.0, P = 0.01, CI = 1.3-6.8; OPN-b: RR = 3.4, P = 0.01, CI = 1.4-8.2). In particular, we found that high mRNA expression levels of OPN-b and OPN-c correlated with a high risk of tumor-related death in STS patients that received radiotherapy (n = 52; OPN-b: RR = 10.3, P < 0.01, CI = 2.0-53.7; OPN-c: RR = 11.4, P < 0.01, CI = 2.2-59.3). Our study shows that elevated mRNA expression levels of OPN splice variants are negative prognostic and predictive markers for STS patients. Further studies are needed to clarify the impact of the OPN splice variants on prognosis.

Modified combination of platelet count and neutrophil "to" lymphocyte ratio as a prognostic factor in patients with advanced head and neck cancer.

PubMed

Nakayama, Masahiro; Gosho, Masahiko; Hirose, Yuki; Nishimura, Bungo; Tanaka, Shuho; Tabuchi, Keiji; Okubo, Hideki; Wada, Tetsuro; Hara, Akira

2018-06-01

We evaluated the prognostic potential of the combination of platelet count and neutrophil to lymphocyte ratio (COP-NLR) in patients with advanced head and neck cancer. We proposed a modified COP-NLR scoring system defined as follows: score 0 (platelet count level <300 × 10 9 /L and NLR <3); score 1 (platelet count level ≥300 × 10 9 /L and NLR <3); and score 2 (NLR ≥3). We assessed whether the modified scoring system had better performance as an indicator of prognosis than the existing COP-NLR scoring system (original and 4-group scores). A total of 248 patients were enrolled. The Akaike Information Criterion value with the modified COP-NLR score was the smallest among the 3 models. The 3-year survival rates according to the modified COP-NLR scores of 0, 1, and 2 were 80.6%, 59.9%, and 23.8%, respectively. The modified COP-NLR score is a useful prognostic marker in patients with advanced head and neck cancer. © 2018 Wiley Periodicals, Inc.

Prognostics for Electronics Components of Avionics Systems

NASA Technical Reports Server (NTRS)

Celaya, Jose R.; Saha, Bhaskar; Wysocki, Philip F.; Goebel, Kai F.

2009-01-01

Electronics components have and increasingly critical role in avionics systems and for the development of future aircraft systems. Prognostics of such components is becoming a very important research filed as a result of the need to provide aircraft systems with system level health management. This paper reports on a prognostics application for electronics components of avionics systems, in particular, its application to the Isolated Gate Bipolar Transistor (IGBT). The remaining useful life prediction for the IGBT is based on the particle filter framework, leveraging data from an accelerated aging tests on IGBTs. The accelerated aging test provided thermal-electrical overstress by applying thermal cycling to the device. In-situ state monitoring, including measurements of the steady-state voltages and currents, electrical transients, and thermal transients are recorded and used as potential precursors of failure.

Towards Prognostics for Electronics Components

NASA Technical Reports Server (NTRS)

Saha, Bhaskar; Celaya, Jose R.; Wysocki, Philip F.; Goebel, Kai F.

2013-01-01

Electronics components have an increasingly critical role in avionics systems and in the development of future aircraft systems. Prognostics of such components is becoming a very important research field as a result of the need to provide aircraft systems with system level health management information. This paper focuses on a prognostics application for electronics components within avionics systems, and in particular its application to an Isolated Gate Bipolar Transistor (IGBT). This application utilizes the remaining useful life prediction, accomplished by employing the particle filter framework, leveraging data from accelerated aging tests on IGBTs. These tests induced thermal-electrical overstresses by applying thermal cycling to the IGBT devices. In-situ state monitoring, including measurements of steady-state voltages and currents, electrical transients, and thermal transients are recorded and used as potential precursors of failure.

Low blood levels of sTWEAK are related to locoregional failure in head and neck cancer.

PubMed

Avilés-Jurado, Francesc Xavier; Terra, Ximena; Gómez, David; Flores, Joan Carles; Raventós, Antoni; Maymó-Masip, Elsa; León, Xavier; Serrano-Gonzalvo, Vicente; Vendrell, Joan; Figuerola, Enric; Chacón, Matilde R

2015-07-01

Identifying serum pre-treatment molecular markers that can predict response to therapy is of great interest in head and neck oncology and is required to develop personalized treatments that maximize survival while minimizing morbidity. The main aim was to investigate the potential prognostic significance of tumor necrosis factor-like weak inducer of apoptosis (TWEAK), and its receptors, fibroblast growth factor-inducible 14 (Fn14) and CD163, in head and neck squamous cell carcinoma (HNSCC). The study comprised 37 consecutive patients with pathologically confirmed, untreated HNSCC. Serum and tissue samples from these patients were available for study. We determined sTWEAK and sCD163 levels in serum from 37 HNSCC patients by ELISA. TWEAK, CD163, Fn14 and TNF-α gene expression were detected by real-time RT-PCR in 111 matched tissue samples (tumoral, adjacent and distal/normal mucosa). Our results showed a significant relationship between low sTWEAK levels and poor locoregional control of the disease. Kaplan-Meier curves indicated that the locoregional recurrence-free survival rate in patients with low sTWEAK circulating levels was significantly lower than in patients with high levels, and that high CD136/TWEAK expression ratio in tumors was also related to poor prognosis. sTWEAK pre-treatment serum levels might be used as prognostic non-invasive biomarkers for locoregional control in patients with HNSCC. Future investigations are warranted to determine the potential prognostic significance of this non-invasive biomarker in the rapid discrimination according to the locoregional control achieved in patients who received a non-surgical organ preservation treatment.

Epigenetic Reprogramming Strategies to Reverse Global Loss of 5-Hydroxymethylcytosine, a Prognostic Factor for Poor Survival in High-grade Serous Ovarian Cancer

PubMed Central

Tucker, Douglass W.; Getchell, Christopher R.; McCarthy, Eric T.; Ohman, Anders W.; Sasamoto, Naoko; Xu, Shuyun; Ko, Joo Yeon; Gupta, Mamta; Shafrir, Amy; Medina, Jamie E.; Lee, Jonathan J.; MacDonald, Lauren A.; Malik, Ammara; Hasselblatt, Kathleen T; Li, Wenjing; Zhang, Hong; Kaplan, Samuel J.; Murphy, George F.; Hirsch, Michelle S.; Liu, Joyce F.; Matulonis, Ursula A.; Terry, Kathryn L.; Lian, Christine G.; Dinulescu, Daniela M.

2018-01-01

Purpose A major challenge in platinum-based cancer therapy is the clinical management of chemoresistant tumors, which have a largely unknown pathogenesis at the level of epigenetic regulation. Experimental Design We evaluated the potential of using global loss of 5-hydroxymethylcytosine (5-hmC) levels as a novel diagnostic and prognostic epigenetic marker to better assess platinum-based chemotherapy response and clinical outcome in high-grade serous tumors (HGSOC), the most common and deadliest subtype of ovarian cancer. Furthermore, we identified a targetable pathway to reverse these epigenetic changes, both genetically and pharmacologically. Results This study shows that decreased 5-hmC levels are an epigenetic hallmark for malignancy and tumor progression in HGSOC. In addition, global 5-hmC loss is associated with a decreased response to platinum-based chemotherapy, shorter time to relapse, and poor overall survival in patients newly diagnosed with HGSOC. Interestingly, the rescue of 5-hmC loss restores sensitivity to platinum chemotherapy in vitro and in vivo, decreases the percentage of tumor cells with cancer stem cell markers, and increases overall survival in an aggressive animal model of platinum-resistant disease. Conclusions Consequently, a global analysis of patient 5-hmC levels should be included in future clinical trials, which use pretreatment with epigenetic adjuvants to elevate 5-hmC levels and improve the efficacy of current chemotherapies. Identifying prognostic epigenetic markers and altering chemotherapeutic regimens to incorporate DNMTi pretreatment in tumors with low 5-hmC levels could have important clinical implications for newly diagnosed HGSOC disease. PMID:29263182

Serum uric acid level as a cardio-cerebrovascular event risk factor in middle-aged and non-obese Chinese men.

PubMed

Li, Zhi-Jun; Yi, Chen-Ju; Li, Jing; Tang, Na

2017-04-11

The role of uric acid as a risk factor for cardio-cerebrovascular diseases is controversial. In this study, we aimed to investigate the relationship between serum uric acid level and the risk of cardio-cerebrovascular events in middle-aged and non-obese Chinese men. We included 3152 participants from the health examination center of Tongji Hospital from June 2007 to June 2010. Clinical examination and medical records were collected at the annual health examination. The hazard ratios (HRs) of uric acid for cardio-cerebrovascular events were calculated by Cox proportional hazards models. Generalized additive model and threshold effect analysis were used to explore the non-linear relationship between serum uric acid level and the incidence of cardio-cerebrovascular event. The mean follow-up time was 52 months. When the participants were classified into four groups by the serum acid quarter (Q1-Q4), the HRs (95% CI) of Q2-Q4 for cardio-cerebrovascular events were 1.26 (0.83, 1.92), 1.97 (1.33, 2.91) and 2.05 (1.40, 3.01), respectively, compared with the reference (Q1). The actual incidence and conditional incidence of cardio-cerebrovascular events in the high serum acid group were higher than those in the low serum acid group, which were stratified by the turning point (sUA = 372 μmol/L). We also showed a strong prognostic accuracy of the multiple variable-based score in 3 years and 5 years, with area under the receiver operating characteristic (ROC) curve of 0.790 (0.756-0.823) and 0.777 (0.749-0.804), respectively. Serum uric acid level is a strong risk factor for cardio-cerebrovascular events.

Prognostic Factors in Cholinesterase Inhibitor Poisoning.

PubMed

Sun, In O; Yoon, Hyun Ju; Lee, Kwang Young

2015-09-28

Organophosphates and carbamates are insecticides that are associated with high human mortality. The purpose of this study is to investigate the prognostic factors affecting survival in patients with cholinesterase inhibitor (CI) poisoning. This study included 92 patients with CI poisoning in the period from January 2005 to August 2013. We divided these patients into 2 groups (survivors vs. non-survivors), compared their clinical characteristics, and analyzed the predictors of survival. The mean age of the included patients was 56 years (range, 16-88). The patients included 57 (62%) men and 35 (38%) women. When we compared clinical characteristics between the survivor group (n=81, 88%) and non-survivor group (n=11, 12%), there were no differences in renal function, pancreatic enzymes, or serum cholinesterase level, except for serum bicarbonate level and APACHE II score. The serum bicarbonate level was lower in non-survivors than in survivors (12.45±2.84 vs. 18.36±4.73, P<0.01). The serum APACHE II score was higher in non-survivors than in survivors (24.36±5.22 vs. 12.07±6.67, P<0.01). The development of pneumonia during hospitalization was higher in non-survivors than in survivors (n=9, 82% vs. n=31, 38%, P<0.01). In multiple logistic regression analysis, serum bicarbonate concentration, APACHE II score, and pneumonia during hospitalization were the important prognostic factors in patients with CI poisoning. Serum bicarbonate and APACHE II score are useful prognostic factors in patients with CI poisoning. Furthermore, pneumonia during hospitalization was also important in predicting prognosis in patients with CI poisoning. Therefore, prevention and active treatment of pneumonia is important in the management of patients with CI poisoning.

Serum Chloride and Sodium Interplay in Patients With Acute Myocardial Infarction and Heart Failure With Reduced Ejection Fraction: An Analysis From the High-Risk Myocardial Infarction Database Initiative.

PubMed

Ferreira, João Pedro; Girerd, Nicolas; Duarte, Kevin; Coiro, Stefano; McMurray, John J V; Dargie, Henry J; Pitt, Bertram; Dickstein, Kenneth; Testani, Jeffrey M; Zannad, Faiez; Rossignol, Patrick

2017-02-01

Serum chloride levels were recently found to be independently associated with mortality in heart failure (HF). We investigated the relationship between serum chloride and clinical outcomes in 7195 subjects with acute myocardial infarction complicated by reduced left ventricular function and HF. The studied outcomes were all-cause mortality, cardiovascular mortality, and hospitalization for HF. Both chloride and sodium had a nonlinear association with the studied outcomes (P<0.05 for linearity). Patients in the lowest chloride tertile (chloride ≤100) were older, had more comorbidities, and had lower sodium levels (P<0.05 for all). Serum chloride showed a significant interaction with sodium with regard to all studied outcomes (P for interaction <0.05 for all). The lowest chloride tertile (≤100 mmol/L) was associated with increased mortality rates in the context of lower sodium (≤138 mmol/L; adjusted hazard ratio [95% confidence interval] for all-cause mortality=1.42 (1.14-1.77); P=0.002), whereas in the context of higher sodium levels (>141 mmol/L), the association with mortality was lost. Spline-transformed chloride and its interaction with sodium did not add significant prognostic information on top of other well-established prognostic variables (P>0.05 for all outcomes). In post-myocardial infarction with systolic dysfunction and HF, low serum chloride was associated with mortality (but not hospitalization for HF) in the setting of lower sodium. Overall, chloride and its interaction with sodium did not add clinically relevant prognostic information on top of other well-established prognostic variables. Taken together, these data support an integrated and critical consideration of chloride and sodium interplay. © 2017 American Heart Association, Inc.

Decoy receptor 3 is a prognostic factor in renal cell cancer.

PubMed

Macher-Goeppinger, Stephan; Aulmann, Sebastian; Wagener, Nina; Funke, Benjamin; Tagscherer, Katrin E; Haferkamp, Axel; Hohenfellner, Markus; Kim, Sunghee; Autschbach, Frank; Schirmacher, Peter; Roth, Wilfried

2008-10-01

Decoy receptor 3 (DcR3) is a soluble protein that binds to and inactivates the death ligand CD95L. Here, we studied a possible association between DcR3 expression and prognosis in patients with renal cell carcinomas (RCCs). A tissue microarray containing RCC tumor tissue samples and corresponding normal tissue samples was generated. Decoy receptor 3 expression in tumors of 560 patients was examined by immunohistochemistry. The effect of DcR3 expression on disease-specific survival and progression-free survival was assessed using univariate analysis and multivariate Cox regression analysis. Decoy receptor 3 serum levels were determined by ELISA. High DcR3 expression was associated with high-grade (P = .005) and high-stage (P = .048) RCCs. The incidence of distant metastasis (P = .03) and lymph node metastasis (P = .002) was significantly higher in the group with high DcR3 expression. Decoy receptor 3 expression correlated negatively with disease-specific survival (P < .001) and progression-free survival (P < .001) in univariate analyses. A multivariate Cox regression analysis retained DcR3 expression as an independent prognostic factor that outperformed the Karnofsky performance status. In patients with high-stage RCCs expressing DcR3, the 2-year survival probability was 25%, whereas in patients with DcR3-negative tumors, the survival probability was 65% (P < .001). Moreover, DcR3 serum levels were significantly higher in patients with high-stage localized disease (P = .007) and metastatic disease (P = .001). DcR3 expression is an independent prognostic factor of RCC progression and mortality. Therefore, the assessment of DcR3 expression levels offers valuable prognostic information that could be used to select patients for adjuvant therapy studies.

Clinical and histopathological factors associated with Ki-67 expression in breast cancer patients

PubMed Central

ALCO, GUL; BOZDOGAN, ATILLA; SELAMOGLU, DERYA; PILANCI, KEZBAN NUR; TUZLALI, SITKI; ORDU, CETIN; IGDEM, SEFIK; OKKAN, SAIT; DINCER, MAKTAV; DEMIR, GOKHAN; OZMEN, VAHIT

2015-01-01

The aim of the present study was to identify the optimal Ki-67 cut-off value in breast cancer (BC) patients, and investigate the association of Ki-67 expression levels with other prognostic factors. Firstly, a retrospective search was performed to identify patients with stage I–III BC (n=462). A range of Ki-67 index values were then assigned to five groups (<10, 10–14, 15–19, 20–24 and ≥25%). The correlation between the Ki-67 index and other prognostic factors [age, tumor type, histological and nuclear grade, tumor size, multifocality, an in situ component, lymphovascular invasion (LVI), estrogen and progesterone receptor (ER/PR) expression, human epidermal growth factor receptor (HER-2) status, axillary involvement and tumor stage] were investigated in each group. The median Ki-67 value was revealed to be 20% (range, 1–95%). A young age (≤40 years old), tumor type, size and grade, LVI, ER/PR negativity and HER-2 positivity were revealed to be associated with the Ki-67 level. Furthermore, Ki-67 was demonstrated to be negatively correlated with ER/PR expression (P<0.001), but positively correlated with tumor size (P<0.001). The multivariate analysis revealed that a Ki-67 value of ≥15% was associated with the largest number of poor prognostic factors (P=0.036). In addition, a Ki-67 value of ≥15% was identified to be statistically significant in association with certain luminal subtypes. The rate of disease-free survival was higher in patients with luminal A subtype BC (P=0.036). Following the correlation analysis for the Ki-67 index and the other prognostic factors, a Ki-67 value of ≥15% was revealed to be the optimal cut-off level for BC patients. PMID:25663855

Patients with metastatic breast cancer leading to CD4+ T cell lymphopaenia have poor outcome.

PubMed

Trédan, Olivier; Manuel, Manuarii; Clapisson, Gilles; Bachelot, Thomas; Chabaud, Sylvie; Bardin-dit-Courageot, Christine; Rigal, Chantal; Biota, Cathy; Bajard, Agathe; Pasqual, Nicolas; Blay, Jean-Yves; Caux, Christophe; Ménétrier-Caux, Christine

2013-05-01

Low lymphocyte count is a prognostic factor in cancer patients including metastatic breast cancer patients (MBC) but the relative role of each lymphocyte subtype is unclear in MBC. The impact of lymphocyte subsets was analysed in two prospective MBC patients' cohorts. Cohort A patients (n=103) were included before the first line of chemotherapy and cohort B patients (n=101) were included after at least one line of chemotherapy. Extensive phenotypic analyses were performed on fresh whole blood. Plasma cytokines levels were measured using commercially available Luminex-based multiplex kits. Prognostic value of lymphocyte subsets and circulating cytokines was analysed. In both cohorts, severe lymphopaenia (<0.7 Giga/L) correlated with poor overall survival (OS) (median OS: 6.6 months versus 21.7 months in cohort A and 4.5 versus 9 months in cohort B). CD8(+), CD19(+) and CD56(+) T cell counts had no significant prognostic value for OS. After stratification (≤0.2, [0.20-0.45], >0.45 Giga/L), CD4 lymphopaenia appeared to be correlated with poor OS in both cohorts. Furthermore, severe CD4(+) lymphopaenia (≤0.2 Giga/L) was strongly correlated with poor OS in both cohorts (1.2 months versus 24.9 months in cohort A and 5.7 versus 13.1 months in cohort B). In multivariate analysis, after stratification CD4(+) lymphopaenia appeared to be an independent prognostic factor for OS in both cohorts. CD4(+) lymphopaenia correlated with low plasmatic levels of CCL22 that might directly contribute to CD4(+) lymphopaenia. CD4(+) lymphopaenia was associated with reduced OS in MBC patients regardless of the chemotherapy line. Decreased levels of plasmatic CCL22 may contribute to CD4(+) lymphopaenia. Copyright © 2012 Elsevier Ltd. All rights reserved.

Low T3 syndrome as a predictor of poor prognosis in chronic lymphocytic leukemia.

PubMed

Gao, Rui; Chen, Rui-Ze; Xia, Yi; Liang, Jin-Hua; Wang, Li; Zhu, Hua-Yuan; Zhu Wu, Jia-; Fan, Lei; Li, Jian-Yong; Yang, Tao; Xu, Wei

2018-02-19

Low triiodothyronine (T3) state is associated with poor prognosis in critical acute and prolonged illness. However, the information on thyroid dysfunction and cancer is limited. The aim of our study was to evaluate the prognostic value of low T3 syndrome in chronic lymphocytic leukemia (CLL). Two hundred and fifty-eight patients with detailed thyroid hormone profile at CLL diagnosis were enrolled. Low T3 syndrome was defined by low free T3 (FT3) level accompanied by normal-to-low free tetraiodothyronine (FT4) and thyroid-stimulating hormone (TSH) levels. A propensity score-matched method was performed to balance the baseline characteristics. Multivariate Cox regression analyses screened the independent prognostic factors related to time-to-first-treatment (TTFT) and cancer-specific survival (CSS). Area under the curve (AUC) assessed the predictive accuracy of CLL-International Prognostic Index (IPI) together with low T3 syndrome. The results showed that 37 (14.34%) patients had low T3 syndrome, which was significantly associated with unfavorable TTFT and CSS in the propensity-matched cohort, and it was an independent prognostic indicator for both TTFT and CSS. Serum FT3 level was positively related to protein metabolism and anemia, and inversely related to inflammatory state. Patients with only low FT3 demonstrated better survival than those with synchronously low FT3 and FT4, while those with synchronously low FT3, FT4 and TSH had the worst clinical outcome. Low T3 syndrome together with CLL-IPI had larger AUCs compared with CLL-IPI alone in TTFT and CSS prediction. In conclusion, low T3 syndrome may be a good candidate for predicting prognosis in future clinical practice of CLL. © 2018 UICC.

Sudden sensorineural hearing loss with positional vertigo: Initial findings of positional nystagmus and hearing outcomes.

PubMed

Kim, Chang-Hee; Shin, Jung Eun; Yang, Young Soo; Im, Donghyuk

2016-10-01

To investigate the initial findings of positional nystagmus in patients with sudden sensorineural hearing loss (SSNHL) and positional vertigo, and to compare hearing improvement among patients with different types of positional nystagmus. The characteristics of positional nystagmus upon initial examination were analysed, and the initial mean pure-tone audiometry (PTA) threshold was compared with that at three months after treatment. Forty-four SSNHL patients with concomitant positional vertigo were included. Positional nystagmus was classified into five subgroups; persistent geotropic direction-changing positional nystagmus (DCPN) in head-roll test (HRT) and negative Dix-Hallpike test (DHT), persistent apogeotropic DCPN in HRT and negative DHT, positive DHT and negative HRT, persistent geotropic DCPN in HRT and positive DHT, and persistent apogeotropic DCPN in HRT and positive DHT. PTA threshold improvement was significantly greater in SSNHL patients with negative DHT than with positive DHT (p = 0.027). When geotropic DCPN was elicited by HRT, the nystagmus was persistent, which suggests that alteration of specific gravity of the endolymph, rather than the lateral canal canalolithiasis, may be a cause of this characteristic positional nystagmus. Positive DTH may be a prognostic factor for worse hearing recovery among patients with SSNHL and positional vertigo.

Dynamic-thresholding level set: a novel computer-aided volumetry method for liver tumors in hepatic CT images

NASA Astrophysics Data System (ADS)

Cai, Wenli; Yoshida, Hiroyuki; Harris, Gordon J.

2007-03-01

Measurement of the volume of focal liver tumors, called liver tumor volumetry, is indispensable for assessing the growth of tumors and for monitoring the response of tumors to oncology treatments. Traditional edge models, such as the maximum gradient and zero-crossing methods, often fail to detect the accurate boundary of a fuzzy object such as a liver tumor. As a result, the computerized volumetry based on these edge models tends to differ from manual segmentation results performed by physicians. In this study, we developed a novel computerized volumetry method for fuzzy objects, called dynamic-thresholding level set (DT level set). An optimal threshold value computed from a histogram tends to shift, relative to the theoretical threshold value obtained from a normal distribution model, toward a smaller region in the histogram. We thus designed a mobile shell structure, called a propagating shell, which is a thick region encompassing the level set front. The optimal threshold calculated from the histogram of the shell drives the level set front toward the boundary of a liver tumor. When the volume ratio between the object and the background in the shell approaches one, the optimal threshold value best fits the theoretical threshold value and the shell stops propagating. Application of the DT level set to 26 hepatic CT cases with 63 biopsy-confirmed hepatocellular carcinomas (HCCs) and metastases showed that the computer measured volumes were highly correlated with those of tumors measured manually by physicians. Our preliminary results showed that DT level set was effective and accurate in estimating the volumes of liver tumors detected in hepatic CT images.

Identifying humanitarian crises in population surveillance field sites: simple procedures and ethical imperatives.

PubMed

Fottrell, E; Byass, P

2009-02-01

Effective early warning systems of humanitarian crises may help to avert substantial increases in mortality and morbidity, and prevent major population movements. The Butajira Rural Health Programme (BRHP) in Ethiopia has maintained a programme of epidemiological surveillance since 1987. Inspection of the BRHP data revealed large peaks of mortality in 1998 and 1999, well in excess of the normally observed year-to-year variation. Further investigation and enquiry revealed that these peaks related to a measles epidemic, and a serious episode of drought and consequent food insecurity that went undetected by the BRHP. This paper applies international humanitarian crisis threshold definitions to the BRHP data in an attempt to identify suitable mortality thresholds that may be used for the prospective detection of humanitarian crises in population surveillance sites in developing countries. Empirical investigation using secondary analysis of longitudinal population-based cohort data. The daily, weekly and monthly thresholds for crises in Butajira were applied to mortality data for the 5-year period incorporating the crisis periods of 1998-1999. Days, weeks and months in which mortality exceeded each threshold level were identified. Each threshold level was assessed in terms of prospectively identifying the true crisis periods in a timely manner whilst avoiding false alarms. The daily threshold definition is too sensitive to accurately detect impending or real crises in the population surveillance setting of the BRHP. However, the weekly threshold level is useful in identifying important increases in mortality in a timely manner without the excessive sensitivity of the daily threshold. The weekly threshold level detects the crisis periods approximately 2 weeks before the monthly threshold level. Mortality measures are highly specific indicators of the health status of populations, and simple procedures can be used to apply international crisis threshold definitions in population surveillance settings for the prospective detection of important changes in mortality rate. Standards for the timely use of surveillance data and ethical responsibilities of those responsible for the data should be made explicit to improve the public health functioning of current sentinel surveillance methodologies.

PKD1 is a potential biomarker and therapeutic target in triple-negative breast cancer.

PubMed

Spasojevic, Caroline; Marangoni, Elisabetta; Vacher, Sophie; Assayag, Franck; Meseure, Didier; Château-Joubert, Sophie; Humbert, Martine; Karam, Manale; Ricort, Jean Marc; Auclair, Christian; Regairaz, Marie; Bièche, Ivan

2018-05-01

Protein Kinase D1 (PKD1) is a serine/threonine kinase encoded by the PRKD1 gene. PKD1 has been previously shown to be a prognostic factor in ERα+ tamoxifen-resistant breast tumors and PKD1 overexpression confers estrogen independence to ERα+ MCF7 cells. In the present study, our goal was to determine whether PKD1 is a prognostic factor and/or a relevant therapeutic target in breast cancer. We analyzed PRKD1 mRNA levels in 527 primary breast tumors. We found that high PRKD1 mRNA levels were significantly and independently associated with a low metastasis-free survival in the whole breast cancer population and in the triple-negative breast cancer (TNBC) subtype specifically. High PRKD1 mRNA levels were also associated with a low overall survival in TNBC. We identified novel PKD1 inhibitors and assessed their antitumor activity in vitro in TNBC cell lines and in vivo in a TNBC patient-derived xenograft (PDX) model. Pharmacological inhibition and siRNA-mediated depletion of PKD1 reduced colony formation in MDA-MB-436 TNBC cells. PKD1 inhibition also reduced tumor growth in vivo in a TNBC PDX model. Together, these results establish PKD1 as a poor prognostic factor and a potential therapeutic target in TNBC.

EMMPRIN/CD147 is an independent prognostic biomarker in cutaneous melanoma.

PubMed

Caudron, Anne; Battistella, Maxime; Feugeas, Jean-Paul; Pages, Cécile; Basset-Seguin, Nicole; Mazouz Dorval, Sarra; Funck Brentano, Elisa; Sadoux, Aurélie; Podgorniak, Marie-Pierre; Menashi, Suzanne; Janin, Anne; Lebbé, Céleste; Mourah, Samia

2016-08-01

CD147 has been implicated in melanoma invasion and metastasis mainly through increasing metalloproteinase synthesis and regulating VEGF/VEGFR signalling. In this study, the prognostic value of CD147 expression was investigated in a cohort of 196 cutaneous melanomas including 136 consecutive primary malignant melanomas, 30 lymph nodes, 16 in-transit and 14 visceral metastases. A series of 10 normal skin, 10 blue nevi and 10 dermal nevi was used as control. CD147 expression was assessed by immunohistochemistry, and the association of its expression with the clinicopathological characteristics of patients and survival was evaluated using univariate and multivariate statistical analyses. Univariate analysis showed that high CD147 expression was significantly associated with metastatic potential and with a reduced overall survival (P < 0.05 for both) in primary melanoma patients. CD147 expression level was correlated with histological factors which were associated with prognosis: Clark level, ulceration status and more particularly with Breslow index (r = 0.7, P < 10(-8) ). Multivariate analysis retained CD147 expression level and ulceration status as predicting factors for metastasis and overall survival (P < 0.05 for both). CD147 emerges as an important factor in the aggressive behaviour of melanoma and deserves further evaluation as an independent prognostic biomarker. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Investigative clinical study on prostate cancer part III: exploring total PSA and free testosterone distributions and linear correlations in groups and subgroups of operated prostate cancer patients according to the total PSA/FT ratio.

PubMed

Porcaro, Antonio B; Petrozziello, Aldo; Romano, Mario; Sava, Teodoro; Ghimenton, Claudio; Caruso, Beatrice; Migliorini, Filippo; Zecchini Antoniolli, Stefano; Rubilotta, Emanuele; Lacola, Vincenzo; Monaco, Carmelo; Comunale, Luigi

2010-01-01

Prostate cancer is an interesting tumor for endocrine investigation. The prostate-specific antigen/free testosterone (PSA/FT) ratio has been shown to be effective in clustering patients in prognostic groups as follows: low risk (PSA/FT ≤0.20), intermediate risk (PSA/FT >0.20 and ≤0.40) and high risk (PSA/FT >0.40 and ≤1.5). In the present study we explored the total PSA and FT distributions, and linear regression of FT predicting PSA in the different groups (PSA/FT, pT and pG) and subgroups (pT and pG) of patients according to the prognostic PSA/FT ratio. The study included 128 operated prostate cancer patients. Pretreatment simultaneous serum samples were obtained for measuring free testosterone (FT) and total PSA levels. Patients were grouped according to the total PSA/FT ratio prognostic clusters (≤0.20, >0.20 and ≤0.40, >0.40), pT (2, 3a and 3b+4) and pathological Gleason score (pG) (≤6, = 7 >3 + 4, ≥7 >4 + 3). The pT and pG sets were subgrouped according to the prognostic PSA/FT ratio. Linear regression analysis of FT predicting total PSA was computed according to the different PSA/FT prognostic clusters for the: (1) total sample population, (2) pT and pG groups, (3) intraprostatic (pT2) and extraprostatic disease (pT3a/3b/4), and (4) low-intermediate grade (pG ≤6) and high-grade (pG ≥7) prostate cancer. Analysis of variance always showed highly significant different PSA distributions for (1) the different PSA/FT, pT and pG groups; and (2) the pT and pG prognostic subgroups. Significant FT distributions were detected for the (1) PSA/FT and pT groups; and (2) the pT2, pT3a and pG ≤6 prognostic PSA/FT subgroups. Correlation, variance and linear regression analysis of FT predicting total PSA was significant for (1) the PSA/FT prognostic clusters, (2) all the pT2 and pT3a subgroups, and (3) the pT3b/4 subgroup with PSA/FT >0.20 and ≤0.40, and (4) all the pG subsets. Linear regression analysis showed that the slopes of the predicting variable (FT) were always highly significant for patients with (1) intraprostate and extraprostate disease, and (2) low-grade and high-grade prostate cancer. According to the prognostic PSA/FT ratio, significantly lower levels of FT are detected in prostate cancer patients with extensive and high-grade disease. Also, significant linear correlations of FT predicting PSA are assessed in the different groups and subgroups of patients clustered according to the prognostic PSA/FT ratio. Confirmatory studies are needed. Copyright © 2010 S. Karger AG, Basel.

The relation between the effect of a subhypnotic dose of thiopental on claw pain threshold in rats and adrenalin, noradrenalin and dopamine levels.

PubMed

Aksoy, Mehmet; Ahiskalioglu, Ali; Ince, Ilker; Celik, Mine; Dostbil, Aysenur; Kuyrukluyildiz, Ufuk; Altuner, Durdu; Kurt, Nezahat; Suleyman, Halis

2015-01-01

Thiopental sodium (TPS) needs to be applied together with adrenalin in order to establish its analgesic effect in general anesthesia. We aimed to investigate the effect of TPS on the claw pain threshold in rats and evaluated its relationship with endogenous adrenalin (ADR), noradrenalin (NDR), and dopamine (DOP) levels. Intact and adrenalectomized rats were used in the experiment. Intact animals were divided into the following groups: 15 mg/kg TPS (TS), 0.3 mg/kg ADR+15 mg/kg TPS (ATS) and 0.3 mg/kg ADR alone (ADR). Adrenalectomized animals were divided into the following groups: 15 mg/kg TPS (A-TS), 0.3 mg/kg ADR+15 mg/kg TPS (A-ATS) and 0.3 mg/kg ADR alone (A-ADR). Claw pain threshold and blood ADR, NDR, and DOP levels were measured. The TS group's claw pain threshold was found low. However, the claw pain thresholds of the ATS and ADR groups increased significantly. In the A-TS group, the pain threshold decreased compared with normal, and in the A-ATS and A-ADR groups, the pain threshold increased. TPS reduced the blood ADR levels in intact rats; however, no significant changes were observed in the NDR and DOP levels. #TPS provides hyperalgesia by reducing the production of ADR in rats. The present study shows that to achieve analgesic activity, TPS needs to be applied together with ADR.

The relation between the effect of a subhypnotic dose of thiopental on claw pain threshold in rats and adrenalin, noradrenalin and dopamine levels

PubMed Central

Aksoy, Mehmet; Ahiskalioglu, Ali; Ince, Ilker; Celik, Mine; Dostbil, Aysenur; Kuyrukluyildiz, Ufuk; Altuner, Durdu; Kurt, Nezahat; Suleyman, Halis

2015-01-01

Thiopental sodium (TPS) needs to be applied together with adrenalin in order to establish its analgesic effect in general anesthesia. We aimed to investigate the effect of TPS on the claw pain threshold in rats and evaluated its relationship with endogenous adrenalin (ADR), noradrenalin (NDR), and dopamine (DOP) levels. Intact and adrenalectomized rats were used in the experiment. Intact animals were divided into the following groups: 15 mg/kg TPS (TS), 0.3 mg/kg ADR+15 mg/kg TPS (ATS) and 0.3 mg/kg ADR alone (ADR). Adrenalectomized animals were divided into the following groups: 15 mg/kg TPS (A-TS), 0.3 mg/kg ADR+15 mg/kg TPS (A-ATS) and 0.3 mg/kg ADR alone (A-ADR). Claw pain threshold and blood ADR, NDR, and DOP levels were measured. The TS group’s claw pain threshold was found low. However, the claw pain thresholds of the ATS and ADR groups increased significantly. In the A-TS group, the pain threshold decreased compared with normal, and in the A-ATS and A-ADR groups, the pain threshold increased. TPS reduced the blood ADR levels in intact rats; however, no significant changes were observed in the NDR and DOP levels. #TPS provides hyperalgesia by reducing the production of ADR in rats. The present study shows that to achieve analgesic activity, TPS needs to be applied together with ADR. PMID:26211784

Facilitation and refractoriness of the electrically evoked compound action potential.

PubMed

Hey, Matthias; Müller-Deile, Joachim; Hessel, Horst; Killian, Matthijs

2017-11-01

In this study we aim to resolve the contributions of facilitation and refractoriness at very short pulse intervals. Measurements of the refractory properties of the electrically evoked compound action potential (ECAP) of the auditory nerve in cochlear implant (CI) users at inter pulse intervals below 300 μs are influenced by facilitation and recovery effects. ECAPs were recorded using masker pulses with a wide range of current levels relative to the probe pulse levels, for three suprathreshold probe levels and pulse intervals from 13 to 200 μs. Evoked potentials were measured for 21 CI patients by using the masked response extraction artifact cancellation procedure. During analysis of the measurements the stimulation current was not used as absolute value, but in relation to the patient's individual ECAP threshold. This enabled a more general approach to describe facilitation as a probe level independent effect. Maximum facilitation was found for all tested inter pulse intervals at masker levels near patient's individual ECAP threshold, independent from probe level. For short inter pulse intervals an increased N 1 P 1 amplitude was measured for subthreshold masker levels down to 120 CL below patient's individual ECAP threshold in contrast to the recreated state. ECAPs recorded with inter pulse intervals up to 200 μs are influenced by facilitation and recovery. Facilitation effects are most pronounced for masker levels at or below ECAP threshold, while recovery effects increase with higher masker levels above ECAP threshold. The local maximum of the ECAP amplitude for masker levels around ECAP threshold can be explained by the mutual influence of maximum facilitation and minimal refractoriness. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Deregulated HOXB7 expression predicts poor prognosis of patients with malignancies of digestive system.

PubMed

Liu, Fang-Teng; Chen, Han-Min; Xiong, Ying; Zhu, Zheng-Ming

2017-07-26

Numerous studies have investigated the relationship between deregulated HOXB7 expression with the clinical outcome in patients with digestive stem cancers, HOXB7 has showed negative impacts but with varying levels. We aimed to comprehensively evaluate the prediction and prognostic value of HOXB7 in digestive stem cancers. Electronic databases updated to December 1, 2016 were retrieved to collect relevant eligible studies to quantitatively explore the potential roles of HOXB7 as a prognostic indicator in digestive system cancers. A total of 9 studies (n = 1298 patients) was included in this synthetical meta-analysis. The pooled hazard ratios suggested that high expression of HOXB7 protein was associated with poor prognosis of OS in patients with digestive system cancers (HR = 1.97, 95% CI: 1.65-2.28, p= 0.000), and HOXB7 protein could act as an independent prognostic factor for predicting OS of patients with digestive system cancers (HR: 2.02, 95% CI: 1.69-2.36, p = 0.000). Statistical significance was also observed in subgroup meta-analysis based on the cancer type, histology type, country, sample size and publication date. Furthermore, we examined the correlations between HOXB7 protein and clinicopathological features. It showed that altered expression of HOXB7 protein was correlated with tumor invasion (p = 0.000), lymph node status (p = 0.000), distant metastasis (p = 0.001) and TNM stage (p = 0.000). However, the expression of HOXB7 protein was not associated with age (p = 0.64), gender (p = 0.40) or levels of differentiation (p = 0.19). High expression of HOXB7 protein was associated with poor prognosis of patients with digestive system cancers, as well as clinicopathologic characteristics, including the tumor invasion, lymph node status, distant metastasis and TNM stage. The expression of HOXB7 protein was not associated with age, gender or levels of differentiation. HOXB7 protein expression level in tumor tissue might serve as a novel prognostic marker for digestive system cancers.

Meta-analysis of the prognostic value of abnormally expressed lncRNAs in hepatocellular carcinoma.

PubMed

Qu, Zhen; Yuan, Chun-Hui; Yin, Chang-Qing; Guan, Qing; Chen, Hao; Wang, Fu-Bing

2016-01-01

Many long noncoding RNAs (lncRNAs) have been reported to be abnormally expressed in hepatocellular carcinoma (HCC), and may have the potential to serve as prognostic markers. In this study, a meta-analysis was conducted to systematically evaluate the prognostic value of various lncRNAs in HCC. Eligible literatures were systematically collected from PubMed, Embase, Web of Science, and Cochrane Library (up to December 30, 2015). The main outcomes including overall survival, relapse-free survival, and disease-free survival were analyzed. Pooled hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated using random- or fixed-effects models. A total of 2,991 patients with HCC in People's Republic of China from 27 studies were included in the analysis. The level of lncRNAs showed a significant association with clinical outcomes. Abnormally elevated lncRNA transcription level predicted poor overall survival (HR: 1.68, 95% CI: 1.20-2.34, P=0.002; I (2)=75.5%, P=0.000) and relapse-free survival (HR: 2.08, 95% CI: 1.65-2.61, P<0.001; I (2)=24.0%, P=0.215), while no association was observed with disease-free survival of HCC patients (HR: 1.39, 95% CI: 0.51-3.78, P=0.524; I (2)=81.3%, P=0.005). Subgroup analysis further showed that lncRNA transcription level was significantly associated with tumor size (relative risk [RR]: 1.19, 95% CI: 1.01-1.39, P=0.035), microvascular invasion (RR: 1.44, 95% CI: 1.10-1.89, P=0.009), and portal vein tumor thrombus (RR: 1.50, 95% CI: 1.03-2.20, P=0.036). Publication bias and sensitivity analysis further confirmed the stability of our results. Our present meta-analysis indicates that abnormal lncRNA transcription level may serve as a promising indicator for prognostic evaluation of patients with HCC in People's Republic of China.

Pre-treatment carbohydrate antigen 19-9 does not predict the response to neoadjuvant therapy in patients with localized pancreatic cancer

PubMed Central

Aldakkak, Mohammed; Christians, Kathleen K; Krepline, Ashley N; George, Ben; Ritch, Paul S; Erickson, Beth A; Johnston, Fabian M; Evans, Douglas B; Tsai, Susan

2015-01-01

Background The prognostic value of CA19-9 in patients with pancreatic cancer (PC) treated with neoadjuvant therapy has not been well described. Methods Pre-treatment CA19-9 levels (with concomitant normal bilirubin level) in patients with localized PC were categorized as normal (≤35), low (36–200), moderate (201–1000), or high (>1000). Post-treatment CA19-9 was measured after neoadjuvant therapy, prior to surgery. Results Pre-treatment CA19-9 levels were evaluable in 235 patients, levels were normal in 60 (25%) patients, low in 78 (33%) patients, moderate in 69 (29%) and high in 28 (12%). After neoadjuvant therapy, post-treatment CA19-9 normalized (≤ 35) in 40 (51%) of the patients in the low group, 14 (21%) of the moderate and 5 (19%) of the high group (P < 0.001). Of the 235 patients, 168 (71%) completed all intended therapy including a pancreatectomy; 44 (73%), 62 (79%), 46 (67%) and 16 (57%) of the normal, low, moderate and high groups (P = 0.10). Among these 168 patients, the median overall survival was 38.4, 43.6, 44.7, 27.2 and 26.4 months for normal, low, moderate and high CA19-9 groups (log rank P = 0.72). Among resected patients, an elevated pre-treatment CA19-9 was of little prognostic value; instead, it was the CA19-9 response to neoadjuvant therapy that was prognostic [hazard ratio (HR): 1.80, P = 0.02]. Conclusions Among patients who completed neoadjuvant therapy and surgery, pre-treatment CA19-9 obtained at the time of diagnosis was not predictive of overall survival, but normalization of post-treatment CA19-9 in response to neoadjuvant therapy was highly prognostic. PMID:26255895

Screening differential circular RNA expression profiles reveal that hsa_circ_0128298 is a biomarker in the diagnosis and prognosis of hepatocellular carcinoma.

PubMed

Chen, Dawei; Zhang, Chenyue; Lin, Jiamao; Song, Xinyu; Wang, Haiyong

2018-01-01

The aim of this study was to analyze the diagnostic and prognostic values of the circular RNA (circRNA) hsa_circ_0128298 in hepatocellular carcinoma (HCC). The global circRNA expression was measured using circRNA microarray using three pairs of cancer and noncancerous tissues from HCC patients. The microarray analysis revealed that two circRNAs were differentially expressed in the three pairs of cancerous and noncancerous tissues. The higher levels of two representative circRNAs, such as hsa_circ_0128298 and hsa_circ_0091582, were further confirmed by real-time polymerase chain reaction. In addition, the association between the expression level of hsa_circ_0128298 and the clinicopathological features of patients with HCC was further analyzed. The clinical diagnosis value was confirmed by receiver operating characteristic (ROC) curve analysis. Independent prognostic factors of patient outcome were identified using the Cox regression model. The survival data were analyzed by the Kaplan-Meier method, and the differences were evaluated using log-rank tests. Two-sided P -values <0.05 were considered statistically significant. The expression levels of hsa_circ_0128298 in HCC were significantly higher than those of paratumorous tissues ( P <0.001). Additionally, hsa_circ_0128298 was a diagnostic factor, with the area under the ROC curve of 0.668 (95% CI =0.503-0.794, P <0.001). The sensitivity and specificity values were 0.716 and 0.815, respectively. The AFP and hsa_circ_0128298 expression levels were independent prognostic factors. The overall survival of patients with low hsa_circ_0128298 expression was significantly higher than that of patients with high hsa_circ_0128298 expression. hsa_circ_0128298 may promote proliferation and metastasis and potentially represents a novel diagnostic and prognostic biomarker for HCC patients. However, studies with larger sample size are needed to confirm our conclusion.

Significance of KRAS, NRAS, BRAF and PIK3CA mutations in metastatic colorectal cancer patients receiving Bevacizumab: a single institution experience

PubMed Central

Baltruškevičienė, Edita; Mickys, Ugnius; Žvirblis, Tadas; Stulpinas, Rokas; Pipirienė Želvienė, Teresė; Aleknavičius, Eduardas

2016-01-01

Background. KRAS mutation is an important predictive and prognostic factor for patients receiving anti-EGFR therapy. An expanded KRAS, NRAS, BRAF, PIK3CA mutation analysis provides additional prognostic information, but its role in predicting bevacizumab efficacy is unclear. The aim of our study was to evaluate the incidence of KRAS, NRAS, BRAF and PIK3CA mutations in metastatic colorectal cancer patients receiving first line oxaliplatin based chemotherapy with or without bevacizumab and to evaluate their prognostic and predictive significance. Methods. 55 patients with the first-time diagnosed CRC receiving FOLFOX ± bevacizumab were involved in the study. Tumour blocks were tested for KRAS mutations in exons 2, 3 and 4, NRAS mutations in exons 2, 3 and 4, BRAF mutation in exon 15 and PIK3CA mutations in exons 9 and 20. The association between mutations and clinico-pathological factors, treatment outcomes and survival was analyzed. Results. KRAS mutations were detected in 67.3% of the patients, BRAF in 1.8%, PIK3CA in 5.5% and there were no NRAS mutations. A significant association between the high CA 19–9 level and KRAS mutation was detected (mean CA 19–9 levels were 276 and 87 kIU/l, respectively, p = 0.019). There was a significantly higher response rate in the KRAS, NRAS, BRAF and PIK3CA wild type cohort receiving bevacizumab compared to any gene mutant type (100 and 60%, respectively, p = 0.030). The univariate Cox regression analysis did not confirm KRAS and other tested mutations as prognostic factors for PFS or OS. Conclusions. Our study revealed higher KRAS and lower NRAS, BRAF and PIK3CA mutation rates in the Lithuanian population than those reported in the literature. KRAS mutation was associated with the high CA 19–9 level and mucinous histology type, but did not show any predictive or prognostic significance. The expanded KRAS, NRAS, BRAF and PIK3CA mutation analysis provided additional significant predictive information. PMID:28356789

A new prognostic score for elderly patients with diffuse large B-cell lymphoma treated with R-CHOP: the prognostic role of blood monocyte and lymphocyte counts is absent.

PubMed

Procházka, Vít; Pytlík, Robert; Janíková, Andrea; Belada, David; Sálek, David; Papajík, Tomáš; Campr, Vít; Fürst, Tomáš; Furstova, Jana; Trněný, Marek

2014-01-01

Absolute lymphocyte count (ALC) and absolute monocyte count (AMC) have been documented as independent predictors of survival in patients with newly diagnosed Diffuse Large B-cell Lymphoma (DLBCL). Analysis of the prognostic impact of ALC and AMC in the context of International Prognostic Index (IPI) and other significant variables in elderly population treated in the R-CHOP regime has not been carried out yet. In this retrospective study, a cohort of 443 newly diagnosed DLBCL patients with age ≥ 60 was analyzed. All patients were treated with the R-CHOP therapy. An extensive statistical analysis was performed to identify risk factors of 3-year overall survival (OS). In multivariate analysis, only three predictors proved significant: Eastern Cooperative Oncology Group performance status (ECOG), age and bulky disease presence. These predictors were dichotomized (ECOG ≥ 1, age ≥ 70, bulk ≥ 7.5) to create a novel four-level score. This score predicted 3-year OS of 94.0%, 77.4%, 62.7% and 35.4% in the low-, low-intermediate, high-intermediate and high-risk groups, respectively (P<0.001). Further, a three-level score was tested which stratifies the population better (3-year OS: 91.9%, 67.2%, 36.2% in the low, intermediate and high-risk groups, respectively) but is more difficult to interpret. Both the 3- and 4-level scores were compared to standard scoring systems and, in our population, were shown to be superior in terms of patients risk stratification with respect to 3-year OS prediction. The results were successfully validated on an independent cohort of 162 patients of similar group characteristics. The prognostic role of baseline ALC, AMC or their ratio (LMR) was not confirmed in the multivariate context in elderly population with DLBCL treated with R-CHOP. The newly proposed age-specific index stratifies the elderly population into risk groups more precisely than the conventional IPI and its existing variants.

Melanoma inhibiting activity protein (MIA), beta-2 microglobulin and lactate dehydrogenase (LDH) in metastatic melanoma.

PubMed

Cao, M González; Auge, J M; Molina, R; Martí, R; Carrera, C; Castel, T; Vilella, R; Conill, C; Sánchez, M; Malvehy, J; Puig, S

2007-01-01

Serum levels of melanoma markers may have a role in monitoring disease evolution in metastatic melanoma. Serial measurements of melanoma inhibiting activity protein (MIA), lactate dehydrogenase (LDH), S-100 and beta2-microglubulin were obtained from 42 metastatic melanoma patients during their biochemotherapy treatment. High pre-treatment serum levels of S-100, LDH, MIA and P2-microglobulin were detected in 50%, 57%, 50% and 24% of the patients, respectively. Only S-100 had prognostic significance for both disease-free (p=0.011) and overall survival (p=0.021). In patients who responded to treatment, S-100 levels decreased significantly from pre-treatment to the time of response (p = 0.050). When patients progressed, levels of MIA and P2-microglobulin increased significantly (p =0.028 and p =0.030, respectively). Correlation with disease evolution was found for S-100, MIA and P2-microglobulin levels. Despite the small sample size of the study, S-100 was a significant prognostic marker for overall survival and disease-free survival.

Diagnostic and Prognostic Significance of Serum and Tissue Galectin 3 Expression in Patients with Carcinoma of the Bladder

PubMed Central

Gendy, Hoda El; Madkour, Bothina; Abdelaty, Sara; Essawy, Fayza; Khattab, Dina; Hammam, Olfat; Nour, Hani H.

2014-01-01

Background Galectins are group of proteins found in the cytoplasm, nucleus, cell surface and extracellular matrix. Galectin 3 (Gal-3) displays pathological expression in a variety of processes such as tumorigenesis. Patients and Method 70 patients classified into the control group, cystitis group, transitional cell carcinoma group, and squamous cell carcinoma group were enrolled in this study which aimed to detect the serum level and the intensity of tissue expression of Gal-3. Results Both serum level and tissue expression of Gal-3 were statistically higher in bladder cancer patients compared to the other groups. Gal-3 level expression increased from low to high grade urothelial tumors, with a statistically significant increase of its level and expression between muscle invasive and non-muscle invasive Ta urothelial tumors. Conclusion The serum Gal-3 level is sensitive and specific for the diagnosis of bladder cancer. The prognostic significance of tissue expression is to be confirmed. PMID:26195948

Plasma insulin-like growth factors, insulin-like binding protein-3, and outcome in metastatic colorectal cancer: results from intergroup trial N9741.

PubMed

Fuchs, Charles S; Goldberg, Richard M; Sargent, Daniel J; Meyerhardt, Jeffrey A; Wolpin, Brian M; Green, Erin M; Pitot, Henry C; Pollak, Michael

2008-12-15

Insulin-like growth factor (IGF)-I and IGF-II stimulate neoplastic cell growth and inhibit apoptosis, whereas IGF-binding protein-3 (IGFBP-3) inhibits the bioavailability of IGF-I and has independent proapoptotic activity. We examined the influence of baseline plasma levels of IGF-I, IGF-II, IGFBP-3, and C-peptide on outcome among patients receiving first-line chemotherapy for metastatic colorectal cancer. The plasma levels of IGF-I, IGF-II, IGFBP-3, and C-peptide as well as data on prognostic factors and body size were measured at baseline among 527 patients participating in a randomized trial of first-line chemotherapy for metastatic colorectal cancer. Higher baseline plasma IGFBP-3 levels were associated with a significantly greater chemotherapy response rate (P = 0.03) after adjusting for other prognostic factors, whereas neither IGF-I nor IGF-II levels significantly predicted tumor response. Higher levels of IGF-I, IGF-II, and IGFBP-3 were all univariately associated with improved overall survival (P = 0.0001 for all). In a model that mutually adjusted for IGF-I and IGFBP-3, as well as other prognostic factors, increasing baseline-circulating IGFBP-3 was associated with a significantly longer time to tumor progression (P = 0.03), whereas circulating IGF-I was not associated with disease progression (P = 0.95). Levels of C-peptide were not associated with any measure of patient outcome. Among colorectal cancer patients receiving first-line chemotherapy, increasing levels of IGFBP-3, an endogenous antagonist to IGF-I, are associated with an improved objective treatment response and a prolonged time to cancer progression. The IGF pathway may represent an important target for future treatment strategies.

Serum levels of interleukin-9 correlate with negative prognostic factors in extranodal NK/T-cell lymphoma.

PubMed

Zhang, Jing; Wang, Wei-da; Geng, Qi-Rong; Wang, Liang; Chen, Xiao-Qin; Liu, Cheng-Cheng; Lv, Yue

2014-01-01

Interleukin-9 (IL-9) is more functionally diverse than previously expected, especially with regards to lymphomagenesis. However, the relationship between IL-9 and the clinicopathological features of extranodal NK/T-cell lymphoma is less well established. Patients with this lymphoma in Sun Yat-Sen University Cancer Center between January 2003 and March 2013 were systematically reviewed in an intention-to-treat analysis. Baseline serum IL-9 levels were determined using sandwich enzyme-linked immunosorbent assays. A total of seventy-four patients were enrolled in this study. The mean concentration of serum IL-9 for all patients was 6.48 pg/mL (range: 1.38-51.87 pg/mL). Age, B symptoms and local lymph node involvement were found to be related to high serum IL-9 levels. Patients with low IL-9 levels tended to have higher rates of complete remission. Notably, the median progression-free survival (PFS) and overall survival (OS) were longer in the low IL-9 level group than in the high IL-9 level group (PFS: 68.7 months vs. 28.3 months, P<0.001; OS: 86 months vs. 42.8 months, P = 0.001). Multivariate analysis revealed independent prognostic factors for PFS. Similarly, high IL-9 levels (P = 0.003) and old age (P = 0.007) were independently predictive of shorter OS. Serum IL-9 is closely related to several clinical features, such as age, B symptoms and local lymph node involvement. It can also be a significant independent prognostic factor for extranodal NK/T-cell lymphoma, which suggests a role for IL-9 in the pathogenesis of this disease and offers new insight into potential therapeutic strategies.

Circulating anti-mullerian hormone as predictor of ovarian response to clomiphene citrate in women with polycystic ovary syndrome.

PubMed

Xi, Wenyan; Yang, Yongkang; Mao, Hui; Zhao, Xiuhua; Liu, Ming; Fu, Shengyu

2016-02-11

To investigate the impact of high circulating AMH on the outcome of CC ovulation induction in women with PCOS. This prospective cohort observational study included 81 anovulatory women with PCOS who underwent 213 cycles of CC ovarian stimulation. Serum AMH concentrations were measured on cycle day 3 before the commencement of CC in the first cycle, which were compared between responders and CC-resistant anovulation (CRA). Logistic regression analysis was applied to study the value of serum AMH for the prediction of ovarian responsiveness to CC stimulation. The receiver-operating characteristic (ROC) curve was used to evaluate the prognostic value of circulating AMH. Serum AMH levels. Women who ovulated after CC therapy had a significantly lower AMH compared with the CRA (5.34 ± 1.97 vs.7.81 ± 3.49, P < 0.001). There was a significant gradient increase of serum AMH levels with the increasing dose of CC required to achieve ovulation (P < 0.05). In multivariate logistic regression analysis, AMH was an independent predictor of ovulation induction by CC in PCOS patients. ROC curve analysis showed AMH to be a useful predictor of ovulation induction by CC in PCOS patients, having 92 % specificity and 65 % sensitivity when the threshold AMH concentration was 7.77 ng/ml. Serum AMH may be clinically useful to predict which PCOS women are more likely to respond to CC treatment and thus to direct the selection of protocols of ovulation induction.

Prognostic implications of stress hyperglycemia in acute ST elevation myocardial infarction. Prospective observational study.

PubMed

Sanjuán, Rafael; Núñez, Julio; Blasco, M Luisa; Miñana, Gema; Martínez-Maicas, Helena; Carbonell, Nieves; Palau, Patricia; Bodí, Vicente; Sanchis, Juan

2011-03-01

In patients with acute myocardial infarction, elevation of plasma glucose levels is associated with worse outcomes. The aim of this study was to evaluate the association between stress hyperglycemia and in-hospital mortality in patients with acute myocardial infarction with ST-segment elevation (STEMI). We analyzed 834 consecutive patients admitted for STEMI to the Coronary Care Unit of our center. Association between admission glucose and mortality was assessed with Cox regression analysis. Discriminative accuracy of the multivariate model was assessed by Harrell's C statistic. Eighty-nine (10.7%) patients died during hospitalization. Optimal threshold glycemia level of 140mg/dl on admission to predict mortality was obtained by ROC curves. Those who presented glucose ≥140mg/dl showed higher rates of malignant ventricular tachyarrhythmias (28% vs. 18%, P=.001), complicative bundle branch block (5% vs. 2%, P=.005), new atrioventricular block (9% vs. 5%, P=.05) and in-hospital mortality (15% vs. 5%, P<.001). Multivariate analysis showed that those with glycemia ≥140mg/dl exhibited a 2-fold increase of in-hospital mortality risk (95% CI: 1.2-3.5, P=.008) irrespective of diabetes mellitus status (P-value for interaction=0.487 and 0.653, respectively). Stress hyperglycemia on admission is a predictor of mortality and arrhythmias in patients with STEMI and could be used in the stratification of risk in these patients. Copyright © 2010 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

A novel threshold criterion in transcranial motor evoked potentials during surgery for gliomas close to the motor pathway.

PubMed

Abboud, Tammam; Schaper, Miriam; Dührsen, Lasse; Schwarz, Cindy; Schmidt, Nils Ole; Westphal, Manfred; Martens, Tobias

2016-10-01

OBJECTIVE Warning criteria for monitoring of motor evoked potentials (MEP) after direct cortical stimulation during surgery for supratentorial tumors have been well described. However, little is known about the value of MEP after transcranial electrical stimulation (TES) in predicting postoperative motor deficit when monitoring threshold level. The authors aimed to evaluate the feasibility and value of this method in glioma surgery by using a new approach for interpreting changes in threshold level involving contra- and ipsilateral MEP. METHODS Between November 2013 and December 2014, 93 patients underwent TES-MEP monitoring during resection of gliomas located close to central motor pathways but not involving the primary motor cortex. The MEP were elicited by transcranial repetitive anodal train stimulation. Bilateral MEP were continuously evaluated to assess percentage increase of threshold level (minimum voltage needed to evoke a stable motor response from each of the muscles being monitored) from the baseline set before dural opening. An increase in threshold level on the contralateral side (facial, arm, or leg muscles contralateral to the affected hemisphere) of more than 20% beyond the percentage increase on the ipsilateral side (facial, arm, or leg muscles ipsilateral to the affected hemisphere) was considered a significant alteration. Recorded alterations were subsequently correlated with postoperative neurological deterioration and MRI findings. RESULTS TES-MEP could be elicited in all patients, including those with recurrent glioma (31 patients) and preoperative paresis (20 patients). Five of 73 patients without preoperative paresis showed a significant increase in threshold level, and all of them developed new paresis postoperatively (transient in 4 patients and permanent in 1 patient). Eight of 20 patients with preoperative paresis showed a significant increase in threshold level, and all of them developed postoperative neurological deterioration (transient in 4 patients and permanent in 4 patients). In 80 patients no significant change in threshold level was detected, and none of them showed postoperative neurological deterioration. The specificity and sensitivity in this series were estimated at 100%. Postoperative MRI revealed gross-total tumor resection in 56 of 82 patients (68%) in whom complete tumor resection was attainable; territorial ischemia was detected in 4 patients. CONCLUSIONS The novel threshold criterion has made TES-MEP a useful method for predicting postoperative motor deficit in patients who undergo glioma surgery, and has been feasible in patients with preoperative paresis as well as in patients with recurrent glioma. Including contra- and ipsilateral changes in threshold level has led to a high sensitivity and specificity.

Development and External Validation of a Prognostic Nomogram for Metastatic Uveal Melanoma

PubMed Central

Valpione, Sara; Moser, Justin C.; Parrozzani, Raffaele; Bazzi, Marco; Mansfield, Aaron S.; Mocellin, Simone; Pigozzo, Jacopo; Midena, Edoardo; Markovic, Svetomir N.; Aliberti, Camillo; Campana, Luca G.; Chiarion-Sileni, Vanna

2015-01-01

Background Approximately 50% of patients with uveal melanoma (UM) will develop metastatic disease, usually involving the liver. The outcome of metastatic UM (mUM) is generally poor and no standard therapy has been established. Additionally, clinicians lack a validated prognostic tool to evaluate these patients. The aim of this work was to develop a reliable prognostic nomogram for clinicians. Patients and Methods Two cohorts of mUM patients, from Veneto Oncology Institute (IOV) (N=152) and Mayo Clinic (MC) (N=102), were analyzed to develop and externally validate, a prognostic nomogram. Results The median survival of mUM was 17.2 months in the IOV cohort and 19.7 in the MC cohort. Percentage of liver involvement (HR 1.6), elevated levels of serum LDH (HR 1.6), and a WHO performance status=1 (HR 1.5) or 2–3 (HR 4.6) were associated with worse prognosis. Longer disease-free interval from diagnosis of UM to that of mUM conferred a survival advantage (HR 0.9). The nomogram had a concordance probability of 0.75 (SE .006) in the development dataset (IOV), and 0.80 (SE .009) in the external validation (MC). Nomogram predictions were well calibrated. Conclusions The nomogram, which includes percentage of liver involvement, LDH levels, WHO performance status and disease free-interval accurately predicts the prognosis of mUM and could be useful for decision-making and risk stratification for clinical trials. PMID:25780931

High anaplastic lymphoma kinase immunohistochemical staining in neuroblastoma and ganglioneuroblastoma is an independent predictor of poor outcome.

PubMed

Duijkers, Floor A M; Gaal, José; Meijerink, Jules P P; Admiraal, Pieter; Pieters, Rob; de Krijger, Ronald R; van Noesel, Max M

2012-03-01

Anaplastic lymphoma kinase (ALK) mutations occur in 3% to 11% of neuroblastoma (NBL) cases and are associated with high ALK levels. However, high ALK levels appear to be a mutation-independent hallmark of NBL. Evidence about the prognostic relevance of ALK mutations and ALK tumor positivity in patients with NBL has been inconclusive. In this study, we investigated the prognostic relevance of ALK positivity by IHC and ALK mutation status by PCR sequencing in 71 NBL, 12 ganglioneuroblastoma (GNBL), and 20 ganglioneuroma samples in a multivariate model. ALK mutations were present in 2 of 72 NBL and 2 of 12 GNBL samples, which all contained many ALK-positive cells (>50%). In addition, half of all NBL samples showed ALK positivity in most (>50%) of tumor cells, whereas half of the GNBL showed staining in <20% of the tumor cells. In most ganglioneuroma samples, a low percentage of tumor cells stained positive for ALK, which mainly involved ganglion cells. Higher percentages of ALK-positive cells in NBL and GNBL patient samples correlated with inferior survival in univariate and multivariate analyses with established prognostic factors, such as stage, age, and MYCN status. In conclusion, ALK positivity by IHC is an independent, poor prognostic factor in patients with GNBL and NBL. ALK IHC is an easy test suitable for future risk stratification in patients with NBL and GNBL. Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Outcome and prognostic factors in metastatic urothelial carcinoma patients receiving second-line chemotherapy: an analysis of real-world clinical practice data in Japan.

PubMed

Matsumoto, Ryuji; Abe, Takashige; Ishizaki, Junji; Kikuchi, Hiroshi; Harabayashi, Toru; Minami, Keita; Sazawa, Ataru; Mochizuki, Tango; Akino, Tomoshige; Murakumo, Masashi; Osawa, Takahiro; Maruyama, Satoru; Murai, Sachiyo; Shinohara, Nobuo

2018-06-25

The objective of the present study was to investigate the survival outcome and prognostic factors of metastatic urothelial carcinoma patients treated with second-line systemic chemotherapy in real-world clinical practice. Overall, 114 patients with metastatic urothelial carcinoma undergoing second-line systemic chemotherapy were included in this retrospective analysis. The dominant second-line chemotherapy was a paclitaxel-based combination regimen (60%, 68/114). We assessed the progression-free survival and overall survival times using the Kaplan-Meier method. The Cox proportional hazards model was applied to identify the factors affecting overall survival. The median progression-free survival and overall survival times were 4 and 9 months, respectively. In the multivariate analysis, an Eastern Cooperative Oncology Group performance status score greater than 0 at presentation, C-reactive protein level ≧1 mg/dl and poor response to prior chemotherapy were adverse prognostic indicators. Patients with 0, 1, 2 and 3 of those risk factors had a median overall survival of 17, 12, 7 and 3 months, respectively. The Eastern Cooperative Oncology Group performance status at presentation, C-reactive protein level and response to prior chemotherapy were prognostic factors for metastatic urothelial carcinoma patients undergoing second-line chemotherapy. In the future, this information might help guide the choice of salvage treatment, such as second-line chemotherapy or immune checkpoint inhibitors, after the failure of first-line chemotherapy.

Dynamic Stress Testing Is Unnecessary for Unimalleolar Supination-External Rotation Ankle Fractures with Minimal Fracture Displacement on Lateral Radiographs.

PubMed

Nortunen, Simo; Leskelä, Hannu-Ville; Haapasalo, Heidi; Flinkkilä, Tapio; Ohtonen, Pasi; Pakarinen, Harri

2017-03-15

This study aimed to identify factors from standard radiographs that contributed to the stability of the ankle mortise in patients with isolated supination-external rotation fractures of the lateral malleolus (OTA/AO 44-B). Non-stress radiographs of the mortise and lateral views, without medial clear space widening or incongruity, were prospectively collected for 286 consecutive patients (mean age, 45 years [range, 16 to 85 years]), including 144 female patients (mean age, 50 years [range, 17 to 85 years]) and 142 male patients (mean age, 40 years [range, 16 to 84 years]) from 2 trauma centers. The radiographs were analyzed for fracture morphology by 2 orthopaedic surgeons, who were blinded to each other's measurements and to the results of external rotation stress radiographs (the reference for stability). Factors significantly associated with ankle mortise stability were tested in multiple logistic regression. Receiver operating characteristic analyses were performed for continuous variables to determine optimal thresholds. A sensitivity of >90% was used as the criterion for an optimal threshold. According to external rotation stress radiographs, 217 patients (75.9%) had a stable injury, defined as that with a medial clear space of <5 mm. Independent factors that predicted stable ankle mortise were female sex (odds ratio [OR], 2.5 [95% confidence interval (CI), 1.4 to 4.6]), a posterior diastasis of <2 mm (corresponding with a sensitivity of 0.94 and specificity of 0.39) on lateral radiographs (OR, 10.8 [95% CI, 3.7 to 31.5]), and only 2 fracture fragments (OR, 7.3 [95% CI, 2.1 to 26.3]). When the posterior diastasis was <2 mm and only 2 fracture fragments were present, the probability of a stable ankle mortise was 0.98 for 48 female patients (16.8%) and 0.94 for 37 male patients (12.9%). Patients with noncomminuted lateral malleolar fractures (85 patients [29.7%]) could be diagnosed with a stable ankle mortise without further stress testing, when the fracture line widths were <2 mm on lateral radiographs. Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

The prognostic value of preoperative inflammation-based prognostic scores and nutritional status for overall survival in resected patients with nonmetastatic Siewert type II/III adenocarcinoma of esophagogastric junction.

PubMed

Zhang, Lixiang; Su, Yezhou; Chen, Zhangming; Wei, Zhijian; Han, Wenxiu; Xu, Aman

2017-07-01

Immune and nutritional status of patients have been reported to predict postoperative complications, recurrence, and prognosis of patients with cancer. Therefore, this retrospective study aimed to explore the prognostic value of preoperative inflammation-based prognostic scores [neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR)] and nutritional status [prognostic nutritional index (PNI), body mass index (BMI), hemoglobin, albumin, and prealbumin] for overall survival (OS) in adenocarcinoma of esophagogastric junction (AEG) patients. A total of 355 patients diagnosed with Siewert type II/III AEG and underwent surgery between October 2010 and December 2011 were followed up until October 2016. Receiver operating characteristic (ROC) curve analysis was used to determine the cutoff values of NLR, PLR, and PNI. Kaplan-Meier curves and Cox regression analyses were used to calculate the OS characteristics. The ideal cutoff values for predicting OS were 3.5 for NLR, 171 for PLR, and 51.3 for PNI according to the ROC curve. The patients with hemoglobin <120 g/L (P = .001), prealbumin <180 mg/L (P = .000), PNI <51.3 (P = .010), NLR >3.5 (P = .000), PLR >171 (P = .006), and low BMI group (P = .000) had shorter OS. And multivariate survival analysis using the Cox proportional hazards model showed that the tumor-node-metastasis stage, BMI, NLR, and prealbumin levels were independent risk factors for the OS. Our study demonstrated that preoperative prealbumin, BMI, and NLR were independent prognostic factors of AEG patients.

A contemporary review of management and prognostic factors of upper tract urothelial carcinoma.

PubMed

Leow, Jeffrey J; Orsola, Anna; Chang, Steven L; Bellmunt, Joaquim

2015-04-01

Upper tract urothelial carcinoma (UTUC) accounts for <5% of all urothelial cancers. Although the main treatment is radical nephroureterectomy (NU), oncologic outcomes are not comparable to lower tract urothelial cancers. Identifying prognostic factors can help guide management and potentially improve outcomes. This article systematically reviews current literature on prognostic factors and management options for UTUC. A comprehensive literature search was performed to identify all studies examining prognostic factors and management options for UTUC. The search included the Medline, Embase, Cochrane Central Register of Controlled Trials databases, and abstracts from the American Society of Clinical Oncology meetings up to November 2014. An updated systematic review was performed. Preoperative prognostic factors for UTUC patients include age, race, performance status, obesity, smoking status, elevated fibrinogen levels, hydronephrosis, tumor size, multi-focality, location, clinical grade and previous/synchronous bladder cancer. Postoperative variables include tumor stage/grade, multifocality, nodal involvement, lympho-vascular invasion, initial ureteral location, necrosis, sessile architecture, variant histologies and presence of tissue ALDH1 and SOX2. Curative treatment of choice is NU, with lymphadenectomy conferring survival benefits. Minimally invasive surgery has equivalent oncologic and better peri-operative outcomes compared to open surgery. Conservative therapy includes adjuvant BCG and intravesical mitomycin C. Two randomized trials investigating postoperative instillation of mitomycin C suggest bladder recurrence benefits. Adjuvant chemo-radiotherapy may be useful for patients with advanced T3/4 and/or N+ disease. Gold-standard treatment for UTUC remains NU, increasingly performed using minimally invasive surgery. Nomograms including pre- and post-operative variables can aid prognostication and guide further therapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Prognostic value of combined preoperative fibrinogen and neutrophil–lymphocyte ratio in patients with hepatocellular carcinoma after liver transplantation

PubMed Central

Chen, Mao-Gen; Wang, Xiao-Ping; Ju, Wei-Qiang; Zhao, Qiang; Wu, Lin-Wei; Ren, Qing-Qi; Guo, Zhi-Yong; Wang, Dong-Ping; Zhu, Xiao-Feng; Ma, Yi; He, Xiao-Shun

2017-01-01

Objectives Elevated plasma fibrinogen (Fib) correlated with patient's prognosis in several solid tumors. However, few studies have illuminated the relationship between preoperative Fib and prognosis of HCC after liver transplantation. We aimed to clarify the prognostic value of Fib and whether the prognostic accuracy can be enhanced by the combination of Fib and neutrophil–lymphocyte ratio (NLR). Results Fib was correlated with Child-pugh stage, alpha-fetoprotein (AFP), size of largest tumor, macro- and micro-vascular invasion. Univariate analysis showed preoperative Fib, AFP, NLR, size of largest tumor, tumor number, macro- and micro- vascular invasion were significantly associated with disease-free survival (DFS) and overall survival (OS) in HCC patients with liver transplantation. After multivariate analysis, only Fib and macro-vascular invasion were independently correlated with DFS and OS. Survival analysis showed that preoperative Fib > 2.345 g/L predicted poor prognosis of patients HCC after liver transplantation. Preoperative Fib showed prognostic value in various subgroups of HCC. Furthermore, the predictive range was expanded by the combination of Fib and NLR. Materials and Methods Data were collected retrospectively from 130 HCC patients who underwent liver transplantation. Preoperative Fib, NLR and clinicopathologic variables were analyzed. The survival analysis was performed by the Kaplan-Meier method, and compared by the log-rank test. Univariate and multivariate analyses were performed to identify the prognostic factors for DFS and OS. Conclusions Preoperative Fib is an independent effective predictor of prognosis for HCC patients, higher levels of Fib predict poorer outcomes and the combination of Fib and NLR enlarges the prognostic accuracy of testing. PMID:27935864

Prognostic relevance of proliferation markers (Ki-67, PHH3) within the cross-relation of ERG translocation and androgen receptor expression in prostate cancer.

PubMed

Goltz, Diane; Montani, Matteo; Braun, Martin; Perner, Sven; Wernert, Nicolas; Jung, Klaus; Dietel, Manfred; Stephan, Carsten; Kristiansen, Glen

2015-12-01

We evaluated the prognostic value of the mitosis-associated marker phosphorylated histone H3 (PHH3) and Ki-67 in prostate cancer with respect to ERG status and androgen receptor (AR) expression.PHH3 and Ki-67 expression was immunohistochemically detected and digitally quantitated in a radical prostatectomy cohort (n = 640). The results were correlated to clinicopathological parameters including biochemical recurrence times. Prognostic values of PHH3 and Ki-67 were analysed by Cox regression and Kaplan-Meier statistics.In prostate cancer, mean Ki-67 and PHH3 rates were 3.40% (95%CI 3.16-3.63%) and 0.0152% (95%CI 0.0112-0.0191%), respectively.Ki-67 showed a significant correlation with Gleason scores, pT status, margin status, and AR expression, while PHH3 showed a significant correlation with Gleason scores and pT status. Univariate analyses for biochemical recurrence times demonstrated a significant prognostic value for median Ki-67 rate and for the PHH3 rate of the 90th percentile. Of importance, in patient subgroups stratified according to AR expression and ERG translocation, the prognostic power of proliferation markers PHH3 and Ki-67 was markedly enhanced in ERG translocation negative and high-level AR expressing ERG translocation positive prostate cancers.As expected, the proliferation markers PHH3 and Ki-67 predict adverse outcome of prostate cancer and have a particularly pronounced prognostic value in specific molecular subsets of prostate cancer (ERG- or AR+).

Sliding mode control of outbreaks of emerging infectious diseases.

PubMed

Xiao, Yanni; Xu, Xiaxia; Tang, Sanyi

2012-10-01

This paper proposes and analyzes a mathematical model of an infectious disease system with a piecewise control function concerning threshold policy for disease management strategy. The proposed models extend the classic models by including a piecewise incidence rate to represent control or precautionary measures being triggered once the number of infected individuals exceeds a threshold level. The long-term behaviour of the proposed non-smooth system under this strategy consists of the so-called sliding motion-a very rapid switching between application and interruption of the control action. Model solutions ultimately approach either one of two endemic states for two structures or the sliding equilibrium on the switching surface, depending on the threshold level. Our findings suggest that proper combinations of threshold densities and control intensities based on threshold policy can either preclude outbreaks or lead the number of infected to a previously chosen level.

Thresholds for Shifting Visually Perceived Eye Level Due to Incremental Pitches

NASA Technical Reports Server (NTRS)

Scott, Donald M.; Welch, Robert; Cohen, M. M.; Hill, Cyndi

2001-01-01

Visually perceived eye level (VPEL) was judged by subjects as they viewed a luminous grid pattern that was pitched by 2 or 5 deg increments between -20 deg and +20 deg. Subjects were dark adapted for 20 min and indicated--VPEL by directing the beam of a laser pointer to the rear wall of a 1.25 m cubic pitch box that rotated about a horizontal axis midpoint on the rear wall. Data were analyzed by ANOVA and the Tukey HSD procedure. Results showed a 10.0 deg threshold for pitches P(sub i) above the reference pitch P(sub 0), and a -10.3 deg threshold for pitches P(sub i) below-the reference-pitch P(sub 0). Threshold data for pitches P(sub i) < P(sub 0) suggest an asymmetric threshold for VPEL below and above physical eye level.

Appropriate threshold levels of cardiac beat-to-beat variation in semi-automatic analysis of equine ECG recordings.

PubMed

Flethøj, Mette; Kanters, Jørgen K; Pedersen, Philip J; Haugaard, Maria M; Carstensen, Helena; Olsen, Lisbeth H; Buhl, Rikke

2016-11-28

Although premature beats are a matter of concern in horses, the interpretation of equine ECG recordings is complicated by a lack of standardized analysis criteria and a limited knowledge of the normal beat-to-beat variation of equine cardiac rhythm. The purpose of this study was to determine the appropriate threshold levels of maximum acceptable deviation of RR intervals in equine ECG analysis, and to evaluate a novel two-step timing algorithm by quantifying the frequency of arrhythmias in a cohort of healthy adult endurance horses. Beat-to-beat variation differed considerably with heart rate (HR), and an adaptable model consisting of three different HR ranges with separate threshold levels of maximum acceptable RR deviation was consequently defined. For resting HRs <60 beats/min (bpm) the threshold level of RR deviation was set at 20%, for HRs in the intermediate range between 60 and 100 bpm the threshold was 10%, and for exercising HRs >100 bpm, the threshold level was 4%. Supraventricular premature beats represented the most prevalent arrhythmia category with varying frequencies in seven horses at rest (median 7, range 2-86) and six horses during exercise (median 2, range 1-24). Beat-to-beat variation of equine cardiac rhythm varies according to HR, and threshold levels in equine ECG analysis should be adjusted accordingly. Standardization of the analysis criteria will enable comparisons of studies and follow-up examinations of patients. A small number of supraventricular premature beats appears to be a normal finding in endurance horses. Further studies are required to validate the findings and determine the clinical significance of premature beats in horses.

Differential responses to acoustic damage and furosemide in auditory brainstem and otoacoustic emission measures

NASA Astrophysics Data System (ADS)

Mills, David M.

2003-02-01

Characteristics of distortion product otoacoustic emissions (DPOAEs) and auditory brainstem responses (ABRs) were measured in Mongolian gerbil before and after the introduction of two different auditory dysfunctions: (1) acoustic damage with a high-intensity tone, or (2) furosemide intoxication. The goal was to find emission parameters and measures that best differentiated between the two dysfunctions, e.g., at a given ABR threshold elevation. Emission input-output or ``growth'' functions were used (frequencies f1 and f2, f2/f1=1.21) with equal levels, L1=L2, and unequal levels, with L1=L2+20 dB. The best parametric choice was found to be unequal stimulus levels, and the best measure was found to be the change in the emission threshold level, Δx. The emission threshold was defined as the stimulus level required to reach a criterion emission amplitude, in this case -10 dB SPL. (The next best measure was the change in emission amplitude at high stimulus levels, specifically that measured at L1×L2=90×70 dB SPL.) For an ABR threshold shift of 20 dB or more, there was essentially no overlap in the emission threshold measures for the two conditions, sound damage or furosemide. The dividing line between the two distributions increased slowly with the change in ABR threshold, ΔABR, and was given by Δxt=0.6 ΔABR+8 dB. For a given ΔABR, if the shift in emission threshold was more than the calculated dividing line value, Δxt, the auditory dysfunction was due to acoustic damage, if less, it was due to furosemide.

NASA IVHM Technology Experiment for X-vehicles (NITEX)

NASA Technical Reports Server (NTRS)

Sandra, Hayden; Bajwa, Anupa

2001-01-01

The purpose of the NASA IVHM Technology Experiment for X-vehicles (NITEX) is to advance the development of selected IVHM technologies in a flight environment and to demonstrate the potential for reusable launch vehicle ground processing savings. The technologies to be developed and demonstrated include system-level and detailed diagnostics for real-time fault detection and isolation, prognostics for fault prediction, automated maintenance planning based on diagnostic and prognostic results, and a microelectronics hardware platform. Complete flight The Evolution of Flexible Insulation as IVHM consists of advanced sensors, distributed data acquisition, data processing that includes model-based diagnostics, prognostics and vehicle autonomy for control or suggested action, and advanced data storage. Complete ground IVHM consists of evolved control room architectures, advanced applications including automated maintenance planning and automated ground support equipment. This experiment will advance the development of a subset of complete IVHM.

Plasticity after pediatric cochlear implantation: Implication from changes in peripheral plasma level of BDNF and auditory nerve responses.

PubMed

Alemi, Razieh; Motassadi Zarandy, Masoud; Joghataei, Mohammad Taghi; Eftekharian, Ali; Zarrindast, Mohammad Reza; Vousooghi, Nasim

2018-02-01

Sensory neural hearing loss could lead to some structural and physiological changes in the auditory pathways, such as alteration in the expression of neurotrophins. These factors, especially Brain-Derived Neurotrophic Factor (BDNF), play an important role in synaptic functions and experience-related plasticity. Restoring cochlear function after hearing loss is possible through cochlear implantation (CI). Evaluation of the blood concentration changes of neurotrophins as prerequisites of plasticity could help scientists to determine the prognosis of CI as in the candidacy procedure or enhancing prosthesis function by adding the exact needed amount of BDNF to the electrode array. Here we have studied the plasma BDNF concentration before CI surgery and 6 months after using CI device in 15 pediatric CI recipients and compared this level with changes of BDNF concentration in 10 children who were using hearing aid (H.A). In addition, we searched for a possible correlation between post-surgery plasma BDNF concentration and electrical compound action potential (ECAP) and comfort-level (C-level) thresholds. Plasma BDNF concentration in children with CI increased significantly after CI surgery, while this difference in H.A group was not significant. Analysis of repeated measures of ECAP and C-level thresholds in CI group showed that there were some kinds of steadiness during follow- up sessions for ECAP thresholds in basal and E16 of middle electrodes, whereas C-level thresholds for all selected electrodes increased significantly up to six months follow-up. Interestingly, we did not find any significant correlation between post-surgery plasma BDNF concentration and ECAP or C-level threshold changes. It is concluded that changes in C-level threshold and steady state of ECAP thresholds and significant changes in BDNF concentration could be regarded as an indicator of experienced-related plasticity after CI stimulation. Copyright © 2017 Elsevier B.V. All rights reserved.

Alkaline phosphatase: the next independent predictor of the poor 90-day outcome in alcoholic hepatitis.

PubMed

Kasztelan-Szczerbinska, Beata; Slomka, Maria; Celinski, Krzysztof; Szczerbinski, Mariusz

2013-01-01

Determination of risk factors relevant to 90-day prognosis in AH. Comparison of the conventional prognostic models such as Maddrey's modified discriminant function (mDF) and Child-Pugh-Turcotte (CPT) score with newer ones: the Glasgow Alcoholic Hepatitis Score (GAHS); Age, Bilirubin, INR, Creatinine (ABIC) score, Model for End-Stage Liver Disease (MELD), and MELD-Na in the death prediction. The clinical and laboratory variables obtained at admission were assessed. The mDF, CPT, GAHS, ABIC, MELD, and MELD-Na scores' different areas under the curve (AUCs) and the best threshold values were compared. Logistic regression was used to assess predictors of the 90-day outcome. One hundred sixteen pts fulfilled the inclusion criteria. Twenty (17.4%) pts died and one underwent orthotopic liver transplantation (OLT) within 90 days of follow-up. No statistically significant differences in the models' performances were found. Multivariate logistic regression identified CPT score, alkaline phosphatase (AP) level higher than 1.5 times the upper limit of normal (ULN), and corticosteroids (CS) nonresponse as independent predictors of mortality. The CPT score, AP > 1.5 ULN, and the CS nonresponse had an independent impact on the 90-day survival in AH. Accuracy of all studied scoring systems was comparable.

Improving efficacy of metastatic tumor segmentation to facilitate early prediction of ovarian cancer patients' response to chemotherapy

NASA Astrophysics Data System (ADS)

Danala, Gopichandh; Wang, Yunzhi; Thai, Theresa; Gunderson, Camille C.; Moxley, Katherine M.; Moore, Kathleen; Mannel, Robert S.; Cheng, Samuel; Liu, Hong; Zheng, Bin; Qiu, Yuchen

2017-02-01

Accurate tumor segmentation is a critical step in the development of the computer-aided detection (CAD) based quantitative image analysis scheme for early stage prognostic evaluation of ovarian cancer patients. The purpose of this investigation is to assess the efficacy of several different methods to segment the metastatic tumors occurred in different organs of ovarian cancer patients. In this study, we developed a segmentation scheme consisting of eight different algorithms, which can be divided into three groups: 1) Region growth based methods; 2) Canny operator based methods; and 3) Partial differential equation (PDE) based methods. A number of 138 tumors acquired from 30 ovarian cancer patients were used to test the performance of these eight segmentation algorithms. The results demonstrate each of the tested tumors can be successfully segmented by at least one of the eight algorithms without the manual boundary correction. Furthermore, modified region growth, classical Canny detector, and fast marching, and threshold level set algorithms are suggested in the future development of the ovarian cancer related CAD schemes. This study may provide meaningful reference for developing novel quantitative image feature analysis scheme to more accurately predict the response of ovarian cancer patients to the chemotherapy at early stage.

NMR metabolomic analysis of dairy cows reveals milk glycerophosphocholine to phosphocholine ratio as prognostic biomarker for risk of ketosis.

PubMed

Klein, Matthias S; Buttchereit, Nina; Miemczyk, Sebastian P; Immervoll, Ann-Kathrin; Louis, Caridad; Wiedemann, Steffi; Junge, Wolfgang; Thaller, Georg; Oefner, Peter J; Gronwald, Wolfram

2012-02-03

Ketosis is a common metabolic disease in dairy cows. Diagnostic markers for ketosis such as acetone and beta-hydroxybutyric acid (BHBA) are known, but disease prediction remains an unsolved challenge. Milk is a steadily available biofluid and routinely collected on a daily basis. This high availability makes milk superior to blood or urine samples for diagnostic purposes. In this contribution, we show that high milk glycerophosphocholine (GPC) levels and high ratios of GPC to phosphocholine (PC) allow for the reliable selection of healthy and metabolically stable cows for breeding purposes. Throughout lactation, high GPC values are connected with a low ketosis incidence. During the first month of lactation, molar GPC/PC ratios equal or greater than 2.5 indicate a very low risk for developing ketosis. This threshold was validated for different breeds (Holstein-Friesian, Brown Swiss, and Simmental Fleckvieh) and for animals in different lactations, with observed odds ratios between 1.5 and 2.38. In contrast to acetone and BHBA, these measures are independent of the acute disease status. A possible explanation for the predictive effect is that GPC and PC are measures for the ability to break down phospholipids as a fatty acid source to meet the enhanced energy requirements of early lactation.

The Neural Substrate for Binaural Masking Level Differences in the Auditory Cortex

PubMed Central

Gilbert, Heather J.; Krumbholz, Katrin; Palmer, Alan R.

2015-01-01

The binaural masking level difference (BMLD) is a phenomenon whereby a signal that is identical at each ear (S0), masked by a noise that is identical at each ear (N0), can be made 12–15 dB more detectable by inverting the waveform of either the tone or noise at one ear (Sπ, Nπ). Single-cell responses to BMLD stimuli were measured in the primary auditory cortex of urethane-anesthetized guinea pigs. Firing rate was measured as a function of signal level of a 500 Hz pure tone masked by low-passed white noise. Responses were similar to those reported in the inferior colliculus. At low signal levels, the response was dominated by the masker. At higher signal levels, firing rate either increased or decreased. Detection thresholds for each neuron were determined using signal detection theory. Few neurons yielded measurable detection thresholds for all stimulus conditions, with a wide range in thresholds. However, across the entire population, the lowest thresholds were consistent with human psychophysical BMLDs. As in the inferior colliculus, the shape of the firing-rate versus signal-level functions depended on the neurons' selectivity for interaural time difference. Our results suggest that, in cortex, BMLD signals are detected from increases or decreases in the firing rate, consistent with predictions of cross-correlation models of binaural processing and that the psychophysical detection threshold is based on the lowest neural thresholds across the population. PMID:25568115

Thresholds of sea-level rise rate and sea-level acceleration rate in a vulnerable coastal wetland

NASA Astrophysics Data System (ADS)

Wu, W.; Biber, P.; Bethel, M.

2017-12-01

Feedback among inundation, sediment trapping, and vegetation productivity help maintain coastal wetlands facing sea-level rise (SLR). However, when the SLR rate exceeds a threshold, coastal wetlands can collapse. Understanding the threshold help address the key challenge in ecology - nonlinear response of ecosystems to environmental change, and promote communication between ecologists and policy makers. We studied the threshold of SLR rate and developed a new threshold of SLR acceleration rate on sustainability of coastal wetlands as SLR is likely to accelerate due to the enhanced anthropogenic forces. We developed a mechanistic model to simulate wetland change and derived the SLR thresholds for Grand Bay, MS, a micro-tidal estuary with limited upland freshwater and sediment input in the northern Gulf of Mexico. The new SLR acceleration rate threshold complements the threshold of SLR rate and can help explain the temporal lag before the rapid decline of wetland area becomes evident after the SLR rate threshold is exceeded. Deriving these two thresholds depends on the temporal scale, the interaction of SLR with other environmental factors, and landscape metrics, which have not been fully accounted for before this study. The derived SLR rate thresholds range from 7.3 mm/yr to 11.9 mm/yr. The thresholds of SLR acceleration rate are 3.02×10-4 m/yr2 and 9.62×10-5 m/yr2 for 2050 and 2100 respectively. Based on the thresholds developed, predicted SLR that will adversely impact the coastal wetlands in Grand Bay by 2100 will fall within the likely range of SLR under a high warming scenario (RCP8.5), and beyond the very likely range under a low warming scenario (RCP2.6 or 3), highlighting the need to avoid the high warming scenario in the future if these marshes are to be preserved.

Threshold responses of Amazonian stream fishes to timing and extent of deforestation.

PubMed

Brejão, Gabriel L; Hoeinghaus, David J; Pérez-Mayorga, María Angélica; Ferraz, Silvio F B; Casatti, Lilian

2017-12-06

Deforestation is a primary driver of biodiversity change through habitat loss and fragmentation. Stream biodiversity may not respond to deforestation in a simple linear relationship. Rather, threshold responses to extent and timing of deforestation may occur. Identification of critical deforestation thresholds is needed for effective conservation and management. We tested for threshold responses of fish species and functional groups to degree of watershed and riparian zone deforestation and time since impact in 75 streams in the western Brazilian Amazon. We used remote sensing to assess deforestation from 1984 to 2011. Fish assemblages were sampled with seines and dip nets in a standardized manner. Fish species (n = 84) were classified into 20 functional groups based on ecomorphological traits associated with habitat use, feeding, and locomotion. Threshold responses were quantified using threshold indicator taxa analysis. Negative threshold responses to deforestation were common and consistently occurred at very low levels of deforestation (<20%) and soon after impact (<10 years). Sensitive species were functionally unique and associated with complex habitats and structures of allochthonous origin found in forested watersheds. Positive threshold responses of species were less common and generally occurred at >70% deforestation and >10 years after impact. Findings were similar at the community level for both taxonomic and functional analyses. Because most negative threshold responses occurred at low levels of deforestation and soon after impact, even minimal change is expected to negatively affect biodiversity. Delayed positive threshold responses to extreme deforestation by a few species do not offset the loss of sensitive taxa and likely contribute to biotic homogenization. © 2017 Society for Conservation Biology.

Quantification of plasma exosome is a potential prognostic marker for esophageal squamous cell carcinoma.

PubMed

Matsumoto, Yasunori; Kano, Masayuki; Akutsu, Yasunori; Hanari, Naoyuki; Hoshino, Isamu; Murakami, Kentaro; Usui, Akihiro; Suito, Hiroshi; Takahashi, Masahiko; Otsuka, Ryota; Xin, Hu; Komatsu, Aki; Iida, Keiko; Matsubara, Hisahiro

2016-11-01

Exosomes play important roles in cancer progression. Although its contents (e.g., proteins and microRNAs) have been focused on in cancer research, particularly as potential diagnostic markers, the exosome behavior and methods for exosome quantification remain unclear. In the present study, we analyzed the tumor-derived exosome behavior and assessed the quantification of exosomes in patient plasma as a biomarker for esophageal squamous cell carcinoma (ESCC). A CD63-GFP expressing human ESCC cell line (TE2-CD63-GFP) was made by transfection, and mouse subcutaneous tumor models were established. Fluorescence imaging was performed on tumors and plasma exosomes harvested from mice. GFP-positive small vesicles were confirmed in the plasma obtained from TE2-CD63-GFP tumor-bearing mice. Patient plasma was collected in Chiba University Hospital (n=86). Exosomes were extracted from 100 µl of the plasma and quantified by acetylcholinesterase (AChE) activity. The relationship between exosome quantification and the patient clinical characteristics was assessed. The quantification of exosomes isolated from the patient plasma revealed that esophageal cancer patients (n=66) expressed higher exosome levels than non-malignant patients (n=20) (P=0.0002). Although there was no correlation between the tumor progression and the exosome levels, exosome number was the independent prognostic marker and low levels of exosome predicted a poor prognosis (P=0.03). In conclusion, exosome levels may be useful as an independent prognostic factor for ESCC patients.

IKZF1 expression is a prognostic marker in newly diagnosed standard-risk multiple myeloma treated with lenalidomide and intensive chemotherapy: a study of the German Myeloma Study Group (DSMM).

PubMed

Krönke, J; Kuchenbauer, F; Kull, M; Teleanu, V; Bullinger, L; Bunjes, D; Greiner, A; Kolmus, S; Köpff, S; Schreder, M; Mügge, L-O; Straka, C; Engelhardt, M; Döhner, H; Einsele, H; Bassermann, F; Bargou, R; Knop, S; Langer, C

2017-06-01

Lenalidomide is an immunomodulatory compound with high clinical activity in multiple myeloma. Lenalidomide binding to the Cereblon (CRBN) E3 ubiquitin ligase results in targeted ubiquitination and degradation of the lymphoid transcription factors Ikaros (IKZF1) and Aiolos (IKZF3) leading to growth inhibition of multiple myeloma cells. Recently, Basigin (BSG) was identified as another protein regulated by CRBN that is involved in the activity of lenalidomide. Here, we analyzed the prognostic value of IKZF1, IKZF3, CRBN and BSG mRNA expression levels in pretreatment plasma cells from 60 patients with newly diagnosed multiple myeloma uniformly treated with lenalidomide in combination with intensive chemotherapy within a clinical trial. We found that IKZF1 mRNA expression levels are significantly associated with progression-free survival (PFS). Patients in the lowest quartile (Q1) of IKZF1 expression had a superior PFS compared with patients in the remaining quartiles (Q2-Q4; 3-year PFS of 86 vs 51%, P=0.01). This translated into a significant better overall survival (100 vs 74%, P=0.03). Subgroup analysis revealed a significant impact of IKZF1, IKZF3 and BSG expression levels on PFS in cytogenetically defined standard-risk but not high-risk patients. Our data suggest a prognostic role of IKZF1, IKZF3 and BSG expression levels in lenalidomide-treated multiple myeloma.

Evaluation of nuclear chromatin using grayscale intensity and thresholded percentage area in liquid-based cervical cytology.

PubMed

Lee, Hyekyung; Han, Myungein; Yoo, Taejo; Jung, Chanho; Son, Hyun-Jin; Cho, Migyung

2018-05-01

Development of computerized image analysis techniques has opened up the possibility for the quantitative analysis of nuclear chromatin in pathology. We hypothesized that the features extracted from digital images could be used to determine specific cytomorphological findings for nuclear chromatin that may be applicable for establishing a medical diagnosis. Three parameters were evaluated from nuclear chromatin images obtained from the liquid-based cervical cytology samples of patients with biopsy-proven high-grade squamous intraepithelial lesion (HGSIL), and compared between non-neoplastic squamous epithelia and dysplastic epithelia groups: (1) standard deviation (SD) of the grayscale intensity; (2) difference between the maximum and minimum grayscale intensity (M-M); and (3) thresholded area percentage. Each parameter was evaluated at the mean, mean-1SD, and mean-2SD thresholding intensity levels. Between the mean and mean-1SD levels, the thresholded nuclear chromatin pattern was most similar to the chromatin granularity of the unthresholded grayscale images. The SD of the gray intensity and the thresholded area percentage differed significantly between the non-neoplastic squamous epithelia and dysplastic epithelia of HGSIL images at all three thresholding intensity levels (mean, mean-1SD, and mean-2SD). However, the M-M significantly differed between the two sample types for only two of the thresholding intensity levels (mean-1SD and mean-2SD). The digital parameters SD and M-M of the grayscale intensity, along with the thresholded area percentage could be useful in automated cytological evaluations. Further studies are needed to identify more valuable parameters for clinical application. © 2018 Wiley Periodicals, Inc.

Clinical Features and Prognostic Factors of Hodgkin's Lymphoma: A Single Center Experience.

PubMed

Kılıçkap, Saadettin; Barışta, Ibrahim; Ulger, Sükran; Celik, Ismail; Selek, Uğur; Yıldız, Ferah; Kars, Ayşe; Ozışık, Yavuz; Tekuzman, Gülten

2013-06-01

Hodgkin's lymphoma (HL) is a B cell lymphoma characterized by the presence of Reed-Sternberg cells. HL comprises 1% of all cancer cases and 14% of all lymphoma cases. We designed a retrospective study to investigate the clinical features and prognostic factors of HL patients diagnosed at an experienced oncology centre. Retrospective study. Demographic characteristics, histopathological and clinical features, treatment modalities and response to treatment were obtained from hospital records. Dates of initial diagnosis, remission and relapse, last visit and death were recorded for survival analyses. We analysed data of 391 HL patients (61% male, 39% female; mean age 35.7±15.1 years). The most common classical HL histological subtype was nodular sclerosing HL (NSHL) (42.7%). The most common stage was II 50.4%. The most common chemotherapy regimen was doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) (70.6%). Five and 10-year survival rates were 90% and 84%, respectively. Early-stage patients with good prognostic factors had better overall and relapse-free survival rates. The presence of "B" symptoms, albumin level, Eastern Cooperative Oncology Group (ECOG) performance score, and LDH were prognostic factors that affect the survival in both univariate and multivariate analyses. This is the first study that demonstrates the demographic, clinical and prognostic features of HL patients in Turkey, and provides a general picture of the HL patients in our country.

The prognostic significance of circulating serum amyloid A and CXC chemokine ligand 4 in osteosarcoma.

PubMed

Flores, Ricardo J; Kelly, Aaron J; Li, Yiting; Chen, Xiang; McGee, Colin; Krailo, Mark; Barkauskas, Donald A; Hicks, John; Man, Tsz-Kwong

2017-12-01

Osteosarcoma (OS) is the most common pediatric bone cancer.  Despite advances in treatment regimens, the survival rate remains 60-70%.  There is an urgent need to identify prognostic biomarkers, so that targeted therapies can be developed to improve the outcome. Our laboratory has previously identified that circulating serum amyloid A (SAA) and CXC chemokine ligand 4 (CXCL4) are upregulated in patients with OS.  In this study, we tested if they could be used as prognostic biomarkers.  We used enzyme-linked immunosorbent assays to measure their concentrations in serum samples (n = 233) and immunohistochemistry to examine their expressions in primary tumors (n = 37).  Prognostic significance of the serum concentrations and tumor expressions of the biomarkers was then evaluated. Patients with "high SAA" and "low CXCL4" circulating levels at diagnosis significantly correlated with a worse outcome (HR = 1.68, P = 0.014), which was independent of the metastatic status.  These patients also exhibited a significantly higher rate of poor histologic response to chemotherapy.  Furthermore, low tumor expression of CXCL4 correlated with poor survival (HR = 3.57, P = 0.005). Our results demonstrate that circulating SAA and CXCL4 may serve as prognostic biomarkers in OS.  Targeting CXCL4 has been reported, suggesting that it may be exploited as a therapeutic target in OS. © 2017 Wiley Periodicals, Inc.

The Prognostic Significance of Circulating Serum Amyloid A and CXC Chemokine Ligand 4 in Osteosarcoma

PubMed Central

Flores, Ricardo J.; Kelly, Aaron J.; Li, Yiting; Chen, Xiang; McGee, Colin; Krailo, Mark; Barkauskas, Donald A.; Hicks, John; Man, Tsz-Kwong

2017-01-01

BACKGROUND Osteosarcoma is the most common pediatric bone cancer. Despite advances in treatment regimens, the survival rate remains 60–70%. There is an urgent need to identify prognostic biomarkers, so that targeted therapies can be developed to improve the outcome. PROCEDURE Our lab has previously identified that circulating Serum Amyloid A (SAA) and CXC Chemokine Ligand 4 (CXCL4) are upregulated in patients with osteosarcoma. In this study, we tested if they could be used as prognostic biomarkers. We used ELISAs to measure their concentrations in serum samples (n = 233), and immunohistochemistry to examine expressions in primary tumors (n = 37). Prognostic significance of the serum concentrations and tumor expressions of the biomarkers was then evaluated. RESULTS Patients with “High SAA” and “Low CXCL4” circulating levels at diagnosis significantly correlated with a worse outcome (HR = 1.68, p = 0.014), which was independent of the metastatic status. These patients also exhibited a significantly higher rate of poor histological response to chemotherapy. Furthermore, low tumor expression of CXCL4 correlated with poor survival (HR = 3.57, p = 0.005). CONCLUSIONS Our results demonstrate that circulating SAA and CXCL4 may serve as prognostic biomarkers in osteosarcoma. Targeting CXCL4 has been reported, suggesting that it may be exploited as a therapeutic target in osteosarcoma. PMID:28544777

Incidence, characterization and prognostic significance of chromosomal abnormalities in 640 patients with primary myelodysplastic syndromes. Grupo Cooperativo Español de Citogenética Hematológica.

PubMed

Solé, F; Espinet, B; Sanz, G F; Cervera, J; Calasanz, M J; Luño, E; Prieto, F; Granada, I; Hernández, J M; Cigudosa, J C; Diez, J L; Bureo, E; Marqués, M L; Arranz, E; Ríos, R; Martínez Climent, J A; Vallespí, T; Florensa, L; Woessner, S

2000-02-01

Recently, a consensus International Prognostic Scoring System (IPSS) for predicting outcome and planning therapy in the myelodysplastic syndromes (MDS) has been developed. However, the intermediate-risk cytogenetic subgroup defined by the IPSS includes a miscellaneous number of different single abnormalities for which real prognosis at present is uncertain. The main aims of this study were to evaluate in an independent series the prognostic value of the IPSS and to identify chromosomal abnormalities with a previously unrecognized good or poor prognosis in 640 patients. In univariate analyses, cases with single 1q abnormalities experienced poor survival, whereas those with trisomy 8 had a higher risk of acute leukaemic transformation than the remaining patients (P = 0.004 and P = 0.009 respectively). Patients with single del(12p) had a similar survival to patients with a normal karyotype and showed some trend for a better survival than other cases belonging to the IPSS intermediate-risk cytogenetic subgroup (P = 0.045). Multivariate analyses demonstrated that IPSS cytogenetic prognostic subgroup, proportion of bone marrow blasts and haemoglobin level were the main prognostic factors for survival, and the first two characteristics and platelet count were the best predictors of acute leukaemic transformation risk. A large international co-operative study should be carried out to clarify these findings.

Aging and the Kidneys: Anatomy, Physiology and Consequences for Defining Chronic Kidney Disease.

PubMed

Glassock, Richard J; Rule, Andrew D

2016-01-01

The varied functions of the kidneys are influenced by the complex process of aging. The glomerular filtration rate (GFR) steadily declines with normal aging, and the progress of this process can be influenced by superimposed diseases. Microscopically, nephron numbers decrease as global glomerulosclerosis becomes more evident. The precise mechanisms underlying nephron loss with aging are not well understood, but derangements in podocyte biology appear to be involved. Classifications of chronic kidney disease (CKD) incorporate GFR values and attendant risk of adverse events. Arbitrary and fixed thresholds of GFR for defining CKD have led to an overdiagnosis of CKD in the elderly. An age-sensitive definition of CKD could offer a solution to this problem and more meaningfully capture the prognostic implications of CKD. © 2016 S. Karger AG, Basel.

Risk factors and screening instruments to predict adverse outcomes for undifferentiated older emergency department patients: a systematic review and meta-analysis.

PubMed

Carpenter, Christopher R; Shelton, Erica; Fowler, Susan; Suffoletto, Brian; Platts-Mills, Timothy F; Rothman, Richard E; Hogan, Teresita M

2015-01-01

A significant proportion of geriatric patients experience suboptimal outcomes following episodes of emergency department (ED) care. Risk stratification screening instruments exist to distinguish vulnerable subsets, but their prognostic accuracy varies. This systematic review quantifies the prognostic accuracy of individual risk factors and ED-validated screening instruments to distinguish patients more or less likely to experience short-term adverse outcomes like unanticipated ED returns, hospital readmissions, functional decline, or death. A medical librarian and two emergency physicians conducted a medical literature search of PubMed, EMBASE, SCOPUS, CENTRAL, and ClinicalTrials.gov using numerous combinations of search terms, including emergency medical services, risk stratification, geriatric, and multiple related MeSH terms in hundreds of combinations. Two authors hand-searched relevant specialty society research abstracts. Two physicians independently reviewed all abstracts and used the revised Quality Assessment of Diagnostic Accuracy Studies instrument to assess individual study quality. When two or more qualitatively similar studies were identified, meta-analysis was conducted using Meta-DiSc software. Primary outcomes were sensitivity, specificity, positive likelihood ratio (LR+), and negative likelihood ratio (LR-) for predictors of adverse outcomes at 1 to 12 months after the ED encounters. A hypothetical test-treatment threshold analysis was constructed based on the meta-analytic summary estimate of prognostic accuracy for one outcome. A total of 7,940 unique citations were identified yielding 34 studies for inclusion in this systematic review. Studies were significantly heterogeneous in terms of country, outcomes assessed, and the timing of post-ED outcome assessments. All studies occurred in ED settings and none used published clinical decision rule derivation methodology. Individual risk factors assessed included dementia, delirium, age, dependency, malnutrition, pressure sore risk, and self-rated health. None of these risk factors significantly increased the risk of adverse outcome (LR+ range = 0.78 to 2.84). The absence of dependency reduces the risk of 1-year mortality (LR- = 0.27) and nursing home placement (LR- = 0.27). Five constructs of frailty were evaluated, but none increased or decreased the risk of adverse outcome. Three instruments were evaluated in the meta-analysis: Identification of Seniors at Risk, Triage Risk Screening Tool, and Variables Indicative of Placement Risk. None of these instruments significantly increased (LR+ range for various outcomes = 0.98 to 1.40) or decreased (LR- range = 0.53 to 1.11) the risk of adverse outcomes. The test threshold for 3-month functional decline based on the most accurate instrument was 42%, and the treatment threshold was 61%. Risk stratification of geriatric adults following ED care is limited by the lack of pragmatic, accurate, and reliable instruments. Although absence of dependency reduces the risk of 1-year mortality, no individual risk factor, frailty construct, or risk assessment instrument accurately predicts risk of adverse outcomes in older ED patients. Existing instruments designed to risk stratify older ED patients do not accurately distinguish high- or low-risk subsets. Clinicians, educators, and policy-makers should not use these instruments as valid predictors of post-ED adverse outcomes. Future research to derive and validate feasible ED instruments to distinguish vulnerable elders should employ published decision instrument methods and examine the contributions of alternative variables, such as health literacy and dementia, which often remain clinically occult. © 2014 by the Society for Academic Emergency Medicine.

Outcome Analysis of Patients With Oral Cavity Cancer and Extracapsular Spread in Neck Lymph Nodes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liao, Chun-Ta, E-mail: liaoct@adm.cgmh.org.tw; Department of Head and Neck Oncology Group, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan; Lee, Li-Yu

Purpose: Extracapsular spread (ECS) in neck lymph nodes is a major adverse prognostic factor in patients with oral cavity squamous cell carcinoma (OSCC). We conducted a retrospective analysis of prognostic factors in this patient group and tried to identify a subset of patients with a worse prognosis suitable for more aggressive therapeutic interventions. Methods and Materials: Enrolled in the study were 255 OSCC patients with ECS in neck nodes and without evidence of distant metastasis. All participants were followed-up for at least 2 years or censored at last follow-up. The 5-year rates of control, distant metastasis, and survival were themore » main outcome measures. Results: Level IV/V lymph node metastases and tumor depth {>=}12 mm were independent predictors of 5-year survival and identified three prognostic groups. In the low-risk group (no level IV/V metastases and tumor depth <12 mm), the 5-year disease-free, disease-specific, and overall survival rates were 60%, 66%, and 50%, respectively. In the intermediate-risk group (no level IV/V metastases and tumor depth {>=}12 mm), the 5-year disease-free, disease-specific, and overall survival rates were 39%, 41%, and 28%, respectively. In the high-risk group (evidence of level IV/V metastases), the 5-year disease-free, disease-specific, and overall survival rates were 14%, 12%, and 10%, respectively. Conclusions: Among OSCC patients with ECS, those with level IV/V metastases appear to have the worst prognosis followed by without level IV/V metastases and tumor depth {>=}12 mm. An aggressive therapeutic approach may be suitable for intermediate- and high-risk patients.« less

Creatine kinase enzyme level correlates positively with serum creatinine and lean body mass, and is a prognostic factor for survival in amyotrophic lateral sclerosis.

PubMed

Rafiq, M K; Lee, E; Bradburn, M; McDermott, C J; Shaw, P J

2016-06-01

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative condition for which there is no single diagnostic test or biomarker. The level of the creatine kinase (CK) enzyme in serum may be mild to moderately elevated in some patients with ALS, the precise cause of which and its behaviour with disease progression is unknown. The aim of this study was to examine the usefulness of monitoring CK serially during the ALS disease trajectory and to determine whether CK levels mirror disease progression. This was a prospective observational cohort study, using the clinical database of the olesoxime (TRO19622) investigational medicinal product trial. The baseline CK was raised in 52% of the trial participants with the mean CK ± SD being 257 ± 239 U/l. The mean CK was significantly higher in male participants than in female participants (P < 0.001) and amongst participants with limb onset ALS compared to participants with bulbar onset ALS (P < 0.001). There was no significant difference in the CK levels between upper limb and lower limb onset disease (P = 0.746). The CK level co-related positively with serum creatinine and estimated lean body mass but there was no relationship between CK and muscle scores and limb function. A higher CKlog was associated with significantly better survival, even when adjusted for prognostic co-variants (P = 0.013). The serum CK level seems to be an independent prognostic factor for survival in ALS. The cellular mechanism of CK enzyme suggests that it may be upregulated to provide energy in the face of metabolic stress in ALS. © 2016 EAN.

NT-pro-BNP is an independent predictor of mortality in patients with end-stage renal disease.

PubMed

Svensson, M; Gorst-Rasmussen, A; Schmidt, E B; Jorgensen, K A; Christensen, J H

2009-04-01

Patients with end-stage renal disease (ESRD) have an increased mortality from cardiovascular disease (CVD). N-terminal pro-brain natriuretic peptide (NT-pro-BNP) is an independent predictor of mortality in patients with ischemic heart disease and congestive heart failure. Previous data have shown markedly elevated levels of NT-pro-BNP in patients with ESRD, while the prognostic value of elevated levels of NT-pro-BNP in patients with ESRD is largely unknown. The aim of the present study was to examine if the level of NT-pro-BNP predicts mortality in patients with ERSD and CVD. We prospectively followed 206 patients with ESRD and documented CVD. Levels of NT-pro-BNP were measured at baseline, and patients were followed for 2 years or until they reached the predefined endpoint of all-cause mortality. During follow-up, the total mortality was 44% (90/206). Patients who died were followed for a median of 314 days (interquartile range 179 - 530). Using Cox regression analysis, age, female sex, systolic blood pressure, dialysis efficiency and plasma levels of NT-pro-BNP were independent prognostic risk factors of mortality. In receiver operating characteristic curve analysis a cut off value for NT-pro-BNP was determined. Patients with values of NT-pro-BNP above 12.200 pg/ml had a 3 times higher risk of death than patients below the cut-off value (HR 3.05 95% CI 1.96 - 4.77, p < 0.0001). In spite of generally elevated levels of NT-pro-BNP, NT-pro-BNP is still an independent predictor of mortality and might add prognostic information in patients with ESRD and documented CVD.

Perioperative changes in osteopontin and TGFβ1 plasma levels and their prognostic impact for radiotherapy in head and neck cancer.

PubMed

Polat, Bülent; Kaiser, Philipp; Wohlleben, Gisela; Gehrke, Thomas; Scherzad, Agmal; Scheich, Matthias; Malzahn, Uwe; Fischer, Thomas; Vordermark, Dirk; Flentje, Michael

2017-01-03

In head and neck cancer little is known about the kinetics of osteopontin (OPN) expression after tumor resection. In this study we evaluated the time course of OPN plasma levels before and after surgery. Between 2011 and 2013 41 consecutive head and neck cancer patients were enrolled in a prospective study (group A). At different time points plasma samples were collected: T0) before, T1) 1 day, T2) 1 week and T3) 4 weeks after surgery. Osteopontin and TGFβ1 plasma concentrations were measured with a commercial ELISA system. Data were compared to 131 head and neck cancer patients treated with primary (n = 42) or postoperative radiotherapy (n = 89; group B1 and B2). A significant OPN increase was seen as early as 1 day after surgery (T0 to T1, p < 0.01). OPN levels decreased to base line 3-4 weeks after surgery. OPN values were correlated with postoperative TGFβ1 expression suggesting a relation to wound healing. Survival analysis showed a significant benefit for patients with lower OPN levels both in the primary and postoperative radiotherapy group (B1: 33 vs 11.5 months, p = 0.017, B2: median not reached vs 33.4, p = 0.031). TGFβ1 was also of prognostic significance in group B1 (33.0 vs 10.7 months, p = 0.003). Patients with head and neck cancer showed an increase in osteopontin plasma levels directly after surgery. Four weeks later OPN concentration decreased to pre-surgery levels. This long lasting increase was presumably associated to wound healing. Both pretherapeutic osteopontin and TGFβ1 had prognostic impact.

Fasting blood glucose level and prognosis in non-small cell lung cancer (NSCLC) patients.

PubMed

Luo, Juhua; Chen, Yea-Jyh; Chang, Li-Jung

2012-05-01

Diabetes has been consistently linked to many forms of cancers, such as liver, colorectal, pancreatic, and breast cancer, however, the role of diabetes in outcome among cancer patients remains unclear. In this study, we retrospectively reviewed electronic medical records of 342 inpatients newly diagnosed with NSCLC referred by a teaching hospital cancer center in southern Taiwan between 2005 and 2007 to examine the effects of fasting glucose levels at time of cancer diagnosis on overall survival in patients with non-small cell lung cancer (NSCLC). All patients were followed up until the end of 2010. The Kaplan-Meier method was used to compare survival curves for patients with and without diabetes. The Cox proportional hazards model was used to estimate hazard ratios for the association between diabetes, other prognostic factors and patient survival. We observed that significant prognostic factors for poor overall survival in patients with NSCLC included older age, smoking, poor performance status, advanced stage (stage IIIB or IV), and no cancer-directed surgery treatment. Particularly, we identified that diabetic state defined by fasting blood glucose level ≥126 mg/dl was another independent prognostic factor for these patients. Compared with those who had normal range of fasting glucose level (70-99 mg/dl), patients with high fasting glucose level (≥126 mg/dl) had 69% excess risk of all-cause mortality in patients with NSCLC. Diabetes as indicated by elevated fasting blood glucose was independently associated with a significantly higher risk of all-cause mortality in patients with NSCLC, indicating that diabetes or hyperglycemia effectively controlled may present an opportunity for improving prognosis in NSCLS patients with abnormal glucose level. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

[Prognostic factors for schizophrenia during first psychotic episode].

PubMed

Cano, Juan F; Fierro-Urresta, Marco; Vanegas, Claudia R; Alzate, Marcela; Olarte, Ana; Cendales, Ricardo; Córdoba, Rodrigo N

2007-01-01

Reviewing the available literature regarding prognosis for first psychotic episode for developing schizophrenia. A systematic review of studies which have evaluated prognostic determinants for the first psychotic episode and its relationship to schizophrenia was made. 161 articles were reviewed which fulfilled the search criteria and which were adjusted to the purpose of the study. Duration of untreated psychosis (DUP), pre-morbid functioning level, the presence or predominance of negative symptoms, co-morbid consumption of psychoactive substances and psychosocial state were the most influential characteristics for developing schizophrenia in patients presenting a first psychotic episode.

Evaluation of an operational malaria outbreak identification and response system in Mpumalanga Province, South Africa.

PubMed

Coleman, Marlize; Coleman, Michael; Mabuza, Aaron M; Kok, Gerdalize; Coetzee, Maureen; Durrheim, David N

2008-04-27

To evaluate the performance of a novel malaria outbreak identification system in the epidemic prone rural area of Mpumalanga Province, South Africa, for timely identification of malaria outbreaks and guiding integrated public health responses. Using five years of historical notification data, two binomial thresholds were determined for each primary health care facility in the highest malaria risk area of Mpumalanga province. Whenever the thresholds were exceeded at health facility level (tier 1), primary health care staff notified the malaria control programme, which then confirmed adequate stocks of malaria treatment to manage potential increased cases. The cases were followed up at household level to verify the likely source of infection. The binomial thresholds were reviewed at village/town level (tier 2) to determine whether additional response measures were required. In addition, an automated electronic outbreak identification system at town/village level (tier 2) was integrated into the case notification database (tier 3) to ensure that unexpected increases in case notification were not missed.The performance of these binomial outbreak thresholds was evaluated against other currently recommended thresholds using retrospective data. The acceptability of the system at primary health care level was evaluated through structured interviews with health facility staff. Eighty four percent of health facilities reported outbreaks within 24 hours (n = 95), 92% (n = 104) within 48 hours and 100% (n = 113) within 72 hours. Appropriate response to all malaria outbreaks (n = 113, tier 1, n = 46, tier 2) were achieved within 24 hours. The system was positively viewed by all health facility staff. When compared to other epidemiological systems for a specified 12 month outbreak season (June 2003 to July 2004) the binomial exact thresholds produced one false weekly outbreak, the C-sum 12 weekly outbreaks and the mean + 2 SD nine false weekly outbreaks. Exceeding the binomial level 1 threshold triggered an alert four weeks prior to an outbreak, but exceeding the binomial level 2 threshold identified an outbreak as it occurred. The malaria outbreak surveillance system using binomial thresholds achieved its primary goal of identifying outbreaks early facilitating appropriate local public health responses aimed at averting a possible large-scale epidemic in a low, and unstable, malaria transmission setting.

Discrimination of rippled-spectrum patterns in noise: A manifestation of compressive nonlinearity

PubMed Central

Milekhina, Olga N.; Nechaev, Dmitry I.; Klishin, Vladimir O.

2017-01-01

In normal-hearing listeners, rippled-spectrum discrimination was psychophysically investigated in both silence and with a simultaneous masker background using the following two paradigms: measuring the ripple density resolution with the phase-reversal test and measuring the ripple-shift threshold with the ripple-shift test. The 0.5-oct wide signal was centered on 2 kHz, the signal levels were 50 and 80 dB SPL, and the masker levels varied from 30 to 100 dB SPL. The baseline ripple density resolutions were 8.7 oct-1 and 8.6 oct-1 for the 50-dB and 80-dB signals, respectively. The baseline ripple shift thresholds were 0.015 oct and 0.018 oct for the 50-dB and 80-dB signals, respectively. The maskers were 0.5-oct noises centered on 2 kHz (on-frequency) or 0.75 to 1.25 oct below the signal (off-frequency maskers). The effects of the maskers were as follows: (i) both on- and low-frequency maskers reduced the ripple density resolution and increased the ripple shift thresholds, (ii) the masker levels at threshold (the ripple density resolution decrease down to 3 oct–1 or ripple shift threshold increased up to 0.1 oct) increased with increasing frequency spacing between the signal and masker, (iii) the masker levels at threshold were higher for the 80-dB signal than for the 50-dB signal, and (iv) the difference between the masker levels at threshold for the 50-dB and 80-dB signals decreased with increasing frequency spacing between the masker and signal. Within the 30-dB (from 50 to 80 dB SPL) signal level, the growth of the masker level at threshold was 27.8 dB for the on-frequency masker and 9 dB for the low-frequency masker. It is assumed that the difference between the on- and low-frequency masking of the rippled-spectrum discrimination reflects the cochlear compressive non-linearity. With this assumption, the compression was 0.3 dB/dB. PMID:28346538

(t, n) Threshold d-Level Quantum Secret Sharing.

PubMed

Song, Xiu-Li; Liu, Yan-Bing; Deng, Hong-Yao; Xiao, Yong-Gang

2017-07-25

Most of Quantum Secret Sharing(QSS) are (n, n) threshold 2-level schemes, in which the 2-level secret cannot be reconstructed until all n shares are collected. In this paper, we propose a (t, n) threshold d-level QSS scheme, in which the d-level secret can be reconstructed only if at least t shares are collected. Compared with (n, n) threshold 2-level QSS, the proposed QSS provides better universality, flexibility, and practicability. Moreover, in this scheme, any one of the participants does not know the other participants' shares, even the trusted reconstructor Bob 1 is no exception. The transformation of the particles includes some simple operations such as d-level CNOT, Quantum Fourier Transform(QFT), Inverse Quantum Fourier Transform(IQFT), and generalized Pauli operator. The transformed particles need not to be transmitted from one participant to another in the quantum channel. Security analysis shows that the proposed scheme can resist intercept-resend attack, entangle-measure attack, collusion attack, and forgery attack. Performance comparison shows that it has lower computation and communication costs than other similar schemes when 2 < t < n - 1.

Quinine reduces the dynamic range of the human auditory system.

PubMed

Berninger, E; Karlsson, K K; Alván, G

1998-01-01

The aim of the study was to evaluate and quantify quinine-induced changes in the human auditory dynamic range, as a model for cochlear hearing loss. Six otologically normal volunteers (21-40 years old) received quinine hydrochloride (15 mg/kg body weight) in two identical oral doses and one intravenous infusion. Refined hearing tests were performed monaurally at threshold, at moderate hearing levels and at high hearing levels. Quinine induced a maximal pure-tone threshold shift of 23 dB (1000-2000 Hz). The increase in the psychoacoustical click threshold agreed with an increase in the detection threshold of click-evoked otoacoustic emissions. The change in the stimulus-response relationship of the emissions reflected recruitment. The self-attained most comfortable speech level and the acoustic stapedius reflex thresholds were not affected by quinine administration. Quinine is a useful model substance for reversibly inducing complete loudness recruitment in humans as it acts specifically on some parts of the hearing function. Its mechanism of action on the molecular level is likely to reveal further information on the physiology of hearing.

Prognostic impact of MYC protein expression in central nervous system diffuse large B-cell lymphoma: comparison with MYC rearrangement and MYC mRNA expression.

PubMed

Son, Seung-Myoung; Ha, Sang-Yun; Yoo, Hae-Yong; Oh, Dongryul; Kim, Seok-Jin; Kim, Won-Seog; Ko, Young-Hyeh

2017-01-01

The prognostic role of MYC has been well documented in non-central nervous system diffuse large B-cell lymphoma; however, it remains controversial in central nervous system diffuse large B-cell lymphoma. To investigate the prognostic value of MYC, we analyzed the MYC protein expression by immunohistochemistry, mRNA expression by RNA in situ hybridization, and gene status by fluorescence in situ hybridization in 74 cases of central nervous system diffuse large B-cell lymphoma. Moreover, we examined the correlation between MYC translocation, mRNA expression, and protein expression. The mean percentage of MYC immunopositive cells was 49%. Using a 44% cutoff value, 49 (66%) cases showed MYC protein overexpression. The result of mRNA in situ hybridization using the RNA scope technology was obtained using the H-scoring system; the median value was 34.2. Using the cutoff value of 63.5, 16 (22%) cases showed MYC mRNA overexpression. MYC gene rearrangement was detected in five out of 68 (7%) cases. MYC translocation showed no statistically significant correlation with mRNA expression; however, all MYC translocation-positive cases showed MYC protein overexpression, with a higher mean percentage of MYC protein expression than that of translocation-negative cases (78 vs 48%, P=0.001). The level of MYC mRNA expression was moderately correlated with the level of MYC protein expression (P<0.001). The mean percentage of MYC protein expression in the high MYC mRNA group was higher than that in the low MYC mRNA group (70 vs 47%, P<0.001). A univariate analysis showed that age over 60 years, Eastern Cooperative Oncology Group (ECOG) performance status ≥2 and MYC protein overexpression were significantly associated with an increased risk of death. MYC translocation and MYC mRNA expression had no prognostic significance. On multivariate analysis, MYC protein overexpression and ECOG score retained prognostic significance.

Skeletal muscle radiodensity is prognostic for survival in patients with advanced non-small cell lung cancer.

PubMed

Sjøblom, Bjørg; Grønberg, Bjørn H; Wentzel-Larsen, Tore; Baracos, Vickie E; Hjermstad, Marianne J; Aass, Nina; Bremnes, Roy M; Fløtten, Øystein; Bye, Asta; Jordhøy, Marit

2016-12-01

Recent research indicates that severe muscular depletion (sarcopenia) is frequent in cancer patients and linked to cachexia and poor survival. Our aim was to investigate if measures of skeletal muscle hold prognostic information in advanced non-small cell lung cancer (NSCLC). We included NSCLC patients with disease stage IIIB/IV, performance status 0-2, enrolled in three randomised trials of first-line chemotherapy (n = 1305). Computed tomography (CT) images obtained before start of treatment were used for body composition analyses at the level of the third lumbar vertebra (L3). Skeletal muscle mass was assessed by measures of the cross sectional muscle area, from which the skeletal muscle index (SMI) was obtained. Skeletal muscle radiodensity (SMD) was measured as the mean Hounsfield unit (HU) of the measured muscle area. A high level of mean HU indicates a high SMD. Complete data were available for 734 patients, mean age 65 years. Both skeletal muscle index (SMI) and muscle radiodensity (SMD) varied largely. Mean SMI and SMD were 47.7 cm 2 /m 2 and 37.4 HU in men (n = 420), 39.6 cm 2 /m 2 and 37.0 HU in women (n = 314). Multivariable Cox regression analyses, adjusted for established prognostic factors, showed that SMD was independently prognostic for survival (Hazard ratio (HR) 0.98, 95% CI 0.97-0.99, p = 0.001), whereas SMI was not (HR 0.99, 95% CI 0.98-1.01, p = 0.329). Low SMD is associated with poorer survival in advanced NSCLC. Further research is warranted to establish whether muscle measures should be integrated into routine practice to improve prognostic accuracy. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

A study of the threshold method utilizing raingage data

NASA Technical Reports Server (NTRS)

Short, David A.; Wolff, David B.; Rosenfeld, Daniel; Atlas, David

1993-01-01

The threshold method for estimation of area-average rain rate relies on determination of the fractional area where rain rate exceeds a preset level of intensity. Previous studies have shown that the optimal threshold level depends on the climatological rain-rate distribution (RRD). It has also been noted, however, that the climatological RRD may be composed of an aggregate of distributions, one for each of several distinctly different synoptic conditions, each having its own optimal threshold. In this study, the impact of RRD variations on the threshold method is shown in an analysis of 1-min rainrate data from a network of tipping-bucket gauges in Darwin, Australia. Data are analyzed for two distinct regimes: the premonsoon environment, having isolated intense thunderstorms, and the active monsoon rains, having organized convective cell clusters that generate large areas of stratiform rain. It is found that a threshold of 10 mm/h results in the same threshold coefficient for both regimes, suggesting an alternative definition of optimal threshold as that which is least sensitive to distribution variations. The observed behavior of the threshold coefficient is well simulated by assumption of lognormal distributions with different scale parameters and same shape parameters.

Interleukin-6 enhances cancer stemness and promotes metastasis of hepatocellular carcinoma via up-regulating osteopontin expression.

PubMed

Wang, Chao-Qun; Sun, Hao-Ting; Gao, Xiao-Mei; Ren, Ning; Sheng, Yuan-Yuan; Wang, Zheng; Zheng, Yan; Wei, Jin-Wang; Zhang, Kai-Li; Yu, Xin-Xin; Zhu, Yin; Luo, Qin; Yang, Lu-Yu; Dong, Qiong-Zhu; Qin, Lun-Xiu

2016-01-01

Interleukin-6 (IL-6), one of the most important inflammatory cytokines, plays a pivotal role in metastasis and stemness of solid tumors. However, the underlying mechanisms of IL-6 in HCC metastasis remain unclear. In the present study, we demonstrated that stemness and metastatic potential of HCC cells were significantly enhanced after IL-6 stimulation. IL-6 could induce expression of osteopontin (OPN), along with other stemness-related genes, including HIF1α, BMI1, and HEY1. Block of OPN induction could significantly abrogate the effect of IL-6 on stemness and metastasis of HCC cells. Furthermore, IL-6 level was positively correlated with OPN in HCC. Patients with high plasma IL-6 or OPN level had poorer prognosis. In multivariate analysis, IL-6 and OPN were demonstrated to be independent prognostic indicators for HCC patients, and their combination had a better prognostic performance than IL-6 or OPN alone. Collectively, our findings indicate that IL-6 could enhance stemness and promote metastasis of HCC via up-regulating OPN expression, which can be a potential therapeutic target for combating HCC metastasis, and the combination of IL-6 and OPN serves as a promising prognostic predictor for HCC.

Time from prior chemotherapy enhances prognostic risk grouping in the second-line setting of advanced urothelial carcinoma: a retrospective analysis of pooled, prospective phase 2 trials.

PubMed

Sonpavde, Guru; Pond, Gregory R; Fougeray, Ronan; Choueiri, Toni K; Qu, Angela Q; Vaughn, David J; Niegisch, Guenter; Albers, Peter; James, Nicholas D; Wong, Yu-Ning; Ko, Yoo-Joung; Sridhar, Srikala S; Galsky, Matthew D; Petrylak, Daniel P; Vaishampayan, Ulka N; Khan, Awais; Vogelzang, Nicholas J; Beer, Tomasz M; Stadler, Walter M; O'Donnell, Peter H; Sternberg, Cora N; Rosenberg, Jonathan E; Bellmunt, Joaquim

2013-04-01

Outcomes for patients in the second-line setting of advanced urothelial carcinoma (UC) are dismal. The recognized prognostic factors in this context are Eastern Cooperative Oncology Group (ECOG) performance status (PS) >0, hemoglobin level (Hb) <10 g/dl, and liver metastasis (LM). The purpose of this retrospective study of prospective trials was to investigate the prognostic value of time from prior chemotherapy (TFPC) independent of known prognostic factors. Data from patients from seven prospective trials with available baseline TFPC, Hb, PS, and LM values were used for retrospective analysis (n=570). External validation was conducted in a second-line phase 3 trial comparing best supportive care (BSC) versus vinflunine plus BSC (n=352). Cox proportional hazards regression was used to evaluate the association of factors, with overall survival (OS) and progression-free survival (PFS) being the respective primary and secondary outcome measures. ECOG-PS >0, LM, Hb <10 g/dl, and shorter TFPC were significant prognostic factors for OS and PFS on multivariable analysis. Patients with zero, one, two, and three to four factors demonstrated median OS of 12.2, 6.7, 5.1, and 3.0 mo, respectively (concordance statistic=0.638). Setting of prior chemotherapy (metastatic disease vs perioperative) and prior platinum agent (cisplatin or carboplatin) were not prognostic factors. External validation demonstrated a significant association of TFPC with PFS on univariable and most multivariable analyses, and with OS on univariable analyses. Limitations of retrospective analyses are applicable. Shorter TFPC enhances prognostic classification independent of ECOG-PS >0, Hb <10 g/dl, and LM in the setting of second-line therapy for advanced UC. These data may facilitate drug development and interpretation of trials. Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Time from Prior Chemotherapy Enhances Prognostic Risk Grouping in the Second-line Setting of Advanced Urothelial Carcinoma: A Retrospective Analysis of Pooled, Prospective Phase 2 Trials

PubMed Central

Sonpavde, Guru; Pond, Gregory R.; Fougeray, Ronan; Choueiri, Toni K.; Qu, Angela Q.; Vaughn, David J.; Niegisch, Guenter; Albers, Peter; James, Nicholas D.; Wong, Yu-Ning; Ko, Yoo-Joung; Sridhar, Srikala S.; Galsky, Matthew D.; Petrylak, Daniel P.; Vaishampayan, Ulka N.; Khan, Awais; Vogelzang, Nicholas J.; Beer, Tomasz M.; Stadler, Walter M.; O’Donnell, Peter H.; Sternberg, Cora N.; Rosenberg, Jonathan E.; Bellmunt, Joaquim

2014-01-01

Background Outcomes for patients in the second-line setting of advanced urothelial carcinoma (UC) are dismal. The recognized prognostic factors in this context are Eastern Cooperative Oncology Group (ECOG) performance status (PS) >0, hemoglobin level (Hb) <10 g/dl, and liver metastasis (LM). Objectives The purpose of this retrospective study of prospective trials was to investigate the prognostic value of time from prior chemotherapy (TFPC) independent of known prognostic factors. Design, setting, and participants: Data from patients from seven prospective trials with available baseline TFPC, Hb, PS, and LM values were used for retrospective analysis (n = 570). External validation was conducted in a second-line phase 3 trial comparing best supportive care (BSC) versus vinflunine plus BSC (n = 352). Outcome measurements and statistical analysis Cox proportional hazards regression was used to evaluate the association of factors, with overall survival (OS) and progression-free survival (PFS) being the respective primary and secondary outcome measures. Results and limitations ECOG-PS >0, LM, Hb <10 g/dl, and shorter TFPC were significant prognostic factors for OS and PFS on multivariable analysis. Patients with zero, one, two, and three to four factors demonstrated median OS of 12.2, 6.7, 5.1, and 3.0 mo, respectively (concordance statistic = 0.638). Setting of prior chemotherapy (metastatic disease vs perioperative) and prior platinum agent (cisplatin or carboplatin) were not prognostic factors. External validation demonstrated a significant association of TFPC with PFS on univariable and most multivariable analyses, and with OS on univariable analyses. Limitations of retrospective analyses are applicable. Conclusions Shorter TFPC enhances prognostic classification independent of ECOG-PS>0, Hb<10 g/ dl, and LM in the setting of second-line therapy for advanced UC. These data may facilitate drug development and interpretation of trials. PMID:23206856

A novel H-FABP assay and a fast prognostic score for risk assessment of normotensive pulmonary embolism.

PubMed

Dellas, Claudia; Tschepe, Merle; Seeber, Valerie; Zwiener, Isabella; Kuhnert, Katherina; Schäfer, Katrin; Hasenfuß, Gerd; Konstantinides, Stavros; Lankeit, Mareike

2014-05-05

We tested whether heart-type fatty acid binding protein (H-FABP) measured by a fully-automated immunoturbidimetric assay in comparison to ELISA provides additive prognostic value in patients with pulmonary embolism (PE), and validated a fast prognostic score in comparison to the ESC risk prediction model and the simplified Pulmonary Embolism Severity Index (sPESI). We prospectively examined 271 normotensive patients with PE; of those, 20 (7%) had an adverse 30-day outcome. H-FABP levels determined by immunoturbidimetry were higher (median, 5.2 [IQR; 2.7-9.8] ng/ml) than those by ELISA (2.9 [1.1-5.4] ng/ml), but Bland-Altman plot demonstrated a good agreement of both assays. The area under the curve for H-FABP was greater for immunoturbidimetry than for ELISA (0.82 [0.74-0.91] vs 0.78 [0.68-0.89]; P=0.039). H-FABP measured by immunoturbidimetry (but not by ELISA) provided additive prognostic information to other predictors of 30-day outcome (OR, 12.4 [95% CI, 1.6-97.6]; P=0.017). When H-FABP determined by immunoturbidimetry was integrated into a novel prognostic score (H-FABP, Syncope, and Tachycardia; FAST score), the score provided additive prognostic information by multivariable analysis (OR, 14.2 [3.9-51.4]; p<0.001; c-index, 0.86) which were superior to information obtained by the ESC model (c-index, 0.62; net reclassification improvement (NRI), 0.39 [0.21-0.56]; P<0.001) or the sPESI (c-index, 0.68; NRI, 0.24 [0.05-0.43]; P=0.012). In conclusion, determination of H-FABP by immunoturbidimetry provides prognostic information superior to that of ELISA and, if integrated in the FAST score, appears more suitable to identify patients with an adverse 30-day outcome compared to the ESC model and sPESI.

Expression of Estrogen Receptors in Relation to Hormone Levels and the Nottingham Prognostic Index.

PubMed

Fahlén, Mia; Zhang, Hua; Löfgren, Lars; Masironi, Britt; VON Schoultz, Eva; VON Schoultz, B O; Sahlin, Lena

2016-06-01

Estrogen hormones have a large impact on both normal development and tumorigenesis of the breast. Breast tissue samples from 49 women undergoing surgery were included. The estrogen receptors (ERα and ERβ), ERα36 and G-coupled estrogen receptor-1 (GPER) were determined in benign and malignant breast tissue. The ERα36 and ERα mRNA levels were highest in malignant tumors. Stromal ERβ immunostaining in benign tumors was higher than in the paired normal tissue. GPER expression was lowest in benign tumors. In the malignant tumors, the Nottingham Prognostic Index (NPI) correlated positively with stromal GPER and the serum testosterone level. The serum insulin-like growth factor-1 (IGF-1) level correlated negatively with GPER mRNA and glandular ERα. The expression of ERα36 is stronger in malignant breast tissue. The strong positive correlation between NPI and GPER in malignant breast stroma indicates an important role for GPER in breast cancer prognosis. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

A Cyfip2-Dependent Excitatory Interneuron Pathway Establishes the Innate Startle Threshold.

PubMed

Marsden, Kurt C; Jain, Roshan A; Wolman, Marc A; Echeverry, Fabio A; Nelson, Jessica C; Hayer, Katharina E; Miltenberg, Ben; Pereda, Alberto E; Granato, Michael

2018-04-17

Sensory experiences dynamically modify whether animals respond to a given stimulus, but it is unclear how innate behavioral thresholds are established. Here, we identify molecular and circuit-level mechanisms underlying the innate threshold of the zebrafish startle response. From a forward genetic screen, we isolated five mutant lines with reduced innate startle thresholds. Using whole-genome sequencing, we identify the causative mutation for one line to be in the fragile X mental retardation protein (FMRP)-interacting protein cyfip2. We show that cyfip2 acts independently of FMRP and that reactivation of cyfip2 restores the baseline threshold after phenotype onset. Finally, we show that cyfip2 regulates the innate startle threshold by reducing neural activity in a small group of excitatory hindbrain interneurons. Thus, we identify a selective set of genes critical to establishing an innate behavioral threshold and uncover a circuit-level role for cyfip2 in this process. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Prognostic Factors Affecting Locally Recurrent Rectal Cancer and Clinical Significance of Hemoglobin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rades, Dirk; Kuhn, Hildegard; Schultze, Juergen

2008-03-15

Purpose: To investigate potential prognostic factors, including hemoglobin levels before and during radiotherapy, for associations with survival and local control in patients with unirradiated locally recurrent rectal cancer. Patients and Methods: Ten potential prognostic factors were investigated in 94 patients receiving radiotherapy for recurrent rectal cancer: age ({<=}68 vs. {>=}69 years), gender, Eastern Cooperative Oncology Group performance status (0-1 vs. 2-3), American Joint Committee on Cancer (AJCC) stage ({<=}II vs. III vs. IV), grading (G1-2 vs. G3), surgery, administration of chemotherapy, radiation dose (equivalent dose in 2-Gy fractions: {<=}50 vs. >50 Gy), and hemoglobin levels before (<12 vs. {>=}12 g/dL)more » and during (majority of levels: <12 vs. {>=}12 g/dL) radiotherapy. Multivariate analyses were performed, including hemoglobin levels, either before or during radiotherapy (not both) because these are confounding variables. Results: Improved survival was associated with better performance status (p < 0.001), lower AJCC stage (p = 0.023), surgery (p = 0.011), chemotherapy (p = 0.003), and hemoglobin levels {>=}12 g/dL both before (p = 0.031) and during (p < 0.001) radiotherapy. On multivariate analyses, performance status, AJCC stage, and hemoglobin levels during radiotherapy maintained significance. Improved local control was associated with better performance status (p = 0.040), lower AJCC stage (p = 0.010), lower grading (p = 0.012), surgery (p < 0.001), chemotherapy (p < 0.001), and hemoglobin levels {>=}12 g/dL before (p < 0.001) and during (p < 0.001) radiotherapy. On multivariate analyses, chemotherapy, grading, and hemoglobin levels before and during radiotherapy remained significant. Subgroup analyses of the patients having surgery demonstrated the extent of resection to be significantly associated with local control (p = 0.011) but not with survival (p = 0.45). Conclusion: Predictors for outcome in patients who received radiotherapy for locally recurrent rectal cancer were performance status, AJCC stage, chemotherapy, surgery, extent of resection, histologic grading, and hemoglobin levels both before and during radiotherapy.« less

Estimating the effect of a rare time-dependent treatment on the recurrent event rate.

PubMed

Smith, Abigail R; Zhu, Danting; Goodrich, Nathan P; Merion, Robert M; Schaubel, Douglas E

2018-05-30

In many observational studies, the objective is to estimate the effect of treatment or state-change on the recurrent event rate. If treatment is assigned after the start of follow-up, traditional methods (eg, adjustment for baseline-only covariates or fully conditional adjustment for time-dependent covariates) may give biased results. We propose a two-stage modeling approach using the method of sequential stratification to accurately estimate the effect of a time-dependent treatment on the recurrent event rate. At the first stage, we estimate the pretreatment recurrent event trajectory using a proportional rates model censored at the time of treatment. Prognostic scores are estimated from the linear predictor of this model and used to match treated patients to as yet untreated controls based on prognostic score at the time of treatment for the index patient. The final model is stratified on matched sets and compares the posttreatment recurrent event rate to the recurrent event rate of the matched controls. We demonstrate through simulation that bias due to dependent censoring is negligible, provided the treatment frequency is low, and we investigate a threshold at which correction for dependent censoring is needed. The method is applied to liver transplant (LT), where we estimate the effect of development of post-LT End Stage Renal Disease (ESRD) on rate of days hospitalized. Copyright © 2018 John Wiley & Sons, Ltd.

Application of threshold concepts to ecological management problems: occupancy of Golden Eagles in Denali National Park, Alaska: Chapter 5

USGS Publications Warehouse

Eaton, Mitchell J.; Martin, Julien; Nichols, James D.; McIntyre, Carol; McCluskie, Maggie C.; Schmutz, Joel A.; Lubow, Bruce L.; Runge, Michael C.; Edited by Guntenspergen, Glenn R.

2014-01-01

In this chapter, we demonstrate the application of the various classes of thresholds, detailed in earlier chapters and elsewhere, via an actual but simplified natural resource management case study. We intend our example to provide the reader with the ability to recognize and apply the theoretical concepts of utility, ecological and decision thresholds to management problems through a formalized decision-analytic process. Our case study concerns the management of human recreational activities in Alaska’s Denali National Park, USA, and the possible impacts of such activities on nesting Golden Eagles, Aquila chrysaetos. Managers desire to allow visitors the greatest amount of access to park lands, provided that eagle nesting-site occupancy is maintained at a level determined to be acceptable by the managers themselves. As these two management objectives are potentially at odds, we treat minimum desired occupancy level as a utility threshold which, then, serves to guide the selection of annual management alternatives in the decision process. As human disturbance is not the only factor influencing eagle occupancy, we model nesting-site dynamics as a function of both disturbance and prey availability. We incorporate uncertainty in these dynamics by considering several hypotheses, including a hypothesis that site occupancy is affected only at a threshold level of prey abundance (i.e., an ecological threshold effect). By considering competing management objectives and accounting for two forms of thresholds in the decision process, we are able to determine the optimal number of annual nesting-site restrictions that will produce the greatest long-term benefits for both eagles and humans. Setting a utility threshold of 75 occupied sites, out of a total of 90 potential nesting sites, the optimization specified a decision threshold at approximately 80 occupied sites. At the point that current occupancy falls below 80 sites, the recommended decision is to begin restricting access to humans; above this level, it is recommended that all eagle territories be opened to human recreation. We evaluated the sensitivity of the decision threshold to uncertainty in system dynamics and to management objectives (i.e., to the utility threshold).

Adaptive gain and filtering circuit for a sound reproduction system

NASA Technical Reports Server (NTRS)

Engebretson, A. Maynard (Inventor); O'Connell, Michael P. (Inventor)

1998-01-01

Adaptive compressive gain and level dependent spectral shaping circuitry for a hearing aid include a microphone to produce an input signal and a plurality of channels connected to a common circuit output. Each channel has a preset frequency response. Each channel includes a filter with a preset frequency response to receive the input signal and to produce a filtered signal, a channel amplifier to amplify the filtered signal to produce a channel output signal, a threshold register to establish a channel threshold level, and a gain circuit. The gain circuit increases the gain of the channel amplifier when the channel output signal falls below the channel threshold level and decreases the gain of the channel amplifier when the channel output signal rises above the channel threshold level. A transducer produces sound in response to the signal passed by the common circuit output.

Effect of acute stress on taste perception: in relation with baseline anxiety level and body weight.

PubMed

Ileri-Gurel, Esin; Pehlivanoglu, Bilge; Dogan, Murat

2013-01-01

We aimed to determine the effect of acute stress on taste perception and its modulation in relation to body weight and baseline anxiety in this study. The anxiety of the participants, randomly allocated to stress (n = 35) or control (n = 16) groups, was assessed by State Trait Anxiety Inventory. Stroop color-word interference and cold pressor tests were applied as stress protocol. Glucose and salt taste detection thresholds were evaluated before and after the stress protocol in the stress group and corresponding times in the control group. Stress protocol increased heart rate and blood pressure as an indicator of stress system activation. Following stress glucose and salt thresholds decreased in the stress group, unchanged in the control group. Prestress salt thresholds were positively and decrements in salt thresholds were negatively correlated with trait anxiety scores of participants. The state anxiety levels of stress group positively correlated with the decrease in glucose thresholds. Waist-to-hip ratio was negatively correlated with prestress salt thresholds of the subjects. Our results revealed that thresholds for sweet and salty tastes are modulated during stressful conditions. Our data also demonstrated a relationship between taste perception and baseline anxiety levels of healthy individuals, which may be important to understand the appetite alterations in individuals under stressful conditions.

Pancreatic neuroendocrine neoplasms: a current summary of diagnostic, prognostic, and differential diagnostic information.

PubMed

Wick, M R; Graeme-Cook, F M

2001-06-01

Pancreatic endocrine tumors (PETs) continue to be challenging diagnostic and prognostic lesions in surgical pathology and clinical medicine. These neoplasms can be graded into 1 of 3 tiers, based on histologic characteristics in likeness to epithelial neuroendocrine tumors in other anatomic sites. However, grade 1 tumors are by far the most common and are the most difficult to prognosticate. The most helpful features by which to gauge the behavior of such lesions include size (3 cm or larger); mitotic activity (2 or more mitoses per 10 high-power [x400] microscopic fields); marked nuclear atypia, especially with atypical mitoticfigures; predominant tumor synthesis of gastrin, vasoactive intestinal polypeptide, somatostatin, glucagon, calcitonin, or adrenocorticotropic hormone; complete nonfunctionality of the tumor at an immunohistochemical level; or invasion of blood vessels, nerves, or adjacent organs by the neoplasm. Differential diagnosis of PETs includes lesions such as solid-pseudopapillary neoplasms, acinar carcinomas, metastatic neuroendocrine tumors, and plasmacytomas.

Assessment of corticosteroid-induced alkaline phosphatase as a prognostic indicator in canine lymphoma.

PubMed

Wiedemann, A L; Charney, S C; Barger, A M; Schaeffer, D J; Kitchell, B E

2005-04-01

To examine the incidence of elevated corticosteroid-induced alkaline phosphatase (sALP) in dogs with lymphoma and to determine if sALP is a reliable prognostic indicator in canine lymphoma. The medical records of 62 canine lymphoma patients treated with a combination chemotherapy protocol from 1994 to 2003 at the University of Illinois Veterinary Teaching Hospital were examined. Variables assessed with respect to response rate and remission duration included age, bodyweight, sex, breed, World Health Organization stage (I to V), substage (a or b), pretreatment administration of corticosteroid, and serum levels of alkaline phosphatase, sALP and alanine aminotransferase. sALP was not statistically significant with respect to response rate or duration of remission, nor was preinduction glucocorticoid administration. Stage was significant with respect to achieving remission. It was found that sALP is not a useful prognostic indicator for response rate and remission duration in dogs with lymphoma.

Evaluation of an inflammation-based prognostic score in patients with metastatic renal cancer.

PubMed

Ramsey, Sara; Lamb, Gavin W A; Aitchison, Michael; Graham, John; McMillan, Donald C

2007-01-15

Recently, it was shown that an inflammation-based prognostic score, the Glasgow Prognostic Score (GPS), provides additional prognostic information in patients with advanced cancer. The objective of the current study was to examine the value of the GPS compared with established scoring systems in predicting cancer-specific survival in patients with metastatic renal cancer. One hundred nineteen patients who underwent immunotherapy for metastatic renal cancer were recruited. The Memorial Sloan-Kettering Cancer Center (MSKCC) score and the Metastatic Renal Carcinoma Comprehensive Prognostic System (MRCCPS) score were calculated as described previously. Patients who had both an elevated C-reactive protein level (>10 mg/L) and hypoalbuminemia (<35 g/L) were allocated a GPS of 2. Patients who had only 1 of those 2 biochemical abnormalities were allocated a GPS of 1. Patients who had neither abnormality were allocated a GPS of 0. On multivariate analysis of significant individual factors, only calcium (hazard ratio [HR], 3.21; 95% confidence interval [95% CI], 1.51-6.83; P = .002), white cell count (HR, 1.66; 95% CI, 1.17-2.35; P = .004), albumin (HR, 2.63; 95% CI, 1.38-5.03; P = .003), and C-reactive protein (HR, 2.85; 95% CI; 1.49-5.45; P = .002) were associated independently with cancer-specific survival. On multivariate analysis of the different scoring systems, the MSKCC (HR, 1.88; 95% CI, 1.22-2.88; P = .004), the MRCCPS (HR, 1.42; 95% CI, 0.97-2.09; P = .071), and the GPS (HR, 2.35; 95% CI, 1.51-3.67; P < .001) were associated independently with cancer-specific survival. An inflammation-based prognostic score (GPS) predicted survival independent of established scoring systems in patients with metastatic renal cancer.

Glasgow Prognostic Score is a predictor of perioperative and long-term outcome in patients with only surgically treated esophageal cancer.

PubMed

Vashist, Yogesh K; Loos, Julian; Dedow, Josephine; Tachezy, Michael; Uzunoglu, Guentac; Kutup, Asad; Yekebas, Emre F; Izbicki, Jakob R

2011-04-01

Systemic inflammation (SI) plays a pivotal role in cancer. C-reactive protein (CRP) and albumin as parameters of SI form the Glasgow Prognostic Score (GPS). The purpose of the study was to evaluate the potential prognostic role of GPS in a homogeneous population of esophageal cancer (EC) patients undergoing only resection. GPS was evaluated on the basis of admission blood sample taken before surgery. Patients with a CRP < 10 mg/L and albumin > 35 g/L were allocated to GPS0 group. If only CRP was increased or albumin decreased patients were allocated to the GPS1 and patients in whom CRP was ≥10 mg/L and albumin level ≤35 g/L were classified as GPS2. GPS was correlated to clinicopathological parameters and clinical outcome. Increasing GPS significantly correlated with more aggressive tumor biology in terms of tumor size (P < 0.001), presence of regional (P = 0.01) and nonregional lymph node metastasis (P = 0.02), and higher tumor recurrence rate (P < 0.001). Furthermore, GPS was identified as an independent prognosticator of perioperative morbidity (odds ratio 1.9; P = 0.03). In addition, a gradual decrease in disease-free and overall survival was evident between the three GPS subgroups. Survival differences between the GPS groups remained apparent even after stratification of the study population to underlying tumor type and nodal status. GPS was identified as a strong prognosticator of tumor recurrence (hazard ratio 2.5; P < 0.001) and survival (hazard ratio 3.0; P < 0.001) in EC. GPS represents a strong prognosticator of perioperative morbidity and long-term outcome in resected EC patients without neoadjuvant or adjuvant treatment.

Amino acid tracers in PET imaging of diffuse low-grade gliomas: a systematic review of preoperative applications.

PubMed

Näslund, Olivia; Smits, Anja; Förander, Petter; Laesser, Mats; Bartek, Jiri; Gempt, Jens; Liljegren, Ann; Daxberg, Eva-Lotte; Jakola, Asgeir Store

2018-05-24

Positron emission tomography (PET) imaging using amino acid tracers has in recent years become widely used in the diagnosis and prediction of disease course in diffuse low-grade gliomas (LGG). However, implications of preoperative PET for treatment and prognosis in this patient group have not been systematically studied. The aim of this systematic review was to evaluate the preoperative diagnostic and prognostic value of amino acid PET in suspected diffuse LGG. Medline, Cochrane Library, and Embase databases were systematically searched using keywords "PET," "low-grade glioma," and "amino acids tracers" with their respective synonyms. Out of 2137 eligible studies, 28 met the inclusion criteria. Increased amino acid uptake (lesion/brain) was consistently reported among included studies; in 25-92% of subsequently histopathology-verified LGG, in 83-100% of histopathology-verified HGG, and also in some non-neoplastic lesions. No consistent results were found in studies reporting hot spot areas on PET in MRI-suspected LGG. Thus, the diagnostic value of amino acid PET imaging in suspected LGG has proven difficult to interpret, showing clear overlap and inconsistencies among reported results. Similarly, the results regarding the prognostic value of PET in suspected LGG and the correlation between uptake ratios and the molecular tumor status of LGG were conflicting. This systematic review illustrates the difficulties with prognostic studies presenting data on group-level without adjustment for established clinical prognostic factors, leading to a loss of additional prognostic information. We conclude that the prognostic value of PET is limited to analysis of histological subgroups of LGG and is probably strongest when using kinetic analysis of dynamic FET uptake parameters.

The utility of long non-coding RNA ZEB1-AS1 as a prognostic biomarker in human solid tumors: A meta-analysis.

PubMed

Zuo, Xue-Liang; Cai, Juan; Chen, Zhi-Qiang; Zhang, Yao; Liang, Lin-Hu; Wang, Jun-Feng; Wang, Jin-Guo; Wu, Jian; Mao, Jia-Ding

2018-06-12

This meta-analysis aims to assess the prognostic value of long non-coding RNA ZEB1-AS1 in human solid tumors. We searched the available databases up to January 2018. Pooled hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) were used to examine the prognostic impact of ZEB1-AS1 on patient survival. Eight eligible studies with a total of 586 patients were enrolled. A significant association was observed between ZEB1-AS1 overexpression and poor overall survival (OS; HR = 2.195, 95% CI: 1.749-2.755) as well as unfavorable recurrence-free survival (pooled HR = 2.205, 95% CI: 1.486-3.270), and no heterogeneity was found across these studies (p = .962, I 2  = 0%). Subsequent subgroup analyses showed that cancer type, sample size, follow up months, and HR estimation method did not alter the significant prognostic value of ZEB1-AS1. ZEB1-AS1 expression was indicated to be an independent prognostic factor for tumor OS (pooled HR = 2.177, 95% CI:1.545-3.069). Furthermore, we found that increased ZEB1-AS1 expression was significantly associated with tumor stage [III-IV vs. I-II: odds ratio (OR) = 1.644, 95% CI: 1.201-2.249] and lymph node metastasis (Positive vs. Negative: OR = 2.413, 95% CI: 1.504-3.873). High expression level of ZEB1-AS1 was associated with unfavorable survival outcome for cancer patients, and ZEB1-AS1 could be used as a prognostic predictor for cancers. Copyright © 2018 Elsevier B.V. All rights reserved.

Hilar fat infiltration: A new prognostic factor in metastatic clear cell renal cell carcinoma with first-line sunitinib treatment.

PubMed

Kammerer-Jacquet, Solène-Florence; Brunot, Angelique; Bensalah, Karim; Campillo-Gimenez, Boris; Lefort, Mathilde; Bayat, Sahar; Ravaud, Alain; Dupuis, Frantz; Yacoub, Mokrane; Verhoest, Gregory; Peyronnet, Benoit; Mathieu, Romain; Lespagnol, Alexandra; Mosser, Jean; Edeline, Julien; Laguerre, Brigitte; Bernhard, Jean-Christophe; Rioux-Leclercq, Nathalie

2017-10-01

The selection of patients with metastatic clear cell renal cell carcinoma (ccRCC) who may benefit from targeted tyrosine kinase inhibitors has been a challenge, even more so now with the advent of new therapies. Hilar fat infiltration (HFI) is a validated prognostic factor in nonmetastatic ccRCC (TNM 2009 staging system) but has never been studied in metastatic patients. We aimed to assess its phenotype and prognostic effect in patients with metastatic ccRCC treated with first-line sunitinib. In a multicentric study, we retrospectively included 90 patients and studied the corresponding ccRCC at the pathological, immunohistochemical, and molecular levels. Patient and tumor characteristics were compared using univariate and multivariate analysis. All the features were then studied by Cox models for prognostic effect. HFI was found in 42 patients (46.7%), who had worse prognosis (Heng criteria) (P = 0.003), liver metastases (P = 0.036), and progressive diseases at first radiological evaluation (P = 0.024). The corresponding ccRCC was associated with poor pathological prognostic factors that are well known in nonmetastatic ccRCC. For these patients, median progression-free survival was 4 months vs. 13 months (P = 0.02), and median overall survival was 14 months vs. 29 months (P = 0.006). In a multivariate Cox model integrating all the variables, only poor prognosis, according to the Heng criteria and HFI, remained independently associated with both progression-free survival and overall survival. HFI was demonstrated for the first time to be an independent poor prognostic factor. Its potential role in predicting resistance to antiangiogenic therapy warrants further investigation. Copyright © 2017 Elsevier Inc. All rights reserved.

A systematic review of prognostic factors for return to work following work-related traumatic hand injury.

PubMed

Shi, Qiyun; Sinden, Kathryn; MacDermid, Joy C; Walton, David; Grewal, Ruby

2014-01-01

Systematic review. Traumatic hand injuries are frequent cause of work related injuries and can result in prolonged durations of time loss from work. To systematically review available evidence to determine which prognostic factors predict return-to-work (RTW) following work-related traumatic hand injuries. We searched Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL and PsycINFO from 1980 to September 2013 and reference lists of articles. Studies investigating any prognostic factors of RTW after traumatic hand injury were included. Two reviewers performed study selection, assessment of methodological quality and data extraction independently of each other. Identified factors were grouped into conceptual prognostic factor categories. We assessed 8 studies, which addressed 11 potential prognostic factors (i.e., sociodemographic factors, occupation, work compensation status, treatment related factors, impairment severity, location of injury, etc.). The quality of the studies was low to moderate. Across all included studies, RTW (original or modified work) occurred in over 60% of individuals by 6 months. There was consistent low-moderate quality evidence that individuals with more severe impairments and lower pre-injury income were less likely to RTW, and low-moderate quality evidence that age, gender and level of education had no impact on RTW. Evidence on other commonly cited prognostic factors were limited in the literature. Impairment severity and lower pre-injury income showed a consistent association with RTW following occupational hand injury, while other factors demonstrated no or variable effects across studies. Additional high-quality studies are warranted toward improving our understanding of the complex factors that mediate RTW following a traumatic work-related hand injury. 2a. Copyright © 2014 Hanley & Belfus. Published by Elsevier Inc. All rights reserved.

Increased hs-CRP and decreased 1,25-dihydroxyvitamin D are associated with increased left ventricle lead threshold.

PubMed

Gözübüyük, Gökhan; Koç, Mevlüt; Kaypaklı, Onur; Şahin, Durmuş Yıldıray

2016-11-01

There are not enough data about threshold changes in patients with CRT. In this study, we aimed to investigate frequency of significant threshold increase of left ventricle lead and to determine clinical, demographic, medical and laboratory parameters that associated with threshold increase in CRT implanted patients. We included CRT implanted 200 patients (124 males, 76 females; mean age 65.8 ± 10.3 years) to this study. Basal and third month LV R wave amplitude, electrode impedance, and threshold values were recorded. Threshold increase was accepted as ≥0.1 V and significant increase as >1 V. Patients were divided into two groups: increased threshold and non-increased threshold for LV lead. Number of patients with increased LV threshold was 68 (37.6 %). Furthermore, 8 % of patients had severe increase (≥1 V) in LV threshold. We observed that serum levels of hs-CRP and 1,25 (OH)2 vitamin D were independently associated with increased LV threshold. We showed that 1 mg/dl increase in hs-CRP and the 1 mg/dl decrease in vitamin D are associated with 25.3 and 4.5 % increase in the odds of increased LV threshold, respectively. Increased hs-CRP and decreased 1,25 (OH)2 vitamin D are the strongest predictors of increased LV lead thresholds. We suggest that hs-CRP and 1,25 (OH)2 vitamin D may be used as markers to predict and follow the patients with increased thresholds. It may be useful to finalize CRT procedure with more appropriate basal threshold in patients with high serum hs-CRP and low 1,25 (OH)2 vitamin D levels.

Defining operating rules for mitigation of drought effects on water supply systems

NASA Astrophysics Data System (ADS)

Rossi, G.; Caporali, E.; Garrote, L.; Federici, G. V.

2012-04-01

Reservoirs play a pivotal role for water supply systems regulation and management especially during drought periods. Optimization of reservoir releases, related to drought mitigation rules is particularly required. The hydrologic state of the system is evaluated defining some threshold values, expressed in probabilistic terms. Risk deficit curves are used to reduce the ensemble of possible rules for simulation. Threshold values can be linked to specific actions in an operational context in different levels of severity, i.e. normal, pre-alert, alert and emergency scenarios. A simplified model of the water resources system is built to evaluate the threshold values and the management rules. The threshold values are defined considering the probability to satisfy a given fraction of the demand in a certain time horizon, and are validated with a long term simulation that takes into account the characteristics of the evaluated system. The threshold levels determine some curves that define reservoir releases as a function of existing storage volume. A demand reduction is related to each threshold level. The rules to manage the system in drought conditions, the threshold levels and the reductions are optimized using long term simulations with different hypothesized states of the system. Synthetic sequences of flows with the same statistical properties of the historical ones are produced to evaluate the system behaviour. Performances of different values of reduction and different threshold curves are evaluated using different objective function and performances indices. The methodology is applied to the urban area Firenze-Prato-Pistoia in central Tuscany, in Central Italy. The considered demand centres are Firenze and Bagno a Ripoli that have, accordingly to the census ISTAT 2001, a total of 395.000 inhabitants.

Synchronization of low- and high-threshold motor units.

PubMed

Defreitas, Jason M; Beck, Travis W; Ye, Xin; Stock, Matt S

2014-04-01

We examined the degree of synchronization for both low- and high-threshold motor unit (MU) pairs at high force levels. MU spike trains were recorded from the quadriceps during high-force isometric leg extensions. Short-term synchronization (between -6 and 6 ms) was calculated for every unique MU pair for each contraction. At high force levels, earlier recruited motor unit pairs (low-threshold) demonstrated relatively low levels of short-term synchronization (approximately 7.3% extra firings than would have been expected by chance). However, the magnitude of synchronization increased significantly and linearly with mean recruitment threshold (reaching 22.1% extra firings for motor unit pairs recruited above 70% MVC). Three potential mechanisms that could explain the observed differences in synchronization across motor unit types are proposed and discussed. Copyright © 2013 Wiley Periodicals, Inc.

Prognostic Value of microRNA-9 in Various Cancers: a Meta-analysis.

PubMed

Zhang, Yunyuan; Zhou, Jun; Sun, Meiling; Sun, Guirong; Cao, Yongxian; Zhang, Haiping; Tian, Runhua; Zhou, Lan; Duan, Liang; Chen, Xian; Lun, Limin

2017-07-01

Recently, there are more and more evidences from studies have revealed the association between microRNA-9 (miR-9) expression and outcome in multiple cancers, but inconsistent results have also been reported. It is necessary to rationalize a meta analysis of all available data to clarify the prognostic role of miR-9. Eligible studies were selected through multiple search strategies and the quality was assessed by MOOSE. Data was extracted from studies according to the key statistics index. All analyses were performed using STATA software. Twenty studies were selected in the meta-analysis to evaluate the prognostic role of miR-9 in multiple tumors. MiR-9 expression level was an independent prognostic biomarker for OS in tumor patients using multivariate and univariate analyses. High expression levels of miR-9 was demonstrated to associated with poor overall survival (OS) (HR = 2.23, 95 % CI: 1.56-3.17, P < 0.05) and recurrence free survival/progress free survival (RFS/PFS) (HR = 2.08, 95 % CI: 1.33-3.27, P < 0.05). Subgroup analysis showed that residence region (China and Japan), sample size, cancer type (solid or leukemia), follow-up months and analysis method (qPCR) did not alter the predictive value of miR-9 on OS in various cancers. Furthermore, no significant associations were detected for miR-9 expression and lymph node metastasis or distant metastasis. The present results suggest that promoted miR-9 expression is associated with poor OS in patients with general cancers.

The Value of lncRNA NEAT1 as a Prognostic Factor for Survival of Cancer Outcome: A Meta-Analysis.

PubMed

Zhang, Yunyuan; Lun, Limin; Li, Hui; Wang, Qing; Lin, Jieru; Tian, Runhua; Pan, Huazheng; Zhang, Haiping; Chen, Xian

2017-10-12

The present meta-analysis aimed to analyze available data to identify the prognostic role of NEAT1 in multiple carcinomas. A systematic search was performed by using several computerized databases from inception to June 7, 2017. The quantity of the publications was assessed according to MOOSE checklist. Pooled HRs with 95% CI was calculated to summarize the effect. A total of 12 studies with 3,262 cancer patients were pooled in the analysis to evaluate the prognostic value of NEAT1 in multiple tumors. High expression levels of NEAT1 were demonstrated to be associated with poor OS (HR = 1.71, 95%CI: 1.37-2.14, P < 0.001) and tumor progression (III/IV vs. I/II: HR 1.76, 95%CI: 1.40-2.21, P < 0.00001). Subgroup analysis showed that NEAT1 detection method (qRT-PCR) and sample size (more or less than 100) did not alter the predictive value of NEAT1 on OS in various cancers. According to the meta-regression results, the large heterogeneity of meta-analysis may be attributed to the differences of NEAT1 detection method. Furthermore, elevated NEAT1 expression significantly predicted lymph node metastasis (HR: 2.10, 95%CI: 1.32-3.33, P = 0.002) and distant metastasis (HR: 2.80, 95%CI: 1.60-4.91, P = 0.0003) respectively. The results indicate that NEAT1 expression level is a prognostic biomarker for OS and metastasis in general tumors.

Quantitative Assessment of the Safety Benefits Associated with Increasing Clinical Peanut Thresholds Through Immunotherapy.

PubMed

Baumert, Joseph L; Taylor, Steve L; Koppelman, Stef J

Peanut immunotherapy studies are conducted with the aim to decrease the sensitivity of patients to peanut exposure with the outcome evaluated by testing the threshold for allergic response in a double-blind placebo-controlled food challenge. The clinical relevance of increasing this threshold is not well characterized. We aimed to quantify the clinical benefit of an increased threshold for peanut-allergic patients. Quantitative risk assessment was performed by matching modeled exposure to peanut protein with individual threshold levels. Exposure was modeled by pairing US consumption data for various food product categories with potential contamination levels of peanut that have been demonstrated to be present on occasion in such food products. Cookies, ice cream, doughnuts/snack cakes, and snack chip mixes were considered in the risk assessment. Increasing the baseline threshold before immunotherapy from 100 mg or less peanut protein to 300 mg peanut protein postimmunotherapy reduces the risk of experiencing an allergic reaction by more than 95% for all 4 food product categories that may contain trace levels of peanut residue. Further increase in the threshold to 1000 mg of peanut protein had an additional quantitative benefit in risk reduction for all patients reacting to 300 mg or less at baseline. We conclude that achieving thresholds of 300 mg and 1000 mg of peanut protein by peanut immunotherapy is clinically relevant, and that the risk for peanut-allergic patients who have achieved this increased threshold to experience an allergic reaction is reduced in a clinically meaningful way. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Determination of minimal steady-state plasma level of diazepam causing seizure threshold elevation in rats.

PubMed

Dhir, Ashish; Rogawski, Michael A

2018-05-01

Diazepam, administered by the intravenous, oral, or rectal routes, is widely used for the management of acute seizures. Dosage forms for delivery of diazepam by other routes of administration, including intranasal, intramuscular, and transbuccal, are under investigation. In predicting what dosages are necessary to terminate seizures, the minimal exposure required to confer seizure protection must be known. Here we administered diazepam by continuous intravenous infusion to obtain near-steady-state levels, which allowed an assessment of the minimal levels that elevate seizure threshold. The thresholds for various behavioral seizure signs (myoclonic jerk, clonus, and tonus) were determined with the timed intravenous pentylenetetrazol seizure threshold test in rats. Diazepam was administered to freely moving animals by continuous intravenous infusion via an indwelling jugular vein cannula. Blood samples for assay of plasma levels of diazepam and metabolites were recovered via an indwelling cannula in the contralateral jugular vein. The pharmacokinetic parameters of diazepam following a single 80-μg/kg intravenous bolus injection were determined using a noncompartmental pharmacokinetic approach. The derived parameters V d , CL, t 1/2α (distribution half-life) and t 1/2β (terminal half-life) for diazepam were, respectively, 608 mL, 22.1 mL/min, 13.7 minutes, and 76.8 minutes, respectively. Various doses of diazepam were continuously infused without or with an initial loading dose. At the end of the infusions, the thresholds for various behavioral seizure signs were determined. The minimal plasma diazepam concentration associated with threshold elevations was estimated at approximately 70 ng/mL. The active metabolites nordiazepam, oxazepam, and temazepam achieved levels that are expected to make only minor contributions to the threshold elevations. Diazepam elevates seizure threshold at steady-state plasma concentrations lower than previously recognized. The minimally effective plasma concentration provides a reference that may be considered when estimating the diazepam exposure required for acute seizure treatment. Wiley Periodicals, Inc. © 2018 International League Against Epilepsy.

Branched-chain amino acids to tyrosine ratio (BTR) predicts intrahepatic distant recurrence and survival for early hepatocellular carcinoma.

PubMed

Ishikawa, Toru; Kubota, Tomoyuki; Horigome, Ryoko; Kimura, Naruhiro; Honda, Hiroki; Iwanaga, Akito; Seki, Keiichi; Honma, Terasu; Yoshida, Toshiaki

2013-01-01

The Child-Pugh classification system is the most widely used system for assessing hepatic functional reserve in HCC treatment. In the Child-Pugh classification system, serum albumin levels are used to accurately assess the status of protein metabolism and nutrition. To date, a lack of attention has been given to amino acid metabolism. In the present study, we investigated whether the branched-chain amino acids to tyrosine ratio (BTR) as an indicator of amino acid metabolism can serve as both a prognostic factor for early HCC and a predictive factor for recurrence. We conducted a cohort study of 50 patients with stage I/II HCC enrolled between May 2002 and December 2010. It was investigated whether BTR can serve as both a prognostic factor and a predictive factor for HCC recurrence. Overall survival rates were significantly higher in patients with high baseline BTR than in those with low BTR. Multivariate analysis showed that both BTR and serum albumin were prognostic factors, and that BTR was the best predictive factor for recurrence. BTR was a prognostic factor for early HCC and the most predictive factor for intrahepatic distant recurrence and contributing factors for survival.

Prognostic Impact of PHIP Copy Number in Melanoma: Linkage to Ulceration

PubMed Central

Nosrati, Mehdi; Tong, Schuyler; Wu, Clayton; Thummala, Suresh; Dar, Altaf A.; Leong, Stanley P.L.; Cleaver, James E.; Sagebiel, Richard W.; Miller, James R.; Kashani-Sabet, Mohammed

2013-01-01

Ulceration is an important prognostic factor in melanoma whose biologic basis is poorly understood. Here we assessed the prognostic impact of pleckstrin homology domain-interacting protein (PHIP) copy number and its relationship to ulceration. PHIP copy number was determined using fluorescence in situ hybridization (FISH) in a tissue microarray cohort of 238 melanomas. Elevated PHIP copy number was associated with significantly reduced DMFS (P = 0.01) and DSS (P = 0.009) by Kaplan-Meier analyses. PHIP FISH scores were independently predictive of DMFS (P = 0.03) and DSS (P = 0.03). Increased PHIP copy number was an independent predictor of ulceration status (P = 0.04). The combined impact of increased PHIP copy number and tumor vascularity on ulceration status was highly significant (P< 0.0001). Stable suppression of PHIP in human melanoma cells resulted in significantly reduced glycolytic activity in vitro, with lower expression of LDH5, HIF1A, and VEGF, and was accompanied by reduced microvessel density in vivo. These results provide further support for PHIP as a molecular prognostic marker of melanoma, and reveal a significant linkage between PHIP levels and ulceration. Moreover, they suggest that ulceration may be driven by increased glycolysis and angiogenesis. PMID:24005052

Preoperative Magnetic Resonance Volumetry in Predicting Myometrial Invasion, Lymphovascular Space Invasion, and Tumor Grade: Is It Valuable in International Federation of Gynecology and Obstetrics Stage I Endometrial Cancer?

PubMed

Sahin, Hilal; Sarioglu, Fatma Ceren; Bagci, Mustafa; Karadeniz, Tugba; Uluer, Hatice; Sanci, Muzaffer

2018-05-01

The aim of this retrospective single-center study was to evaluate the relationship between maximum tumor size, tumor volume, tumor volume ratio (TVR) based on preoperative magnetic resonance (MR) volumetry, and negative histological prognostic parameters (deep myometrial invasion [MI], lymphovascular space invasion, tumor histological grade, and subtype) in International Federation of Gynecology and Obstetrics stage I endometrial cancer. Preoperative pelvic MR imaging studies of 68 women with surgical-pathologic diagnosis of International Federation of Gynecology and Obstetrics stage I endometrial cancer were reviewed for assessment of MR volumetry and qualitative assessment of MI. Volume of the tumor and uterus was measured with manual tracing of each section on sagittal T2-weighted images. Tumor volume ratio was calculated according to the following formula: TVR = (total tumor volume/total uterine volume) × 100. Receiver operating characteristics curve was performed to investigate a threshold for TVR associated with MI. The Mann-Whitney U test, Kruskal-Wallis test, and linear regression analysis were applied to evaluate possible differences between tumor size, tumor volume, TVR, and negative prognostic parameters. Receiver operating characteristics curve analysis of TVR for prediction of deep MI was statistically significant (P = 0.013). An optimal TVR threshold of 7.3% predicted deep myometrial invasion with 85.7% sensitivity, 46.8% specificity, 41.9% positive predictive value, and 88.0% negative predictive value. Receiver operating characteristics curve analyses of TVR, tumor size, and tumor volume for prediction of tumor histological grade or lymphovascular space invasion were not significant. The concordance between radiologic and pathologic assessment for MI was almost excellent (κ value, 0.799; P < 0.001). Addition of TVR to standard radiologic assessment of deep MI increased the sensitivity from 90.5% to 95.2%. Tumor volume ratio, based on preoperative MR volumetry, seems to predict deep MI independently in stage I endometrial cancer with insufficient sensitivity and specificity. Its value in clinical practice for risk stratification models in endometrial cancer has to be studied in larger cohort of patients.

Prognostic significance of biomarkers in predicting outcome in patients with coronary artery disease and left ventricular dysfunction: results of the biomarker substudy of the Surgical Treatment for Ischemic Heart Failure trials.

PubMed

Feldman, Arthur M; Mann, Douglas L; She, Lilin; Bristow, Michael R; Maisel, Alan S; McNamara, Dennis M; Walsh, Ryan; Lee, Dorellyn L; Wos, Stanislaw; Lang, Irene; Wells, Gretchen; Drazner, Mark H; Schmedtje, John F; Pauly, Daniel F; Sueta, Carla A; Di Maio, Michael; Kron, Irving L; Velazquez, Eric J; Lee, Kerry L

2013-05-01

Patients with heart failure and coronary artery disease often undergo coronary artery bypass grafting, but assessment of the risk of an adverse outcome in these patients is difficult. To evaluate the ability of biomarkers to contribute independent prognostic information in these patients, we measured levels in patients enrolled in the biomarker substudies of the Surgical Treatment for Ischemic Heart Failure (STICH) trials. Patients in STICH Hypothesis 1 were randomized to medical therapy or coronary artery bypass grafting, whereas those in STICH Hypothesis 2 were randomized to coronary artery bypass grafting or coronary artery bypass grafting with left ventricular reconstruction. In substudy patients assigned to STICH Hypothesis 1 (n=606), plasma levels of soluble tumor necrosis factor-α receptor-1 (sTNFR-1) and brain natriuretic peptide (BNP) were highly predictive of the primary outcome variable of mortality by univariate analysis (BNP: χ(2)=40.6; P<0.0001 and sTNFR-1: χ(2)=38.9; P<0.0001). When considered in the context of multivariable analysis, both BNP and sTNFR-1 contributed independent prognostic information beyond the information provided by a large array of clinical factors independent of treatment assignment. Consistent results were seen when assessing the predictive value of BNP and sTNFR-1 in patients assigned to STICH Hypothesis 2 (n=626). Both plasma levels of BNP (χ(2)=30.3) and sTNFR-1 (χ(2)=45.5) were highly predictive in univariate analysis (P<0.0001) and in multivariable analysis for the primary end point of death or cardiac hospitalization. In multivariable analysis, the prognostic information contributed by BNP (χ(2)=6.0; P=0.049) and sTNFR-1 (χ(2)=8.8; P=0.003) remained statistically significant even after accounting for other clinical information. Although the biomarkers added little discriminatory improvement to the clinical factors (increase in c-index ≤0.1), net reclassification improvement for the primary end points was 0.29 for BNP and 0.21 for sTNFR-1 in the Hypothesis 1 cohort, and 0.15 for BNP and 0.30 for sTNFR-1 in the Hypothesis 2 cohort, reflecting important predictive improvement. Elevated levels of sTNFR-1 and BNP are strongly associated with outcomes, independent of therapy, in 2 large and independent studies, thus providing important cross-validation for the prognostic importance of these 2 biomarkers.

The Prognostic Significance of Biomarkers in Predicting Outcome in Patients With Coronary Artery Disease and Left Ventricular Dysfunction: Results of the Biomarker Sub-Study of the Surgical Treatment for Ischemic Heart Failure (STICH) Trials

PubMed Central

Feldman, Arthur M.; Mann, Douglas L.; She, Lilin; Bristow, Michael R.; Maisel, Alan S.; McNamara, Dennis M.; Walsh, Ryan; Lee, Dorellyn L.; Wos, Stanislaw; Lang, Irene; Wells, Gretchen; Drazner, Mark H.; Schmedtje, John F.; Pauly, Daniel F.; Sueta, Carla A.; Di Maio, Michael; Kron, Irving L.; Velazquez, Eric J.; Lee, Kerry L.

2013-01-01

Background Patients with heart failure and coronary artery disease often undergo coronary artery bypass grafting (CABG) but assessment of the risk of an adverse outcome in these patients is difficult. To evaluate the ability of biomarkers to contribute independent prognostic information in these patients, we measured levels in patients enrolled in the Biomarker Sub-studies of the Surgical Treatment for Ischemic Heart Failure (STICH) trials. Patients in STICH Hypothesis 1 were randomized to medical therapy or CABG whereas those in STICH Hypothesis 2 were randomized to CABG or CABG with left ventricular reconstruction. Methods and Results In sub-study patients assigned to STICH Hypothesis 1 (n=606), plasma levels of sTNFR-1 and BNP were highly predictive of the primary outcome variable of mortality by univariate analysis (BNP χ2=40.6; p<0.0001: sTNFR-1 χ2=38,9; p<0.0001). When considered in the context of multivariable analysis, both BNP and sTNFR-1 contributed independent prognostic information beyond the information provided by a large array of clinical factors independent of treatment assignment. Consistent results were seen when assessing the predictive value of BNP and sTNFR-1 in patients assigned to STICH Hypothesis 2 (n=626). Both plasma levels of BNP (χ2=30.3) and sTNFR-1 (χ2=45.5) were highly predictive in univariate analysis (p<0.0001) as well as in multivariable analysis for the primary endpoint of death or cardiac hospitalization. In multivariable analysis, the prognostic information contributed by BNP (χ2=6.0; p=0.049) and sTNFR-1 (χ2=8.8; p=0.003) remained statistically significant even after accounting for other clinical information. Although the biomarkers added little discriminatory improvement to the clinical factors (increase in c-index ≤ 0.1), Net Reclassification Improvement (NRI) for the primary endpoints was 0.29 for BNP and 0.21 for sTNFR-1in the Hypothesis 1 cohort, and 0.15 for BNP and 0.30 for sTNFR-1 in the Hypothesis 2 cohort, reflecting important predictive improvement. Conclusions Elevated levels of sTNFR-1 and BNP are strongly associated with outcomes, independent of therapy, in two large and independent studies, thus providing important cross-validation for the prognostic importance of these two biomarkers. PMID:23584092

Forecasting the probability of future groundwater levels declining below specified low thresholds in the conterminous U.S.

USGS Publications Warehouse

Dudley, Robert W.; Hodgkins, Glenn A.; Dickinson, Jesse

2017-01-01

We present a logistic regression approach for forecasting the probability of future groundwater levels declining or maintaining below specific groundwater-level thresholds. We tested our approach on 102 groundwater wells in different climatic regions and aquifers of the United States that are part of the U.S. Geological Survey Groundwater Climate Response Network. We evaluated the importance of current groundwater levels, precipitation, streamflow, seasonal variability, Palmer Drought Severity Index, and atmosphere/ocean indices for developing the logistic regression equations. Several diagnostics of model fit were used to evaluate the regression equations, including testing of autocorrelation of residuals, goodness-of-fit metrics, and bootstrap validation testing. The probabilistic predictions were most successful at wells with high persistence (low month-to-month variability) in their groundwater records and at wells where the groundwater level remained below the defined low threshold for sustained periods (generally three months or longer). The model fit was weakest at wells with strong seasonal variability in levels and with shorter duration low-threshold events. We identified challenges in deriving probabilistic-forecasting models and possible approaches for addressing those challenges.

An elevated respiratory quotient predicts complications after cardiac surgery under extracorporeal circulation: an observational pilot study.

PubMed

Piot, J; Hébrard, A; Durand, M; Payen, J F; Albaladejo, P

2018-04-17

Following cardiac surgery, hyperlactatemia due to anaerobic metabolism is associated with an increase in both morbidity and mortality. We previously found that an elevated respiratory quotient (RQ) predicts anaerobic metabolism. In the present study we aimed to demonstrate that it is also associated with poor outcome following cardiac surgery. This single institution, prospective, observational study includes all those patients that were consecutively admitted to the intensive care unit (ICU) after cardiac surgery with cardiopulmonary bypass, that had also been monitored using pulmonary artery catheter. Data were recorded at admission (H0) and after one hour (H1) including: oxygen consumption ([Formula: see text]), carbon dioxide production ([Formula: see text]), RQ ([Formula: see text]), lactate levels and mixed venous oxygen saturation ([Formula: see text]). The primary endpoint was defined as mortality at 30 days. Comparison of the area under the curve (AUC) for receiver operating characteristic curves was used to analyze the prognostic predictive value of RQ, lactate levels and [Formula: see text], in terms of patient outcome. We studied 151 patients admitted to the ICU between May 2015 and February 2016. Seventy eight patients experienced a worse than expected outcome in the post-operative period, and among those seven died. RQ at H1 in non-survivors ([Formula: see text]) was higher than in survivors ([Formula: see text]; p = 0.02). The AUC for RQ to predict mortality was 0.77 (IC 95% [0.70-0.84]), with a threshold value of 0.76 (sensitivity 64%, specificity 100%). By comparison, the AUC for lactate levels was significantly superior (AUClact 0.89, IC 95% [0.83-0.93], p = 0.02). In this study, elevated RQ appeared to be predictive of mortality after cardiac surgery with CPB.

Prognostic value of plasma fibrinogen levels in patients with localized upper tract urothelial carcinoma.

PubMed

Tanaka, Nobuyuki; Kikuchi, Eiji; Matsumoto, Kazuhiro; Hayakawa, Nozomi; Ide, Hiroki; Miyajima, Akira; Nakamura, So; Oya, Mototsugu

2013-05-01

WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Upper tract urothelial carcinoma (UTUC) is relatively uncommon, accounting for only ~5% of urothelial malignancies and 10% of all renal tumours. Radical nephroureterectomy (RNU) with bladder cuff excision is the surgical standard of care for treating localized UTUC, but the prognosis for patients who undergo RNU remains poor. Evidence suggests that an interactive relationship exists between haemostatic factors and tumour biology. A number of procoagulant and fibrinolytic factors have been found to be overexpressed in tumours. One of these factors is plasma fibrinogen. Recent studies have shown that elevated pre-therapeutic plasma fibrinogen levels are associated with worse outcome in various malignancies; however, the prognostic value of plasma fibrinogen levels for UTUC has not yet been reported. To the best of our knowledge, this is the first paper to evaluate the prognostic impact of preoperative plasma fibrinogen levels in patients with localized UTUC treated surgically. We believe that the present results may assist in decision-making with respect to the need for lymph node dissection and neoadjuvant chemotherapy. To investigate the prognostic value of plasma fibrinogen levels as a predictor of patient outcome in upper tract urothelial carcinoma (UTUC). A total of 218 patients who underwent radical nephroureterectomy (RNU) for localized UTUC (pTa-4N0M0) were identified between 1995 and 2009. The association between preoperative plasma fibrinogen levels and clinicopathological variables was analysed. Forty-five patients experienced tumour recurrence, and 36 died from disease during the mean follow-up of 51 months. The mean (sd) preoperative plasma fibrinogen level was 362 (103) mg/dL. Kaplan-Meier curves showed that subsequent tumour recurrence was strongly predicted in patients with preoperative plasma fibrinogen levels ≥450 mg/dL, and similar results were observed for cancer-specific survival. On multivariate analysis we found that a preoperative plasma fibrinogen level of ≥450 mg/dL was an independent risk factor for subsequent tumour recurrence and cancer-specific survival. The 5-year recurrence-free survival rate was 56.9% in patients with plasma fibrinogen levels ≥450 mg/dL and 81.5% in patients with plasma fibrinogen levels <450 mg/dL (P < 0.001). The 5-year cancer-specific survival rate was 59.5% in patients with plasma fibrinogen levels of ≥450 mg/dL and 84.8% in patients with plasma fibrinogen levels <450 mg/dL (P < 0.001). On multivariate analysis, controlling for preoperative indicators, a preoperative plasma fibrinogen level of ≥450 mg/dL predicted worse pathological features, such as ≥pT3 disease and positive lymphovascular invasion, in surgical specimens. Preoperative elevated plasma fibrinogen level was an independent predictor for poor survival after RNU and for worse pathological features. Plasma fibrinogen levels may become a useful biomarker, particularly because of its low associated cost and easy accessibility. © 2012 BJU International.

The Diagnostic and Prognostic Value of Tumor Markers (CEA, SCC, CYFRA 21-1, TPS) in Head and Neck Cancer Patients.

PubMed

Barak, Vivian; Meirovitz, Amichay; Leibovici, Vera; Rachmut, Jacob; Peretz, Tamar; Eliashar, Ron; Gross, Menachem

2015-10-01

Establishing prognostic factors is very important in the management of cancer patients. Our aim was to evaluate the clinical significance of a panel of tumor markers, including CEA (Carcino Embryonic Antigen), SCC (Squamous Cell Carcinoma Antigen), TPS (Tissue Polypeptide Specific Antigen) and CYFRA 21-1 in head and neck cancer patients, for assessing treatment response and prognosis of patients. We evaluated 312 blood samples from 143 head and neck cancer patients, from several sub-groups: 82 Larynx Carcinoma pre- and 38 post-therapy, 46 Oral Cavity pre and 29 post-therapy, 12 nasopharynx, 16 parotid and other salivary gland patients. Blood tumor markers levels were evaluated by conventional ELISA assays. Correlations of marker levels to stage of disease, lymph node involvement and therapy, were performed. Serum levels of all four tumor markers were higher before therapy and decreased thereafter in all patients. The decrease in TPS level following therapy was significant (p=0.03). Significantly higher levels of TPS and similarly higher levels of the other tumor markers were demonstrated in advanced disease (stages III and IV) patients, as opposed to early disease (stages I and II) patients (p=0.012). Node positive patients had significantly higher TPS levels as compared to node negative (p=0.02). The same trend was shown by the other markers as well, but did not reach statistical significance. TPS was best correlated to survival of patients; those having low levels had the best clinical outcome and longer survival. CEA, SCC, TPS and CYFRA 21-1 can all serve as useful tumor markers in HNC patients. They assessed response to therapy and were prognostic for recurrence. TPS proved to be the most sensitive predictor of advanced disease and poor prognosis. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Prognostic value of carcinoembryonic antigen level in patients with colorectal cancer liver metastasis treated with percutaneous microwave ablation under ultrasound guidance.

PubMed

Peng, Shaoyong; Huang, Pinzhu; Yu, Huichuan; Wen, Yanlin; Luo, Yanxin; Wang, Xiaolin; Zhou, Jiaming; Qin, Si; Li, Tuoyang; Chen, Yao; Liu, Guangjian; Huang, Meijin

2018-03-01

Thermal ablation is an alternative treatment for colorectal cancer liver metastasis (CRLM). However, prognostic factors in patients with CRLM who have undergone microwave ablation (MWA) have not been clearly defined. Therefore, this study aimed to analyze the risk factors associated with early recurrence in patients with CRLM treated with MWA.Herein, we retrospectively analyzed data for 140 patients with CRLM who underwent MWA from 2013 to 2015 in our institution. Patients were grouped by median pretreatment carcinoembryonic antigen (CEA) level into the high CEA level (>3.7 ng/mL) group and low CEA level (≤3.7 ng/mL) group. Variables that might affect overall survival were subjected to univariable and multivariable Cox regression analysis.Our results showed a median progression-free survival (PFS) and median liver progression-free survival (LPFS) of 9 and 11.5 months, respectively, for the 99 CRLM patients analyzed. Both the median PFS duration (7.5 vs. 12.0 months; hazard ratio [HR]: 1.852; 95% confidence interval [CI]: 1.131-3.034; P = .014) and LPFS duration (7.5 vs 14.0 months; HR: 2.117; 95% CI: 1.247-3.593; P = .005) were significantly shorter in the high CEA level group than in the low level group. In multivariable analysis, high CEA level, >3 tumors, and positive node status for the primary tumor were independent factors for PFS, with corrected HRs of 2.11 (95% CI: 1.257-3.555; P = .005), 2.450 (95% CI: 1.420-4.226; P = .001), and 2.265 (95% CI: 1.304-3.935; P = .004), respectively. However, age, tumor size, regional lymph node were not associated with LPFS.CEA level could be a valuable prognostic factor for early recurrence in patients with CRLM after MWA irrespective of the presence of early local recurrence in the liver or disease progression.

Prognostic value of carcinoembryonic antigen level in patients with colorectal cancer liver metastasis treated with percutaneous microwave ablation under ultrasound guidance

PubMed Central

Peng, Shaoyong; Huang, Pinzhu; Yu, Huichuan; Wen, Yanlin; Luo, Yanxin; Wang, Xiaolin; Zhou, Jiaming; Qin, Si; Li, Tuoyang; Chen, Yao; Liu, Guangjian; Huang, Meijin

2018-01-01

Abstract Thermal ablation is an alternative treatment for colorectal cancer liver metastasis (CRLM). However, prognostic factors in patients with CRLM who have undergone microwave ablation (MWA) have not been clearly defined. Therefore, this study aimed to analyze the risk factors associated with early recurrence in patients with CRLM treated with MWA. Herein, we retrospectively analyzed data for 140 patients with CRLM who underwent MWA from 2013 to 2015 in our institution. Patients were grouped by median pretreatment carcinoembryonic antigen (CEA) level into the high CEA level (>3.7 ng/mL) group and low CEA level (≤3.7 ng/mL) group. Variables that might affect overall survival were subjected to univariable and multivariable Cox regression analysis. Our results showed a median progression-free survival (PFS) and median liver progression-free survival (LPFS) of 9 and 11.5 months, respectively, for the 99 CRLM patients analyzed. Both the median PFS duration (7.5 vs. 12.0 months; hazard ratio [HR]: 1.852; 95% confidence interval [CI]: 1.131–3.034; P = .014) and LPFS duration (7.5 vs 14.0 months; HR: 2.117; 95% CI: 1.247–3.593; P = .005) were significantly shorter in the high CEA level group than in the low level group. In multivariable analysis, high CEA level, >3 tumors, and positive node status for the primary tumor were independent factors for PFS, with corrected HRs of 2.11 (95% CI: 1.257–3.555; P = .005), 2.450 (95% CI: 1.420–4.226; P = .001), and 2.265 (95% CI: 1.304–3.935; P = .004), respectively. However, age, tumor size, regional lymph node were not associated with LPFS. CEA level could be a valuable prognostic factor for early recurrence in patients with CRLM after MWA irrespective of the presence of early local recurrence in the liver or disease progression. PMID:29517661

Preoperative serum HER2 extracellular domain levels in primary invasive breast cancer.

PubMed

Lee, Sae Byul; Lee, Jong Won; Yu, Jong Han; Ko, Beom Seok; Kim, Hee Jeong; Son, Byung Ho; Gong, Gyungyub; Lee, Hee Jin; Kim, Sung-Bae; Jung, Kyung Hae; Ahn, Jin-Hee; Lee, Woochang; Sung, Joohon; Ahn, Sei-Hyun

2014-12-10

Despite the preclinical outcomes and biologic significance of the presence of the human epidermal growth factor receptor-2 (HER2) extracellular domain (ECD), there is little evidence supporting the measurement of ECD levels in any clinical setting. The aim of this study was to determine the prevalence of elevated serum HER2 ECD levels, the association between these levels and tissue HER2 overexpression, and the potential clinical prognostic value of HER2 ECD in primary invasive breast cancer. Serum HER2 ECD levels were examined preoperatively in 2,862 consecutive stage I-III primary breast cancer patients between 2007 and 2009. Serum HER2 ECD levels were measured by chemiluminescence immunoassay (ADVIA Centaur), and the tissue HER2 status was assessed by immunohistochemistry and fluorescence in situ hybridization. The cutoff value for the serum level of HER2 ECD was set at 15.2 ng/ml. Among the 2,862 patients, 126 (4.4%) had elevated serum HER2 ECD levels, and HER2 was overexpressed in the tumor tissue of 692 patients (24.2%), with a concordance of 78.7%. Multivariate analysis revealed that elevated serum HER2 ECD was a significant independent prognostic factor for worse distant-metastasis-free survival [DMFS; hazard ratio (HR) = 2.50, 95% confidence interval (CI) = 1.5-4.3, P = 0.001] and breast-cancer-specific survival (BCSS; HR = 2.0, 95% CI = 1.1-3.8, P = 0.036), which were much stronger in patients with tissue HER2-positive tumors (DMFS: HR = 3.8, 95% CI = 2.0-7.0, P < 0.001; BCSS: HR = 2.6, 95% CI = 1.2-5.3, P = 0.012). Given the prevalence of HER2 expression, its measurement as an independent prognostic factor can be clinically useful, particularly in patients with tissue HER2-positive tumors.

Performance of the Prognocean Plus system during the El Niño 2015/2016: predictions of sea level anomalies as tools for forecasting El Niño

NASA Astrophysics Data System (ADS)

Świerczyńska-Chlaściak, Małgorzata; Niedzielski, Tomasz; Miziński, Bartłomiej

2017-04-01

The aim of this paper is to present the performance of the Prognocean Plus system, which produces long-term predictions of sea level anomalies, during the El Niño 2015/2016. The main objective of work is to identify such ocean areas in which long-term forecasts of sea level anomalies during El Niño 2015/2016 reveal a considerable accuracy. At present, the system produces prognoses using four data-based models and their combinations: polynomial-harmonic model, autoregressive model, threshold autoregressive model and multivariate autoregressive model. The system offers weekly forecasts, with lead time up to 12 weeks. Several statistics that describe the efficiency of the available prediction models in four seasons used for estimating Oceanic Niño index (ONI) are calculated. The accuracies/skills of the predicting models were computed in the specific locations in the equatorial Pacific, namely the geometrically-determined central points of all Niño regions. For the said locations, we focused on the forecasts which targeted at the local maximum of sea level, driven by the El Niño 2015/2016. As a result, a series of the "spaghetti" graphs (for each point, season and model) as well as plots presenting the prognostic performance of every model - for all lead times, seasons and locations - were created. It is found that the Prognocean Plus system has a potential to become a new solution which may enhance the diagnostic discussions on the El Niño development. The forecasts produced by the threshold autoregressive model, for lead times of 5-6 weeks and 9 weeks, within the Niño1+2 region for the November-to-January (NDJ) season anticipated the culmination of the El Niño 2015/2016. The longest forecasts (8-12 weeks) were found to be the most accurate in the phase of transition from El Niño to normal conditions (the multivariate autoregressive model, central point of Niño1+2 region, the December-to-February season). The study was conducted to verify the ability and usefulness of sea level anomaly forecasts in predicting phenomena that are controlled by the ocean-atmosphere processes, such as El Niño Southern Oscillation or North Atlantic Oscillation. The results may support further investigations into long-term forecasting of the quantitative indices of these oscillations, solely based on prognoses of sea level change. In particular, comparing the accuracies of prognoses of the North Atlantic Oscillation index remains one of the tasks of the research project no. 2016/21/N/ST10/03231, financed by the National Science Center of Poland.